CROSS-REFERENCE This application is a continuation of U.S. application Ser. No. 16/809,343, filed Mar. 4, 2020, which application is a continuation of International Application No. PCT/US20181050029, filed Sep. 7, 2018, which claims priority to U.S. Provisional Application No. 62/555,564 filed Sep. 7, 2017, and U.S. Provisional Application No. 62/652,047 filed Apr. 3, 2018, which applications are incorporated herein by reference in their entireties.
SEQUENCE LISTING The instant application contains a Sequence Listing conforming to the rules of WIPO Standard ST.26 which is hereby incorporated by reference in its entirety. The electronic Sequence Listing file, entitled 079445-001630US_ST26.xml, was updated on Feb. 21, 2023, and is 1,273,377 bytes in size.
BACKGROUND With the rapid progress being made in genome sciences, effective genome engineering holds great promise both in understanding the molecular bases of human diseases and in treating human disorders with identifiable alterations in the genome. The past few years have witnessed a rapid rise of the RNA-guided CRISPR/Cas9 technology from obscurity. Significant efforts are being devoted to optimizing the current CRISPR/Cas9 system and/or to identifying more Cas9-like nucleases with better efficiency and specificity.
Similarly, significant efforts are being employed to identify new systems that can be harnessed for genome editing with improved specificity and efficiency.
INCORPORATION BY REFERENCE All publications, patents, and patent applications herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. In the event of a conflict between a term herein and a term in an incorporated reference, the term herein controls.
SUMMARY OF THE INVENTION Disclosed herein is a polypeptide construct comprising: a prokaryotic RNase H-like domain-containing (RHDC) polypeptide sequence and a nucleic acid unwinding polypeptide sequence. In some cases, the RHDC polypeptide sequence cleaves a nucleic acid in a target polynucleotide sequence at a mesophilic temperature. In some cases the target polynucleotide sequence is bound by a guide DNA. In some cases, the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide sequence. In some cases, at least one of the RHDC polypeptide sequence or said nucleic acid unwinding polypeptide sequence are derived from a mesophilic organism. In some cases, the RHDC polypeptide sequence cleaves a nucleic acid in the target polynucleotide sequence at about 30° C., 31° C., 32° C., 33° C., 34° C., 35° C., 36° C., 37° C., 38° C. or 39° C. In some cases, the RHDC polypeptide sequence cleaves a nucleic acid in said target polynucleotide sequence at about 19° C., 20° C. 21° C., 22° C. 23 C, 24° C., 25° C., 26° C., 27° C. 28° C., 29° C. or 30° C. In some cases, the RHDC polypeptide sequence cleaves a nucleic acid in said target polynucleotide sequence at 37° C. In some cases, the mesophilic organism is a prokaryotic organism. In some cases, the prokaryotic organism is from a family selected from the group consisting of: bacteroidetes, proteobacteria, acidobacteria, actinobacteria, firmicutes, cyanobacteria, spirochactes, deinococcus, verrucomicrobia, planctomycetes, balneolaeota, and chloroflexi. In some cases, the RHDC polypeptide sequence is derived from a polypeptide encoded by a gene located in an adjacent operon to at least one of a P-element induced WImpy testis (PIWI) gene, RuvC, Cas, Sir2, Mrr, TIR, PLD, REase, restriction endonuclease, DExD/H, superfamily II helicase, RRXRR (SEQ ID NO: 380), DUF460, DUF3010, DUF429, DUF1092, COG5558, OrfB_IS605, Peptidase_A17, Ribonuclease H-like domain, 3′-5′ exonuclease domain, 3′-5′ exoribonuclease Rv2179c-like domain, Bacteriophage Mu, transposase, DNA-directed DNA polymerase, family B, exonuclease domain, Exonuclease, RNase T/DNA polymerase III, yqgF gene, HEPN, RNase LS domain, LsoA catalytic domain, KEN domain, RNaseL, Ire1, RNase domain, RloC, or PrrC. In some cases, the RHDC polypeptide sequence is derived from a polypeptide encoded by a gene located in an adjacent operon to at least one of a gene involved in defense, stress response, a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), Argonaute, or DNA repair. In some cases, the RHDC polypeptide sequence is an Argonaute domain sequence. In some cases, the RHDC polypeptide sequence comprises a nuclease, nickase, RNase, recombinase, flippase, transposase, or a combination thereof. In some cases, the polypeptide construct further comprises an additional functional polypeptide sequence fused to the RHDC polypeptide sequence and the nucleic acid unwinding polypeptide sequence. In some cases, the nucleic acid unwinding polypeptide is of prokaryotic or archaeal origin. In some cases, the nucleic acid unwinding polypeptide comprises a helicase, a topoisomerase, a Cas, or a combination thereof. In some cases, the Cas is a catalytically dead Cas or partially dead Cas (nickase). In some cases, the catalytically dead Cas is selected from the group consisting of catalytically dead derivatives of: Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csc5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, Cas9HiFi, xCas9, CasX, CasY, and CasRX. In some cases, the polypeptide construct further comprises an ATPase sequence. In some cases, the RHDC polypeptide sequence and the nucleic acid unwinding polypeptide sequence are fused by a linker sequence. In some cases, the linker is a polypeptide linker that comprises: a GSGSGS sequence or multiple copies of GSGSGS (SEQ ID NO: 381), non-charged amino acids, alpha-helical domains, or peptides with ligand-inducible conformational changes. In some cases, the linker is a polypeptide linker. In some cases, the nucleic acid unwinding polypeptide sequence and the RHDC polypeptide sequence are expressed in the same frame. In some cases, the polypeptide construct binds to the guide DNA. In some cases, the guide DNA is from about 1 base pair to about 30 base pairs in length. In some cases, the guide DNA is complementary to the target polynucleotide sequence. In some cases, the target polynucleotide sequence comprises a gene sequence. In some cases, the polypeptide construct produces a disruption in the gene sequence when introduced into a cell. In some cases, the disruption comprises a double strand break or a single strand break. In some cases, the RHDC polypeptide sequence comprises a firmicutes Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C. In some cases, the RHDC polypeptide sequence comprises a Clostridium Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C. In some cases, the Clostridium Argonaute domain comprises a Clostridium disporicum Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide sequence comprises a Thermoactinomyces Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C. In some cases, the Thermoactinomyces Argonaute domain comprises a Thermoactinomyces sp CDF Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide sequence comprises a Methylobacter Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C. In some cases, the Methylobacter Argonaute domain comprises a Methylobacter whittenburyi Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide sequence comprises a Thermosynechococcus Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C. In some cases, the Thermosynechococcus Argonaute domain comprises a Thermosynechococcus elongates Argonaute domain, or a functional fragment or variant thereof.
Disclosed herein is a polypeptide construct comprising a synthetic fusion of an Argonaute polypeptide sequence and a nucleic acid unwinding polypeptide sequence. In some cases, the Argonaute polypeptide sequence cleaves a target nucleic acid at a mesophilic temperature. In some cases, at least one of the Argonaute polypeptide sequence or the nucleic acid unwinding polypeptide sequence are derived from a mesophilic organism. In some cases, the Argonaute polypeptide sequence cleaves the target nucleic acid at about 19° C. to 40° C. In some cases, the Argonaute polypeptide sequence cleaves the target nucleic acid at about 30° C., 31° C., 32° C., 33° C., 34° C. 35° C. 36° C., 37° C., 38° C. or 39° C. In some cases, the Argonaute polypeptide sequence cleaves the target nucleic acid at 37° C. In some cases, the Argonaute polypeptide sequence is an archaeal Argonaute polypeptide sequence. In some cases, the Argonaute polypeptide sequence comprises a nuclease, nickase, RNase, recombinase, flippase, transposase, or a combination thereof. In some cases, the Argonaute polypeptide sequence and the nucleic acid unwinding polypeptide sequence are fused by a linker sequence.
Provided herein is an ex vivo cell comprising a polypeptide construct.
Provided herein is a nucleic acid encoding a polypeptide construct.
Provided herein is a composition comprising a polypeptide construct.
Provided herein is a method of genomic editing comprising contacting a cell with a polypeptide construct.
Provided herein is a kit comprising: a polypeptide construct and instructions for use thereof. In some cases, a kit can further comprise a container.
Provided herein is a polypeptide construct comprising: an RNase H-like domain-containing (RHDC) polypeptide sequence, a nucleic acid unwinding polypeptide sequence, and a nucleic-acid insertion polypeptide sequence. In some cases, the RHDC polypeptide sequence cleaves a nucleic acid in a target polynucleotide sequence at a mesophilic temperature to generate a cleaved nucleic acid. In some cases, the target polynucleotide sequence is bound by a guide DNA. In some cases, the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide sequence. In some cases, the nucleic-acid insertion polypeptide sequence inserts a nucleic acid sequence in the cleaved nucleic acid.
Provided herein is a polypeptide construct comprising: an RNase H-like domain-containing (RHDC) polypeptide sequence and a regulatory domain polypeptide (RDP) sequence. In some cases, the polypeptide construct further comprises a nucleic acid unwinding domain sequence. In some cases, the nucleic acid unwinding domain sequence comprises a catalytically dead Cas, a helicase, or a topoisomerase. In some cases, the RDP sequence is a Rad51 polypeptide, a recombinase, an epigenetic modulator, or a domain involved in germ cell repair. In some cases, the RHDC polypeptide sequence comprises a Firmicutes Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid in said target polynucleotide sequence at 37° C. In some cases, the RHDC polypeptide sequence comprises a Clostridium Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid in said target polynucleotide sequence at 37° C. In some cases, the Clostridium Argonaute domain comprises a Clostridium disporicum Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide sequence comprises a Thermoactinomyces Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid in said target polynucleotide sequence at 37° C. In some cases, the Thermoactinomyces Argonaute domain comprises a Thermoactinomyces sp CDF Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide comprises a Methylobacter Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid in said target polynucleotide sequence at 37° C. In some cases, the Methylobacter Argonaute domain comprises a Methylobacter whittenburyi Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide comprises a Thermosynechococcus Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid in said target polynucleotide sequence at 37° C. In some cases, the Thermosynechococcus Argonaute domain comprises a Thermosynechococcus elongates Argonaute domain, or a functional fragment or variant thereof.
Disclosed herein is a polypeptide construct comprising: an Argonaute polypeptide sequence, a nucleic acid unwinding polypeptide sequence, and a nucleic-acid insertion polypeptide sequence. In some cases, the Argonaute polypeptide sequence cleaves a nucleic acid at a mesophilic temperature and the nucleic acid-insertion polypeptide sequence inserts a nucleic acid sequence in the cleaved nucleic acid. In some cases, at least one of the Argonaute polypeptide sequence or the nucleic acid unwinding polypeptide sequence are derived from a mesophilic organism. In some cases, the Argonaute polypeptide sequence cleaves a nucleic acid from 19° C. to 40° C. In some cases, the Argonaute polypeptide sequence cleaves a nucleic acid at about 30° C. 31° C., 32° C., 33° C., 34° C., 35° C., 36° C., 37° C., 38° C. or 39° C. In some cases, the Argonaute polypeptide sequence cleaves a nucleic acid at 37° C. In some cases, the Argonaute polypeptide sequence is an archaeal Argonaute polypeptide sequence. In some cases, the Argonaute polypeptide sequence comprises a nuclease, nickase, RNase, recombinase, flippase, transposase, or a combination thereof. In some cases, the Argonaute polypeptide sequence and the nucleic acid unwinding polypeptide sequence are joined by a linker.
Provided herein is an ex vivo cell comprising a polypeptide construct.
Provided herein is a nucleic acid encoding a polypeptide construct.
Provided herein is a composition comprising a polypeptide construct.
Provided herein is a method of genomic editing comprising contacting a cell with a polypeptide construct.
Provided herein is a method comprising: contacting a cell with a nucleic acid editing system that comprises: (i) an RNase H-like domain-containing (RHDC) polypeptide sequence; (ii) a nucleic acid unwinding agent sequence; (iii) a guide nucleic acid; and (iv) a regulatory domain polypeptide (RDP) sequence. In some cases, the contacting results in editing of a nucleic acid in the cell. In some cases, the RHDC sequence, the nucleic acid unwinding agent sequence, and the RDP sequence are in a protein complex. In some cases, the protein complex associates with the guide nucleic acid to form a guided editing complex. In some cases, the guide nucleic acid is a guide DNA. In some cases, the guide nucleic acid is a guide RNA. In some cases, the RHDC domain is from an Argonaute. In some cases, the nucleic acid unwinding agent sequence comprises a helicase, a topoisomerase, a Cas, or a combination thereof. In some cases, the Cas is a catalytically dead or partially catalytically dead Cas. In some cases, the RDP sequence comprises a recombinase, an epigenetic modulator, a germ cell repair domain, a DNA repair protein, or a combination thereof. In some cases, the RDP sequence controls, in whole or in part, the nucleic acid editing. In some cases, the guide nucleic acid is complementary to the nucleic acid in the cell. In some cases, the nucleic acid in the cell encodes for a disease-related antigen. In some cases, the disease is a heart disease, diabetes, cancer, neurological disease, mental illness, a genetic disease, or a combination thereof. In some cases, the method has a lower energy requirement as compared to a corresponding nucleic acid editing method without the RDP sequence, and wherein the energy requirement is determined by calculating difference in ATP usage by providing a predetermined amount of ATP into a nucleic acid editing system, and calculating ATP usage based on ([ATP]-[ADP])/[modified DNA] after the editing. In some cases, the energy level is reduced by about 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, or up to 25% when the nucleic acid editing system comprising the RDP sequence is utilized as compared to the comparable nucleic acid editing system without the RDP sequence. In some cases, the method favors a genomic editing repair towards homology directed repair over non-homologous end joining, in some cases, the method further comprises introducing a transgene into a genome of the cell. In some cases, the introducing is performed non-virally. In some cases, the introducing is performed virally. In some cases, the cell is a primary cell or a recombinant cell. In some cases, the cell is a human cell. In some cases, the nucleic acid editing system is electroporated into the cell. In some cases, the method further comprises introducing a cell edited by the method to a subject in need thereof. In some cases, the RHDC polypeptide sequence comprises a firmicutes Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C. In some cases, the RHDC polypeptide sequence comprises a Clostridium Argonaute domain, or a functional fragment or variant thereof, that cleaves the nucleic acid at 37° C. In some cases, the Clostridium Argonaute domain comprises a Clostridium disporicum Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide sequence comprises a Thermoactinomyces Argonaute domain, or a functional fragment or variant thereof, that cleaves the nucleic acid at 37° C. In some cases, the Thermoactinomyces Argonaute domain comprises a Thermoactinomyces sp CDF Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide sequence comprises a Methylobacter Argonaute domain, or a functional fragment or variant thereof, that cleaves the nucleic acid at 37° C. In some cases, the Methylobacter Argonaute domain comprises a Methylobacter whittenburyi Argonaute domain, or a functional fragment or variant thereof. In some cases, the RHDC polypeptide sequence comprises a Thermosynechococcus Argonaute domain, or a functional fragment or variant thereof, that cleaves the nucleic acid at 37° C. In some cases, the Thermosynechococcus Argonaute domain comprises a Thermosynechococcus elongates Argonaute domain, or a functional fragment or variant thereof.
Provided herein is an isolated nucleic acid sequence comprising at least 60% identity to any one of SEQ ID NOs: 161 to 252. In some cases, the isolated nucleic acid sequence comprises at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 161 to 252.
Provided herein is a cell comprising an isolated nucleic acid sequence.
Provided herein is a cell comprising a protein encoded by an isolated nucleic acid sequence. In some cases, the cell further comprises a guide nucleic acid. In some cases, the cell further comprises a regulatory domain polypeptide (RDP).
Provided herein is an isolated polypeptide sequence comprising at least 60% identity to any one of SEQ ID NOs: 20 to 38. In some cases, the isolated polypeptide sequence further comprises at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to anyone of SEQ ID NOs: 20 to 38.
Provided herein is a cell comprising an isolated polypeptide sequence. In some cases, the cell further comprises a guide nucleic acid. In some cases, the cell further comprises a regulatory domain polypeptide (RDP) sequence.
Provided herein is a method of genome editing comprising: contacting a population of cells with a polypeptide construct, wherein at least about 5% of the population comprises a genomic disruption after the contacting. In some cases, at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60% of the population comprises the genomic disruption after the contacting.
Provided herein is a method of genome editing comprising: contacting a population of cells with an isolated polynucleic acid encoding a polypeptide construct, wherein at least about 5% of the population comprises a genomic disruption after the contacting. In some cases, at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60% of the population comprises the genomic disruption after the contacting.
Provided herein is a method of genome editing comprising: (a) unwinding a genomic sequence with a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) protein, thereby generating an unwound genomic sequence; and (b) introducing a genomic disruption in the unwound genomic sequence by contacting the unwound genomic sequence with a mesophilic RNase H-like domain-containing (RHDC) polypeptide, thereby editing the genome. In some cases, the CRISPR protein is a catalytically dead Cas or partially dead Cas (nickase). In some cases, the catalytically dead Cas is selected from the group consisting of catalytically dead derivatives of Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csc5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, Cas9HiFi, xCas9, CasX, CasY, and CasRX. In some cases, the Cas is dCas9. In some cases, the RHDC polypeptide comprises a polypeptide selected from RuvC, HNH, RNase H, PIWI, or a combination thereof. In some cases, the method further comprises a regulatory domain polypeptide (RDP). In some cases, the RDP comprises Rad51, a recombinase, an epigenetic modulator, or a domain involved in germ cell repair. In some cases, the genomic sequence is in a primary cell or a recombinant cell. In some cases, the genomic sequence is in a human cell.
Provided herein is a method of treating a disease in a subject in need thereof comprising administering a cell edited by a method disclosed herein. In some cases, the disease is heart disease, diabetes, cancer, neurological disease, immunological disease, mental illness, a genetic disease, or a combination thereof. In some cases, a measure of the disease is reduced by about 10% to about 50% after the administering.
Provided herein is a method of stabilizing a disease in a subject in need thereof comprising administering a cell edited by a method disclosed herein. In some cases, the stabilizing comprises a less than 5% change in a level of a disease in the subject after the administering.
Provided herein is a nucleic acid construct encoding a prokaryotic RNase H-like domain-containing (RHDC) polypeptide sequence and a nucleic acid unwinding polypeptide sequence, wherein the RHDC polypeptide sequence cleaves a nucleic acid in a target polynucleotide sequence at a mesophilic temperature, wherein the target polynucleotide sequence is bound by a guide DNA, and wherein the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide sequence in a polypeptide encoded by the nucleic acid construct.
Provided herein is a nucleic acid construct encoding an RNase H-like domain-containing (RHDC) polypeptide sequence, a nucleic acid unwinding polypeptide sequence, and a nucleic-acid insertion polypeptide sequence, wherein a protein encoded by said RHDC polypeptide sequence cleaves a nucleic acid in a target polynucleotide sequence at a mesophilic temperature, wherein the target polynucleotide sequence is bound by a guide DNA, wherein the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide sequence in a polypeptide encoded by the nucleic acid construct, and wherein the nucleic-acid insertion polypeptide sequence inserts a nucleic acid sequence in the cleaved nucleic acid.
Provided herein is a cell comprising: a polypeptide construct comprising a prokaryotic RNase H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide, wherein the RHDC polypeptide sequence cleaves a nucleic acid at a mesophilic temperature, wherein the nucleic acid-cleaving activity is bound by a guide DNA, and wherein the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide.
Provided herein is a cell comprising: a polypeptide construct comprising an RNase H-like domain-containing (RHDC) polypeptide sequence, a nucleic acid unwinding polypeptide sequence, and a nucleic-acid insertion polypeptide sequence, wherein a polypeptide encoded by the RHDC polypeptide sequence cleaves a nucleic acid in a target polynucleotide sequence at a mesophilic temperature, wherein the target polynucleotide sequence is bound by a guide DNA, wherein the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide, and wherein the nucleic-acid insertion polypeptide sequence inserts a nucleic acid sequence in the cleaved nucleic acid.
Provided herein is a cell comprising: a nucleic acid construct encoding a prokaryotic RNase H-like domain-containing (RHDC) polypeptide sequence and a nucleic acid unwinding polypeptide sequence, wherein the RHDC polypeptide sequence cleaves a nucleic acid in a target polynucleotide sequence at a mesophilic temperature, wherein the target polynucleotide sequence is bound by a guide DNA, and wherein the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide sequence.
Provided herein is a cell comprising: a nucleic acid construct encoding an RNase H-like domain-containing (RHDC) polypeptide sequence, a nucleic acid unwinding polypeptide sequence, and a nucleic-acid insertion polypeptide sequence, wherein the RHDC polypeptide sequence cleaves a nucleic acid in a target polynucleotide sequence at a mesophilic temperature, wherein the target polynucleotide sequence is bound by a guide DNA, wherein the RHDC polypeptide sequence is fused to the nucleic acid unwinding polypeptide sequence, and wherein the nucleic-acid insertion polypeptide sequence inserts a nucleic acid sequence in the cleaved nucleic acid.
Disclosed herein is a prokaryotic polypeptide construct comprising an RNase H-like domain-containing (RHDC) polypeptide sequence and a nucleic acid unwinding polypeptide. The RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature. The nucleic acid-cleaving activity is directed by a guide DNA, and the RHDC polypeptide is fused to the nucleic acid unwinding polypeptide.
Disclosed herein is a polypeptide construct comprising an RNase H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide. The RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature. The nucleic acid-cleaving activity is directed by a guide DNA, and the RHDC polypeptide is fused to the nucleic acid unwinding polypeptide.
Disclosed herein is a polypeptide construct comprising an Argonaute polypeptide and a nucleic acid unwinding polypeptide. The Argonaute polypeptide cleaves a nucleic acid at a mesophilic temperature. In some cases, at least one of the RHDC polypeptide or the nucleic acid unwinding polypeptide are derived from a mesophilic organism. In some cases, at least one of the Argonaute polypeptide or the nucleic acid unwinding polypeptide are derived from a mesophilic organism. The RHDC polypeptide can cleave a nucleic acid from about 30° C., 31° C., 32° C., 33° C. 34° C. 35° C., 36° C., 37° C., 38° C. to about 39° C. In some cases, the RHDC polypeptide cleaves a nucleic acid from about 19° C. to about 40° C. In some cases, the RHDC polypeptide cleaves a nucleic acid at 37° C. In some cases, the Argonaute polypeptide cleaves a nucleic acid at about 30° C., 31° C. 32° C., 33° C., 34° C., 35° C., 36° C. 37° C., 38° C. or 39° C. In some cases, the Argonaute polypeptide cleaves a nucleic acid at 37° C. In some cases, the mesophilic organism is a prokaryotic organism. The prokaryotic organism can be from a family selected from the group consisting of: bacteroidetes, proteobacteria, acidobacteria, actinobacteria, firmicutes, cyanobacteria, spirochaetes, deinococcus, verrucomicrobia, planctomycetes, balneolaeota, and chloroflexi. The RHDC polypeptide can be an archaeal Argonaute polypeptide. The Argonaute polypeptide can be an archaeal Argonaute polypeptide. The RHDC polypeptide can be encoded by a gene located in an adjacent operon to at least one of a P-element induced Wimpy testis (PIWI) gene, RuvC, Cas, Sir2, Mrr, TIR, PLD, REase, restriction endonuclease, DExD/H, superfamily II helicase, RRXRR SEQ ID NO: 380), DUF460, DUF3010, DUF429, DUF1092, COG5558, OrfB_IS605, Peptidase_A17, Ribonuclease H-like domain, 3′-5′ exonuclease domain, 3′-5′ exoribonuclease Rv2179c-like domain, Bacteriophage Mu, transposase, DNA-directed DNA polymerase, family B, exonuclease domain, Exonuclease, RNase T/DNA polymerase III, yqgF gene, HEPN, RNase LS domain, LsoA catalytic domain, KEN domain, RNaseL, Ire1, RNase domain, RloC, or PrrC, in some cases, the RHDC polypeptide is encoded by a gene located in an adjacent operon to at least one of a gene involved in defense, stress response, a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), Argonaute, or DNA repair. In some cases, the RHDC polypeptide is an Argonaute domain. In some cases, the RHDC polypeptide encodes for a nuclease, nickase, RNase, recombinase, flippase, transposase, or a combination thereof. In some cases, the Argonaute polypeptide encodes for a nuclease, nickase, RNase, recombinase, flippase, transposase, or a combination thereof. In some cases, the RHDC polypeptide encodes for an RNase. The nucleic acid unwinding polypeptide can be of prokaryotic or archaeal origin. In some cases, the nucleic acid unwinding polypeptide encodes for a helicase, a topoisomerase, a Cas, or a combination thereof. A Cas can be a catalytically dead Cas or partially dead Cas (nickase). A Cas can be partially catalytically dead. A Cas can be partially dead. In some cases, a catalytically dead Cas is selected from the group consisting of: Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csc5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, Cas9HiFi, xCas9, CasX, CasY, and CasRX. In some cases, a polypeptide construct further comprises an ATPase-encoding sequence. In some cases, the RHDC polypeptide and the nucleic acid unwinding polypeptide are joined by a linker. A linker can be a polypeptide linker that comprises: GSGSGS, non-charged amino acids, alpha-helical domains, and peptides with ligand-inducible conformational changes. In some cases, an Argonaute polypeptide and a nucleic acid unwinding polypeptide are joined by a linker. A linker can be a polypeptide linker. In some cases, a nucleic acid unwinding polypeptide and an RHDC polypeptide are expressed in the same frame. In some cases, a nucleic acid unwinding polypeptide and an Argonaute polypeptide are expressed in the same frame. In some cases, a protein encoded by a polypeptide construct is bound to a guide DNA. In some cases, a polypeptide construct can be bound to a guide nucleic acid. In some cases, a guide polynucleic acid can be a guide DNA (gDNA) or a guide RNA (gRNA). A guide DNA can be from about 1 base pair to about 30 base pairs in length. A guide DNA can be complementary to a target polynucleotide sequence. In some cases, a target polynucleotide sequence comprises a gene sequence. In some cases, a protein encoded by a polypeptide construct produces a disruption in a gene sequence when introduced into a cell. A disruption can comprise a double strand break or a single strand break.
Disclosed herein is an ex vivo cell comprising a polypeptide construct.
Disclosed herein is a method of genomic editing comprising contacting a cell with a protein encoded by a polypeptide construct.
Disclosed herein is a kit comprising a polypeptide construct and instructions for use thereof. A kit can further comprise a container.
Disclosed herein is a polypeptide construct comprising an RNase H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide. A protein encoded by the RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature. A nucleic acid-cleaving activity can be directed by a guide DNA. An RHDC polypeptide can be fused to a nucleic acid unwinding polypeptide, and a protein encoded by a polypeptide construct can further demonstrate nucleic acid-insertion activity.
Disclosed herein is a polypeptide construct comprising an Argonaute polypeptide and a nucleic acid unwinding polypeptide, a protein encoded by the Argonaute polypeptide cleaves a nucleic acid at a mesophilic temperature, and a protein encoded by the polypeptide construct further demonstrates nucleic acid-insertion activity.
Disclosed herein is a polypeptide construct comprising an RNase H-like domain-containing (RHDC) polypeptide and a regulatory domain polypeptide (RDP). A polypeptide construct can further comprise a nucleic acid unwinding domain. A nucleic acid unwinding domain can be a catalytically dead Cas, a helicase, or a topoisomerase. In some cases, an RDP is a Rad51 polypeptide, a recombinase, an epigenetic modulator, or a domain involved in germ cell repair.
Disclosed herein is a cell comprising a polypeptide construct.
Disclosed herein is a composition comprising a polypeptide construct.
Disclosed herein is a method comprising contacting a cell with a nucleic acid editing system that comprises an RNase H-like domain-containing (RHDC) polypeptide, a nucleic acid unwinding agent, a guide nucleic acid, and a regulatory domain polypeptide (RDP). In some cases, the RHDC, the nucleic acid unwinding agent, and the RDP are comprised m a protein complex. The protein complex associates with the guide nucleic acid to form a guided editing complex. In some cases, the guide nucleic acid is a guide DNA, a guide RNA, or a combination thereof. The RHDC domain can be from an Argonaute. The nucleic acid unwinding agent comprises a helicase, a topoisomerase, a Cas, or a combination thereof. In some cases, the Cas can be a catalytically dead Cas. A Cas can be partially catalytically dead. The RDP can comprise a recombinase, an epigenetic modulator, a germ cell repair domain, a DNA repair protein, or a combination thereof. In some cases, the RDP allows for tuning of nucleic acid editing. A guide nucleic acid can be complementary to a genomic sequence comprising a gene in a cell. In some cases, a gene encodes for a protein involved in a disease. A disease can be a heart disease, diabetes, cancer, neurological disease, immunological disease, mental illness, a genetic disease, or a combination thereof. In some cases, a method disclosed herein has a lower energy requirement as compared to a corresponding nucleic acid editing system without an RDP, and wherein the energy requirement is determined by calculating difference in ATP usage by providing a predetermined amount of ATP into nucleic acid editing systems, and calculating ATP usage based on ([ATP]-[ADP])/[modified DNA] after editing. In some cases, an energy level can be reduced by about 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, or up to 25% when the nucleic acid editing system is utilized as compared to said comparable nucleic acid editing system without the RDP. In some cases, a method skews a genomic editing repair towards homology directed repair over non-homologous end joining. Disclosed herein can be a method further comprising introducing a transgene into a genome of a cell. In some cases, introducing a transgene is performed non-virally or virally. A cell can be a primary cell or a recombinant cell. A cell can be human or non-human. A nucleic acid editing system can be electroporated into a cell. A method can further comprise introducing a cell edited by a nucleic acid editing system to a subject in need thereof.
Disclosed herein is an isolated nucleic acid sequence comprising at least 60% percent identity to any one of SEQ ID NOs: 161 to 252. An isolated nucleic acid sequence can further comprise at least about 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about 100% identity to a sequence disclosed herein.
Disclosed herein is a cell comprising a protein encoded by an isolated nucleic acid sequences. A cell can further comprise a guide nucleic acid. A cell can further comprise a protein encoded by a regulatory domain polypeptide (RDP).
Disclosed herein is a method of genome editing comprising contacting a population of cells with a protein encoded by the polypeptide construct or the polypeptide construct, wherein at least about 5% of said population comprises a genomic disruption after the contacting. In some cases, at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60% of said population of cells comprises a genomic disruption after the contacting.
Disclosed herein is a method of genome editing comprising unwinding a genomic sequence with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) protein thereby generating an unwound genomic sequence; and introducing a genomic disruption in said unwound genomic sequence by contacting with an RNase H-like domain-containing (RHDC) polypeptide thereby editing the genome. A CRISPR protein can be a catalytically dead Cas or partially dead Cas (nickase). A Cas can be partially catalytically dead. The catalytically dead Cas can be selected from the group consisting of: Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8 Cas9, Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csc5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, Cas9HiFi, xCas9, CasX, CasY, and CasRX. The Cas can be dCas9. An RHDC comprises a protein selected from RuvC, HNH, RNase H, PIWI, or a combination thereof. A method can further comprise a regulatory domain polypeptide (RDP). In some cases, an RDP can be Rad51, a recombinase, an epigenetic modulator, or a domain involved in germ cell repair. A cell can be a primary cell or a recombinant cell. A cell can be human or non-human.
Disclosed herein is a method of treating a disease in a subject in need thereof comprising administering a cell edited by the method. A disease can be heart disease, diabetes, cancer, neurological disease, immunological disease, mental illness, a genetic disease, or a combination thereof. In some cases, a level of a disease is reduced by about 10% to about 50% after said administering.
Disclosed herein is a method of stabilizing a disease in a subject in need thereof comprising administering a cell edited by the method. Stabilizing a disease can comprise less than a 5% change in a level of a disease in a subject.
In one embodiment, the present disclosure provides a polypeptide construct comprising an RNase-H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide, wherein the RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature, wherein the nucleic acid-cleaving activity is directed by a guide DNA, and wherein the RHDC polypeptide is fused to the nucleic acid unwinding polypeptide.
In some embodiments, the present disclosure provides a polypeptide construct comprising an Argonaute polypeptide and a nucleic acid unwinding polypeptide, wherein the Argonaute polypeptide cleaves a nucleic acid at a mesophilic temperature.
In some embodiments, the present disclosure provides a method of genome editing comprising introducing into a cell: (a) an RNase-H-like domain-containing (RHDC) polypeptide; (b) a nucleic acid unwinding agent; and (c) a guide DNA, wherein the guide DNA comprises a sequence that is complementary to at least a portion of a target nucleic acid sequence in the cell, wherein the nucleic acid unwinding agent unwinds at least a portion of the target sequence, and wherein the RHDC polypeptide introduces a genomic disruption into the target sequence at a mesophilic temperature.
In some embodiments, the present disclosure provides a method of genome editing comprising introducing into a cell: (a) an Argonaute polypeptide; (b) a nucleic acid unwinding agent: and (c) a guide polynucleic acid, wherein the guide polynucleic acid comprises a sequence that is complementary to at least a portion of a target nucleic acid sequence in the cell, wherein the nucleic acid unwinding agent unwinds at least a portion of the target sequence, and wherein the Argonaute polypeptide introduces a genomic disruption into the target sequence at a mesophilic temperature.
In some embodiments, the method further comprises introducing into the cell an exogenous nucleic acid sequence. In some embodiments, the exogenous nucleic acid sequence is introduced into a genomic disruption. In some embodiments, the exogenous nucleic acid sequence is introduced into a random genomic location. In some embodiments, the exogenous nucleic acid sequence is introduced via non-viral introduction or viral introduction. In some embodiments, the viral introduction comprises a retrovirus, lentivirus, adenovirus, or adeno-associated virus. In some embodiments, the non-viral introduction of the exogenous nucleic acid sequence comprises an electroporation, microinjection, liposome, or conjugation. In some embodiments, the exogenous nucleic acid sequence is DNA or RNA. In some embodiments, the exogenous nucleic acid sequence is single stranded DNA or double stranded DNA. In some embodiments, the exogenous nucleic acid sequence comprises double stranded DNA it comprises plasmid DNA or minicircle DNA. In some embodiments, the exogenous nucleic acid sequence encodes an exogenous receptor.
In some embodiments, the method comprises stimulating the cell prior to, concurrent with, or after the introducing. In some embodiments, the cell is stimulated prior to the introducing. In some embodiments, the cell is stimulated from about 1 hour to about 48 hours prior to the introducing. In some embodiments, the stimulation comprises contacting the cell with at least one of: an anti-CD3 antibody, an anti-CD28 antibody, or an interleukin. In some embodiments, the introducing comprises at least one of electroporation, microinjection, liposome, or conjugation. In some embodiments, the introducing comprises electroporation. In some embodiments, the electroporation comprises introducing the Argonaute polypeptide, the nucleic acid unwinding agent, the guiding polynucleic acid, or a combination thereof, at a voltage from about 1000 V to about 2000V for about 1 ms to about 30 ms. In some embodiments, the voltage is from about 1400V for about 10 ms. In some embodiments, the electroporation comprises about 1 pulse to about 5 pulses. In some embodiments, the electroporation is 3 pulses.
In some embodiments, the method further comprises expanding the cells. In some embodiments, the method further comprises selecting one or more of the cells. In some embodiments, the selection comprises at least one of a magnetic separation, a flow cytometric separation, and/or an antibiotic. In some embodiments, the selection comprises selecting a population of cells that express a cellular marker or an exogenous receptor. In some embodiments, the cellular marker comprises at least one of: CD3, CD4, CD8, CCR7, CD45RA, CD62L+, CD27, CD28, and IL-7Rα. In some embodiments, the method is performed in a closed system. In some embodiments, the method further comprises repeating the method on the cells.
In some embodiments, the polypeptide comprises at least one RHDC polypeptide and a nucleic acid unwinding polypeptide. In some embodiments, the at least one RHDC polypeptide and the nucleic acid unwinding polypeptide are derived from a mesophilic organism.
In some embodiments, the polypeptide comprises at least one Argonaute polypeptide and a nucleic acid unwinding polypeptide. In some embodiments, the at least one Argonaute polypeptide and the nucleic acid unwinding polypeptide are derived from a mesophilic organism.
In one embodiment, the present disclosure provides an ex vivo system for use in targeting a predetermined gene, the system comprising an RNase-H-like domain-containing (RHDC) polypeptide, a nucleic acid unwinding agent, and a guide DNA (gDNA), wherein the gDNA binds to the gene or to a nucleic acid sequence adjacent to the gene, and wherein the RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature, wherein the nucleic acid-cleaving activity is directed by a guide DNA.
In one embodiment, the present disclosure provides an ex vivo system for use in targeting a predetermined gene, the system comprising an Argonaute polypeptide and a nucleic acid unwinding agent, wherein the Argonaute polypeptide cleaves a nucleic acid at a mesophilic temperature.
In some embodiments, the ex vivo system further comprises a cell.
In some embodiments, the ex vivo system for use in targeting a predetermined gene, comprises at least one RHDC polypeptide and a nucleic acid unwinding polypeptide. In some embodiments, the at least one RHDC polypeptide and the nucleic acid unwinding polypeptide are derived from a mesophilic organism.
In some embodiments, the ex vivo system for use in targeting a predetermined gene, comprises at least one Argonaute polypeptide and a nucleic acid unwinding polypeptide. In some embodiments, the at least one Argonaute polypeptide and the nucleic acid unwinding polypeptide are derived from a mesophilic organism.
In some embodiments, the RHDC polypeptide cleaves a nucleic acid from about 30° C. to about 39° C. In some embodiments, the RHDC polypeptide cleaves a nucleic acid from about 35° C. to about 39° C. In some embodiments, the RHDC polypeptide cleaves a nucleic acid at 37° C. In some embodiments, the RHDC polypeptide demonstrates nuclease activity from 5° C. to 40° C.
In some embodiments, the Argonaute polypeptide cleaves a nucleic acid from about 30° C. to about 39° C. In some embodiments, the Argonaute polypeptide cleaves a nucleic acid from about 35° C. to about 39° C. In some embodiments, the Argonaute polypeptide cleaves a nucleic acid at 37° C. In some embodiments, the Argonaute polypeptide demonstrates nuclease activity from 5° C. to 40° C.
In some embodiments, the mesophilic organism is a prokaryotic organism. In some embodiments, the mesophilic organism is from a family selected from the group consisting of: bacteroidetes, proteobacteria, actinobacteria, firmicutes, cyanobacteria, spirochactes, deinococcus, verrucomicrobia, planctomycetes, balneolaeota, and chloroflexi. In some embodiments, the mesophilic organism is from a family selected from the group consisting of: proteobacteria, acidobacteria, actinobacteria, and bacteroidetes.
In some embodiments, the RHDC polypeptide is an archaeal Argonaute polypeptide. In some embodiments, the Argonaute polypeptide is an archaeal Argonaute polypeptide.
In some embodiments, the RHDC polypeptide is encoded by a gene located in an adjacent operon to at least one of a P-element induced Wimpy testis (PIWI) gene, RuvC, Cas, Sir2, Mrr, TIR, PLD, REase, restriction endonuclease, DExD/H, superfamily 11 helicase. RRXRR, DUF460, DUF3010, DUF429, DUF1092, COG5558, OrfB_IS605, Peptidase_A17, Ribonuclease H-like domain, 3′-5′ exonuclease domain, 3′-5′ exoribonuclease Rv2179c-like domain. Bacteriophage Mu, transposase, DNA-directed DNA polymerase, family B, exonuclease domain, Exonuclease. RNase T/DNA polymerase III, yqgF gene, HEPN, RNase LS domain, LsoA catalytic domain, KEN domain, RNaseL, Ire1, RNase domain, RloC, or PrrC.
In some embodiments, the RHDC polypeptide is encoded by a gene located in an adjacent operon to at least one of a gene involved in defense, stress response, a CRISPR system, or DNA repair.
In some embodiments, the RHDC polypeptide comprises an Argonaute domain. In some embodiments, the RHDC polypeptide has nuclease activity. In some embodiments, the Argonaute polypeptide has nuclease activity. In some embodiments, the nuclease activity is double stranded DNA cleaving activity.
In some embodiments, the RHDC polypeptide has nickase activity. In some embodiments, the Argonaute polypeptide has nickase activity. In some embodiments, the nickase activity is single stranded DNA cleaving activity.
In some embodiments, the RHDC polypeptide has RNAse activity. In some embodiments, the Argonaute polypeptide has RNase activity. In some embodiments, the RNase activity is double stranded RNA cleaving activity. In some embodiments, the RNase activity is RNA cleaving activity.
In some embodiments, the RHDC polypeptide has RNase-H activity. In some embodiments, the Argonaute polypeptide has RNase-H activity. In some embodiments, the RNase-H activity is RNA cleaving activity.
In some embodiments, the RHDC polypeptide has recombinase activity. In some embodiments, the RHDC polypeptide has DNA base flipping activity. In some embodiments, the RHDC polypeptide has transposase activity.
In some embodiments, the nucleic acid unwinding polypeptide is of prokaryotic origin. In some embodiments, the nucleic acid unwinding polypeptide is of archaeal origin.
In some embodiments, the nucleic acid unwinding polypeptide comprises a helicase domain. In some embodiments, the nucleic acid unwinding polypeptide comprises a topoisomerase domain. In some embodiments, the nucleic acid unwinding polypeptide comprises a Cas protein domain. In some embodiments, the Cas protein domain is selected from the group consisting of: Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csc5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, and Cas9HiFi.
In some embodiments, the nucleic acid unwinding polypeptide comprises a catalytically dead nucleic acid unwinding domain. In some embodiments, the catalytically dead nucleic acid unwinding domain is a dCas domain. In some embodiments, the catalytically dead nucleic acid unwinding domain is a dCas9 domain.
In some embodiments, the nucleic acid unwinding polypeptide comprises an ATPase domain. In some embodiments, the nucleic acid unwinding polypeptide has ATPase activity. In some embodiments.
In some embodiments, the polypeptide construct comprises a polypeptide with ATPase activity. In some embodiments, the ex vivo system comprises a functional ATPase domain.
In some embodiments, the RHDC polypeptide and the nucleic acid unwinding polypeptide are joined by a linker. In some embodiments, the Argonaute polypeptide and the nucleic acid unwinding polypeptide are joined by a linker. In some embodiments, the linker is a polypeptide linker.
In some embodiments, the nucleic acid unwinding polypeptide and the RHDC polypeptide are expressed in the same frame. In some embodiments, the nucleic acid unwinding polypeptide and the Argonaute polypeptide are expressed in the same frame.
In some embodiments, the polypeptide construct is bound to the guide DNA. In some embodiments, the polypeptide construct comprising an RNase-H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide construct is bound to the guide DNA.
In some embodiments, the at least one of the RHDC polypeptide and the nucleic acid unwinding agent is bound to a guide DNA.
In some embodiments, the polypeptide construct is bound to a guide nucleic acid. In some embodiments, the polypeptide construct comprising an Argonaute polypeptide and a nucleic acid unwinding polypeptide is bound to a guide nucleic acid.
In some embodiments, the guide polynucleic acid is a guide DNA (gDNA). In some embodiments, the guide DNA is from about 1 base pair to about 30 base pairs. In some embodiments, the guide DNA forms a secondary structure. In some embodiments, the guide DNA is complementary to a target polynucleotide sequence. In some embodiments, the target polynucleotide sequence is a gene sequence. In some embodiments, the gene sequence is a sequence of a disease-associated gene.
In some embodiments, the guide nucleic acid is a guide RNA (gRNA).
In some embodiments, the guide polynucleic acid is from about 1 base pair to about 30 base pairs. In some embodiments, the guide polynucleic acid forms a secondary structure. In some embodiments, the guide polynucleic acid is complementary to a target polynucleotide sequence. In some embodiments, the target polynucleotide sequence is a gene sequence. In some embodiments, the gene sequence is a sequence of a disease-associated gene. In some embodiments, the polypeptide construct produces a disruption when introduced into a cell. In some embodiments, the ex vivo system produces a disruption when introduced to a cell.
In some embodiments, the disruption comprises a double strand break or a single strand break. In some embodiments, the cell is a prokaryotic cell. In some embodiments, the cell is a eukaryotic cell. In some embodiments, the eukaryotic cell is a plant cell. In some embodiments, the eukaryotic cell is an animal cell. In some embodiments, the animal cell is a mammalian cell. In some embodiments, the mammalian cell is a human cell. In some embodiments, the human cell is a stem cell. In some embodiments, the human cell is an immune cell. In some embodiments, the immune cell is a lymphoid cell. In some embodiments, the lymphoid cell is a T cell, B cell, NK cell, stem cell, or TIL. In some embodiments, the cell is a primary cell.
In some embodiments, the polypeptide construct is good-manufacturing practices (GMP) compatible. In some embodiments, the ex vivo system is good-manufacturing practices (GMP) compatible.
In some embodiments, the present disclosure provides an ex vivo cell comprising any one of the polypeptide constructs disclosed herein.
In some embodiments, the present disclosure provides an ex vivo cell comprising a polypeptide construct comprising an RNase-H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide, wherein the RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature, wherein the nucleic acid-cleaving activity is directed by a guide DNA, and wherein the RHDC polypeptide is fused to the nucleic acid unwinding polypeptide.
In some embodiments, the present disclosure provides an ex vivo cell comprising a polypeptide construct comprising an Argonaute polypeptide and a nucleic acid unwinding polypeptide, wherein the Argonaute polypeptide cleaves a nucleic acid at a mesophilic temperature.
In some embodiments, the ex vivo cell is a primary cell. In some embodiments, the ex vivo cell is a recombinant cell. In some embodiments, the ex vivo cell is a prokaryotic cell. In some embodiments, the ex vivo cell is a eukaryotic cell. In some embodiments, the eukaryotic cell is a plant cell. In some embodiments, the eukaryotic cell is an animal cell. In some embodiments, the animal cell is a mammalian cell. In some embodiments, the mammalian cell is a human cell. In some embodiments, the human cell is a stem cell. In some embodiments, the human cell is an immune cell. In some embodiments, the immune cell is a lymphoid cell. In some embodiments, the lymphoid cell is a T cell. B cell, NK cell, stem cell, or TIL. In some embodiments, the cell is a primary cell.
In some embodiments, the present disclosure provides a polynucleic acid encoding any one of the polypeptide constructs disclosed herein.
In some embodiments, the present disclosure provides a polynucleic acid encoding a polypeptide construct comprising an RNase-H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide, wherein the RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature, wherein the nucleic acid-cleaving activity is directed by a guide DNA, and wherein the RHDC polypeptide is fused to the nucleic acid unwinding polypeptide.
In some embodiments, the present disclosure provides a polynucleic acid encoding a polypeptide construct comprising an Argonaute polypeptide and a nucleic acid unwinding polypeptide, wherein the Argonaute polypeptide cleaves a nucleic acid at a mesophilic temperature.
In some embodiments, the RHDC polypeptide and the nucleic acid unwinding polypeptide are in the same reading frame.
In some embodiments, the polynucleic acid further comprises a nuclear localization signal.
In some embodiments, the present disclosure provides a pharmaceutical composition comprising: (a) any one of the polypeptide constructs disclosed herein or any one of the ex vivo systems disclosed herein: and (b) at least one of an excipient, a diluent, or a carrier.
In some embodiments, the pharmaceutical composition is in unit dosage form.
In some embodiments, the pharmaceutical composition is in the form of a tablet, a liquid, syrup, an oral formulation, an intravenous formulation, an intranasal formulation, a subcutaneous formulation, an inhalable respiratory formulation, a suppository, and any combination thereof.
In some embodiments, the present disclosure provides a kit comprising: (a) anyone of the polypeptide constructs disclosed herein or any one of the ex vivo systems disclosed herein; and (b) instructions for use thereof.
In some embodiments, the kit further comprises a container.
In some embodiments, the present disclosure provides a method of treating a subject in need thereof, comprising administering a population of cells modified with any one of the methods disclosed herein. In some embodiments, the method further comprises administering at least one of a cytokine, chemotherapeutic, anti-viral, antibiotic, or granulocyte colony-stimulating factor (G-CSF) analog. In some embodiments, the cytokine is IL-2. In some embodiments, a cancer is reduced in the subject in need thereof after the administering as measured by CT scan.
In some embodiments, the present disclosure provides an ex vino system comprising an RNase H-like domain-containing (RHDC) polypeptide, a nucleic acid unwinding agent, and a guide nucleic acid, wherein the guide nucleic acid binds to a predetermined gene or to a nucleic acid sequence adjacent to the predetermined gene, the RHDC polypeptide is capable of introducing a double strand break in the predetermined gene, the nucleic acid unwinding agent lowers the energetic requirement for introducing the double strand break in comparison to introducing a double strand break with the RHDC polypeptide alone, and the ex vivo system introduces the double strand break at a range of temperatures from 19° C. to 40° C. In some embodiments the ex vivo system further comprises a regulatory domain polypeptide (RDP).
In some embodiments, provided herein is an ex vivo system comprising an RNase H-like domain-containing (RHDC) polypeptide, a nucleic acid unwinding agent, a guide nucleic acid, and a regulatory domain polypeptide (RDP), wherein the guide nucleic acid binds to a predetermined gene or to a nucleic acid sequence adjacent to the predetermined gene, the RHDC polypeptide is capable of introducing a double strand break in the predetermined gene, the nucleic acid unwinding agent lowers the energetic requirement for introducing the double strand break in comparison to introducing a double strand break with the RHDC alone, and the ex vivo system introduces the double strand break at a range of temperatures from 19° C. to 40° C. In some embodiments the nucleic acid unwinding agent is a polypeptide. In some embodiments the RHDC polypeptide, the nucleic acid unwinding agent, and the RDP are a polypeptide construct. In some cases, the RDP is a Rad51 polypeptide or a recombinase. In some cases, the guide nucleic acid is a guide DNA. In some cases, the ex vivo system introduces a double strand break in the predetermined gene at an efficiency 25%, 50%, or 75% greater than a comparable ex vivo system without said nucleic acid unwinding agent. In some cases, the ex vivo system introduces a first D-loop in the predetermined gene at an efficiency of 25%, 50%, or 75% and a second D-loop in said predetermined nucleic acid sequence at an efficiency of 25%, 50%, or 75%. In some cases, the RHDC polypeptide is an Argonaute polypeptide. In some cases, the Argonaute is selected from the group consisting of MjAgo, TtAgo, HlaAgo, DmcAgo, MsAgo, TsAgo, and PfAgo.
In some embodiments, provided herein is a cell comprising an ex vivo system.
In some embodiments, provided herein is a composition comprising an ex vivo system.
In some embodiments, provided herein is a polypeptide construct comprising an RNAse H-like domain-containing (RHDC) polypeptide and a regulatory domain polypeptide (RDP). In some cases, the polypeptide construct further comprises a nucleic acid unwinding domain. In some cases, the nucleic acid unwinding domain is a dCas9 domain. In some cases, the polypeptide construct further comprises a regulatory domain polypeptide (RDP). In some cases, the RDP is a Rad51 polypeptide or a recombinase.
Provided herein is a cell comprising a polypeptide construct.
Provided herein is a composition comprising a polypeptide construct.
Provided herein is a method for reducing an energy requirement associated with a nucleic acid editing system, comprising contacting a cell with a nucleic acid editing system, wherein the nucleic acid editing system comprises an RNase H-like domain-containing (RHDC) polypeptide, a nucleic acid unwinding agent, a guide nucleic acid, and a regulatory domain polypeptide (RDP), wherein the energy required for nucleic acid editing with said nucleic acid editing system is less than a comparable nucleic acid editing system without the RDP.
Provided herein is an Assembled Genetic Editing Molecule (AGEM) comprising an RNase H-like domain-containing (RHDC) polypeptide, a nucleic acid unwinding polypeptide, and an optional regulatory domain polypeptide (RDP), wherein the RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature, wherein said nucleic acid-cleaving activity is directed by a guide nucleic acid, and wherein said RHDC polypeptide is fused to said nucleic acid unwinding polypeptide. In some cases, the RHDC polypeptide is an Argonaute polypeptide. In some cases, the Argonaute is selected from the group consisting of MjAgo, TtAgo, HlaAgo, DmcAgo, MsAgo, TsAgo, and PfAgo. In some cases, the RHDC polypeptide comprises a sequence selected from the group consisting of SEQ ID NOs: 59-160. In some cases, the RDP is a Rad51 polypeptide or a recombinase. In some cases, the nucleic acid unwinding polypeptide comprises a dCas9 domain.
BRIEF DESCRIPTION OF THE DRAWINGS The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
FIG. 1 shows a phylogenetic tree for a PIWI domain in a complete genome of an Argonaute protein. This tree identifies possible PIWI domains in organisms that can be used to identify suitable nuclease or helicase domains.
FIG. 2 shows a mining strategy for nuclease identification based on PIWI domain identification.
FIG. 3 shows features of the PIWI superfamily proteins, including that C-termini may contain a PIWI domain and be conserved among nucleases. Dotted lines indicate separate genes located in the same, predicted, operon.
FIG. 4 shows a phylogenetic tree. On the right is homology between predicted structural alignment. From left to right is position 0 to end of protein. Black boxes are conserved domains.
FIG. 5 shows a C-terminus structural alignment. Red is matching alpha helix, blue is beta sheet. FIG. 5 discloses SEQ ID NOS 385-406, respectively, in order of appearance.
FIG. 6 shows a phylogenetic tree of Argonaute genes with a nearby helicase. Blue indicates that the Argonaute gene is from a mesophilic organism; red indicates that the Argonaute gene is from a thermophilic organism.
FIGS. 7A-7D show a phylogenetic tree of Argonaute proteins. Blue indicates that the Argonaute protein is from a mesophilic organism; red indicates that the Argonaute protein is from a thermophilic organism.
FIGS. 8A-8D show a phylogenetic tree. On the right is homology between predicted structural alignments. From left to right is position 0 to end of protein. Black boxes are conserved domains.
FIG. 9 shows a schematic of a gain-of-function gene editing reporter system.
FIG. 10 depicts a map of a lentiviral plasmid integrated into HEK 293T to generate reporter cell line, HEK293T QMS (CMVS-CuO luc-p2A-GFP, EF1alpha-cymR).
FIG. 11 shows a map of the SpCas9 and sgCymR expression plasmid, pX459-sgCymR-94.
FIG. 12 depicts a schematic of RDP-homology directed repair enhancement. To note, artificial genome editor molecule (aGEM).
FIG. 13A shows a coomassie Blue stained gel of lysis condition 1 of Argonaute (SEQ ID NO: 190). FIG. 13B shows a coomassie Blue stained gel of lysis condition 2 of Argonaute (SEQ ID NO: 190). FIG. 13C shows a coomassie Blue stained gel of lysis condition 3 of Argonaute (SEQ ID NO: 190). FIG. 13D shows a coomassie Blue stained gel of lysis condition 4 of Argonaute (SEQ ID NO: 190). FIG. 13E shows a coomassie Blue stained gel of lysis condition 5 of Argonaute (SEQ ID NO: 190). FIG. 13F shows a coomassie Blue stained gel of lysis condition 6 of Argonaute (SEQ ID NO: 190).
FIG. 14A shows a ssDNA gel stained with SYBR Gold of the ssDNA cleavage assay utilizing Argonaute (SEQ ID NO: 190) in conjunction with sgDNA (D1, D2, or non-targeting sgDNA (NT)). Table 25, under different concentrations of NaCl. FIG. 14B shows a ssDNA gel stained with SYBR Gold of the ssDNA cleavage assay utilizing sonicated Argonaute (SEQ ID NO: 190) in conjunction with sgDNA (D1, D2, or NT), Table 25, under different concentrations of NaCl. FIG. 14C shows a ssDNA gel stained with SYBR Gold of the ssDNA cleavage assay utilizing sonicated Argonaute (SEQ ID NO: 190) in conjunction with sgDNA (D1, D2, R1, R2, or NT), Table 25, at a concentration of 250 mM NaCl. FIG. 14D shows a ssDNA gel stained with SYBR Gold of the ssDNA cleavage assay utilizing sonicated Argonaute (SEQ ID NO: 190) under different treatment conditions comprising a heating step of 95° C. in conjunction with sgDNA (D1, D2, R1, R2, or NT) Table 25.
FIG. 15A shows protein quantification standard curve of BSA. FIG. 15B shows protein quantification of Argo #4, Argo #7, Argo #8, Argo #9, and Argo #10. FIG. 15C shows protein quantification of Argo #16, Argo #17, Argo #19, Argo #20, and Argo #21. FIG. 15D shows protein quantification of Argo #23, Argo #25, Argo #26, Argo #27, and Argo #29. FIG. 15E shows protein quantification of Argo #29, Argo #30, Argo #41, Argo #63, and Empty control.
FIG. 16 shows results of a ssDNA cleavage assay utilizing Argo #41, #17 and #30.
FIG. 17 shows a schematic of a dsDNA/ssDNA cleavage assay.
FIG. 18 shows a schematic of the 6808 cell assay.
FIG. 19 shows an example of a possible architecture of a split fluorescent reporter for a DNA cutting/nicking assay. Location of guide DNAs is also included 6819, 6821, sg_02, sg_03, sg_01 relative to the architecture.
FIG. 20 shows an example of a possible architecture of a split fluorescent reporter for a DNA cutting/nicking assay. Location of guide DNAs is also included 6819, 6821, sg_02, sg_03, sg_01 relative to the architecture.
FIG. 21 shows an example of a possible architecture of a split fluorescent reporter for a DNA cutting/nicking assay. Location of guide DNAs is also included 6819, 6821, sg_2, sg_03, sg_01 relative to the architecture.
FIG. 22A shows a negative control experiment performed using HEK293T cells.
FIG. 228 shows a negative control experiment performed using 6808 cells.
FIG. 22C shows a negative control experiment performed using 6808 cells and Cas9.
FIG. 22D shows a negative control experiment performed using 6808 cells, Cas9 and a non-targeting guide RNA.
FIG. 22E shows a negative control experiment performed using 6808 cells, Cas9, a non-targeting guide RNA and a single-stranded oligodeoxynucleotide donor.
FIG. 22F shows a negative control experiment performed using 6808 cells, Cas9, a non-targeting guide RNA and another single-stranded oligodeoxynucleotide donor.
FIG. 22G shows a negative control experiment performed using 6808 cells, Cas9n and a non-targeting guide RNA.
FIG. 22H shows a negative control experiment performed using 6808 cells, Cas9, a non-targeting guide RNA and a single-stranded oligodeoxynucleotide donor.
FIG. 22I shows a negative control experiment performed using 6808 cells, nCas9, anon targeting guide RNA and a single-stranded oligodeoxynucleotide donor.
FIG. 22J shows a negative control experiment performed using 6808 cells and a single-stranded oligodeoxynucleotide donor.
FIG. 22K shows a negative control experiment performed using 6808 cells and a single-stranded oligodeoxynucleotide donor.
FIG. 23 shows a positive control experiment performed using 6808 cells, Cas9 and a guide RNA targeting the 94_linker.
FIG. 24 shows a positive control experiment performed using 6808 cells, nCas9 and a guide RNA targeting the 94_linker.
FIG. 25A shows a positive control experiment performed using 6808 cells, nCas9 a guide RNA targeting the 94_linker, and a single-stranded oligodeoxynucleotide donor.
FIG. 25B shows a positive control experiment performed using 6808 cells, nCas9 a guide RNA targeting the 94_linker, and another single-stranded oligodeoxynucleotide donor.
FIG. 26A shows a coomassie Blue stained gel of a ssDNA cleavage assay utilizing truncated guiding polynucleic acids of Table 22. FIG. 26B shows a ssDNA gel stained with SYBR Gold of a ssDNA cleavage assay utilizing truncated guiding polynucleic acids of Table 22, D1* denotes that D t has no 5′ phosphorylation.
FIG. 27A shows the results of a sequencing reaction performed on untreated 6808 cells.
FIG. 278 shows the results of a sequencing reaction performed on 6808 cells treated with a Cas9n, a non-targeting guide RNA and ssODN_4 donor.
FIG. 28 shows the results of a sequencing reaction performed on 6808 cells treated with nCas9 and sgRNA6821.
FIG. 29 shows the results of a sequencing reaction performed on 6808 cells treated with nCas9, sgRNA6821 and ssODN_4 donor.
FIG. 30 shows the results of a sequencing reaction performed on 6808 cells treated with Cas9 and sgRNA6825.
FIG. 31 shows the results of a sequencing reaction performed on 6808 cells treated with Cas9, sgRNA6825 and ssODN_4 donor.
FIG. 32A and FIG. 32B show the results of the split fluorescence 6808 cell assay for 38 and 44 different Ago proteins respectively.
FIG. 33 shows the first law of genetic thermodynamics and provides a comparison between the AGEM system provided herein (exothermic) and additional gene editing systems (endothermic).
FIG. 34 depicts an exemplary schematic of the anatomy of an artificial genome editor molecule (aGEM). The aGEM contains an RNase-H like domain containing protein, a nucleic acid unwinding agent, and a regulatory domain agent.
FIG. 35 shows an example of a possible architecture of a split fluorescent reporter for a DNA cutting/nicking assay. Location of guide DNAs is also included 68 25 relative to the architecture.
DETAILED DESCRIPTION OF THE INVENTION The following description and examples illustrate embodiments of the invention in detail. It is to be understood that this invention is not limited to the particular embodiments described herein and as such can vary. Those of skill in the art will recognize that there are numerous variations and modifications of this invention, which are encompassed within its scope.
Definitions The term “about” and its grammatical equivalents in relation to a reference numerical value and its grammatical equivalents as used herein can include a range of values plus or minus 10% from that value. For example, the amount “about 10” includes amounts from 9 to 11. The term “about” in relation to a reference numerical value can also include a range of values plus or minus 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% from that value.
The term “activation” and its grammatical equivalents as used herein can refer to a process whereby a cell transitions from a resting state to an active state. This process can comprise a response to an antigen, migration, and/or a phenotypic or genetic change to a functionally active state. For example, the term “activation” can refer to the stepwise process of T cell activation. For example, a T cell can require at least two signals to become fully activated. The first signal can occur after engagement of a TCR by the antigen-MHC complex, and the second signal can occur by engagement of co-stimulatory molecules. Anti-CD3 can mimic the first signal and anti-CD28 can mimic the second signal in vitro.
The term “adjacent” and its grammatical equivalents as used herein can refer to right next to the object of reference. For example, the term adjacent in the context of a nucleotide sequence can mean without any nucleotides in between. For instance, polynucleotide A adjacent to polynucleotide B can mean AB without any nucleotides in between A and B.
The term “argonaute,” “Ago,” and its grammatical equivalents as used herein can refer to a naturally occurring or engineered domain or protein that can be guided by guiding polynucleic acid to specifically recognize a target nucleic acid comprising a complementary sequence to the guiding polynucleic acid. Some Ago domains or proteins, also referred to herein as “Argonaute nucleases” have endonuclease activity, e.g., the ability to cleave an internal phosphodiester bond in a target nucleic acid. Some Ago proteins may not cleave a target nucleic acid.
The term “autologous” and its grammatical equivalents as used herein can refer to as originating from the same being. For example, a sample (e.g., cells) can be removed, processed, and given back to the same subject (e.g., subject) at a later time. An autologous process is distinguished from an allogenic process where the donor and the recipient are different subjects.
The term “cancer” and its grammatical equivalents as used herein can refer to a hyperproliferation of cells whose unique trait-loss of normal controls-results in unregulated growth, lack of differentiation, local tissue invasion, and/or metastasis. With respect to the inventive methods, the cancer can be any cancer, including any of acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bladder cancer, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, rectum, cancer of the eye, cancer of the intrahepatic bile duct, cancer of the joints, cancer of the neck, gallbladder, or pleura, cancer of the nose, nasal cavity, or middle ear, cancer of the oral cavity, cancer of the vulva, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, fibrosarcoma, gastrointestinal carcinoid tumor, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, leukemia, liquid tumors, liver cancer, lung cancer, lymphoma, malignant mesothelioma, mastocytoma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, ovarian cancer, pancreatic cancer, peritoneum, omentum, and mesentery cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, skin cancer, small intestine cancer, soft tissue cancer, solid tumors, stomach cancer, testicular cancer, thyroid cancer, ureter cancer, and/or urinary bladder cancer. As used herein, the term “tumor” refers to an abnormal growth of cells or tissues, e.g., of malignant type or benign type.
The term “cancer neo-antigen” or “neo-antigen” or “neo-epitope” and its grammatical equivalents as used herein can refer to antigens that are not expressed and/or not exposed to immune surveillance in normal, non-cancerous host tissue. For example, a “neo-antigen” may not be encoded in a normal, non-mutated host genome. A “neo-antigen” can in some instances represent either oncogenic viral proteins or abnormal proteins that arise as a consequence of somatic mutations. For example, a neo-antigen can arise by the disruption of cellular mechanisms through the activity of viral proteins. Another example can be an exposure of a carcinogenic compound, which in some cases can lead to a somatic mutation. This somatic mutation can ultimately lead to the formation of a tumor/cancer.
The term “cytotoxicity” as used in this specification, refers to an alteration in the normal state of a cell such that the cell dies. The normal state of a cell can refer to a state that is manifested or exists prior to the cell's exposure to a cytotoxic composition, agent and/or condition. Generally, a cell that is in a normal state is one that is in homeostasis. An unintended or undesirable alteration in the normal state of a cell can be manifested in the form of, for example, cell death (e.g., programmed cell death), a decrease in replicative potential, a decrease in cellular integrity such as membrane integrity, a decrease in metabolic activity, a decrease in developmental capability, or any of the cytotoxic effects disclosed in the present application. Cytotoxicity can be desirable, for example, in the case of tumor cell cytotoxicity, or undesirable, for example, in the case of healthy cell cytotoxicity.
The phrase “reducing cytotoxicity” or “reduce cytotoxicity” refers to a reduction in degree or frequency of unintended or undesirable alterations in the normal state of a cell upon exposure to a cytotoxic composition, agent and/or condition. The phrase can refer to reducing the degree of cytotoxicity in an individual cell that is exposed to a cytotoxic composition, agent and/or condition, or to reducing the number of cells of a population that exhibit cytotoxicity when the population of cells is exposed to a cytotoxic composition, agent and/or condition.
The term “engineered” and its grammatical equivalents as used herein can refer to one or more alterations of a nucleic acid, e.g., the nucleic acid within an organism's genome. The term “engineered” can refer to alterations, additions, and/or deletion of genes. An engineered cell can also refer to a cell with an added, deleted and/or altered gene.
The term “ceil” or “engineered cell” and their grammatical equivalents as used herein can refer to a cell of human or non-human animal origin.
The term “checkpoint gene” and its grammatical equivalents as used herein can refer to any gene that is involved in an inhibitory process (e.g., feedback loop) that acts to regulate the amplitude of an immune response, for example, an immune inhibitory feedback loop that mitigates uncontrolled propagation of harmful responses. These responses can include contributing to a molecular shield that protects against collateral tissue damage that might occur during immune responses to infections and/or maintenance of peripheral self-tolerance. Non-limiting examples of checkpoint genes can include members of the extended CD28 family of receptors and their ligands as well as genes involved in co-inhibitory pathways (e.g., CTLA-4 and PD-1). The term “checkpoint gene” can also refer to an immune checkpoint gene.
A “CRISPR,” “CRISPR system,” or “CRISPR nuclease system” and their grammatical equivalents can include an RNA molecule (e.g., guide RNA) that binds to DNA and a Cas protein (e.g., Cas9) with nuclease functionality (e.g., two nuclease domains). Se, e.g., Sander, J. D., et al., “CRISPR-Cas systems for editing, regulating and targeting genomes,” Nature Biotechnology, 32:347-355 (2014): see also e.g., Hsu. P. D., et al., “Development and applications of CRISPR-Cas9 for genome engineering,” Cell 157(6):1262-1278 (2014). In some embodiments, a CRISPR system includes a Cas protein with nickase functionality (e.g., one catalytically dead nuclease domain and one catalytically active nuclease domain). A Cas can be partially catalytically dead.
The term “disrupting” and its grammatical equivalents as used herein can refer to a process of altering a gene, e.g., by deletion, insertion, mutation, rearrangement, or any combination thereof. For example, a gene can be disrupted by knockout. Disrupting a gene can, for example, partially or completely suppress expression of the gene. Disrupting a gene can also cause activation of a different gene, for example, a downstream gene.
The term “engineered” and its grammatical equivalents as used herein can refer to one or more alterations of a nucleic acid, e.g., the nucleic acid within an organism's genome. The term “engineered” can refer to alterations, additions, and/or deletion of genes. An engineered cell can also refer to a cell with an added, deleted and/or altered gene.
The term “function” and its grammatical equivalents as used herein can refer to the capability of operating, having, or serving an intended purpose. Functional can comprise any percent from baseline to 100% of normal function. For example, functional can comprise or comprise about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, and/or 100% of normal function. In some cases, the term functional can mean over or over about 100% of normal function, for example, 125, 150, 175, 200, 250, 300% and/or above normal function.
The term “gene editing” and its grammatical equivalents as used herein can refer to genetic engineering in which one or more nucleotides are inserted, replaced, or removed from a genome. Gene editing can be performed using a nuclease (e.g., a natural-existing nuclease or an artificially engineered nuclease).
The term “good manufacturing practices” (GMP) and its grammatical equivalents as used herein can refer to products that are safe, effective, or pure according to the FDA. GMP can also sometimes be referred to as “cGMP”. The “c” stands for “current.” Manufacturers of a product can employ technologies and systems which are up-to-date in order to comply with regulation of GMP products. GMP compatible products are typically utilized in the clinical setting as opposed to the research setting.
The term “mutation” and its grammatical equivalents as used herein can include the substitution, deletion, and insertion of one or more nucleotides in a polynucleotide. For example, up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 40, 50, or more nucleotides/amino acids in a polynucleotide (cDNA, gene) or a polypeptide sequence can be substituted, deleted, and/or inserted. A mutation can affect the coding sequence of a gene or its regulatory sequence. A mutation can also affect the structure of the genomic sequence or the structure/stability of the encoded mRNA.
The term “non-human animal” and its grammatical equivalents as used herein can include all animal species other than humans, including non-human mammals, which can be a native animal or a genetically modified non-human animal.
The terms “nucleic acid,” “polynucleotide,” “polynucleic acid.” and “oligonucleotide” and their grammatical equivalents can be used interchangeably and can refer to a deoxyribonucleotide or ribonucleotide polymer, in linear or circular conformation, and in either single- or double-stranded form. For the purposes of the present disclosure, these terms should not to be construed as limiting with respect to length, unless the context clearly indicates otherwise. The terms can also encompass analogues of natural nucleotides, as well as nucleotides that are modified in the base, sugar and/or phosphate moieties (e.g., phosphorothioate backbones). Modifications of the terms can also encompass demethylation, addition of CpG methylation, removal of bacterial methylation, and/or addition of mammalian methylation. In general, an analogue of a particular nucleotide can have the same base-pairing specificity, e.g., an analogue of A can base-pair with T.
The term “construct” can refer to an artificial or synthetic construct. For example, a polypeptide construct can refer to an artificial or synthetic polypeptide, e.g., comprising one or more polypeptide sequences. Similarly, a nucleic acid construct can refer to an artificial or synthetic nucleic acid, e.g., comprising one or more nucleic acid sequences.
The term “percent (%) identity” can be readily determined for nucleic acid or amino acid sequences, over the full-length of a sequence, or a fragment thereof. Generally, when referring to “identity”, “homology”, or “similarity” between two different sequences (e.g., nucleotide or amino acid sequences), “identity”, “homology” or “similarity” is determined in reference to “aligned” sequences. “Aligned” sequences or “alignments” refer to multiple nucleic acid sequences or protein (amino acids) sequences, often containing corrections for missing or additional bases or amino acids as compared to a reference sequence.
The term “peripheral blood lymphocytes” (PBL) and its grammatical equivalents as used herein can refer to lymphocytes that circulate in the blood (e.g., peripheral blood). Peripheral blood lymphocytes can refer to lymphocytes that are not localized to organs. Peripheral blood lymphocytes can comprise T cells, NK cells. B cell, or any combinations thereof.
The term “phenotype” and its grammatical equivalents as used herein can refer to a composite of an organism's observable characteristics or traits, such as its morphology, development, biochemical or physiological properties, phenology, behavior, and/or products of behavior. Depending on the context, the term “phenotype” can sometimes refer to a composite of a population's observable characteristics or traits.
The term “protospacer” and its grammatical equivalents as used herein can refer to a PAM-adjacent nucleic acid sequence capable to hybridizing to a portion of a guide RNA, such as the spacer sequence or engineered targeting portion of the guide RNA. A protospacer can be a nucleotide sequence within gene, genome, or chromosome that is targeted by a guide RNA. In the native state, a protospacer is adjacent to a PAM (protospacer adjacent motif). The site of cleavage by an RNA-guided nuclease is within a protospacer sequence. For example, when a guide RNA targets a specific protospacer, the Cas protein will generate a double strand break within the protospacer sequence, thereby cleaving the protospacer. Following cleavage, disruption of the protospacer can result though non-homologous end joining (NHEJ) or homology-directed repair (HDR). Disruption of the protospacer can result in the deletion of the protospacer. Additionally or alternatively, disruption of the protospacer can result in an exogenous nucleic acid sequence being inserted into or replacing the protospacer.
The term “recipient” and their grammatical equivalents as used herein can refer to a human or non-human animal. The recipient can also be in need thereof.
The term “recombination” and its grammatical equivalents as used herein can refer to a process of exchange of genetic information between two polynucleic acids. For the purposes of this disclosure, “homologous recombination” or “HR” can refer to a specialized form of such genetic exchange that can take place, for example, during repair of double-strand breaks. This process can require nucleotide sequence homology, for example, using a donor molecule to template repair of a target molecule (e.g., a molecule that experienced the double-strand break), and is sometimes known as non-crossover gene conversion or short tract gene conversion. Such transfer can also involve mismatch correction of heteroduplex DNA that forms between the broken target and the donor, and/or synthesis-dependent strand annealing, in which the donor can be used to resynthesize genetic information that can become part of the target, and/or related processes. Such specialized HR can often result in an alteration of the sequence of the target molecule such that part or all of the sequence of the donor polynucleotide can be incorporated into the target polynucleotide. In some cases, the terms “recombination arms” and “homology arms” can be used interchangeably.
The term “RNase-H-like domain-containing (RHDC) polypeptides” and their grammatical equivalents as used herein can refer to polypeptides with shared structural and/or functional features. An RHDC can also be referred to as an RNase-H like domain containing protein. In certain embodiments, an RHDC polypeptide has structural features similar to the structure of RNase-H, for example a secondary structure of β-strands and α-helices as follows: β1-β2-β3-α1-β4-α2-β5-(α3)-α4, wherein α3 is optional. In some embodiments, an RHDC polypeptide has nucleic acid-cleaving activity at, for example, about 19° C. to 40° C., as evidenced by the fact that RHDC polypeptides can be derived from a mesophilic organism. In some embodiments, an RHDC polypeptide has nucleic acid-cleaving activity at, for example, about 19° C. to 40° C. In some embodiments, “derived from a mesophilic organism” can refer to a feature that occurs in a mesophilic organism. In some cases, a feature that can be derived from mesophilic organism can share a domain organization of β1-β2-β3-α1-β4-α2-β5-(α3)-α4, wherein α3 is optional, while also have at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to an RHDC polypeptide that occurs in a mesophilic organism. In some embodiments, an RHDC polypeptide has nucleic acid-cleaving activity or assists in nucleic acid-cleaving activity.
The term “transgene” and its grammatical equivalents as used herein can refer to a gene or genetic material that is transferred into an organism. For example, a transgene can be a stretch or segment of DNA containing a gene that is introduced into an organism. When a transgene is transferred into an organism, the organism is then referred to as a transgenic organism. A transgene can retain its ability to produce RNA or polypeptides (e.g., proteins) in a transgenic organism. A transgene can be composed of different nucleic acids, for example RNA or DNA. A transgene can encode for an engineered T cell receptor, for example a TCR transgene. A transgene can be a TCR sequence. A transgene can be a receptor. A transgene can comprise recombination arms. A transgene can comprise engineered sites.
A “therapeutic effect” can occur if there is a change in the condition being treated. The change can be positive or negative. For example, a ‘positive effect’ can correspond to an increase in the number of activated T-cells in a subject. In another example, a ‘negative effect’ can correspond to a decrease in the amount or size of a tumor in a subject. There is a “change” in the condition being treated if there is at least 10% improvement, preferably at least 25%, more preferably at least 50%, even more preferably at least 75%, and most preferably 100%. The change can be based on improvements in the severity of the treated condition in an individual, or on a difference in the frequency of improved conditions in populations of individuals with and without treatment with the therapeutic compositions with which the compositions of the present invention are administered in combination. Similarly, a method of the present disclosure can comprise administering to a subject an amount of cells that is “therapeutically effective”. The term “therapeutically effective” should be understood to have a definition corresponding to ‘having a therapeutic effect’.
The term “sequence” and its grammatical equivalents as used herein can refer to a nucleotide sequence, which can be DNA or RNA: can be linear, circular or branched; and can be either single-stranded or double stranded. A sequence can be mutated. A sequence can be of any length, for example, between 2 and 1,000,000 or more nucleotides in length (or any integer value there between or there above), e.g., between about 100 and about 10,000 nucleotides or between about 200 and about 500 nucleotides.
Overview The present disclosure provides methods, systems, compositions and kits for modifying a target nucleic acid using a system comprising an RHDC polypeptide and a nucleic acid unwinding agent. The systems described herein can comprise, for example, a nuclease, a helicase, and an ATPase. These systems overcome technical challenges associated with RHDC proteins including, for example, a lack of activity at temperatures that are conducive for gene editing in human cells. The methods, systems, compositions and kits described herein allow for this physiologically-relevant gene editing by providing an RHDC polypeptide in combination with a nucleic acid unwinding agent. Without wishing to be bound by theory, this combination overcomes the energetic barrier that RHDC proteins face that prevents RHDC proteins alone from inducing single- or double-stranded nucleic acid breaks because the nucleic acid unwinding agent exposes a nucleic acid sequence such that the RHDC polypeptide can cleave in the exposed region. In some embodiments, the RHDC is an Argonaute protein, for example, from a mesophilic organism. In some embodiments, the nucleic acid unwinding agent is a helicase or a topoisomerase. In some embodiments, the RHDC polypeptide and the nucleic acid unwinding agent are provided as a fusion protein. In some embodiments, the RHDC polypeptide and the nucleic acid unwinding agent are provided such that they co-localize on a nucleic acid, without being present as a fusion protein. The present disclosure also provides for the bioinformatic co-localization as a proxy for bioenergy efficiency of DNA repair. In some cases, the physiologic repair is energy efficient and the natural state. In some aspects, the pathologic failure of a double strand break is energy inefficient and the diseased state.
Nuclease Systems for Genetic Engineering Intracellular genomic transplant can be a method of genetically modifying cells and nucleic acids for therapeutic applications. Provided herein can be a gene editing system containing interchangeable parts. For example, one module of a gene editing system can be replaced whilst not affecting the function of the other modules. The modular gene editing system provided herein can be tunable to allow for dialing-up and dialing-down of a gene editing efficiency and/or the skewing to a particular genomic break repair method. Provided herein are also compositions, constructs, systems, and methods for disrupting a genomic sequence in a subject (e.g. mammal, non-mammal, or plant). Also provided herein are compositions, constructs, systems, and methods of treating or inhibiting a condition caused by a defect in a target sequence in a genomic locus of interest in a subject (e.g., mammal or human) or a non-human subject (e.g., mammal) in need thereof. In some cases, a method can comprise modifying a subject or a non-human subject by manipulation of a target sequence and wherein a condition can be susceptible to treatment or inhibition by manipulation of a target sequence.
Disclosed herein is also a method of genomically editing a system utilizing an RNase-H like domain containing protein that performs a genomic alternation with favorable thermodynamics. A genomic alteration can be exothermic. A genomic alteration can be endothermic. In some cases, A genomic alteration utilizing the disclosed system can be energetically favorable over alternate gene editing systems. An RNase-H-like domain-containing protein system can more thermodynamically favorable as measured by a biochemical system, for example by providing a finite amount of ATP into the reaction and measuring an amount of gene editing before, during, and after the genomic alteration has occurred. In some cases, the disclosed editing system utilizing an RNase-H-like domain-containing protein can reduce an energetic requirement by about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 40%, 50%, or up to about 60% as compared to a system that does not employ an RNase-H-like domain-containing protein. In some cases, the disclosed editing system utilizing an RNase-H-like domain containing protein can reduce an immune response to the RNase-H-like domain containing protein by about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 40%, 50%, or up to about 60% as compared to a system that does not employ the disclosed RNase-H-like domain containing protein. In some cases, an RNase-H-like domain containing protein can be harvested from bacteria that are endogenously present in the human body to prevent eliciting an immune response.
In some cases, a genome that can be disrupted or modified can be from an organism or subject that can be a eukaryote (including mammals including human) or a non-human eukaryote or a non-human animal or a non-human mammal. In some cases, an organism or subject can be a non-human animal, and may be an arthropod, for example, an insect, or may be a nematode. In some cases, an organism or subject can be a plant. In some cases, an organism or subject can be a mammal or a non-human mammal. A non-human mammal may be for example a rodent (preferably a mouse or a rat), an ungulate, or a primate. In some methods of the invention the organism or subject is algae, including microalgae, or is a fungus. In some cases, a subject can be a human. A human subject can be an adult or a pediatric subject. A pediatric subject can be under the age of 18. An adult subject can be about 18 or over 18 years of age.
A protein with nucleic acid-cleaving activity (e.g., a nuclease) can be an enzyme that cleaves a chain of nucleotides in a nucleic acid into smaller units. A protein with nucleic acid-cleaving activity can be from a eukaryote or a prokaryote. A protein with nucleic acid-cleaving activity can be from a eukaryote. A protein with nucleic acid-cleaving activity can be from a prokaryote. In some cases, a protein with nucleic acid-cleaving activity can be from archaea.
In some cases, a protein with nucleic acid-cleaving activity can be an RNase-H like domain containing protein. In some cases, a nuclease can be a protein that has a secondary structure similar to an RNase-H or an RNase-H-like domain-containing protein. RNase-H can belong to a nucleotidyl-transferase superfamily, which can include transposase, retroviral integrase, Holliday junction resolvase, and RISC nuclease Argonaute. In some cases, an RNase-H or RNase-H-like domain-containing protein can utilize two-metal-ion catalysis as a general feature. In nucleases, two metal ions can be asymmetrically coordinated and have distinct roles in activating a nucleophile and stabilizing a transition state. In some cases, an RNase-H or RNase-H like domain-containing protein can have an α/β fold containing a carboxylate triad in a catalytic center. In some cases, two spatially conserved Asps can be present in a nuclease. For example, an Asp residue may be conserved in a majority of Argonaute sequences. An Asp residue may align spatially with a catalytic Asp residue of RNase-H-like catalytic sites. In some cases, a nuclease can be an RNase-H, reverse transcriptase, integrase, Tn5, Argonaute, RuvC, Cas, or a combination thereof. In some cases, a nuclease can be an enzyme that may share an RNase-H domain with any one of RNase-H, reverse transcriptase, integrase, Tn5, Argonaute, RuvC, or Cas. In other cases, a nuclease can be substantially similar in structure to any one of RNase-H, reverse transcriptase, integrase, Tn5, Argonaute, RuvC, or Cas. A substantially similar structure may contain a β-fold containing a central five-stranded mixed β-sheet surrounded by α-helices on both sides. In some cases, an RNase-H structure can also have additional helices and loops inserted between two α-turn-β units, which can form part of a substrate-binding surface. In some cases, a substantially similar structure contains an active site. An active site of an RNase-H or RNase-H like protein can contain a set of three highly conserved carboxylates. In some cases a domain may be RuvC. In some cases, a domain is a PIWI domain. In some cases, a phylogenetic tree identifies possible PIWI domains in organisms that can be used to identify suitable nuclease or helicase domains. FIG. 1.
In some cases, an enzymatic polypeptide can be an RNA-dependent DNase editor, an RNA-dependent RNase editor, a DNA-dependent DNase editor, or a DNA-dependent RNase editor. Examples of an RNA-dependent DNase editor can be Cas9 and Cpf1 to name a couple. An example of an RNA-dependent RNase editor is Cas13. An enzymatic protein can contain multiple domains. For example, an enzymatic polypeptide can contain domains that can bind to a duplex of DNA-RNA, DNA-DNA, or RNA-RNA. For example. RuvC can bind Cas9 and Cpf1; HNH can bind Cas9, RNase-H can bind ribonuclease, and PIWI can bind Ago.
In some cases, an RHDC polypeptide can be expressed by a gene located adjacent to an operon of at least one of P-element induced Wimpy testis (PIWI) gene, RuvC, Cas, Sir2, Mrr, TIR, PLD, REase, restriction endonuclease, DExD/H, superfamily II helicase, RRXRR (SEQ ID NO: 380), DUF460, DUF3010, DUF429, DUF1092, COG5558, OrfB_IS605, Peptidase A17, Ribonuclease H-like domain, 3′-5′ exonuclease domain, 3′-5′ exoribonuclease Rv2179c-like domain, Bacteriophage Mu, transposase, DNA-directed DNA polymerase, family B, exonuclease domain, Exonuclease, RNase T/DNA polymerase III, yqgF gene. HEPN, RNase LS domain, LsoA catalytic domain, KEN domain, RNaseL, Ire1, RNase domain, RloC, PrrC, or modified versions thereof. An RHDC polypeptide disclosed herein can be interchangeable. For example, an RHDC polypeptide domain can be any nuclease domain that can be selected from a list comprising: CRISPR, Argonaute, meganuclease, Zinc finger nuclease (ZFN), TALEN, or a restriction enzyme. In some cases, when a RHDC domain is interchanged, the interchanging may not affect a function of the remaining modules of the gene editing system (a nucleic acid unwinding agent or an RDP). In some cases, a gene editing system can be dialed-up or dialed-down. A dialing up can be performed by interchanging a domain such as RHDC polypeptide for a stronger performing RHDC polypeptide. A dialing up can enhance a double strand break repair by about 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or up to about 100% as compared to a comparable gene editing system. A dialing down can be performed by interchanging a domain such as RHDC polypeptide for a weaker performing RHDC polypeptide for improved homology directed repair (HDR) of a double strand break. In some cases, interchanging a module of a gene editing system can allow for HDR of a double strand break, Use of a gene editing system disclosed herein can allow for preferential HDR of a double strand break over that of comparable or alternate gene editing systems. In some cases, an HDR repair can preferentially occur in a population of cells at %, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or up to about 100% over that which occurs in a comparable gene editing system.
In some cases, an RHDC or a functional fragment thereof can be selected from a phylum of bacteria selected from: Chlorolexi, Proteobacteria, Bacteroidetes, Planctomycetes, Firmicutes, Cyanobacteria, Bacteroidetes, Balneolaeota, Bacteroidetes, Euryarchaeota, Crenarchaeota, Firmicutes, Euryarchaeota, Actinobacteria, Thermotogae, Deinococcus, Spirochaetes, Acidobacteria, modified versions thereof, or any combination thereof.
In some cases, an RHDC or a functional fragment thereof can be selected from a class of bacteria selected from: phylum Chloroflexi (Class: Thermoflexi, dehalococcoidia, anaerolinaea, ardenticatenia, caldilineae, ktedonobacteria, thermomicrobia, chloroflexia), phylum Proteobacteria (class: Alphaproteobacteria, Betaproteobacteria, hydrogenophilalia, Gammaproteobacteria, acidithiobacillia, Deltaproteobacteria, epsilonproteobacteria, oligoflexia), phylum Bacteroidetes (class: rhodothermia, balneolia, cytophagia, sphingobacteria, chitinophagia, bacteroidia, flavobacteria), phylum Planctomycetes (class: phycisphaerae, plantomycetacia), phylum Firmicutes (class: bacillales, clostridia, thermolithobacteria), phylum Cyanobacteria (class: chroococcales, chroococcidiopsidales, gleobacterales, nostocales, oscillatoriales, pleurocapsales, spirulinales, synechococcales, incertae sedis), phylum Bacteroidetes (class: rhodothermia, balneolia, cytophagia, sphingobacteria, chitinophagia, bacteroidia, flavobacteria), phylum Balneolaeota (class: balneolia), phylum Euryarchaeota (class: aciduliprofundum, archaeoglobi, halobacteria, methanobacteria, methanococci, methanomicrobia, methanopyri, nanohaloarchaea, thermococci, thermoplasmata), phylum Crenarchaeota (class: cocyta, eocytes, crenarchaeot garrity and holt), phylum Actinobacteria (class: rubrobacteria, thermoleophilia, coriobacteria, acidimicrobia, nitrilliruptoia. Actinobacteria), phylum Thernotogae (class: Thermotogae), Deinococcus (class: deinococci), phylum Spirochaetes (class: spirochactia), phylum Acidobacteria (class: Acidobacteria, blastocatellia, holophagae), modified versions thereof, or any combination thereof.
In some cases, an RHDC or a functional fragment thereof can be selected from a species selected from: Dehalococcoides mecartyi DCMB5, Cupriavidus metallidurans H1130, Acinetobacter venetianus, Methylobacter whittenburyi, Bacteroides fragilis str.I1345, Candidatus Brocadia sinica JPN1, Clostridium sartagoforme AAU1, Calothrix sp. PCC 7103, Microcystis aeruginosa PCC 9701. Elizabethkingia meningoseptica, Rhodohalobacter halophilus, Parabacteroides goldsteinii CL02T12C30, Sphingobium chlorophenolicum L-1, Methanotorris formicicus Mc-S-70, Hymenobacter psychrotolerans DSM 18569, Vulcanisaeta moutnovskia 768-28, Flavobacterium seoulense, Elizabethkingia anophelis, Rhodopseudomonas palustris DX-1, Lachnospiraceae bacterium VE202-12. Thermococcus barophilus, Rhizobium undicola ORS 992=ATCC 700741, Anoxybacillus gonensis, Bacteroides thetaiotaomicron, Flavobacterium johnsoniae, Microcystis aeruginosa KW, Burkholderia sp. H160, Chroococcidiopsis thermalis PCC 7203, Fischerella major NIES-592, Cyclobacterium marinum DSM 745, Flavobacterium sp. Root186, Nocardia sienata NBRC 100364, Thermoactinomyces sp. CDF, Methylobacterium mesophilicum SR1.6/6, Nonlabens ulvanivorans, Synechococcus sp. PCC 7003, Psychroserpens damuponensis, Flavobacterium soli DSM 19725, Acinetobacter nosocomialis, Methanocaldococcus fervens AG86, Dehalococcoides mecartyi CBDBI, Marinitoga hydrogenitolerans DSM 16785, Thermus brockianus, Thermus scotoductus SA-01, Rhodopirellula maiorica SM1, Hydrogenophaga sp. PBC, Deinococcus sp. YIM 77859, Kurthia massiliensis, Thermococcus onnurineus NA1, Prevotella intermedia ZT, Hyphomonas sp. T16B2, Halopiger djelfimassiliensis, Porphyromonas gingivalis. Natrialba asiatica DSM 12278, Microcystis sp. TI-4, Pseudomonas aeruginosa, Sediminibacterium sp. C3, Fluviicola taffensis DSM 16823, Haloferax sp. BAB2207, Cecembia lonarensis LW9, Leptolinea tardivitalis, Thermosynechococcus elongatus BP-1, Mesorhizobium sp. L2C066B000, Cellulophaga lytica DSM 7489, Halorubrum kocurii JCM 14978, Paenibacillus borealis, Chryseobacterium sp. JM1, Variovorax paradoxus B4, Methylibium sp. YR605, Porphyromonadaceae bacterium COT-184 OH4590, Hyphomonas sp. T16B2, Leptospira noguchii, Clostridiales bacterium NK3B98, Geobacillus sp. FW23, [Clostridium] citroniae WAL-19142, Clostridium disporicum, Burkholderia vietnamiensis, Bacteroides fragilis str. 3397 T14, Leptolyngbya sp. ‘hensonii’, Acidobacterium capsulatum ATCC 51196, Clostridium perfringens WAL-14572, Geobacillus kaustophilus GBlys, Clostridium saudiense, Methylomicrobium buyatense 5G, Enterobacter kobei, Deinococcus sp. RL
In some cases, an RHDC or a functional fragment thereof can be selected from at least one of Vulcanisaeta moutnovskia, Thermoproteus uzoniensis, Pyrobaculum, Modestobacter marinus. Acidovorax avenae, Pseudomonas synxantha, Xanthomonas campestris, Caulobacter segnis, Pseudomonas putida, Xanthomonas vesicatoria, Pseudomonas stutzeri, Pantoea, Cupriavidus, Geobacter sulfurreducens, Chlorobium phaeobacteroides, Bordetella bronchiseptica, Woodsholea maritima, Novosphingobium pentaromativorans, Rhizobium phaseoli, Polymorphum gilvum, Bradyrhizobium elkanii, Bradyrhizobium, Bradyrhizobium oligotrophicum, Geobacter uraniireducens, Planctomyces limnophilus, Parvularcula bermudensis, alpha proteobacterium, Acinetobacter, Acinetobacter ursingii, Acinetobacter bereziniae, Mariprofundus ferrooxydans, Burkholderia sp-H160, Thioalkalivibrio thiocyanoxidans, Variovorax paradoxus, Burkholderia graminis, Burkholderia xenovorans LB400, Bacteroides fragilis 638R, Desulfobacula toluolica Tol2, Clostridium termitidis, Clostridium sp-CAG-264, Clostridium bolteae, Firmicutes bacterium CAG-65, Bacteroides, Bacteroidesovatus, Fluviicola taffensis DSM 16823, Joostella marina, Bacteroides massiliensis. Parabacteroides goldsteinii, Empedobacter brevis, Bacteroides eggerthii, Bacteroides fluxus. Alistipes putredinis, Parabacteroides merdae, Treponema vincentii, Lachnospiraecae bacterium 3 1 57FAA CT1, Brachyspira sp-CAG-484, Clostridiales bacterium NK3B98, Firmicutes bacterium CAG-137, Desulfovibrio sp-6 1 46AFAA, Stenotrophomonas maltophilia R551-3, Owenweeksia hongkongensis DSM, Cyclobacterium marinum DSM 745, Bacteroides coprophilus, Bacteroides intestinalis CAG-564, Pedobacter saltans DSM 12145, Hyphomicrobium denitrificans 1NES1, Sphingomonas sp-517, Rhodopseudomonas palustris BisB5, Agrobacterium sp-H13-3, Elioraea tepidiphila, Rhodanobacter denitrificans, Rhizobium etli CIAT 652, Pelagibacterium halotolerans B2, Tistrella mobilis KA081020-065, Sphingomonas wittichii RW1, Acidobacterium capsulatum ATCC 51196, Gluconacetobacter diazotrophicus PA1 5, Mesorhizobium sp-STM 4661, Sinordizobium fredii NGR234, Sinorhizobium medicae WSM419, Mesorhizobium metallidurans, Methanosarcina acetivorans C2A, halophilic archaeon DL31, Haloarcula marismortui ATCC 43049, Halorubrum lacusprofundi ATCC 49239, Halosarcina pallida, Halorubrum tebenquichense, Rhizobium lupine, Granulicella tundricola MPSACTX9, Methylomicrobium album, Novosphingobium sp-PPIY, Rhodopirellula maiorica, Flavobacterium indicum GPTSA100-9, Planctomyces maris, Leptolyngbya sp-PCC 7375, Bacteroides thetaiotaomicron, Bacteroides sp-3 1 19, Parabacteroides, Sphingobacterium spiritivorum, Fibrella aestuarina BUZ 2, Anaerophaga thermohalophila, Vibrio tubiashii, Gilvimarinus chinensis, Shewanella sp-ANA-3, Providencia rettgeri, Alishewanella agri, Pseudomonas plecoglossicida, Pseudomonas alcaligenes. Pseudomonas aeruginosa, Novosphingobium pcntaromativorans, Methylobacterium mesophilicum, Azospirillum amazonense, Methylibium petroleiphilum PM1, Methylohalobius crimeensis, Parvularcula bermudensis HTCC2503, Opitutaceae bacterium TAV5, Pedosphaera parvula, Acidobacteriaceae bacterium TAA166, Cupriavidus metallidurans CH34, Cupriavidus taiwanensis, Mycobacterium sp-KMS, Modestobacter marinus, Rhizobium phaseoli, Sphingomonas sp-KC8, Bradyrhizobium sp-YR681, Methylobacterium sp-88A, Novosphingobium pcntaromativorans, Maritimibacter alkaliphilus, Sphingobium yanoikuyae, Beijerinckia indica subsp-indica ATCC 9039, Brucella inopinata, Mesorhizobium loti MAFF303099, Afipia broomeae, Asticcacaulis biprosthecium, Sphingopyxis baekryungensis, Fodinicurvata sediminis, Sulfitobacter sp-NAS-14-1, Rhodovulum sp-PH10, Xanthobacter autotrophicus Py2, Sulfolobus islandicus M-16-27, Caldanaerobacter subterraneus, Cytophaga hutchinsonii ATCC 33406, Solitalea canadensis DSM 3403, Bacteroides sp-CAG-189, Winogradskyella psychrotolerans, Ceccmbia lonarensis, Flavobacterium sp-WG21, Sphingobium chlorophenolicum L-1, Streptomyces coelicolor A3-2, Methylobacterium mesophilicum, Parvularcula bermudensis HTCC2503, Rhodopseudomonas palustris DX-1, Pelotomaculum thermopropionicum SI, Syntrophobacter fumaroxidans MPOB, Acinetobacter baumannii, Acinetobacter nosocomialis, Hydrogenophaga sp-PBC, Salmonella enterica, Gemmata obscuriglobus, Zavarzinella Formosa, Acidovorax ebreus TPSY, Rhodopirellula maiorica, Cyanothece sp-PCC 8801, Rhodobacter sphaeroides ATCC 17025, Acidobacterium capsulatum ATCC 51196, Archaeoglobus fulgidus DSM 4304, Calditerrivibrio nitroreducens DSM 19672, Marinimicrobia bacterium JGI 0000039-D08, Cellulophaga lytica DSM 7489, Belliella baitica DSM 15883, Cyclobacterium marinum DSM 745, Acinetobacter baumannii, Acinetobacter nosocomialis, Treponema medium, Pirellula stalcyi DSM 6068, Leptospira interrogans, Pedobacter heparinus DSM 2366, Spirosoma linguale DSM 74, Leptospira santarosai, Anoxybacillus sp-DT3-1, Methylovulum miyakonense, Sulfolobus tokodaii str-7, Candidatus Nitrososphaera gargensis Ga9-2, Scytonema hofmanni, Cyanothece sp-PCC 8802, Calothrix sp-PCC 7103, Oryza sativa Japonica Group, Natronobacterium gregoryi SP2, Halobacterium sp-DL1, Prochlorothrix hollandica, Halopiger xanaduensis SH-6, Haloferax elongans, Haloferax denitrificans, Natronorubrum tibetense, Natrinema pellirubrum DSM 15624, Pseudoalteromonas luteoviolacca, Aromatoleum aromaticum EbN1, Synechococcus sp-PCC 7002, Synechococcus elongatus PCC 7942, Synechococcus sp-JA-3-3Ab. Cyanothece sp-PCC 7822, Stanieria cyanosphaera PCC 7437, Thermus scotoductus SA-01, Thermus sp-CCB US3 UF1, Halorubrum lacusprofundi ATCC 49239, Ignisphaera aggregans DSM 17230, Aquifex acolicus VF5, Chamaesiphon minutus PCC 6605, Oscillatoria acuminata PCC 6304, Lyngbya sp-PCC 8106, Chroococcidiopsis thermalis PCC 7203, Rivularia sp-PCC 7116, Microcystis aeruginosa NIES-843, Crinalium epipsammum PCC 9333, Anabaena cylindrical PCC 7122, Fischerella sp-JSC-11, Calothrix sp-PCC 7507, Burkholderia ambifaria, and/or Thioalkalivibrio thiocyanoxidans.
In some cases, a polypeptide construct can comprise a Clostridium disporicum Argonaute domain, or a functional fragment or variant thereof. In some cases, a polypeptide construct can comprise an RHDC polypeptide that comprises a Thermoactinomyces Argonaute domain, or a functional fragment or variant thereof, that can demonstrate nucleic acid-cleaving activity at 37° C. In some cases, a polypeptide construct comprises a domain from Thermoactinomyces sp CDF Argonaute domain, or a functional fragment or variant thereof. In some cases, a polypeptide construct can comprise an RHDC polypeptide that comprises a Methylobacter Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C. In some cases, a polypeptide construct comprises a Methylobacter Argonaute domain that comprises a Methylobacter whittenburyi Argonaute domain, or a functional fragment or variant thereof. In some cases, a polypeptide construct comprises an RHDC polypeptide that comprises a Thermosynechococcus Argonaute domain, or a functional fragment or variant thereof, that cleaves a nucleic acid at 37° C., in some cases, a polypeptide construct comprises an Thermoactinomyces Argonaute domain that comprises a Thermosynechococcus elongates Argonaute domain, or a functional fragment or variant thereof.
In some cases, a nucleic acid construct as described herein can encode a prokaryotic RNase H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide. In some cases, an RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature. Nucleic acid-cleaving activity can be directed by a guide DNA. In some cases, an RHDC polypeptide can be fused to a nucleic acid unwinding polypeptide. In some cases, a nucleic acid construct as described herein can encode an RNase H-like domain-containing (RHDC) polypeptide and a nucleic acid unwinding polypeptide. In some cases, a protein encoded by an RHDC polypeptide cleaves a nucleic acid at a mesophilic temperature. In some cases, nucleic acid-cleaving activity can be directed by a guide DNA. In some cases, an RHDC polypeptide can be fused to a nucleic acid unwinding polypeptide. In some cases, a protein encoded by a polypeptide construct further demonstrates nucleic acid-insertion activity. In some cases, an insertion can be of an exogenous transgene. An exogenous transgene can be a cellular receptor in some cases, such as a chimeric antigen receptor or a T cell receptor.
In some cases, an RHDC polypeptide can be chosen based on proximity to a secondary gene in a genome. For example, an RHDC polypeptide may be chosen based on its location adjacent to a helicase gene such ssDNA helicase SF1. In some cases, an RHDC polypeptide can be chosen based on proximity to DNA repair associated genes. In some cases, an RHDC polypeptide can be chosen based on a predicted alignment (e.g., structural analysis) or phylogenetic analysis, FIGS. 4-8D. For example, an RHDC polypeptide may have homology or be conserved in relation to a gene sequence of a secondary gene. In some cases, an RHDC polypeptide can be highly conserved in relation to RNase-H. Conservation can refer to a sequence or structure. Structural conservation can refer to the presence or absence of structural features. A structural feature can be a secondary structural feature such as an alpha helix or beta pleated sheet, FIG. 5. An RHDC polypeptide can be screened or chosen based on a secondary structure. An RHDC polypeptide can be RNase-HI, RNase-HII, RVE/Trasp, Argonaute, Ptp8, RuvC, RuvX, RNase T, or DNA PolIII. An RHDC polypeptide can share a secondary structure similar to at least one of RNase-HI, RNase-HII, RVE/Trasp, Argonaute, Prp8, RuvC, RuvX, RNase T, or DNA PolIII. In some cases, a nuclease is chosen based on a presence of an RHDC polypeptide fold in a structure. In some cases, an RHDC polypeptide is chosen based on conservation in an N-terminus or C-terminus. For example, a C-terminus may contain a PIWI domain and be conserved among a suitable nuclease, FIG. 3.
In some cases, a nuclease can be identified by the presence or absence of an RNase-H fold. An RNase-H fold can be one of the evolutionarily oldest protein folds that may be shared amongst different nucleases. In some cases, in the course of divergent evolution sequences of nuclease members accumulated numerous substitutions, insertions, deletions and underwent fusions with various domains. Due to this divergence, sequence similarity between different families of RNHL proteins can be low. In some cases, sequence similarity can be undetectable. The length of an RNase-H-like domain in different proteins can vary significantly owing to a presence of numerous insertions in a catalytic core. In some cases, a sequencing analysis can be performed to identify nucleases that share a domain, such as RNase-H or RNase-H-like.
In some cases, an RHDC polypeptide can be fused to at least one additional element, for example a helicase. In some cases, a nuclease can be fused to an ATPase. In some cases, an RHDC polypeptide can be fused to another RHDC polypeptide. In some cases, an RHDC polypeptide can be fused with a targeting polynucleic acid or targeting protein. In some cases, an RHDC polypeptide can be a fusion construct of an RHDC polypeptide and a nucleic acid unwinding polypeptide. In some cases, fusion proteins are comprised of polypeptides derived from a mesophilic organism. A mesophilic organism can be from a family selected from the group consisting of: bacteroidetes, proteobacteria, actinobacteria, firmicutes, cyanobacteria, spirochaetes, deinococcus, verrucomicrobia, planctomycetes, balneolaeota, and chloroflexi. A mesophilic organism can be from a family selected from the group consisting of: proteobacteria, acidobacteria, actinobacteria, and bacteroidetes.
In some cases, an RHDC polypeptide can be a polypeptide that can have nuclease activity. Nuclease activity can be double stranded polynucleic acid cleaving activity, such as DNA or RNA. In some cases, nuclease activity can be single stranded polynucleic acid cleaving activity. In some cases, an RHDC polypeptide can have nickase activity. Nickase activity can be single stranded DNA or RNA cleaving activity. In some cases, an RHDC polypeptide can have RNase activity. In some cases, RNase activity can be double stranded RNA cleaving activity. In some cases, RNase activity can be RNA cleaving activity. In some cases, an RHDC protein or polypeptide can have RNase-H activity. In some cases, RNase-H activity can be RNA cleaving activity. In some cases, an RHDC polypeptide can have recombinase activity. An RHDC polypeptide can also have DNA-Ripping activity. In some cases, an RHDC polypeptide can have transposase activity.
Fusion proteins can be synthesized using known technologies, for instance, recombination DNA technology where the coding sequences of various portions of the fusion proteins can be linked together at the nucleic acid level. Subsequently a fusion protein can be produced using a host cell. In some embodiments, a fusion protein comprises a cleavable or non-cleavable linker between the different sections or domains of the protein (e.g, between a nucleic acid unwinding domain and an RHDC polypeptide). For example, a linker can be a polypeptide linker, such as a linker that is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or more amino acids long. As described herein, two polypeptide sequences that are “fused” need not be directly adjacent to each other. Fused polypeptide sequences can be fused by a linker, or by an additional functional polypeptide sequence that is fused to the polypeptide sequences.
A linker can be a GSGSGS linker (SEQ ID NO: 381). In some cases, there can be from 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 linkers on a genome editing construct. For example, there can be from 1 to 10 GSGSGS linkers. A linker can comprise non-charged or charged amino acids. A linker can comprise alpha-helical domains. A linker can comprise a chemical cross linker. In some cases, a linker can be of different lengths to adjust the function of fused domains and their physical proximity. In some cases, a linker can comprise peptides with ligand-inducible conformational changes.
In some embodiments, a nuclease can be an Argonaute protein or polypeptide or functional domain or variant thereof. Argonaute proteins can be relatively large proteins of about 800 to about 1200 amino acids. An Argonaute protein or polypeptide or functional domain or variant thereof can be of eukaryote origin. An Argonaute protein or polypeptide or functional domain or variant thereof can be of prokaryote origin. A eukaryotic Argonaute protein can include mouse Argonaute proteins, such as AG02. An Argonaute protein may be derived from an archaeal or a bacterial organism. An Argonaute protein may be derived from a mesophilic organism. A mesophilic organism can be an organism that is active at temperatures from about 19° C. to 40° C. In some embodiments, a mesophilic organism can be active from temperatures of about 17° C., about 18° C., 19° C., about 20° C., about 21° C., about 22° C., about 23° C., about 24° C., about 25° C., about 26° C., about 27° C., about 28° C., about 29° C., about 30° C., about 31° C., about 32° C., about 33° C., about 34° C., about 35° C., about 36° C., about 37° C., about 38° C., about 39° C., or up to 40° C. In some embodiments, a mesophilic organism can be active at temperatures from about 17° C. to 40′° C. In some embodiments, a mesophilic organism can be active at temperatures of at least about 17° C. In some embodiments, a mesophilic organism can be active at temperatures of at most 40° C. In some embodiments, a mesophilic organism can be active at temperatures of about 17° C. to about 19° C. about 17° C. to about 21° C., about 17° C. to about 23° C., about 17° C. to about 25° C., about 17° C. to about 27° C., about 17° C. to about 29° C., about 17° C. to about 31° C., about 17° C. to about 33° C., about 17° C. to about 35° C., about 17° C. to about 37° C. about 17° C. to 40° C., about 19° C. to about 21° C., about 19° C. to about 23° C., about 19° C. to about 25° C., about 19° C. to about 27° C., about 19° C. to about 29° C., about 19° C. to about 31° C., about 19° C. to about 33° C., about 19° C. to about 35° C., about 19° C. to about 37° C., about 19° C. to 40° C., about 21° C. to about 23° C., about 21° C. to about 25° C., about 21° C. to about 27° C., about 21° C. to about 29° C., about 21° C. to about 31° C., about 21° C. to about 33° C., about 21° C. to about 35° C., about 21° C. to about 37° C. about 21° C. to 40′C, about 23° C. to about 25° C., about 23° C. to about 27° C., about 23° C. to about 29° C., about 23° C. to about 31° C. about 23° C. to about 33° C., about 23° C. to about 35° C., about 23° C. to about 37° C., about 23° C. to 40° C., about 25° C. to about 27° C., about 25° C. to about 29° C., about 25° C. to about 31° C., about 25° C. to about 33° C., about 25° C. to about 35° C. about 25° C. to about 37° C., about 25° C. to 40° C. about 27° C. to about 29° C., about 27° C. to about 31° C., about 27° C. to about 33° C. about 27° C. to about 35° C., about 27° C. to about 37° C., about 27° C. to 40° C., about 29° C. to about 31° C., about 29° C. to about 33° C., about 29° C. to about 35° C., about 29° C. to about 37° C. about 29° C. to 40° C. about 31° C. to about 33° C., about 31° C. to about 35° C., about 31° C. to about 37° C., about 31° C. to 40° C., about 33° C. to about 35° C., about 33° C. to about 37° C., about 33° C. to 40° C. about 35° C. to about 37° C., about 35° C. to 40° C., or about 37° C. to 40° C. In certain embodiments described herein an Argonaute polypeptide can comprise a functional domain from an Argonaute protein described herein, or variant thereof.
In some cases, an RHDC polypeptide can demonstrate nucleic acid-cleaving activity in a range of temperatures including about 19° C. to about 41° C. In some cases, a nuclease or RHDC polypeptide can be from a mesophilic organism. An RHDC polypeptide can be an Argonaute protein, polypeptide or functional portion thereof. In some embodiments, an RHDC polypeptide has nucleic acid-cleaving activity at temperatures of about 17° C., about 18° C. 19° C., about 20° C., about 21° C., about 22° C., about 23° C., about 24° C., about 25° C., about 26° C., about 27° C., about 28° C., about 29° C. about 30° C., about 31° C., about 32° C., about 33° C., about 34° C., about 35° C., about 36° C., about 37° C., about 38° C., about 39° C., or up to 40° C. In some embodiments, an RHDC polypeptide has nucleic acid-cleaving activity at temperatures from about 17° C. to 4) ° C. In some embodiments, a mesophilic organism can be active at temperatures of at least about 17° C. In some embodiments, a mesophilic organism can be active at temperatures of at most 40° C. In some embodiments, a mesophilic organism can be active at temperatures from about 17° C. to about 19° C., about 17° C. to about 21° C., about 17° C. to about 23° C., about 17° C. to about 25° C., about 17° C. to about 27° C., about 17° C. to about 29° C., about 17° C. to about 31° C., about 17° C. to about 33° C., about 17° C. to about 35° C., about 17° C. to about 37° C., about 17° C. to 40° C., about 19° C. to about 21° C., about 19° C. to about 23° C., about 19° C. to about 25° C., about 19° C. to about 27° C., about 19° C. to about 29° C., about 19° C. to about 31° C., about 19° C. to about 33° C., about 19° C. to about 35° C., about 19° C. to about 37° C., about 19° C. to 40° C. about 21° C. to about 23° C., about 21° C. to about 25° C., about 21° C. to about 27° C. about 21° C. to about 29° C., about 21° C. to about 31° C., about 21° C. to about 33° C., about 21° C. to about 35° C., about 21° C. to about 37° C., about 21° C. to 40° C., about 23° C. to about 25° C., about 23° C. to about 27° C. about 23° C. to about 29° C., about 23° C. to about 31° C., about 23° C. to about 33° C., about 23° C. to about 35° C., about 23° C. to about 37° C., about 23° C. to 40° C., about 25° C. to about 27° C. about 25° C. to about 29° C., about 25° C. to about 31° C., about 25° C. to about 33° C., about 25° C. to about 35° C., about 25° C. to about 37° C., about 25° C. to 40° C., about 27° C. to about 29° C., about 27° C. to about 31° C., about 27° C. to about 33° C., about 27° C. to about 35° C., about 27 T to about 37° C., about 27° C. to 40° C., about 29° C. to about 31° C., about 29° C. to about 33° C., about 29° C. to about 35° C. about 29° C. to about 37° C., about 29° C. to 40° C., about 31° C. to about 33° C., about 31° C. to about 35° C., about 31° C. to about 37° C., about 31° C. to 40° C., about 33° C. to about 35° C., about 33° C. to about 37° C., about 33° C. to 40° C., about 35° C. to about 37° C., about 35° C. to 40° C., or about 37° C. to 40° C.
An Argonaute polypeptide can be from Homo sapiens, Arabidopsis thaliana, Oryza sativa japonica, Entamoeba dispar, Paramecium tetraurelia, Drosophila melanogaster, Caenorhabditis elegans. An Argonaute polypeptide can be Homo sapiens Ago2, Arabidopsis thaliana Ago, Oryza sativa japonica Ago, Entamoeba dispar SAW760 Ago, Paramecium tetraurelia strain d4-2 Ago, Drosophila melanogaster Ago, Caenorhabditis elegans Ago, or Homo sapiens Ago. In some cases, an RHDC polypeptide can comprise an Argonaute protein or functional domain.
In some cases, an Argonaute polypeptide or portion thereof can be a naturally-occurring Argonaute polypeptide (e.g, naturally occurs in bacterial and/or archaeal cells). In other cases, an Argonaute polypeptide may not be a naturally-occurring polypeptide (e.g., an Argonaute polypeptide can be a variant, chimeric, or fusion). In some cases, an Argonaute polypeptide can have nuclease activity. In some cases, an Argonaute polypeptide may not have nuclease activity.
In some cases, an Argonaute polypeptide can be a type I prokaryotic Argonaute. In some cases, a type I prokaryotic Argonaute can carry a DNA nucleic acid-targeting nucleic acid. In some cases, a DNA nucleic acid-targeting nucleic acid targets one strand of a double stranded DNA (dsDNA) to produce a nick or a break of the dsDNA. A nick or break can trigger host DNA repair. In some cases, a host DNA repair can be nonhomologous end joining (NHEJ) or homologous directed recombination (HDR). In some cases, a dsDNA can be selected from a genome, a chromosome, and a plasmid. A type I prokaryotic Argonaute can be a long type I prokaryotic Argonaute, which may possess an N-PAZ-MID-PIWI domain architecture. In some cases a long type I prokaryotic Argonaute possesses a catalytically active PIWI domain. The long type I prokaryotic Argonaute can possess a catalytic tetrad encoded by aspartate-glutamate-aspartate-aspartate/histidine (DEDX). The catalytic tetrad can bind one or more magnesium ions or manganese ions. In some cases, the type I prokaryotic Argonaute anchors the 5′ phosphate end of a DNA guide. In some cases, a DNA guide can have a deoxy-cytosine at its 5′ end.
In some embodiments, a prokaryotic Argonaute is a type II Ago. A type II prokaryotic Argonaute can carry an RNA nucleic acid-targeting nucleic acid. An RNA nucleic acid-targeting nucleic acid can target one strand of a double stranded DNA (dsDNA) to produce a nick or a break of the dsDNA which may trigger host DNA repair; the host DNA repair can be non-homologous end joining (NHEJ) or homologous directed recombination (HDR). In some cases, a dsDNA can be selected from a genome, a chromosome and a plasmid. A type II prokaryotic Argonaute may be a long type II prokaryotic Argonaute or a short type II prokaryotic Argonaute. A long type II prokaryotic Argonaute may have an N-PAZ-MID-PIWI domain architecture. A short type II prokaryotic Argonaute may have a MID and PrWI domain, but may not have a PAZ domain. In some cases, a short type II Ago can have an analog of a PAZ domain. In some cases a type II Ago may not have a catalytically active PIWI domain. A type II Ago may lack a catalytic tetrad encoded by aspartate-glutamate-aspartate-aspartate/histidine (DEDX). In some cases, a gene encoding a type II prokaryotic Argonaute clusters with one or more genes encoding a nuclease, a helicase or a combination thereof. A nuclease may be natural, designed or a domain thereof. In some cases, the nuclease is selected from a Sir2, RE1 and TIR. The type II Ago may anchor the 5′ phosphate end of an RNA guide. In some cases, the RNA guide has a uracil at its 5′ end. In some cases, the type II prokaryotic Argonaute is a Rhodobacter sphaeroides Argonaute. In some cases, it may be desirable to use an Argonaute nuclease that has lost its ability to cleave a nucleic acid, such as in applications where the Argonaute: guide molecule complex is used as a probe. In some cases, a dead Argonaute system may utilize secondary nucleases to perform a genomic disruption. In such cases, one or more of the amino acid residues in a catalytic domain can be substituted or deleted, such that catalytic activity can be abolished, or diminished. In other cases, using a cleavage temperature-inducible Argonaute may be desired to control the timing of cleavage, or if cleavage should be inhibited at non-inducible temperatures.
In some cases, an Argonaute polypeptide can have at least one active domain. For example, an Argonaute's active domain can be a PIWI domain. In addition to a catalytic PIWI domain an Argonaute can contain non-catalytic domains such as PAZ (PIWI-Argonaute-Zwille), MID (Middle) and N domain, along with two domain linkers, L1 and L2. A MID domain can be utilized for binding the 5′-end of a guiding polynucleic acid and can be present in an Ago protein. A PAZ domain can contain an OB-fold core. An OB-fold core can be involved in stabilizing a guiding polynucleic acid from a 3′end. An N domain may contribute to a dissociation of the second, passenger strand of a loaded double stranded genome and to a target cleavage. In some cases, an Argonaute family may contain PIWI and MID domains. In some cases, an Argonaute family may or may not contain PAZ and N domains.
In some cases, an Argonaute polypeptide can be or can comprise a naturally-occurring polypeptide (e.g. naturally occurs in bacterial and/or archaeal cells), such as a nuclease. In other cases, an Argonaute polypeptide can be or can comprise a non-naturally-occurring polypeptide, such as a nuclease. A non-naturally occurring polypeptide can be engineered. An engineered Argonaute polypeptide can be a chimeric nuclease, mutated, conjugated, or otherwise modified version thereof. In some cases, an Argonaute polypeptide can comprise a sequence encoded by any one of SEQ ID NO: 1 to SEQ ID NO: 19. In some cases, a polypeptide sequence of an Argonaute polypeptide can comprise a sequence encoded by any one of SEQ ID NO: 20 to SEQ ID NO: 38. In some cases, a polypeptide can comprise a sequence encoded by any one of SEQ ID NO: 39 to SEQ ID NO: 57. In some cases, a construct can comprise a sequence encoded by any one of the sequences of Table 16 (SEQ ID NO: 59-SEQ ID NO: 67), modified versions thereof, derivatives thereof, or truncations thereof. In some cases, a construct can comprise a sequence encoded by any one of the sequences of Table 17 (SEQ ID NO: 68-SEQ ID NO: 160), modified versions thereof, derivatives thereof, or truncations thereof. In some cases, a construct can comprise a sequence encoded by any one of the sequences of Table 18 (SEQ ID NO: 161-SEQ ID NO: 252), modified versions thereof, derivatives thereof, or truncations thereof. In some cases, a construct can comprise a sequence encoded by any one of the sequences of Table 19 (SEQ ID NO: 253-SEQ ID NO: 344), modified, versions thereof, derivatives thereof, or truncations thereof.
In some cases, an Argonaute nucleic acid or portion thereof can comprise a percent identity to any one of SEQ ID NO: 1 to SEQ ID NO: 19, or SEQ ID NO: 39 to SEQ ID NO: 57 from at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, up to at least about 100%. In some cases, an Argonaute polypeptide or portion thereof can comprise a percent identify to any one of SEQ ID NO: 20 to SEQ ID NO: 38 from at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, up to at least about 100%. In some cases, a polypeptide or portion thereof can be from a sequence that comprises a percent identity to any one of SEQ ID NO: 59 to SEQ ID NO: 344 from at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, up to at least about 100%.
TABLE 1
Bacterial Argonaute functional domain nucleic acid sequences identified by PIWI domain
SEQ
ID NO Sequence
1 GATCACGTCGCCCACCGCGTCGGCGAAACGTATCGTCACCGGCAATCGATCGTTATGCAGGCAAGAATTGAAATTGATCTTGGT
CAGGCCCATCACGTCCCCGAGAACCGTTTCAAGTTCGCAATCTCCGCGGTGAATGCGGACTTCTATCGGATTCGGCGTCTCTGG
CCCTTGGGAGGTATCAAGGCGCGGGGCGAATCCCGACGTCCAGAGGAACGCGCGGCGTTCGTGCAATATCAAGGCCGTTCCGCG
GATGACCGGATATCGACCGGGCCGGTATAGCTTCATGCGGTCTTTCGCATCGGAAATCTGCACTCCTACGACATTGGTCCCCGG
AGCAGCGGCCTTGAAGCCTTTCCATTCCGGGTCCGCGAACGAGGACTTGGCATGAATGAACAGCTCAGCGGGCGGCTGTCCATC
ATGCATTTGTTGATATTCGCCGATAACCATCTCAACTAAACTGCTTGCCGCGTCCTCGCTCAGATGAAATTGCTTGGATTCGGA
ATGAAACCATGGGCCGAGCGCACCGCGAAATACGACGCCTTCACCGCTCGAAAGAAACATCTGGGCGGCGCAACAGGCGAAGCG
ATCATCGGAACTATTGTCCTGTCGCTTATAGGCGAGGCCGACATAGCAAACGCCGGGTCTGACGTCGGCCAACTGCCATGGTCG
TCCACCATCCTTGTAATAGGCGCCGGTCAATATTTTCCAGGCGATCGTTGCAGGGTCCTCCAATCGTCGCAGTGGCTTGCCGAT
TTTGTTCAGGAAATCGTTAGGCGCCAATGTGGTTTCCCTAACGATCTGAGTGACGATACGGTCTCTGAGCAGACGTGCCTTCAA
CTG
2 GATCTGCATCACCAGCTCAAAGCCTTCACCGCCGCGCGGCAGCTGCCCATTCAGATTGTGCGCGAAGACAGCGCACTATCCTAT
CGATGCCGGGCCAGCGTCATGTGGCGGATCGGCCTGGCGCTCTACGCCAAGGCTGGCGGCGTTCCTTGGAAACTGGCCGATGTG
GAGCCGGACACTGCCTATATTGGTATCTCCTATGCGCTCCGGCCCGCAGAATCGGAGCTTGCCCGCTTCGTAACCTGTTGCAGC
CAGGTCTTCGACGCCGACGGTGCTGGACTGGAATTCATCGCCTATGACACCGGCGATGTGAACGTACAGCGGGAGAACCCGTTT
CTCTCGCATACCGAGATGTTTCGGGTCATCACCCGTTCGCTGGACCTTTATCGCCGGCGCCATGGCGGCAGACTGCCGACACGT
GTGATGATCCACAAATCGACCGAGTTCAAGGAAGCCGAAATAGAAGGCTGCTTCGAAGCGCTGAAACATATCGAGTCGGTCGAT
CTCATCCAGATCGTCGAGGACAATGGCTGGCAGGGCGTGCGATGGGAACAGGACCGTAACGATCCGGAGATATCACAAGCGGAT
GGGTATCCGGTGAAACGCGGAACCTTGCTCGGGCTCAGCGGCAAAGACGCTTTGCTCTGGATGCACGGGGCAGTCGATGGTTTC
GGGCGCCGCCCCTATTTTCAAGGTGGCAAAGGTACACCGCGACCGTTGCGACTGGTCCGACATGCCGGGCATGGAACATGGGAC
GATACCGCGAAGGCGGCCCTGGCGCTGTCGAAAATGAACTGGAACAATGACGGGCTCTATGATCCACTTCCGGTGACGATGAGC
TACGCAAAGACCTTAGCA
3 GATCACGTCGCCCACCGCGTCGGCGAAACGTATCGTCACCGGCAATCGATCGTTATGCAGGCAAGAATTGAAATTGATCTTGGT
CAGGCCCATCACGTCCCCGAGAACCGTTTCAAGTTCGCAATCTCCGCGGTGAATGCGGACTTCTATCGGATTCGGCGTCTCTGG
CCCTTGGTAGGTATCAAGGCGCGGGGCGAATCCCGACGTCCAGAGGAACGCGCGGCGTTCGTGCAATATCAAGGCCGTTCCGCG
GATGACCGGATATCGACCGGGCCGGTATAGCTTCATGCGGTCTTTCGCATCGGAAATCTGCACTCCTACGACATTGGTCCCCGG
AGCAGCGGCCTTGAAGCCTTTCCATTCCGGGTCCGCGAACGAGGACTTGGCATGAATGAACAGCTCAGCGGGCGGCTGTCCATC
ATGCATTTGTTGATATTCGCCGATAACCATCTCAACTAAACTGCTTGCCGCGTCCTCGCTCAGATGAAATTGCTTGGATTCGGA
ATGAAACCATGGGCCGAGCGCACCGCGAAATACGACGCCTTCACCGCTCGAAAGAAACATCTGGGCGGCGCAACAGGCGAAGCG
ATCATCGGAACTATTGTCCTGTCGCTTATAGGCGAGGCCGACATAGCAAACGCCGGGTCTGACGTCGGCCAACTGCCATGGTCG
TCCACCATCCTTGTAATAGGCGCCGGTCAATATTTTCCAGGCGATCGTTGCAGGGTCCTCCAATCGTCGCAGTGGCTTGCCGAT
TTTGTTCAGGAAATCGTTAGGCGCCAATGTGGTTTCCCTAACGATCTGAGTGACGATACGGTCTCTGAGCAGACGTGCCTTCAA
CTG
4 GACCTGCACGACCGGTTGAAGGCGACGGCCGCGCTGCTGGGCTGTCCTATCCAGATGATCCGCGAGACCTCCGCGCTGCAGTTC
AGGTACAAGTGCTCCATGTACTGGCGGCTGTCGATTGCGCTGCTGACGAAGGCTGGCGGCGTGCCGTTCCGGATGATGCGTCCC
ACTGAGTCCGACACTGCCTACCTCGGGCTGGCCTACGCGATTCGCGGCGGGACCGCCAACGAGTTCGTCACCTGCTGCTCGCAG
GTCTTCGACGCCGAAGGCGGCGGCTTCGAATTTATCGCCTACAACGTCGGCGCCGACCGTGACCTGGAGAACCCGCATCTGACC
CGCGACGAGATGCGCACCGTCATGGCGCGCAGCGCTCGCCTCTACCAGCGGCGCAGGGCCGGGTCTCTGCCCCAGCGGCTTGTG
ATCCACAAGACGACAACCTGGCGTGAGGAAGAAGTCGCAGGGGTCTTCGACGCGTGGAGCCCGGCCGTTCCTGACATCGAGTGC
CTCCAGGTACGTCTAGACACACCCTGGACCGGGGTTGCCCTCCGCGGCGGCAAGGGCAACTCGGCGGTCGCCAACGAATGGCCT
GTGGGCCGCGGGTCTCTTCAGTATCTCTCTGGGCGGGAGGCACTCCTGTGGATCGCCGGTACGGCGAAGGGTGTCGCGCTGACG
GGTGAGAACTATAATCAGGCAGCCAAGGCTCTACCGACCCCGATTGCGTTCAAGCGTGACGCGGGTGCTGGCCCCCTGGAGATT
CCTGCCAGCGAAATCCTTGCCCTGTCGAAGCTCGACTGGAACAACGACGCCCTTTACGGTGTGACCCCG
5 CATTTCCACAACCAGCTCAGGGCCAGGCTACTTGGCTGCGAGGCGATCACCCAGCTCGTGCGCAGACCGCCATTGCCCCGCGCG
AATACCTCAACAGCAAGGGCGAGCTTTCCCGCAAGATGCAGGATGACGCACCGTCGCGTGGAATCTCAC
6 CAAGATGCAGGATGACGCACCGTCGCGTGGAATCTCACGACTGGTGTCTATTACAAAGCGGGCGAGAAGCCGTGGTCTCTTGCC
GACATCCGGGATGGCGTCTGCTACACAGGCCTCGTCTTCAAGCGTACAAACAACCCGGTCGAAGCGAAGGAGGCGTGCTGTGGC
GCGCAGATGTTCCCTCATACCGGCGAAGGCATCGAACGCCGCGGCTGC
7 GAGGACATCTCCGACCGCGTTGGCGAAACGGATCGTCACCGGTAACCGGTCATTGTGAAGGCACGAATTGAAGTTGATCTTCGT
GAGCCCGAGCACGTCGGCGAGGACCGTCGTCAGTGGGCACTCGCCGCGAAGAACGCGAACCGAAATCGGGTTCGGGGTCTCAGG
CCCCATATAGGTGTCCAGCCGTGGCACATAGCCCGAGGTCCACAGAAGTGCGTGACGTTCACCGATCTGCAGCGCCGTGCCGCG
AATGACGGGATACTCTCCAGGACGATAGAGCTTCAGGTCATCACGAGCCTCGGCAATCTGCACACCGACGAGGTTGGTCTCATC
CCCGCAGGCGGACGAAAAACCGCGCCATTCGTTGTCGGTAAAGGCGGACTTCGCGTGGATGAAGAGTTCGGTTGGTGGGCCATC
GTGCAGGCGGGTGTATTCGCCCACCACCATCTTGATAAGGTTCCTGGCGGCATCCTTATCAAGGTGGAACTGCTTCGTATCGGT
TTGGAACCAAGGGCCGAGCGCGCCGCGGAAGACCACGCCTTCCCCGTCAGCGAGAAACATTTGGGCTGCGCAGCAGGCATGACG
CTTGTCGCTTGTTAGTTCGCTGCGTTTGTAGACCAGTCCGACATAACAGACGCCCGGTCGAACATCGGCCAACTGCCAAGGCTT
CCCGCCAGCCTTGTAGTAGGCGCCCGTTCCCATTTTCCAGGCGATAGTCGC
8 GATGCTCACGACACACTCAAGGCATTGGGCGCGAAATATAATATACCAACGCAGGTGCTCAATGACCGTGTCTTTGCGTTTTCA
CACCCTGCGTCGCGATCCTGGCGGCTGGCGATAGCGCTTTATGTTAAGGCAGCGGGCACACCTTGGAAGCTTGCGCCCCTGAAA
GGTGTACCTGAGGACACGGCTTACATCGGCCTCGCCTACGCCTTACGGGGCGACCAGCGGGATGCGCACTATGTGACGTGCTGT
TCCCAGGTGTTTGATATGGATGGCGGAGGAATGCAGTTCGTTGCCTTCGAGGCCAAGGATCCTATCGCCGATGTCGCAGAAGCG
CGTCGAAATCCATTTCTCAGTCGAGATGATATGCGCGCGGTTCTTGCTCGCAGCCTCGAGCTCTATCAAGGAAGAAATGGAGGA
ACACTGCCGAAGCGGCTTGTCATTCATAAGACCACAGCATTCAAACCGGATGAGATCGAGGGTGCGTTTGATGCACTTGCCGGG
GTGCAAGAAATCGAGTGCATTGAAGTTAGCCCAGCTTCCGGTTGGCGTGGGGTATGGCTGGTACCGAGCGGACAGCCGAAGCCG
CCGACCAAGCCTGCGGGCTACCCTGTTCCGAGAGGCACCGTTGTCGTCCGGTCCGGGACCTCGGCGCTTGTTTGGGTCGCGGGC
AATGCTCCCGAAGTGTCTAATAAGGGCGACTATTATCAGGGAAAGAAGAGCATTCCAAAGCCGTTGCAGCTGATCAGGCACGCA
GGCAGTGGACCGTTGGAGCTATCGGCTCACGAGGCCTTGGCTCTCACCAAGATGGATTGGAACAATGATGCTCTCTACGATCCT
GTGCCTGTTAGCATCCGATACTCGCAACGCTTAGCCAAGACGATC
9 GATCTACACGATTTCGTCAAGGCGGCGGCGATTCCGAAAGGTTGCGCCACACAGTTTGTCGAAGAGGACACCCTCCGTAACACG
CAGCAGCAATGCCGCGTGCGCTGGTGGCTCTCGCTTGCCCTGTACGTGAAAAGCATGCGCACGCCGTGGACTTTGGAAGGCCTC
AGCGAGAAATCCGCCTACGTGGGTCTCGGCTTCAGCGTCAAACGCAAGACGACACAGAATGCGGGCGCACACGTCGTGCTGGGC
TGTAGCCACCTCTATAGCCCGAACGGCATCGGTCTGCAGTTCCGCCTGAGCAAGATCGAAGATCCAATTATGCGCAACAAGAAT
CCCTTCATGAGCTTCGACGATGCAAGACGGCTCGGTGAGGGCATCCGTGAACTGTTTTTCGCCGCCCAACTTCGACTTCCTGAG
CGAGTGGTGATCCACAAGCAGACCCCATTCCTTCGCGAAGAACGCAGTGGGCTCCAGGCTGGACTCGAGGGAGTTGCGTGCGTA
GAGCTATTGCAGATCTTCGTTGACGACACGCTACGGTATGTGGCGTCCCATCCGACCTCCGACGGAAAGTTCGAGACCGACAAC
TATCCCATCCGGCGGGGAACGACAGTGGTCATCGACGATCACACGGCTCTTCTGTGGGTCCACGGCGCATCTACTGCACTAAAT
CCCAGAAGGCACTATTTCCAGGGCAAGCGTCGAATTCCAGCCCCCTTGGTAATTCGGCGTCATGCGGGCACGACCGATTTGATG
ACGATCGCCGACGAAGTTCTCGGCTTGTCGAAGATGAATTTCAACAGCTTCGACCTTTACGGGCAACTTCCAGCGACGATCGAG
ACGTCACGCCGCGTTGCGAAGATC
10 ACCGATGCGCGCGACCCGTTGAGAGGTTTCGATGGTTGCGGGCAACTGCCCATAGAGATCAAAGCTGTTGAAGTTCATCTTGGA
CAGGCCAAGGATTTCATCGGCCAGCATCATGAGATCGCTAGTGCCGGCGTGGCGGCGCATCACGAGCGGGGCCGGAATTCGGCG
CTTCCCCTGAAAGTAGGATTGCCTAGGGTTGAGAGCGGTAGAGGTTCCGTGCACCCACAGCAATGCTGTCTGATCGTCCACTAC
AACCGTTGTGCCGCGTCGAATCGGATAGCCGTGAATCTCGAAGTCGCCATTGGGCATCGGGCGCGATGCCACGTACCGCAAGGT
GTCATCGACGAAGATCTGCAACAACTCGACGCAGGCCACGCCCTCCAGGCCAGCTTGCAGCCCCTCGCGCTCCTCCTTCAGGAA
AGGCGTTTGCTTGTGCACCACGACGCGATTGGGAAGGCGTAGGTGGGCGTCGAAGAACAGCTCTCGGATGCCTTCCCCAAGCTT
TCGCGCGTCGTCGAAGCTCATGAAGGGGTTCTTGCGCAGCATGATCGGGTTGTCGATCTTGCTCAGGCGGAATTGAAGGCCGTG
ACCATTGGGGCTGTAGAGGTGGCTGCAGCCCAGCGCGACATGGCCTTCGCCGTCGATCTTTCGGCGGACGCTGAAGCCGAGGCC
CACGAAGGCGGAATCCCTATCAAGGCCGGTGAGGGCCCAGGGGGTGCGCATGGCTTTCACGTACACAGCCAGAGACAACCACCA
TCGAACGCGGCATTGCTGACCGTTGGCGAGAGTGCTTTCTTCGAGAAACTGAGTGGAGCAACCAGCCGGGATGGCCGCGGCCTT
CACAAAATCGTG
11 GATCACGTCGCCCACCGCGTCGGCGAAACGTATCGTCACCGGCAATCGATCGTTATGCAGGCAAGAATTGAAATTGATCTTGGT
CAGGCCCATCACGTCCCCGAGAACCGTTTCAAGTTCGCAATCTCCGCGGTGAATGCGGACTTCTATCGGATTCGGCGTCTCTGG
CCCTTGGTAGGTATCAAGGCGCGGGGCGAATCCCGACGTCCAGAGGAACGCGCGGCGTTCGTGCAATATCAAGGCCGTTCCGCG
GATGACCGGATATCGACCGGGCCGGTATAGCTTCATGCGGTCTTTCGCATCGGAAATCTGCACTCCTACGACATTGGTCCCCGG
AGCAGCGGCCTTGAAGCCTTTCCATTCCGGGTCCGCGAACGAGGACTTGGCATGAATGAACAGCTCAGCGGGCGGCTGTCCATC
ATGCATTTGTTGATATTCGCCGATAACCATCTCAACTAAACTGCTTGCCGCGTCCTCGCTCAGATGAAATTGCTTGGATTCGGA
ATGAAACCATGGGCCGAGCGCACCGCGAAATACGACGCCTTCACCGCTCGAAAGAAACATCTGGGCGGCGCAACAGGCGAAGCG
ATCATCGGAACTATTGTCCTGTCGCTTATAGGCGAGGCCGACATAGCAAACGCCGGGTCTGACGTCGGCCAACTGCCATGGTCG
TCCACCATCCTTGTAATAGGCGCCGGTCAATATTTTCCAGGCGATCGTTGCAGGGTCCTCCAATCGTCGCAGTGGCTTGCCGAT
TTTGTTCAGGAAATCGTTAGGCGCCAATGTGGTTTCCCTAACGATCTGAGTGACGATACGGTCTCTGAGCAGACGTGCCTTCAA
CTG
12 GACGCCCACGACGCGTTGAAGGCCCTTGGAGCCCGGTACGCCATCCCAACGCAGGTCATCAACGATCGCGTTTTCACATTCCGG
CTCAAGGCGTCGTTGGCCTGGCGCCTGGCCATCGCGCTCTTCACCAAGGCGGGCGGCATTCCCTGGAAACTCGCGCCGATGGTC
GGTGTACCAGAAGACACGGCCTATATCGGTCTCGCCTACGCGTTGCGCGGGGACCCCAAGTCCGCGCAGTTCGTCACGTGCTGC
TCGCAGGTGTTCGACGCGGACGGCGGTGGCATGCAGTTCGTCGCTTTCGAGGCCAAGGAGCAGGTGGCGGATCCGCGCGAAGCC
AGACGGAACCCGTTTCTCAGTCGGAGCGACATGCGGGCGGTAATGGCACGTAGCCTGAGCCTCTACCTTGGGCGTAATGGTGGA
CGGCTGCCGCGACGTCTCGTCGTCCACAAAACGACGTCGTTCAAGGACGAAGAACTCCAAGGCGTTTTCGACGGCCTGTCGACG
GTTCCAGAGGTGGAGTGCATCGAGATCGGCAGCAGCGCCACATGGCGTGGCGTGTGGCTGAAGCAGGGAAAGAAGGGCGGACCC
AAAAGTGTGCCTGATCGAGCGCCGGTGCCGCGGGGAACTGTCCTCACGCGAACGGACCGGTCGGCGCTGTTGTGGGCATCGGGC
AATGCCCCGTCGGCAGCGCTCAGCGGTGCCTTGTTTTTCCAGGGAAGCAAGAGCATTCCGCGCCCGCTCAACATCATCCGTCAC
GCGGGCAGCGGTCCGCTGGAAGTTGCTGCGTTGGAAACCCTCGCGCTGACCAAAATGGACTGGAACAACGACGCGTTGTACGAC
CCGGTTCCGGTGACCATTCGCTATTCGCAACGGCTCGCACGTACCATC
13 AGCCCTTACTGGTGGGCGAAGGCTGCGTTCCTGCGGCGCGACGTGCCAGTGCAGGCACTCTCCGCCGAGATGATGGCCATGGGC
GACTTCGAGTACGCCTGCGCTTTGGCAAACGTCAGCTTGGCCACTTACGCCAAGCTCGGCGGTACCCCTTGGCTGCTGAAGGCC
CGGCCCTCGACAGATCACGAGCTTGTCTTTGGCCTCGGATCTCATACCCACAAGGAGCGACGTCGAGGTGCAGGGGAACGGGTC
GTCGGGATCACGACCGTGTTCTCTAGCCAGGGTAACTATCTACTAGATGCCCGAACGGCTGCAGTACCGTTCGACCGCTACCCG
GAGGCACTGCGCGCCACGCTCATCGAGGCGGTCAAGCGCATACGGCAAGAGGAGGCCTGGCGCGCGGGCGACACGGTGCGCTTG
GTCTTCCATGCCTTCACCCAGATGCGACAAGAGACTGCGGATGCCGTGGTTGCCGCTGTGGAAAGCATGGGCCTGAGTGGGGTG
AAGTTCGCCTTCCTCCATGTGGCCGAGGACCACCCATTCACGCTGTTCGACCACGCCTCAGCGACTGGCAAGGGTGCCTATGCG
CCCGAGCGTGGGCAGGCCGTAGAACTCAGCGACCACGAGTGGCTCCTTTCCCTCACCGGACGGGATCAGATCAGAGCCGCGTCG
CAGGGCATCCCTGATCCGGTGCTACTCCGCCTGCACGAGAAATCGACCTTTCGCGACATGCGAACGCTGACGCGTCAGGTATCG
GATTTCGCCTGCCACTCCTGGCGTACTTACGAACGAGCTAGGCTCCCGATCACACTCCTCTAC
14 GATCACGTCGCCCACCGCGTCGGCGAAACGTATCGTCACCGGCAATCGATCGTTATGCAGGCAAGAATTGAAATTGATCTTGGT
CAGGCCCATCACGTCCCCGAGAACCGTTTCAAGTTCGCAATCTCCGCGGTGAATGCGGACTTCTATCGGATTCGGCGTCTCTGG
CCCTTGGTAGGTATCAAGGCGCGGGGCGAATCCCGACGTCCAGAGGAACGCGCGGCGTTCGTGCAATATCAAGGCCGTTCCGCG
GATGACCGGATATCGACCGGGCCGGTATAGCTTCATGCGGTCTTTCGCATCGGAAATCTGCACTCCTACGACATTGGTCCCCGG
AGCAGCGGCCTTGAAGCCTTTCCATTCCGGGTCCGCGAACGAGGACTTGGCATGAATGAACAGCTCAGCGGGCGGCTGTCCATC
ATGCATTTGTTGATATTCGCCGATAACCATCTCAACTAAACTGCTTGCCGCGTCCTCGCTCAGATGAAATTGCTTGGATTCGGA
ATGAAACCATGGGCCGAGCGCACCGCGAAATACGACGCCTTCACCGCTCGAAAGAAACATCTGGGCGGCGCAACAGGCGAAGCG
ATCATCGGAACTATTGTCCTGTCGCTTATAGGCGAGGCCGACATAGCAAACGCCGGGTCTGACGTCGGCCAACTGCCATGGTCG
TCCACCATCCTTGTAATAGGCGCCGGTCAATATTTTCCAGGCGATCGTTGCAGGGTCCTCCAATCGTCGCAGTGGCTTGCCGAT
TTTGTTCAGGAAATCGTTAGGCGCCAATGTGGTTTCCCTAACGATCTGAGTGACGATACGGTCTCTGAGCAGACGTGCCTTCAA
CTG
15 GATCACGTCGCCCACCGCGTCGGCGAAACGTATCGTCACCGGCAATCGATCGTTATGCAGGCAAGAATTGAAATTGATCTTGGT
CAGGCCCATCACGTCCCCGAGAACCGTTTCAAGTTCGCAATCTCCGCGGTGAATGCGGACTTCTATCGGATTCGGCGTCTCTGG
CCCTTGGTAGGTATCAAGGCGCGGGGCGAATCCCGACGTCCAGAGGAACGCGCGGCGTTCGTGCAATATCAAGGCCGTTCCGCG
GATGACCGGATATCGACCGGGCCGGTATAGCTTCATGCGGTCTTTCGCATCGGAAATCTGCACTCCTACGACATTGGTCCCCGG
AGCAGCGGCCTTGAAGCCTTTCCATTCCGGGTCCGCGAACGAGGACTTGGCATGAATGAACAGCTCAGCGGGCGGCTGTCCATC
ATGCATTTGTTGATATTCGCCGATAACCATCTCAACTAAACTGCTTGCCGCGTCCTCGCTCAGATGAAATTGCTTGGATTCGGA
ATGAAACCATGGGCCGAGCGCACCGCGAAATACGACGCCTTCACCGCTCGAAAGAAACATCTGGGCGGCGCAACAGGCGAAGCG
ATCATCGGAACTATTGTCCTGTCGCTTATAGGCGAGGCCGACATAGCAAACGCCGGGTCTGACGTCGGCCAACTGCCATGGTCG
TCCACCATCCTTGTAATAGGCGCCGGTCAATATTTTCCAGGCGATCGTTGCAGGGTCCTCCAATCGTCGCAGTGGCTTGCCGAT
TTTGTTCAGGAAATCGTTAGGCGCCAATGTGGTTTCCCTAACGATCTGAGTGACGATACGGTCTCTGAGCAGACGTGCCTTCAA
CTG
16 AACCCGTACTACACCACTAAAGCGCGATTGATGGCGCAAGGTGTTCCAGTACAACTATTGAATATCGAAACCATCCGTCGAAAA
AGCCTTGACTACATTCTCAATAATATCGGGCTTGCTATGTACGCGAAGCTTGGCGGAATCCCTTGGACGCTGACCCAGAACAGC
GATATGGCGCACGAGATTATCGTTGGTATAGGAAGCGCCAGATTGAACGAAAGCCGTCGTGGTGCAGGCGAGCGGGTGATCGGA
ATTACGACCGTTTTCAGCGGCGATGGCCAGTACCTGTTGGCAAACAATACTCAAGAGGTGCCTTCAGAAGAGTACGTTGATGCT
CTGACTCAGTCTCTCTCGGAGACTGTGAGTGAACTCAGGAGCCGATTCGGTTGGAGACCAAAAGACAGGGTCCGATTCATCTTC
CATCAAAAGTTCAAGAAGTACAAAGATGCTGAAGCTGAGGCAGTTGATCGCTTCGCACGATCACTCAAAGATTTCGACGTGCAA
TATGCCTTCGTTCATGTCAGTGACTCGCACAACTGGATGTTGCTAGATCCCGCATCGAGGGGAGTGAAGTTCGGCGACACAATG
AAGGGAGTGGCGGTCCCGCAGAGGGGACAATGTGTGCCTCTAGGGCCAAACGCTGCTCTTTTGACTTTGTCCGGGCCATTTCAG
GTCAAGACGCCACTGCAAGGTTGCCCTCATCCAGTACTGGTGAGCATTCACGAGAAGTCCACGTTCAAGAGCGTGGATTATATC
GCTCGCCAAATTTTCAATCTCAGCTTCATCTCATGGAGGGGTTTCAACCCGTCAACGCTTCCAGTTTCGATTTCTTACTCAGAC
ATGATCGTAGATCTGTTG
17 AATTTTAGAAGAGCATTAAAAGCCCGTGCAATGAAATACAACACACCTATTCAGTTGTTGAGAGAATATGTAATGCACGACAGT
AACAAATCACAAGATAATGCAACTAAGGCATGGAATTTTTGCACTGCTOTTTATTATAAGGGACTTCAAACCATTCCTTGGAAG
TTGGFAGTAGACGAGFACAAACCAAAAGTATGTTTTGTAGGTATTGGATTCTACAAAAGCAGGGACAAGAAAACGATTCAAACC
AGTTTAGCACAAATTTTCAATGAAAATGGAAAAGGTGTGATACTTCGCGGAACTCCTGTAACTGAAGATAAAGACGATAAAAAA
CCTCACTTAACTTATGAGCAATCTTTAAGCCTTCTGAAAGATGCCTTGACCAAATACAAGTTTGCGACAGGTTCAATGCCAGGT
AGAGTAGTTTTACACAAGACTTCAAAATACTATGAGGATGAACTTGACGGCTTTATTCAAGCAATGCAGGATTTGGGTATAACT
GAATACGATATTGTAACTATCATGGAAACCGATTTGCGTTTCTTTAGAAATAATCTTTATCCACCAGTGAGAGGGGCAGTTTTT
TCATTGACTGAACAAAGACACATACTTTACACTAGGGGTTCAGTTCATCAATATCAGACATATCCAGGAATGTATATTCCTGCT
CCATTAGAAGTAAGAATAGTAAGTTCCGTTTCATCTATAAGGACAGTTTGTAAAGAAATTCTTGGCTTGACAAAAATGAATTGG
AACAACACCCAATTCGACAACAAATACCCCATTACAATTGGCTGTGCAAGACGGGTAGGAGAAATAATG
18 AAGAACCTCACCAACCTTTCGTGCGGCCCGGATGGGAATGGGCAGCTTCTGGTTCATCTGGGTCGAATTCCAGTTGATCTTCGT
CATCGACAGCACGTCTTTGGCGATCTGCGCGACGGTGCTGTCGCTGCTTTTGTGCGGACATAGCAGAAATGGCCTGGGATCATA
CTGGCCTGGATAGGTTCCGTAGTACGGGATGCTGCCGTTCGTATAGAGAAGCCCTTTCCCGTCGAGTTCGACAAAGGTGCCGCG
CATCACGGGATAGTTCCCGTCGCGGAGGACTTTCACCGACGAGGATTCCTGGACCCATACAAGGTCCTTCATCTCCGTGCCCGC
AGCGTCGAGCGCCTCCACGTTCCGTCCGCTTCCTCGTCACGGAAACGCGAGGTTTTCAGGACGGCGACACGGACCGGGTAGTGC
CGATGATGGTTCTTGTAGGCGGTCAGCACCGC
19 GATTTTCACCGCCAGGTGAAAGCGCGTCTGCTCAAGCTAGGTCGCACTTCGCAACTCATCCGCGAAACGACGTTGGCACCCGAC
AAATTCCTAAATAACGCGGGCTATCCAAAGCGTGGGTTGCAGGATCCGGCGACAGTGGCGTGGAATCTGGCAACTGGACTTTAC
TACAAAACCCAACCCTTGCCGCCGTGGAAACTCGCGCATGTCAGGCCGGGCGTTTGTTACATCGGACTTGTTTTCAAGATGATT
CCGAATGATCCAAAGGAACATGCCTGCTGTGCGGCGCAGATGTTTCTTAATGAGAGCGACGCCGTTGTTTTCAGGGGCGCAAAT
GGCCCGTGGAAAACCGACGACTTTGAATTCCACCTTCAACCCAAAGAGGCGCAAAGCCTGATTGCCAAAGTGCTCAAAACCTTC
GAGGAGAAGCACGGTGTGCCACCAAAGGAATTTTTCATCCACGGGTGCACAACCTTCAACGAGGATGAATGGAAAGCCTTCAAA
AAGGCCACGCCGAAGGGCACCAATCTTGTCGGCGTCCGCATCAAGGAAACCAAAGGGGAATCCAAGCTGTTCCGTGATGGTGAT
TATCCGGTAATGAGGGGAACGGCCATCATTCTTGATCACCGAAACGCCTTGCTGTGGACGAATGGATTTGTGCCACGGCTGGAC
ACCTATATTGGGCCTGAGACGCCAAACCCGCTTTTGATAACCGTTCTGCGTAGTACGGGTCGGCGACCTAACATTCGCACCGTT
CTTGCTGACATCATGGGCCTTACCAAGATCAACTACAACGCCTGCAACTACAATGACGGATTGCCCGTCACGATCCGCTTTGCG
AGCAAGGTGGGCGATGTGCTG
TABLE 2
Corresponding Argonaute domain polypeptide acid sequences to those disclosed in Table 1 that
were identified by PIWI domain
SEQ
ID NO Sequence
20 MLEFRYGQRMVYPRDGLFLFGPGDGGRAPINFGVIGTPAGVARFRQWMGSVGNVIDAANDDPQHVPFPGYGAAFASAWPDKPRHII
DSIDPAAVSRALRLENRNEAIKSTVDLYVDPLVAAADRLEAPPNFWFVVIPEEIYKLGRPQSSVPKADRIRGSVKLSKSAARDLML
EPTFFPEDLEAAEIYQYATHFRRQLKARLLRDRIVTQIVRETTLAPNDFLNKIGKPLRRLEDPATIAWKILTGAYYKDGGRPWQLA
DVRPGVCYVGLAYKRQDNSSDDRFACCAAQMFLSSGEGVVFRGALGPWFHSESKQFHLSEDAASSLVEMVIGEYQQMHDGQPPAEL
FIHAKSSFADPEWKGFKAAAPGTNVVGVQISDAKDRMKLYRPGRYPVIRGTALILHERRAFLWTSGFAPRLDTSQGPETPNPIEVR
IHRGDCELETVLGDVMGLTKINFNSCLHNDRLPVTIRFADAVGDVILAAPRTGEPKLPFKYYI
21 MTSQLQHYVRLPEPNLLFHPDRPSDRDIHPLRGLARFGPYSSMFTPSPIRVATLAPSGESQRLFEFLRELNQPARPQERTDYLPDW
ASFNSVFQTHLAPAASHCRRELDAQLDGELKDCPASGLLLAERLIRSIQLLDANRADFDVLFIYLPERWSPGFYGADDFDLHHQLK
AFTAARQLPIQIVREDSALSYRCRASVMWRIGLALYAKAGGVPWKLADVEPDTAYIGISYALRPAESELARFVTCCSQVFDADGAG
LEFIAYDTGDVNVQRENPFLSHTEMFRVITRSLDLYRRRHGGRLPTRVMIHKSTEFKEAEIEGCFEALKHIESVDLIQIVEDNGWQ
GVRWEQDRNDPEISQADGYPVKRGTLLGLSGKDALLWMHGAVDGFGRRPYFQGGKGTPRPLRLVRHAGHGTWDDTAKAALALSKMN
WNNDGLYDPLPVTMSYAKTLAQVIKRMPGLGKGTYQFRFFM
22 MLEFRYGQRMVYPRDGLFLFGPGDGGRAPINFGVIGTPAGVARFRQWMGSVGNVIDAANDDPQHVPFPGYGAAFASAWPDKPRHII
DSIDPAAVSRALRLENRNEAIKSTVDLYVDPLVAAADRLEAPPNFWFVVIPEEIYKLGRPQSSVPKADRIRGSVKLSKSAARDLML
EPTFFPEDLEAAEIYQYATHFRRQLKARLLRDRIVTQIVRETTLAPNDFLNKIGKPLRRLEDPATIAWKILTGAYYKDGGRPWQLA
DVRPGVCYVGLAYKRQDNSSDDRFACCAAQMFLSSGEGVVFRGALGPWFHSESKQFHLSEDAASSLVEMVIGEYQQMHDGQPPAEL
FIHAKSSFADPEWKGFKAAAPGTNVVGVQISDAKDRMKLYRPGRYPVIRGTALILHERRAFLWTSGFAPRLDTYQGPETPNPIEVR
IHRGDCELETVLGDVMGLTKINFNSCLHNDRLPVTIRFADAVGDVILAAPRTGEPKLPFKYYI
23 MTLDFDSRQPWAPHTILQEPMLKFDSSPTPATAGHPLVGLLDHGPYAGPPTASVRLATITLNGDKPKLYDFLRGATQAHEPSDRLA
YVPRYPGFEALFKAELLPQSDAHVDIRSAEIGTGADAHDRLSEALARAVRHLHTVRDSWDVIVFLLPAAWEPLRLSADGALDLHDR
LKATAALLGCPIQMIRETSALQFRYKCSMYWRLSIALLTKAGGVPFRMMRPTESDTAYLGLAYAIRGGTANEFVTCCSQVFDAEGG
GFEFIAYNVGADRDLENPHLTRDEMRTVMARSARLYQRRRAGSLPQRLVIHKTTTWREEEVAGVFDAWSPAVPDIECLQVRLDTPW
TGVALRGGKGNSAVANEWPVGRGSLQYLSGREALLWIAGTAKGVALTGENYNQAAKALPTPIAFKRDAGAGPLEIPASEILALSKL
DWNNDALYGVTP
24 VEMVFEQVLLRGHIGVVEEDALALYRYLEKKPISPCGARI
25 LTGAVFAAAAFDAFAGMREHLRATARLLRFDRVVCTLEDEACVADAIPDVGKRPRLLARFVIDTSREIPRDGASSCILRESSPLLL
RYSRGAMAVCARAG
26 MTTRPRSFKPQMLYLEEPQLEFRHGQHLVYPRDGLYLYGPVGETKELPTIRYGVIGTPDGVGRFKAWAQSMAGFIDIPPPGPRSRA
VEPQHVPFPGFAAAFHADWPVEPPYIIDSLDPDEIEQTLRIANRHEAVRNTVDMFVSRLVAENNRLESAPQFWFVVIPEKVYELGR
PKSTVRRDDRVAGEVTISQRRAKELQRQPTLFGEDEREAEVYQYATHFRRQLKARLLKERIVTQIVRETTLAPGDFRRESGMPIRR
VEDPATIAWKMGTGAYYKAGGKPWQLADVRPGVCYVGLVYKRSELTSDKRHACCAAQMFLADGEGVVFRGALGPWFQTDTKQFHLD
KDAARNLIKMVVGEYTRLHDGPPTELFIHAKSAFTDNEWRGFSSACGDETNLVGVQIAEARDDLKLYRPGEYPVIRGTALQIGERH
ALLWTSGYVPRLDTYMGPETPNPISVRVLRGECPLTTVLADVLGLTKINFNSCLHNDRLPVTIRFANAVGDVLISAPMDGEPKLPF
KFYI
27 MASLQGSHQPSDRLEYVPPYPGFESLFGIALQSAPAEAHVKWPDAIRDLPGEGNDQVRLFLAMDAALRRLDTMRNEFDVVLFHFPD
SWDATTRTKFFDAHDTLKALGAKYNIPTQVLNDRVFAFSHPASRSWRLAIALYVKAAGTPWKLAPLKGVPEDTAYIGLAYALRGDQ
RDAHYVTCCSQVFDMDGGGMQFVAFEAKDPIADVAEARRNPFLSRDDMRAVLARSLELYQGRNGGTLPKRLVIHKTTAFKPDEIEG
AFDALAGVQEIECIEVSPASGWRGVWLVPSGQPKPPTKPAGYPVPRGTVVVRSGTSALVWVAGNAPEVSNKGDYYQGKKSIPKPLQ
LIRHAGSGPLELSAHEALALTKMDWNNDALYDPVPVSIRYSQRLAKTIANVPDLPRNVYPYRLFM
28 VDALVRSLAVSQDRPLMLFLGAGASMTSGMPSANQCIWEWKRDIFLSNNPGIEEQFSELSLPSVRDRIQTWLDRQRCYPVAGHPDE
YGAYIEACFSRSDDRRRYFERWVKQSTPHTGYRLLAELAASGLIQTVWTTNFDGLIARAAVATNLTSIEIGIDSQQRLYRAPGKDE
LACVSMHGDYRYDRLKNSPGELAQVEVQLRDSLIEALRTHTVVVAGYSGRDESVMQAFRQYAASGPARTDLPLFWTQYGEDPPLDT
VSAFLSTNDDEPSRFIVPGVSFDDLMRRLALYLSKGPARDRVNKILDEHATTPVNQLTAFGLPPLPPTGLIKSNAIPLTPPQELLE
FDLHQWPASGTVWATLRELGDKHNFVAAPFRSKIYAIAIAESLRLAFGENLKGEIKRVPLNDDDLRYEDGVINQLVRRATVLALSA
KANCPSDGESLIWTSEKVENLRLDRVDWKVHQAVLVQIRPLGTEMALVLKPTLYVTDKSGAIAPKDTERLVKQRVLGYQHNKEFND
ATEAWRRRLVPQRDFHVRFPDHEDGIDLTFSGRPLFARITDERERTVSLSSAQELAARQAGLQLAEPRLKFARKSAAGLAFDTHPV
RGLINNRPFDSSLTTTGIASSIRVGIIAPAQDATRVHQYLSQLHVAAQPGKDADYLPPFPGFASAYQCPLEIPAVGEQSFVQLDEP
DSMTPSSARALAGAITRSIASLSASQRPDVTIIYVPDRWAPLRNYMIDDEEFDLHDFVKAAAIPKGCATQFVEEDTLRNTQQQCRV
RWWLSLALYVKSMRTPWTLEGLSEKSAYVGLGFSVKRKTTQNAGAHVVLGCSHLYSPNGIGLQFRLSKIEDPIMRNKNPFMSFDDA
RRLGEGIRELFFAAQLRLPERVVIHKQTPFLREERSGLQAGLEGVACVELLQIFVDDTLRYVASHPTSDGKFETDNYPIRRGTTVV
IDDHTALLWVHGASTALNPRRHYFQGKRRIPAPLVIRRHAGTTDLMTIADEVLGLSKMNFNSFDLYGQLPATIETSRRVAKIGALL
DRFSEHSYDYRLFM
29 MSVDAMIRSIGVARDRPLLVFLGAGASMSSGMPSATQCIWEWKREIFLTNNPDVEKTQFSELSLPSVRLRIQAWLDRQRRYPALDH
PDEYSTYIGECFARSDDRRIYFEKWVKRCSPHLGYQLLAELARQGLVASVWTTNFDALAARAATSINLTAIEIGIDSQQRLYRAPG
EAELACVSLHGDYRYDPLKNTAPELIKQEKELRESLVQAMRTHTVLVCGYSGRDESVMAAFSDAYDAAHFKGHHPLFWTQYGDYPA
SEPVAGLLASPLDQEPAKFHVPGASFDDLMRRIALHVSDGEARERVRKILENFKTAPVNQKLPFALPSLPVTGLVKSNAIPLIPPG
ELIEFDLVRWPPSGEVWSTLREIGDRHGFVAAPFRGKVYALATIEQLTQAFADNVKDGAFNRVPLNNDDLRYEDGTANQLMRRATV
LALAGKAGCANDGDAIVWDTSRSKTERLDRQLWTVYDAVLLQIRPLGTKLALVLKPTLRVTDSTGEVAPKEIERAVKVRVLGYQHN
KEFNQATDFWRKRLLPSRDLLVRFPDLDGGMTFTISGRPIFARLTDERTETVTLNDAQERSASQVGLQLAEPKLVFARTVGTGPAT
DTLPVRGLLQNRPFDANLTDLGIATNLRIAVIAPARDARRVHDYLGQLHQPIDPTKWDADYLMRFPGFSSAFKCPLDIPQPGQAAF
VTLDEPHDESPQSARTLAGRITAALSALRATENPSVTIIYIPARWHALRAFDLESEQFNLHDFVKAAAIPAGCSTQFLEESTLANG
QQCRVRWWLSLAVYVKAMRTPWALTGLDRDSAFVGLGFSVRRKIDGEGHVALGCSHLYSPNGHGLQFRLSKIDNPIMLRKNPFMSF
DDARKLGEGIRELFFDAHLRLPNRVVVHKQTPFLKEEREGLQAGLEGVACVELLQIFVDDTLRYVASRPMPNGDFEIHGYPIRRGT
TVVVDDQTALLWVHGTSTALNPRQSYFQGKRRIPAPLVMRRHAGTSDLMMLADEILGLSKMNFNSFDLYGQLPATIETSQRVARIG
ALLDRYTERSYDYRLFM
30 MLEFRYGQRMVYPRDGLFLFGPGDGGRAPINFGVIGTPAGVARFRQWMGSVGNVIDAANDDPQHVPFPGYGAAFASAWPDKPRHII
DSIDPAAVSRALRLENRNEAIKSTVDLYVDPLVAAADRLEAPPNFWFVVIPEEIYKLGRPQSSVPKADRIRGSVKLSKSAARDLML
EPTFFPEDLEAAEIYQYATHFRRQLKARLLRDRIVTQIVRETTLAPNDFLNKIGKPLRRLEDPATIAWKILTGAYYKDGGRPWQLA
DVRPGVCYVGLAYKRQDNSSDDRFACCAAQMFLSSGEGVVFRGALGPWFHSESKQFHLSEDAASSLVEMVIGEYQQMHDGQPPAEL
FIHAKSSFADPEWKGFKAAAPGTNVVGVQISDAKDRMKLYRPGRYPVIRGTALILHERRAFLWTSGFAPRLDTYQGPETPNPIEVR
IHRGDCELETVLGDVMGLTKINFNSCLHNDRLPVTIRFADAVGDVILAAPRTGEPKLPFKYYI
31 MDYNLSKAPSFSLLDEPALTFNSEDTDLDENPLRGLLRFGAYNGKTFEGYTPKLRVATIAPASGWPKLKGLVDTIRSGHEASDRRN
YVPSFPGFENLFRVPLVAGPKDVHIKWPDDLMALARTGAPHERLFSAMSEAMARLDALHDQFDVVLVHLPDAWATAFTANGFDAHD
ALKALGARYAIPTQVINDRVFTFRLKASLAWRLAIALFTKAGGIPWKLAPMVGVPEDTAYIGLAYALRGDPKSAQFVTCCSQVFDA
DGGGMQFVAFEAKEQVADPREARRNPFLSRSDMRAVMARSLSLYLGRNGGRLPRRLVVHKTTSFKDEELQGVFDGLSTVPEVECIE
IGSSATWRGVWLKQGKKGGPKSVPDRAPVPRGTVLTRTDRSALLWASGNAPSAALSGALFFQGSKSIPRPLNIIRHAGSGPLEVAA
LETLALTKMDWNNDALYDPVPVTIRYSQRLARTIANVPDLPGHAYPYRLFM
32 LSIKSEEDQGLQIADGVPLQFESPLDQAESVPFPPAEVFQRPTFSFDPSGSRNDNWTQRQLDKTGPYDRATFERKRPRIAVICEAR
RRGAMAETVAHFLEGLPEVQSHKGFVPHATGLLGRFRLQKPQVEFFEAKDDSADAYAEAARNALSAAATRDQPWDLALVQVQRSWK
DRPATSSPYWWAKAAFLRRDVPVQALSAEMMAMGDFEYACALANVSLATYAKLGGTPWLLKARPSTDHELVFGLGSHTHKERRRGA
GERVVGITTVFSSQGNYLLDARTAAVPFDRYPEALRATLIEAVKRIRQEEAWRAGDTVRLVFHAFTQMRQETADAVVAAVESMGLS
GVKFAFLHVAEDHPFTLFDHASATGKGAYAPERGQAVELSDHEWLLSLTGRDQIRAASQGIPDPVLLRLHEKSTFRDMRTLTRQVS
DFACHSWRTYERARLPITLLYADEIAKQLAGLERTPGWDPDTAVVGAVMRRPWFL
33 MLEFRYGQRMVYPRDGLFLFGPGDGGRAPINFGVIGTPAGVARFRQWMGSVGNVIDAANDDPQHVPFPGYGAAFASAWPDKPRHII
DSIDPAAVSRALRLENRNEAIKSTVDLYVDPLVAAADRLEAPPNFWFVVIPEEIYKLGRPQSSVPKADRIRGSVKLSKSAARDLML
EPTFFPEDLEAAEIYQYATHFRRQLKARLLRDRIVTQIVRETTLAPNDFLNKIGKPLRRLEDPATIAWKILTGAYYKDGGRPWQLA
DVRPGVCYVGLAYKRQDNSSDDRFACCAAQMFLSSGEGVVFRGALGPWFHSESKQFHLSEDAASSLVEMVIGEYQQMHDGQPPAEL
FIHAKSSFADPEWKGFKAAAPGTNVVGVQISDAKDRMKLYRPGRYPVIRGTALILHERRAFLWTSGFAPRLDTYQGPETPNPIEVR
IHRGDCELETVLGDVMGLTKINFNSCLHNDRLPVTIRFADAVGDVILAAPRTGEPKLPFKYYI
34 MLEFRYGQRMVYPRDGLFLFGPGDGGRAPINFGVIGTPAGVARFRQWMGSVGNVIDAANDDPQHVPFPGYGAAFASAWPDKPRHII
DSIDPAAVSRALRLENRNEAIKSTVDLYVDPLVAAADRLEAPPNFWFVVIPEEIYKLGRPQSSVPKADRIRGSVKLSKSAARDLML
EPTFFPEDLEAAEIYQYATHFRRQLKARLLRDRIVTQIVRETTLAPNDFLNKIGKPLRRLEDPATIAWKILTGAYYKDGGRPWQLA
DVRPGVCYVGLAYKRQDNSSDDRFACCAAQMFLSSGEGVVFRGALGPWFHSESKQFHLSEDAASSLVEMVIGEYQQMHDGQPPAEL
FIHAKSSFADPEWKGFKAAAPGTNVVGVQISDAKDRMKLYRPGRYPVIRGTALILHERRAFLWTSGFAPRLDTYQGPETPNPIEVR
IHRGDCELETVLGDVMGLTKINFNSCLHNDRLPVTIRFADAVGDVILAAPRTGEPKLPFKYYI
35 LHLNYLPLRFTADIFKGGALTFPEGSEKNWTSDDPISKELSKLREKHGDSHVFHRMGNKIACIPVVENAIAIGTETDFNIISDFQL
ANALARSALHRYFKAAGRETVIGFRPVTLLLEKHNLASNRKDVFGIFPEYTLDVRPLAPHEGDIASGVLIGFGIKYVFLQNVAELQ
AQGVSAAGMYAVRLVDESEHQFDRAYLGRIDRFTKDNVTLVDSDYAEYPADQCYFEGSRTNIEAVGRSLLGKDYDAFSSSLLQESY
KVTGAPNQTQRLHQLGAWLEAKSPIPCAVGLGVRIAKKPHECSRGNDAGYSRFFDSPKCVLRPGGSLTVPWPVDKQIDLNGPYDAE
SFPNKRVRIAVICPQEFTGDAEEFLRKLKEGLPNAPDGSPFRKGFVRKYHLSSCDFTFHEVKRSSNSDDIYKDASLEALKQKPDMA
IAIIRSQYRGLPDASNPYYTTKARLMAQGVPVQLLNIETIRRKSLDYILNNIGLAMYAKLGGIPWTLTQNSDMAHEIIVGIGSARL
NESRRGAGERVIGITTVFSGDGQYLLANNTQEVPSEEYVDALTQSLSETVSELRSRFGWRPKDRVRFIFHQKFKKYKDAEAEAVDR
FARSLKDFDVQYAFVHVSDSHNWMLLDPASRGVKFGDTMKGVAVPQRGQCVPLGPNAALLTLSGPFQVKTPLQGCPHPVLVSIHEK
STFKSVDYIARQIFNLSFISWRGFNPSTLPVSISYSDMIVDLLGHLRRVKNWNPETLSTALKERRWFL
36 MKADYIQEPFLLFGKGKSICPREGIAELNVYDTVIEARKNQLLIGIIGIEEDVENLKSWIKRFESYIPADPKGKQKGLFKSFPGFH
QDKGFCAKFIYDSNYERILSPNDIKRILKEPDRNKKVLDAVELFGENIGFLSDIKNCDVIICIIPKSFEGKIVKENKDDEPVEQVA
EDNEGPELELNFRRALKARAMKYNTPIQLLREYVMHDSNKSQDNATKAWNFCTALYYKGLQTIPWKLEVDENKPKVCFVGIGFYKS
RDKKTIQTSLAQIFNENGKGVILRGTPVTEDKDDKKPHLTYEQSLSLLKDALTKYKFATGSMPGRVVLHKTSKYYEDELDGFIQAM
QDLGITEYDIVTIMETDLRFFRNNLYPPVRGAVFSLTEQRHILYTRGSVHQYQTYPGMYIPAPLEVRIVSSVSSIRTVCKEILGLT
KMNWNNTQFDNKYPITIGCARRVGEIMKYVGENEYPKESYAYYM
37 MKDLVWVQESSSVKVLRDGNYPVMRGTFVELDGKGLLYTNGSIPYYGTYPGQYDPRPFLLCPHKSSDSTVAQIAKDVLSMTKINWN
STQMNQKLPIPIRAARKVGEVLKYVSDGKVSSDYTRYM
38 MDLSKKSLKTIHIEEPELSFGHGQTCDHPKDGLFLYGPHSGPTRTREVSVGVIGTKDGLSYFRTWAIAAGGFVPVPPRKKTDKENR
LHLSNFPGLEEAFGIMVSPGDFVQRTVDYTVLDDATRTVNQHEAVRKAVDLYVGEIERYDNNEEKTVDVWMFILPEIIFERCKPLS
RRTGLGLTKGEFAKSQKERIDLPLFKDVIDQSGEDIFDDVPDFHRQVKARLLKLGRTSQLIRETTLAPDKFLNNAGYPKRGLQDPA
TVAWNLATGLYYKTQPLPPWKLAHVRPGVCYIGLVFKMIPNDPKEHACCAAQMFLNESDAVVFRGANGPWKTDDFEFHLQPKEAQS
LIAKVLKTFEEKHGVPPKEFFIHGCTTFNEDEWKAFKKATPKGTNLVGVRIKETKGESKLFRDGDYPVMRGTAIILDHRNALLWTN
GFVPRLDTYIGPETPNPLLITVLRSTGRRPNIRTVLADIMGLTKINYNACNYNDGLPVTIRFASKVGDVLTMGSARDADKQPLKFY
V
TABLE 3
Corresponding Argonaute full genomic nucleic acid sequences identified by PIWI domain as
those disclosed in Table 1.
SEQ
ID NO Sequence
39 ATGCTCGAGTTTCGCTACGGCCAGCGCATGGTCTATCCACGGGACGGACTATTTCTGTTCGGTCCAGGCGACGGAGGGCGAGCAC
CCATCAATTTCGGCGTGATCGGCACTCCCGCGGGAGTCGCTCGCTTCCGGCAGTGGATGGGCTCGGTCGGCAATGTCATAGACGC
CGCCAATGACGACCCGCAGCATGTGCCGTTTCCGGGTTATGGTGCCGCCTTCGCCAGTGCTTGGCCAGACAAGCCACGGCACATC
ATCGATAGCATCGACCCCGCGGCTGTCTCGCGGGCTCTTCGCCTGGAGAACAGGAACGAGGCGATCAAAAGCACCGTGGATCTGT
ATGTCGACCCACTGGTGGCGGCCGCCGATCGCTTGGAGGCACCTCCGAATTTCTGGTTCGTGGTTATTCCTGAGGAAATCTACAA
GCTCGGGCGACCCCAATCAAGCGTCCCCAAGGCGGACCGCATCCGCGGTTCGGTGAAACTGTCCAAGTCTGCTGCCAGGGACTTG
ATGTTGGAGCCGACGTTCTTCCCCGAAGATCTGGAAGCGGCGGAGATCTATCAATATGCCACCCATTTCAGGCGCCAGTTGAAGG
CACGTCTGCTCAGAGACCGTATCGTCACTCAGATCGTTAGGGAAACCACATTGGCGCCTAACGATTTCCTGAACAAAATCGGCAA
GCCACTGCGACGATTGGAGGACCCTGCAACGATCGCCTGGAAAATATTGACCGGCGCCTATTACAAGGATGGTGGACGACCATGG
CAGTTGGCCGACGTCAGACCCGGCGTTTGCTATGTCGGCCTCGCCTATAAGCGACAGGACAATAGTTCCGATGATCGCTTCGCCT
GTTGCGCCGCCCAGATGTTTCTTTCGAGCGGTGAAGGCGTCGTATTTCGCGGTGCGCTCGGCCCATGGTTTCATTCCGAATCCAA
GCAATTTCATCTGAGCGAGGACGCGGCAAGCAGTTTAGTTGAGATGGTTATCGGCGAATATCAACAAATGCATGATGGACAGCCG
CCCGCTGAGCTGTTCATTCATGCCAAGTCCTCGTTCGCGGACCCGGAATGGAAAGGCTTCAAGGCCGCTGCTCCGGGGACCAATG
TCGTAGGAGTGCAGATTTCCGATGCGAAAGACCGCATGAAGCTATACCGGCCCGGTCGATATCCGGTCATCCGCGGAACGGCCTT
GATATTGCACGAACGCCGCGCGTTCCTCTGGACGTCGGGATTCGCCCCGCGCCTTGATACCTCCCAAGGGCCAGAGACGCCGAAT
CCGATAGAAGTCCGCATTCACCGCGGAGATTGCGAACTTGAAACGGTTCTCGGGGACGTGATGGGCCTGACCAAGATCAATTTCA
ATTCTTGCCTGCATAACGATCGATTGCCGGTGACGATACGTTTCGCCGACGCGGTGGGCGACGTGATCCTCGCGGCACCACGGAC
CGGCGAACCGAAGCTGCCGTTCAAGTATTATATATAA
40 ATGACCAGCCAGCTGCAACATTATGTCCGGCTGCCGGAGCCCAATCTGCTGTTCCATCCGGACCGGCCGAGCGATCGAGACATCC
ATCCTCTGCGGGGACTGGCCCGTTTCGGACCCTATTCGAGCATGTTCACCCCGTCCCCCATCCGCGTGGCGACGCTTGCGCCTTC
CGGGGAATCGCAGCGTCTCTTCGAGTTCCTAAGGGAACTCAACCAGCCTGCGAGACCGCAGGAGCGAACCGACTATCTTCCGGAC
TGGGCCAGTTTCAACAGCGTCTTCCAGACGCACCTCGCACCAGCTGCAAGCCATTGTCGGCGGGAACTCGATGCCCAACTGGACG
GAGAGTTGAAGGATTGCCCTGCATCGGGTCTGCTGCTTGCCGAACGGCTCATCCGTTCAATCCAGTTGCTCGACGCCAACCGCGC
GGATTTTGACGTGCTGTTCATTTATCTTCCTGAACGCTGGTCTCCCGGCTTCTACGGAGCCGATGATTTCGATCTGCATCACCAG
CTCAAAGCCTTCACCGCCGCGCGGCAGCTGCCCATTCAGATTGTGCGCGAAGACAGCGCACTATCCTATCGATGCCGGGCCAGCG
TCATGTGGCGGATCGGCCTGGCGCTCTACGCCAAGGCTGGCGGCGTTCCTTGGAAACTGGCCGATGTGGAGCCGGACACTGCCTA
TATTGGTATCTCCTATGCGCTCCGGCCCGCAGAATCGGAGCTTGCCCGCTTCGTAACCTGTTGCAGCCAGGTCTTCGACGCCGAC
GGTGCTGGACTGGAATTCATCGCCTATGACACCGGCGATGTGAACGTACAGCGGGAGAACCCGTTTCTCTCGCATACCGAGATGT
TTCGGGTCATCACCCGTTCGCTGGACCTTTATCGCCGGCGCCATGGCGGCAGACTGCCGACACGTGTGATGATCCACAAATCGAC
CGAGTTCAAGGAAGCCGAAATAGAAGGCTGCTTCGAAGCGCTGAAACATATCGAGTCGGTCGATCTCATCCAGATCGTCGAGGAC
AATGGCTGGCAGGGCGTGCGATGGGAACAGGACCGTAACGATCCGGAGATATCACAAGCGGATGGGTATCCGGTGAAACGCGGAA
CCTTGCTCGGGCTCAGCGGCAAAGACGCTTTGCTCTGGATGCACGGGGCAGTCGATGGTTTCGGGCGCCGCCCCTATTTTCAAGG
TGGCAAAGGTACACCGCGACCGTTGCGACTGGTCCGACATGCCGGGCATGGAACATGGGACGATACCGCGAAGGCGGCCCTGGCG
CTGTCGAAAATGAACTGGAACAATGACGGGCTCTATGATCCACTTCCGGTGACGATGAGCTACGCAAAGACCTTAGCACAGGTGA
TCAAGCGGATGCCGGGGCTCGGCAAGGGCACTTACCAGTTCCGATTTTTCATGTGA
41 ATGCTCGAGTTTCGCTACGGCCAGCGCATGGTCTATCCACGGGACGGACTATTTCTGTTCGGTCCAGGCGACGGAGGGCGAGCAC
CCATCAATTTCGGCGTGATCGGCACTCCCGCGGGAGTCGCTCGCTTCCGGCAGTGGATGGGCTCGGTCGGCAATGTCATAGACGC
CGCCAATGACGACCCGCAGCATGTGCCGTTTCCGGGTTATGGTGCCGCCTTCGCCAGTGCTTGGCCAGACAAGCCACGGCACATC
ATCGATAGCATCGACCCCGCGGCTGTCTCGCGGGCTCTTCGCCTGGAGAACAGGAACGAGGCGATCAAAAGCACCGTGGATCTGT
ATGTCGACCCACTGGTGGCGGCCGCCGATCGCTTGGAGGCACCTCCGAATTTCTGGTTCGTGGTTATTCCTGAGGAAATCTACAA
GCTCGGGCGACCCCAATCAAGCGTCCCCAAGGCGGACCGCATCCGCGGTTCGGTGAAACTGTCCAAGTCTGCTGCCAGGGACTTG
ATGTTGGAGCCGACGTTCTTCCCCGAAGATCTGGAAGCGGCGGAGATCTATCAATATGCCACCCATTTCAGGCGCCAGTTGAAGG
CACGTCTGCTCAGAGACCGTATCGTCACTCAGATCGTTAGGGAAACCACATTGGCGCCTAACGATTTCCTGAACAAAATCGGCAA
GCCACTGCGACGATTGGAGGACCCTGCAACGATCGCCTGGAAAATATTGACCGGCGCCTATTACAAGGATGGTGGACGACCATGG
CAGTTGGCCGACGTCAGACCCGGCGTTTGCTATGTCGGCCTCGCCTATAAGCGACAGGACAATAGTTCCGATGATCGCTTCGCCT
GTTGCGCCGCCCAGATGTTTCTTTCGAGCGGTGAAGGCGTCGTATTTCGCGGTGCGCTCGGCCCATGGTTTCATTCCGAATCCAA
GCAATTTCATCTGAGCGAGGACGCGGCAAGCAGTTTAGTTGAGATGGTTATCGGCGAATATCAACAAATGCATGATGGACAGCCG
CCCGCTGAGCTGTTCATTCATGCCAAGTCCTCGTTCGCGGACCCGGAATGGAAAGGCTTCAAGGCCGCTGCTCCGGGGACCAATG
TCGTAGGAGTGCAGATTTCCGATGCGAAAGACCGCATGAAGCTATACCGGCCCGGTCGATATCCGGTCATCCGCGGAACGGCCTT
GATATTGCACGAACGCCGCGCGTTCCTCTGGACGTCGGGATTCGCCCCGCGCCTTGATACCTACCAAGGGCCAGAGACGCCGAAT
CCGATAGAAGTCCGCATTCACCGCGGAGATTGCGAACTTGAAACGGTTCTCGGGGACGTGATGGGCCTGACCAAGATCAATTTCA
ATTCTTGCCTGCATAACGATCGATTGCCGGTGACGATACGTTTCGCCGACGCGGTGGGCGACGTGATCCTCGCGGCACCACGGAC
CGGCGAACCGAAGCTGCCGTTCAAGTATTATATATAA
42 ATGACCCTCGACTTTGACTCTCGCCAGCCCTGGGCACCGCACACGATTCTTCAGGAACCGATGCTGAAGTTTGACAGCAGCCCGA
CCCCGGCAACCGCGGGTCACCCGCTCGTCGGACTGCTCGACCACGGCCCCTACGCCGGACCGCCGACCGCTAGCGTGCGACTCGC
CACGATCACCCTCAACGGTGACAAGCCGAAGCTCTACGACTTCCTCCGCGGTGCCACCCAGGCACACGAACCCAGCGACCGTCTG
GCATACGTGCCGCGATATCCGGGGTTCGAGGCGCTGTTCAAGGCCGAGCTTCTTCCTCAGTCCGACGCCCACGTCGACATCCGGA
GCGCCGAGATCGGCACCGGTGCTGACGCGCACGACCGACTCAGCGAGGCGCTTGCCCGTGCGGTGCGGCACCTCCACACCGTTCG
CGACTCCTGGGACGTCATCGTCTTCCTACTCCCTGCAGCCTGGGAGCCTCTGAGGCTCAGCGCCGACGGTGCGCTGGACCTGCAC
GACCGGTTGAAGGCGACGGCCGCGCTGCTGGGCTGTCCTATCCAGATGATCCGCGAGACCTCCGCGCTGCAGTTCAGGTACAAGT
GCTCCATGTACTGGCGGCTGTCGATTGCGCTGCTGACGAAGGCTGGCGGCGTGCCGTTCCGGATGATGCGTCCCACTGAGTCCGA
CACTGCCTACCTCGGGCTGGCCTACGCGATTCGCGGCGGGACCGCCAACGAGTTCGTCACCTGCTGCTCGCAGGTCTTCGACGCC
GAAGGCGGCGGCTTCGAATTTATCGCCTACAACGTCGGCGCCGACCGTGACCTGGAGAACCCGCATCTGACCCGCGACGAGATGC
GCACCGTCATGGCGCGCAGCGCTCGCCTCTACCAGCGGCGCAGGGCCGGGTCTCTGCCCCAGCGGCTTGTGATCCACAAGACGAC
AACCTGGCGTGAGGAAGAAGTCGCAGGGGTCTTCGACGCGTGGAGCCCGGCCGTTCCTGACATCGAGTGCCTCCAGGTACGTCTA
GACACACCCTGGACCGGGGTTGCCCTCCGCGGCGGCAAGGGCAACTCGGCGGTCGCCAACGAATGGCCTGTGGGCCGCGGGTCTC
TTCAGTATCTCTCTGGGCGGGAGGCACTCCTGTGGATCGCCGGTACGGCGAAGGGTGTCGCGCTGACGGGTGAGAACTATAATCA
GGCAGCCAAGGCTCTACCGACCCCGATTGCGTTCAAGCGTGACGCGGGTGCTGGCCCCCTGGAGATTCCTGCCAGCGAAATCCTT
GCCCTGTCGAAGCTCGACTGGAACAACGACGCCCTTTACGGTGTGACCCCGTGA
43 GTGGAAATGGTTTTCGAGCAAGTGCTTCTCCGCGGCCACATTGGCGTCGTCGAAGAAGACGCCTTGGCGCTGTACCGCTATTTGG
AGAAGAAGCCTATATCGCCCTGCGGTGCCAGGATCTGA
44 TTGACGGGGGCGGTCTTCGCAGCCGCGGCGTTCGATGCCTTCGCCGGTATGAGGGAACATCTGCGCGCCACAGCACGCCTCCTTC
GCTTCGACCGGGTTGTTTGTACGCTTGAAGACGAGGCCTGTGTAGCAGACGCCATCCCGGATGTCGGCAAGAGACCACGGCTTCT
CGCCCGCTTTGTAATAGACACCAGTCGTGAGATTCCACGCGACGGTGCGTCATCCTGCATCTTGCGGGAAAGCTCGCCCTTGCTG
TTGAGGTATTCGCGCGGGGCAATGGCGGTCTGCGCACGAGCTGGGTGA
45 ATGACGACTAGGCCGCGATCCTTCAAGCCTCAGATGCTCTATCTGGAAGAACCTCAGCTTGAGTTCCGCCACGGTCAGCACCTCG
TCTATCCCCGCGACGGCCTCTACCTCTATGGACCCGTCGGCGAGACAAAAGAACTGCCGACGATCCGATACGGCGTGATTGGCAC
GCCGGATGGCGTAGGTCGCTTCAAAGCCTGGGCACAATCCATGGCAGGATTTATAGATATCCCACCGCCTGGGCCGCGTTCGCGC
GCTGTCGAACCACAGCATGTTCCATTTCCGGGCTTCGCCGCGGCTTTCCATGCTGACTGGCCCGTTGAACCGCCCTACATCATTG
ACAGCCTTGATCCCGACGAGATCGAACAAACGCTCAGGATCGCCAATCGTCATGAGGCGGTGCGCAACACTGTCGACATGTTCGT
GTCGCGCCTCGTCGCTGAGAACAATCGCCTCGAAAGCGCACCGCAATTCTGGTTCGTCGTCATTCCCGAAAAGGTCTACGAACTC
GGCAGACCGAAATCGACGGTTAGACGTGACGATCGCGTTGCGGGCGAAGTGACGATCTCCCAGCGTCGTGCAAAGGAGCTGCAGC
GCCAACCGACCTTGTTTGGCGAGGACGAGCGCGAAGCCGAAGTCTATCAATATGCGACCCATTTCCGCCGGCAACTAAAGGCACG
GCTCCTCAAAGAGCGGATTGTCACGCAGATCGTTCGTGAAACGACGCTGGCGCCCGGCGATTTCCGTCGCGAGAGCGGCATGCCG
ATCAGACGCGTCGAGGATCCTGCGACTATCGCCTGGAAAATGGGAACGGGCGCCTACTACAAGGCTGGCGGGAAGCCTTGGCAGT
TGGCCGATGTTCGACCGGGCGTCTGTTATGTCGGACTGGTCTACAAACGCAGCGAACTAACAAGCGACAAGCGTCATGCCTGCTG
CGCAGCCCAAATGTTTCTCGCTGACGGGGAAGGCGTGGTCTTCCGCGGCGCGCTCGGCCCTTGGTTCCAAACCGATACGAAGCAG
TTCCACCTTGATAAGGATGCCGCCAGGAACCTTATCAAGATGGTGGTGGGCGAATACACCCGCCTGCACGATGGCCCACCAACCG
AACTCTTCATCCACGCGAAGTCCGCCTTTACCGACAACGAATGGCGCGGTTTTTCGTCCGCCTGCGGGGATGAGACCAACCTCGT
CGGTGTGCAGATTGCCGAGGCTCGTGATGACCTGAAGCTCTATCGTCCTGGAGAGTATCCCGTCATTCGCGGCACGGCGCTGCAG
ATCGGTGAACGTCACGCACTTCTGTGGACCTCGGGCTATGTGCCACGGCTGGACACCTATATGGGGCCTGAGACCCCGAACCCGA
TTTCGGTTCGCGTTCTTCGCGGCGAGTGCCCACTGACGACGGTCCTCGCCGACGTGCTCGGGCTCACGAAGATCAACTTCAATTC
GTGCCTTCACAATGACCGGTTACCGGTGACGATCCGTTTCGCCAACGCGGTCGGAGATGTCCTCATTTCCGCCCCGATGGATGGC
GAGCCGAAGCTGCCGTTCAAATTCTACATCTAG
46 ATGGCATCCCTGCAAGGATCGCATCAGCCAAGCGATCGCCTCGAGTATGTGCCGCCTTACCCCGGCTTTGAATCTTTGTTTGGCA
TCGCGTTGCAGTCCGCACCAGCCGAAGCTCACGTGAAATGGCCGGACGCTATTCGCGATCTTCCCGGCGAAGGGAATGATCAGGT
TCGCCTATTCTTAGCGATGGACGCAGCGTTGCGACGTCTTGACACGATGCGAAATGAGTTTGACGTCGTTCTTTTCCATTTTCCA
GATAGCTGGGACGCGACTACGAGAACCAAGTTTTTCGATGCTCACGACACACTCAAGGCATTGGGCGCGAAATATAATATACCAA
CGCAGGTGCTCAATGACCGTGTCTTTGCGTTTTCACACCCTGCGTCGCGATCCTGGCGGCTGGCGATAGCGCTTTATGTTAAGGC
AGCGGGCACACCTTGGAAGCTTGCGCCCCTGAAAGGTGTACCTGAGGACACGGCTTACATCGGCCTCGCCTACGCCTTACGGGGC
GACCAGCGGGATGCGCACTATGTGACGTGCTGTTCCCAGGTGTTTGATATGGATGGCGGAGGAATGCAGTTCGTTGCCTTCGAGG
CCAAGGATCCTATCGCCGATGTCGCAGAAGCGCGTCGAAATCCATTTCTCAGTCGAGATGATATGCGCGCGGTTCTTGCTCGCAG
CCTCGAGCTCTATCAAGGAAGAAATGGAGGAACACTGCCGAAGCGGCTTGTCATTCATAAGACCACAGCATTCAAACCGGATGAG
ATCGAGGGTGCGTTTGATGCACTTGCCGGGGTGCAAGAAATCGAGTGCATTGAAGTTAGCCCAGCTTCCGGTTGGCGTGGGGTAT
GGCTGGTACCGAGCGGACAGCCGAAGCCGCCGACCAAGCCTGCGGGCTACCCTGTTCCGAGAGGCACCGTTGTCGTCCGGTCCGG
GACCTCGGCGCTTGTTTGGGTCGCGGGCAATGCTCCCGAAGTGTCTAATAAGGGCGACTATTATCAGGGAAAGAAGAGCATTCCA
AAGCCGTTGCAGCTGATCAGGCACGCAGGCAGTGGACCGTTGGAGCTATCGGCTCACGAGGCCTTGGCTCTCACCAAGATGGATT
GGAACAATGATGCTCTCTACGATCCTGTGCCTGTTAGCATCCGATACTCGCAACGCTTAGCCAAGACGATCGCGAACGTCCCAGA
TTTGCCCAGAAACGTCTATCCATATCGGCTCTTCATGTGA
47 GTGGACGCCCTCGTTCGGTCGCTGGCCGTGTCCCAAGACCGTCCCTTGATGCTTTTCCTTGGCGCGGGCGCATCGATGACTTCCG
GGATGCCTTCCGCTAACCAATGCATCTGGGAATGGAAGCGGGATATTTTTCTTTCGAATAATCCAGGTATCGAGGAGCAGTTTAG
CGAACTTTCCCTCCCCTCCGTTCGCGACAGAATTCAAACATGGTTGGACAGGCAACGGTGCTATCCGGTCGCCGGGCATCCTGAC
GAATACGGTGCCTACATTGAAGCCTGTTTCTCGCGCAGTGACGATCGTCGTCGCTATTTTGAAAGATGGGTCAAACAGTCTACGC
CTCACACCGGTTATAGGCTGCTAGCCGAACTCGCCGCTTCCGGTTTGATTCAGACCGTGTGGACGACAAATTTCGACGGACTCAT
CGCGCGTGCTGCAGTTGCCACGAATCTGACATCCATCGAAATTGGAATAGATTCCCAGCAACGACTTTACCGCGCGCCGGGTAAA
GACGAACTGGCTTGCGTCTCGATGCACGGCGATTACCGATATGATCGCCTCAAAAATTCGCCAGGAGAACTCGCCCAGGTCGAAG
TCCAGCTTCGTGACTCGCTCATTGAGGCCTTAAGAACGCATACCGTCGTTGTTGCTGGATACAGCGGTCGCGACGAGAGTGTGAT
GCAGGCATTCCGCCAATATGCGGCATCAGGTCCCGCGCGAACAGATTTGCCGCTGTTCTGGACGCAATACGGCGAGGACCCGCCT
TTGGACACGGTCAGCGCCTTCCTCTCGACGAACGACGACGAGCCATCCCGCTTCATCGTTCCGGGCGTTTCCTTCGACGATCTCA
TGCGGCGGTTGGCGCTCTACCTGTCAAAGGGGCCGGCCAGAGACCGCGTCAATAAAATCCTCGACGAGCATGCGACAACGCCCGT
TAACCAGCTCACTGCTTTCGGGCTCCCCCCTCTTCCCCCGACCGGCCTCATCAAAAGCAACGCAATTCCGCTGACACCGCCGCAG
GAGCTTCTTGAGTTTGATTTGCATCAATGGCCGGCCTCCGGAACCGTGTGGGCCACGTTGAGGGAGCTTGGCGACAAACACAATT
TTGTCGCCGCGCCGTTCCGATCGAAGATTTATGCGATCGCTATAGCCGAAAGTCTTCGCCTCGCCTTCGGCGAGAATCTGAAAGG
GGAAATCAAACGGGTTCCCCTGAACGATGACGATCTGCGATACGAAGACGGCGTCATCAACCAGCTTGTCCGCCGTGCGACCGTC
CTCGCCTTATCGGCCAAGGCAAATTGCCCGTCAGACGGAGAGTCGTTGATCTGGACATCCGAGAAGGTCGAGAATTTGCGCCTGG
ACAGGGTCGACTGGAAAGTTCACCAGGCCGTACTGGTCCAGATACGCCCGCTCGGAACCGAGATGGCGCTCGTCCTGAAGCCCAC
CCTGTACGTTACCGACAAGAGCGGAGCGATCGCACCCAAGGATACTGAGCGGCTCGTCAAGCAGCGCGTGCTGGGCTATCAGCAC
AACAAGGAATTCAACGACGCAACCGAAGCGTGGCGACGTCGCCTCGTGCCTCAGCGCGATTTTCATGTCCGCTTCCCTGACCATG
AAGACGGTATCGATCTGACTTTCTCTGGACGACCGCTGTTTGCGCGAATCACTGACGAGCGCGAGCGTACCGTTTCACTCAGTTC
CGCTCAGGAGTTAGCCGCGAGGCAAGCCGGACTTCAACTCGCAGAACCACGACTGAAATTCGCGCGCAAATCGGCAGCCGGACTG
GCATTCGACACCCATCCTGTCCGAGGCCTGATCAACAACAGGCCGTTCGATTCCAGCCTCACCACGACAGGCATAGCTTCCTCCA
TCCGCGTCGGAATCATTGCGCCTGCCCAGGACGCCACACGAGTTCACCAGTACCTGTCCCAGCTTCACGTCGCCGCACAGCCAGG
GAAGGACGCGGATTATCTCCCGCCGTTTCCAGGTTTCGCGTCCGCCTACCAGTGCCCGCTCGAGATCCCTGCGGTTGGTGAACAA
TCTTTCGTCCAGCTTGACGAGCCGGACAGCATGACACCCTCGTCAGCACGCGCTTTGGCCGGAGCAATCACGAGGTCGATTGCCT
CCTTGAGCGCGTCGCAGCGTCCCGACGTAACCATCATTTACGTCCCCGATCGCTGGGCTCCGTTGCGCAACTACATGATCGACGA
TGAAGAGTTCGATCTACACGATTTCGTCAAGGCGGCGGCGATTCCGAAAGGTTGCGCCACACAGTTTGTCGAAGAGGACACCCTC
CGTAACACGCAGCAGCAATGCCGCGTGCGCTGGTGGCTCTCGCTTGCCCTGTACGTGAAAAGCATGCGCACGCCGTGGACTTTGG
AAGGCCTCAGCGAGAAATCCGCCTACGTGGGTCTCGGCTTCAGCGTCAAACGCAAGACGACACAGAATGCGGGCGCACACGTCGT
GCTGGGCTGTAGCCACCTCTATAGCCCGAACGGCATCGGTCTGCAGTTCCGCCTGAGCAAGATCGAAGATCCAATTATGCGCAAC
AAGAATCCCTTCATGAGCTTCGACGATGCAAGACGGCTCGGTGAGGGCATCCGTGAACTGTTTTTCGCCGCCCAACTTCGACTTC
CTGAGCGAGTGGTGATCCACAAGCAGACCCCATTCCTTCGCGAAGAACGCAGTGGGCTCCAGGCTGGACTCGAGGGAGTTGCGTG
CGTAGAGCTATTGCAGATCTTCGTTGACGACACGCTACGGTATGTGGCGTCCCATCCGACCTCCGACGGAAAGTTCGAGACCGAC
AACTATCCCATCCGGCGGGGAACGACAGTGGTCATCGACGATCACACGGCTCTTCTGTGGGTCCACGGCGCATCTACTGCACTAA
ATCCCAGAAGGCACTATTTCCAGGGCAAGCGTCGAATTCCAGCCCCCTTGGTAATTCGGCGTCATGCGGGCACGACCGATTTGAT
GACGATCGCCGACGAAGTTCTCGGCTTGTCGAAGATGAATTTCAACAGCTTCGACCTTTACGGGCAACTTCCAGCGACGATCGAG
ACGTCACGCCGCGTTGCGAAGATCGGCGCACTTCTCGATCGCTTCTCGGAACACTCGTACGATTACCGTCTGTTTATGTAG
48 ATGAGCGTGGACGCCATGATTCGGTCCATCGGGGTTGCGCGAGATCGGCCACTGCTGGTGTTCTTGGGTGCTGGAGCTTCCATGA
GTTCCGGCATGCCATCGGCCACACAGTGCATCTGGGAATGGAAGCGGGAAATATTCCTGACCAACAACCCCGACGTCGAGAAGAC
CCAGTTCAGCGAGTTGTCCCTGCCGTCAGTAAGGCTCCGGATTCAAGCCTGGCTGGATCGCCAGCGCCGCTATCCGGCACTGGAT
CATCCTGACGAATACAGCACCTACATCGGCGAGTGTTTCGCAAGAAGCGACGACCGCCGAATCTACTTCGAGAAATGGGTGAAGA
GATGTTCGCCGCATCTCGGCTATCAACTGCTGGCGGAACTCGCGCGGCAAGGTTTGGTGGCATCGGTCTGGACAACCAACTTCGA
TGCCTTGGCCGCTCGCGCCGCGACCTCCATCAATCTGACCGCCATCGAGATCGGCATCGATAGCCAGCAGCGTCTGTATCGGGCG
CCTGGAGAGGCCGAACTCGCCTGCGTCTCACTCCACGGCGACTATCGATACGATCCGTTGAAGAACACGGCCCCCGAACTCATCA
AGCAGGAGAAAGAACTGCGCGAGTCACTGGTGCAGGCCATGCGAACTCACACCGTTCTCGTATGCGGCTACAGCGGGCGCGATGA
AAGCGTCATGGCGGCCTTTTCGGACGCCTACGATGCGGCGCATTTCAAAGGCCATCACCCGCTGTTCTGGACGCAGTATGGCGAC
TACCCAGCATCGGAGCCGGTCGCCGGACTCCTTGCATCGCCCCTCGATCAGGAACCGGCGAAGTTCCACGTGCCCGGAGCTTCGT
TCGACGATCTGATGCGACGTATTGCACTGCATGTGTCGGACGGCGAGGCACGCGAGCGTGTGCGCAAAATTCTGGAAAATTTCAA
GACAGCGCCGGTCAACCAGAAGTTGCCCTTTGCCCTGCCGTCATTGCCCGTCACCGGTCTGGTCAAAAGCAACGCCATTCCGCTC
ATTCCGCCGGGCGAGTTGATCGAGTTCGATCTGGTGCGGTGGCCGCCGTCAGGTGAAGTCTGGTCGACCTTGAGAGAGATTGGGG
ATCGACATGGCTTCGTGGCTGCACCCTTCAGAGGCAAGGTCTACGCGCTGGCCACCATCGAGCAGTTGACCCAGGCGTTCGCTGA
CAACGTGAAGGATGGCGCGTTCAATCGGGTGCCGCTGAACAATGACGATCTCCGCTACGAGGATGGCACCGCCAACCAACTGATG
CGCAGAGCGACTGTGCTTGCCTTGGCCGGGAAGGCTGGCTGCGCTAACGATGGCGACGCCATTGTCTGGGACACGTCGCGATCCA
AAACGGAGCGCCTGGACCGTCAATTGTGGACGGTGTACGACGCCGTCCTGCTTCAGATTAGGCCTCTTGGGACGAAGCTCGCGCT
GGTGCTCAAGCCCACACTCCGAGTCACTGACAGCACTGGTGAAGTTGCACCGAAGGAGATCGAACGCGCGGTCAAGGTCCGCGTG
CTCGGGTACCAGCACAACAAGGAGTTCAACCAGGCGACGGACTTCTGGCGAAAGCGCTTACTGCCATCGCGTGACCTGCTAGTCC
GCTTCCCCGATCTCGACGGCGGCATGACCTTCACCATCTCCGGCCGCCCGATCTTCGCGCGACTCACGGACGAGCGAACCGAGAC
CGTCACGCTGAATGATGCGCAGGAGCGCTCGGCCTCTCAAGTTGGCCTGCAACTCGCCGAGCCCAAGCTGGTATTTGCCCGAACC
GTCGGCACTGGGCCTGCAACGGACACGCTTCCCGTTCGCGGTCTTTTGCAGAATCGGCCGTTCGATGCCAATCTGACCGACCTCG
GCATTGCCACAAATCTGCGAATCGCGGTGATCGCGCCCGCCCGCGATGCGCGCCGTGTCCACGACTACTTGGGCCAGCTTCATCA
GCCCATCGATCCCACGAAATGGGACGCTGACTACTTGATGAGGTTCCCGGGCTTCAGCAGCGCATTTAAATGCCCGCTGGACATT
CCACAACCAGGTCAGGCCGCCTTCGTCACGTTGGATGAGCCGCATGACGAATCGCCGCAATCTGCGCGCACGCTCGCAGGCCGCA
TCACCGCGGCCCTCTCCGCATTGCGGGCCACGGAAAACCCAAGCGTCACCATCATCTACATACCCGCCAGATGGCATGCCCTTCG
AGCGTTCGACCTTGAGAGCGAACAGTTCAACCTTCACGATTTTGTGAAGGCCGCGGCCATCCCGGCTGGTTGCTCCACTCAGTTT
CTCGAAGAAAGCACTCTCGCCAACGGTCAGCAATGCCGCGTTCGATGGTGGTTGTCTCTGGCTGTGTACGTGAAAGCCATGCGCA
CCCCCTGGGCCCTCACCGGCCTTGATAGGGATTCCGCCTTCGTGGGCCTCGGCTTCAGCGTCCGCCGAAAGATCGACGGCGAAGG
CCATGTCGCGCTGGGCTGCAGCCACCTCTACAGCCCCAATGGTCACGGCCTTCAATTCCGCCTGAGCAAGATCGACAACCCGATC
ATGCTGCGCAAGAACCCCTTCATGAGCTTCGACGACGCGCGAAAGCTTGGGGAAGGCATCCGAGAGCTGTTCTTCGACGCCCACC
TACGCCTTCCCAATCGCGTCGTGGTGCACAAGCAAACGCCTTTCCTGAAGGAGGAGCGCGAGGGGCTGCAAGCTGGCCTGGAGGG
CGTGGCCTGCGTCGAGTTGTTGCAGATCTTCGTCGATGACACCTTGCGGTACGTGGCATCGCGCCCGATGCCCAATGGCGACTTC
GAGATTCACGGCTATCCGATTCGACGCGGCACAACGGTTGTAGTGGACGATCAGACAGCATTGCTGTGGGTGCACGGAACCTCTA
CCGCTCTCAACCCTAGGCAATCCTACTTTCAGGGGAAGCGCCGAATTCCGGCCCCGCTCGTGATGCGCCGCCACGCCGGCACTAG
CGATCTCATGATGCTGGCCGATGAAATCCTTGGCCTGTCCAAGATGAACTTCAACAGCTTTGATCTCTATGGGCAGTTGCCCGCA
ACCATCGAAACCTCTCAACGGGTCGCGCGCATCGGTGCCCTGCTTGATCGGTACACCGAGCGTTCGTATGACTACAGGCTTTTCA
TGTGA
49 ATGCTCGAGTTTCGCTACGGCCAGCGCATGGTCTATCCACGGGACGGACTATTTCTGTTCGGTCCAGGCGACGGAGGGCGAGCAC
CCATCAATTTCGGCGTGATCGGCACTCCCGCGGGAGTCGCTCGCTTCCGGCAGTGGATGGGCTCGGTCGGCAATGTCATAGACGC
CGCCAATGACGACCCGCAGCATGTGCCGTTTCCGGGTTATGGTGCCGCCTTCGCCAGTGCTTGGCCAGACAAGCCACGGCACATC
ATCGATAGCATCGACCCCGCGGCTGTCTCGCGGGCTCTTCGCCTGGAGAACAGGAACGAGGCGATCAAAAGCACCGTGGATCTGT
ATGTCGACCCACTGGTGGCGGCCGCCGATCGCTTGGAGGCACCTCCGAATTTCTGGTTCGTGGTTATTCCTGAGGAAATCTACAA
GCTCGGGCGACCCCAATCAAGCGTCCCCAAGGCGGACCGCATCCGCGGTTCGGTGAAACTGTCCAAGTCTGCTGCCAGGGACTTG
ATGTTGGAGCCGACGTTCTTCCCCGAAGATCTGGAAGCGGCGGAGATCTATCAATATGCCACCCATTTCAGGCGCCAGTTGAAGG
CACGTCTGCTCAGAGACCGTATCGTCACTCAGATCGTTAGGGAAACCACATTGGCGCCTAACGATTTCCTGAACAAAATCGGCAA
GCCACTGCGACGATTGGAGGACCCTGCAACGATCGCCTGGAAAATATTGACCGGCGCCTATTACAAGGATGGTGGACGACCATGG
CAGTTGGCCGACGTCAGACCCGGCGTTTGCTATGTCGGCCTCGCCTATAAGCGACAGGACAATAGTTCCGATGATCGCTTCGCCT
GTTGCGCCGCCCAGATGTTTCTTTCGAGCGGTGAAGGCGTCGTATTTCGCGGTGCGCTCGGCCCATGGTTTCATTCCGAATCCAA
GCAATTTCATCTGAGCGAGGACGCGGCAAGCAGTTTAGTTGAGATGGTTATCGGCGAATATCAACAAATGCATGATGGACAGCCG
CCCGCTGAGCTGTTCATTCATGCCAAGTCCTCGTTCGCGGACCCGGAATGGAAAGGCTTCAAGGCCGCTGCTCCGGGGACCAATG
TCGTAGGAGTGCAGATTTCCGATGCGAAAGACCGCATGAAGCTATACCGGCCCGGTCGATATCCGGTCATCCGCGGAACGGCCTT
GATATTGCACGAACGCCGCGCGTTCCTCTGGACGTCGGGATTCGCCCCGCGCCTTGATACCTACCAAGGGCCAGAGACGCCGAAT
CCGATAGAAGTCCGCATTCACCGCGGAGATTGCGAACTTGAAACGGTTCTCGGGGACGTGATGGGCCTGACCAAGATCAATTTCA
ATTCTTGCCTGCATAACGATCGATTGCCGGTGACGATACGTTTCGCCGACGCGGTGGGCGACGTGATCCTCGCGGCACCACGGAC
CGGCGAACCGAAGCTGCCGTTCAAGTATTATATATAA
50 ATGGACTACAACCTTTCGAAGGCGCCATCGTTTTCCTTGCTGGACGAGCCGGCCCTCACGTTTAACAGCGAAGACACAGACCTCG
ACGAGAACCCGCTGCGCGGCCTTTTGCGTTTCGGTGCCTACAACGGCAAGACGTTCGAGGGCTACACCCCGAAGCTTCGTGTCGC
GACAATCGCCCCTGCATCAGGTTGGCCGAAGCTCAAAGGCTTGGTGGACACGATCCGATCAGGTCACGAGGCGAGCGACCGGCGC
AACTACGTGCCGTCGTTCCCCGGATTTGAAAACCTGTTTCGCGTTCCGCTCGTCGCGGGGCCGAAGGACGTGCACATTAAGTGGC
CCGACGATCTCATGGCCCTGGCGCGTACTGGGGCGCCCCATGAGCGGTTGTTTTCGGCGATGTCGGAAGCCATGGCGCGTCTCGA
TGCGTTGCACGATCAGTTTGATGTCGTCTTGGTACATCTCCCTGATGCGTGGGCAACGGCATTCACGGCCAACGGATTCGACGCC
CACGACGCGTTGAAGGCCCTTGGAGCCCGGTACGCCATCCCAACGCAGGTCATCAACGATCGCGTTTTCACATTCCGGCTCAAGG
CGTCGTTGGCCTGGCGCCTGGCCATCGCGCTCTTCACCAAGGCGGGCGGCATTCCCTGGAAACTCGCGCCGATGGTCGGTGTACC
AGAAGACACGGCCTATATCGGTCTCGCCTACGCGTTGCGCGGGGACCCCAAGTCCGCGCAGTTCGTCACGTGCTGCTCGCAGGTG
TTCGACGCGGACGGCGGTGGCATGCAGTTCGTCGCTTTCGAGGCCAAGGAGCAGGTGGCGGATCCGCGCGAAGCCAGACGGAACC
CGTTTCTCAGTCGGAGCGACATGCGGGCGGTAATGGCACGTAGCCTGAGCCTCTACCTTGGGCGTAATGGTGGACGGCTGCCGCG
ACGTCTCGTCGTCCACAAAACGACGTCGTTCAAGGACGAAGAACTCCAAGGCGTTTTCGACGGCCTGTCGACGGTTCCAGAGGTG
GAGTGCATCGAGATCGGCAGCAGCGCCACATGGCGTGGCGTGTGGCTGAAGCAGGGAAAGAAGGGCGGACCCAAAAGTGTGCCTG
ATCGAGCGCCGGTGCCGCGGGGAACTGTCCTCACGCGAACGGACCGGTCGGCGCTGTTGTGGGCATCGGGCAATGCCCCGTCGGC
AGCGCTCAGCGGTGCCTTGTTTTTCCAGGGAAGCAAGAGCATTCCGCGCCCGCTCAACATCATCCGTCACGCGGGCAGCGGTCCG
CTGGAAGTTGCTGCGTTGGAAACCCTCGCGCTGACCAAAATGGACTGGAACAACGACGCGTTGTACGACCCGGTTCCGGTGACCA
TTCGCTATTCGCAACGGCTCGCACGTACCATCGCGAATGTGCCAGATCTTCCGGGGCATGCGTACCCCTATCGCCTCTTCATGTG
A
51 TTGTCCATCAAATCAGAGGAAGATCAGGGCCTTCAGATCGCCGATGGTGTGCCTCTCCAGTTTGAGAGTCCACTTGACCAAGCGG
AGTCAGTGCCATTTCCGCCAGCTGAGGTGTTCCAACGGCCCACGTTCTCGTTCGACCCAAGCGGCTCTCGCAATGACAACTGGAC
TCAGAGGCAGCTCGATAAGACCGGGCCCTACGATAGAGCGACTTTTGAACGAAAGCGGCCGAGGATTGCTGTCATCTGCGAGGCA
CGCCGGCGCGGTGCCATGGCAGAGACGGTCGCGCACTTCCTTGAGGGTCTCCCCGAAGTTCAATCTCACAAAGGCTTTGTACCCC
ATGCGACGGGGCTGCTGGGCCGCTTCCGGCTTCAGAAGCCGCAAGTTGAATTCTTCGAGGCCAAGGATGACAGCGCTGACGCCTA
CGCTGAAGCCGCCCGTAACGCTCTGTCTGCGGCCGCCACTCGGGACCAGCCATGGGATCTAGCCCTGGTGCAGGTCCAGCGATCC
TGGAAGGATCGTCCTGCCACCAGTAGCCCTTACTGGTGGGCGAAGGCTGCGTTCCTGCGGCGCGACGTGCCAGTGCAGGCACTCT
CCGCCGAGATGATGGCCATGGGCGACTTCGAGTACGCCTGCGCTTTGGCAAACGTCAGCTTGGCCACTTACGCCAAGCTCGGCGG
TACCCCTTGGCTGCTGAAGGCCCGGCCCTCGACAGATCACGAGCTTGTCTTTGGCCTCGGATCTCATACCCACAAGGAGCGACGT
CGAGGTGCAGGGGAACGGGTCGTCGGGATCACGACCGTGTTCTCTAGCCAGGGTAACTATCTACTAGATGCCCGAACGGCTGCAG
TACCGTTCGACCGCTACCCGGAGGCACTGCGCGCCACGCTCATCGAGGCGGTCAAGCGCATACGGCAAGAGGAGGCCTGGCGCGC
GGGCGACACGGTGCGCTTGGTCTTCCATGCCTTCACCCAGATGCGACAAGAGACTGCGGATGCCGTGGTTGCCGCTGTGGAAAGC
ATGGGCCTGAGTGGGGTGAAGTTCGCCTTCCTCCATGTGGCCGAGGACCACCCATTCACGCTGTTCGACCACGCCTCAGCGACTG
GCAAGGGTGCCTATGCGCCCGAGCGTGGGCAGGCCGTAGAACTCAGCGACCACGAGTGGCTCCTTTCCCTCACCGGACGGGATCA
GATCAGAGCCGCGTCGCAGGGCATCCCTGATCCGGTGCTACTCCGCCTGCACGAGAAATCGACCTTTCGCGACATGCGAACGCTG
ACGCGTCAGGTATCGGATTTCGCCTGCCACTCCTGGCGTACTTACGAACGAGCTAGGCTCCCGATCACACTCCTCTACGCCGACG
AAATTGCGAAGCAACTCGCAGGCCTCGAGCGTACCCCGGGATGGGACCCCGATACCGCAGTAGTTGGCGCGGTGATGCGCAGGCC
TTGGTTCTTGTGA
52 ATGCTCGAGTTTCGCTACGGCCAGCGCATGGTCTATCCACGGGACGGACTATTTCTGTTCGGTCCAGGCGACGGAGGGCGAGCAC
CCATCAATTTCGGCGTGATCGGCACTCCCGCGGGAGTCGCTCGCTTCCGGCAGTGGATGGGCTCGGTCGGCAATGTCATAGACGC
CGCCAATGACGACCCGCAGCATGTGCCGTTTCCGGGTTATGGTGCCGCCTTCGCCAGTGCTTGGCCAGACAAGCCACGGCACATC
ATCGATAGCATCGACCCCGCGGCTGTCTCGCGGGCTCTTCGCCTGGAGAACAGGAACGAGGCGATCAAAAGCACCGTGGATCTGT
ATGTCGACCCACTGGTGGCGGCCGCCGATCGCTTGGAGGCACCTCCGAATTTCTGGTTCGTGGTTATTCCTGAGGAAATCTACAA
GCTCGGGCGACCCCAATCAAGCGTCCCCAAGGCGGACCGCATCCGCGGTTCGGTGAAACTGTCCAAGTCTGCTGCCAGGGACTTG
ATGTTGGAGCCGACGTTCTTCCCCGAAGATCTGGAAGCGGCGGAGATCTATCAATATGCCACCCATTTCAGGCGCCAGTTGAAGG
CACGTCTGCTCAGAGACCGTATCGTCACTCAGATCGTTAGGGAAACCACATTGGCGCCTAACGATTTCCTGAACAAAATCGGCAA
GCCACTGCGACGATTGGAGGACCCTGCAACGATCGCCTGGAAAATATTGACCGGCGCCTATTACAAGGATGGTGGACGACCATGG
CAGTTGGCCGACGTCAGACCCGGCGTTTGCTATGTCGGCCTCGCCTATAAGCGACAGGACAATAGTTCCGATGATCGCTTCGCCT
GTTGCGCCGCCCAGATGTTTCTTTCGAGCGGTGAAGGCGTCGTATTTCGCGGTGCGCTCGGCCCATGGTTTCATTCCGAATCCAA
GCAATTTCATCTGAGCGAGGACGCGGCAAGCAGTTTAGTTGAGATGGTTATCGGCGAATATCAACAAATGCATGATGGACAGCCG
CCCGCTGAGCTGTTCATTCATGCCAAGTCCTCGTTCGCGGACCCGGAATGGAAAGGCTTCAAGGCCGCTGCTCCGGGGACCAATG
TCGTAGGAGTGCAGATTTCCGATGCGAAAGACCGCATGAAGCTATACCGGCCCGGTCGATATCCGGTCATCCGCGGAACGGCCTT
GATATTGCACGAACGCCGCGCGTTCCTCTGGACGTCGGGATTCGCCCCGCGCCTTGATACCTACCAAGGGCCAGAGACGCCGAAT
CCGATAGAAGTCCGCATTCACCGCGGAGATTGCGAACTTGAAACGGTTCTCGGGGACGTGATGGGCCTGACCAAGATCAATTTCA
ATTCTTGCCTGCATAACGATCGATTGCCGGTGACGATACGTTTCGCCGACGCGGTGGGCGACGTGATCCTCGCGGCACCACGGAC
CGGCGAACCGAAGCTGCCGTTCAAGTATTATATATAA
53 ATGCTCGAGTTTCGCTACGGCCAGCGCATGGTCTATCCACGGGACGGACTATTTCTGTTCGGTCCAGGCGACGGAGGGCGAGCAC
CCATCAATTTCGGCGTGATCGGCACTCCCGCGGGAGTCGCTCGCTTCCGGCAGTGGATGGGCTCGGTCGGCAATGTCATAGACGC
CGCCAATGACGACCCGCAGCATGTGCCGTTTCCGGGTTATGGTGCCGCCTTCGCCAGTGCTTGGCCAGACAAGCCACGGCACATC
ATCGATAGCATCGACCCCGCGGCTGTCTCGCGGGCTCTTCGCCTGGAGAACAGGAACGAGGCGATCAAAAGCACCGTGGATCTGT
ATGTCGACCCACTGGTGGCGGCCGCCGATCGCTTGGAGGCACCTCCGAATTTCTGGTTCGTGGTTATTCCTGAGGAAATCTACAA
GCTCGGGCGACCCCAATCAAGCGTCCCCAAGGCGGACCGCATCCGCGGTTCGGTGAAACTGTCCAAGTCTGCTGCCAGGGACTTG
ATGTTGGAGCCGACGTTCTTCCCCGAAGATCTGGAAGCGGCGGAGATCTATCAATATGCCACCCATTTCAGGCGCCAGTTGAAGG
CACGTCTGCTCAGAGACCGTATCGTCACTCAGATCGTTAGGGAAACCACATTGGCGCCTAACGATTTCCTGAACAAAATCGGCAA
GCCACTGCGACGATTGGAGGACCCTGCAACGATCGCCTGGAAAATATTGACCGGCGCCTATTACAAGGATGGTGGACGACCATGG
CAGTTGGCCGACGTCAGACCCGGCGTTTGCTATGTCGGCCTCGCCTATAAGCGACAGGACAATAGTTCCGATGATCGCTTCGCCT
GTTGCGCCGCCCAGATGTTTCTTTCGAGCGGTGAAGGCGTCGTATTTCGCGGTGCGCTCGGCCCATGGTTTCATTCCGAATCCAA
GCAATTTCATCTGAGCGAGGACGCGGCAAGCAGTTTAGTTGAGATGGTTATCGGCGAATATCAACAAATGCATGATGGACAGCCG
CCCGCTGAGCTGTTCATTCATGCCAAGTCCTCGTTCGCGGACCCGGAATGGAAAGGCTTCAAGGCCGCTGCTCCGGGGACCAATG
TCGTAGGAGTGCAGATTTCCGATGCGAAAGACCGCATGAAGCTATACCGGCCCGGTCGATATCCGGTCATCCGCGGAACGGCCTT
GATATTGCACGAACGCCGCGCGTTCCTCTGGACGTCGGGATTCGCCCCGCGCCTTGATACCTACCAAGGGCCAGAGACGCCGAAT
CCGATAGAAGTCCGCATTCACCGCGGAGATTGCGAACTTGAAACGGTTCTCGGGGACGTGATGGGCCTGACCAAGATCAATTTCA
ATTCTTGCCTGCATAACGATCGATTGCCGGTGACGATACGTTTCGCCGACGCGGTGGGCGACGTGATCCTCGCGGCACCACGGAC
CGGCGAACCGAAGCTGCCGTTCAAGTATTATATATAA
54 TTGCATCTCAACTACCTGCCGCTACGTTTTACTGCCGACATATTCAAAGGGGGCGCTCTGACCTTTCCTGAAGGTTCAGAAAAAA
ACTGGACCTCCGACGACCCAATCAGCAAAGAGTTGAGCAAGTTGAGAGAGAAGCATGGGGATTCCCATGTTTTTCATCGAATGGG
AAATAAAATCGCCTGCATCCCGGTAGTAGAAAACGCGATCGCAATTGGCACTGAAACAGACTTCAACATCATCTCCGACTTTCAG
TTAGCGAATGCGCTCGCACGCTCAGCATTACATAGATATTTCAAAGCTGCTGGCAGAGAGACTGTTATCGGCTTTCGCCCTGTCA
CGCTCCTACTCGAAAAACATAATCTCGCTTCTAACCGCAAAGACGTATTTGGCATTTTCCCCGAATACACGCTCGACGTTAGGCC
GTTAGCTCCGCACGAGGGGGACATCGCGAGCGGAGTTCTTATTGGATTTGGAATCAAATACGTCTTCCTCCAGAATGTCGCTGAA
CTTCAGGCTCAGGGTGTTTCAGCAGCCGGCATGTACGCCGTGCGGTTAGTTGACGAGTCCGAACATCAGTTTGATCGGGCCTACC
TCGGACGGATCGACCGCTTCACAAAGGACAACGTAACCCTAGTCGATTCTGACTATGCGGAGTATCCAGCCGATCAGTGCTATTT
CGAAGGTAGTCGTACAAATATCGAGGCAGTCGGCCGAAGCCTCCTTGGCAAAGACTACGATGCCTTTTCGAGCTCGCTTCTTCAG
GAAAGCTACAAAGTGACCGGCGCTCCCAATCAGACCCAGCGACTCCATCAACTTGGAGCCTGGTTGGAAGCAAAATCCCCAATTC
CGTGCGCCGTCGGCTTAGGAGTGCGGATCGCTAAGAAACCCCATGAGTGTTCACGAGGCAATGATGCCGGCTACTCCAGATTTTT
CGACTCTCCCAAATGTGTCCTTCGCCCTGGAGGTTCGTTAACCGTTCCTTGGCCTGTCGACAAGCAAATCGACCTCAATGGTCCT
TACGACGCAGAGTCATTTCCAAACAAACGGGTGCGCATCGCCGTCATCTGTCCGCAAGAGTTCACCGGGGATGCCGAAGAGTTTT
TGAGAAAGCTGAAGGAGGGGCTACCCAACGCTCCTGATGGATCGCCTTTCOGGAAAGGTTTCGTCCGCAAATACCACTTGAGCAG
TTGCGATTTTACGTTCCACGAAGTGAAGCGCAGTTCGAATTCCGACGACATTTACAAGGATGCTTCGTTGGAGGCGTTGAAACAG
AAGCCAGACATGGCAATCGCAATCATCCGTTCGCAGTATCGAGGGCTTCCCGATGCGTCGAACCCGTACTACACCACTAAAGCGC
GATTGATGGCGCAAGGTGTTCCAGTACAACTATTGAATATCGAAACCATCCGTCGAAAAAGCCTTGACTACATTCTCAATAATAT
CGGGCTTGCTATGTACGCGAAGCTTGGCGGAATCCCTTGGACGCTGACCCAGAACAGCGATATGGCGCACGAGATTATCGTTGGT
ATAGGAAGCGCCAGATTGAACGAAAGCCGTCGTGGTGCAGGCGAGCGGGTGATCGGAATTACGACCGTTTTCAGCGGCGATGGCC
AGTACCTGTTGGCAAACAATACTCAAGAGGTGCCTTCAGAAGAGTACGTTGATGCTCTGACTCAGTCTCTCTCGGAGACTGTGAG
TGAACTCAGGAGCCGATTCGGTTGGAGACCAAAAGACAGGGTCCGATTCATCTTCCATCAAAAGTTCAAGAAGTACAAAGATGCT
GAAGCTGAGGCAGTTGATCGCTTCGCACGATCACTCAAAGATTTCGACGTGCAATATGCCTTCGTTCATGTCAGTGACTCGCACA
ACTGGATGTTGCTAGATCCCGCATCGAGGGGAGTGAAGTTCGGCGACACAATGAAGGGAGTGGCGGTCCCGCAGAGGGGACAATG
TGTGCCTCTAGGGCCAAACGCTGCTCTTTTGACTTTGTCCGGGCCATTTCAGGTCAAGACGCCACTGCAAGGTTGCCCTCATCCA
GTACTGGTGAGCATTCACGAGAAGTCCACGTTCAAGAGCGTGGATTATATCGCTCGCCAAATTTTCAATCTCAGCTTCATCTCAT
GGAGGGGTTTCAACCCGTCAACGCTTCCAGTTTCGATTTCTTACTCAGACATGATCGTAGATCTGTTGGGGCATTTGAGAAGGGT
TAAGAACTGGAATCCCGAGACGCTTTCGACCGCACTGAAAGAAAGGCGCTGGTTCCTATGA
55 ATGAAAGCGGACTACATACAAGAACCTTTTTTATTATTTGGCAAAGGCAAAAGTATTTGTCCTAGAGAAGGTATTGCCGAATTAA
ATGTATATGACACGGTAATTGAAGCCAGAAAAAATCAATTGCTCATTGGCATAATTGGGATTGAAGAAGATGTAGAAAATCTGAA
AAGTTGGATAAAAAGGTTTGAAAGCTATATTCCTGCAGATCCCAAAGGCAAACAGAAAGGATTGTTCAAATCGTTTCCGGGATTC
CATCAGGACAAAGGGTTCTGTGCAAAATTCATTTACGATTCAAATTATGAGAGGATTCTCTCACCAAATGACATTAAAAGGATTT
TGAAAGAACCTGATAGGAATAAGAAAGTATTGGATGCAGTAGAGTTGTTTGGTGAAAACATTGGCTTTCTCTCTGATATTAAAAA
CTGCGACGTAATAATATGOATCATACCGAAAAGCTTTGAAGGTAAAATAGTAAAAGAGAACAAAGATGATGAACCAGTTGAACAA
GTGGCTGAAGATAACGAAGGACCTGAATTGGAACTGAATTTTAGAAGAGCATTAAAAGCCCGTGCAATGAAATACAACACACCTA
TTCAGTTGTTGAGAGAATATGTAATGCACGACAGTAACAAATCACAAGATAATGCAACTAAGGCATGGAATTTTTGCACTGCTCT
TTATTATAAGGGACTTCAAACCATTCCTTGGAAGTTGGAAGTAGACGAGAACAAACCAAAAGTATGTTTTGTAGGTATTGGATTC
TACAAAAGCAGGGACAAGAAAACGATTCAAACCAGTTTAGCACAAATTTTCAATGAAAATGGAAAAGGTGTGATACTTCGCGGAA
CTCOTGTAACTGAAGATAAAGACGATAAAAAACCTCACTTAACTTATGAGCAATCTTTAAGCCTTCTGAAAGATGCCTTGACCAA
ATACAAGTTTGCGACAGGTTCAATGCCAGGTAGAGTAGTTTTACACAAGACTTCAAAATACTATGAGGATGAACTTGACGGCTTT
ATTCAAGCAATGCAGGATTTGGGTATAACTGAATACGATATTGTAACTATCATGGAAACCGATTTGCGTTTCTTTAGAAATAATC
TTTATCCACCAGTGAGAGGGGCAGTTTTTTCATTGACTGAACAAAGACACATACTTTACACTAGGGGTTCAGTTCATCAATATCA
GACATATCCAGGAATGTATATTCCTGCTCCATTAGAAGTAAGAATAGTAAGTTCCGTTTCATCTATAAGGACAGTTTGTAAAGAA
ATTCTTGGCTTGACAAAAATGAATTGGAACAACACCCAATTCGACAACAAATACCCCATTACAATTGGCTGTGCAAGACGGGTAG
GAGAAATAATGAAATACGTTGGAGAAAATGAATATCCGAAAGAATCTTATGCATATTATATGTGA
56 ATGAAGGACCTTGTATGGGTCCAGGAATCCTCGTCGGTGAAAGTCCTCCGCGACGGGAACTATCCCGTGATGCGCGGCACCTTTG
TCGAACTCGACGGGAAAGGGCTTCTCTATACGAACGGCAGCATCCCGTACTACGGAACCTATCCAGGCCAGTATGATCCCAGGCC
ATTTCTGCTATGTCCGCACAAAAGCAGCGACAGCACCGTCGCGCAGATCGCCAAAGACGTGCTGTCGATGACGAAGATCAACTGG
AATTCGACCCAGATGAACCAGAAGCTGCCCATTCCCATCCGGGCCGCACGAAAGGTTGGTGAGGTTCTTAAATACGTCAGCGATG
GAAAGGTCAGTTCCGACTACACCCGATATATGTGA
57 ATGGACCTGTCGAAGAAATCCCTCAAGACTATCCACATTGAGGAACCGGAGTTGTCTTTCGGCCACGGGCAAACTTGCGACCACC
CGAAAGATGGACTGTTTCTCTACGGGCCGCACTCTGGCCCAACACGCACGCGCGAAGTTTCCGTTGGAGTCATTGGAACGAAAGA
CGGACTCTCGTATTTTCGGACGTGGGCGATTGCGGCTGGCGGCTTTGTTCCCGTCCCGCCGCGAAAGAAAACCGACAAAGAAAAC
AGATTGCACCTCTCGAATTTTCCTGGGTTGGAAGAAGCGTTTGGCATCATGGTCAGCCCGGGAGACTTTGTTCAGCGTACTGTCG
ATTACACGGTACTCGACGACGCCACCCGTACGGTGAACCAGCATGAAGCGGTACGCAAAGCGGTGGACCTCTATGTGGGAGAAAT
TGAACGCTATGACAACAATGAAGAAAAGACGGTAGACGTTTGGATGTTCATTCTCCCCGAAATCATCTTCGAGCGTTGCAAGCCG
CTATCGCGGCGCACCGGCCTTGGCCTGACAAAAGGCGAATTCGCCAAGAGCCAGAAAGAAAGAATTGATCTTCCGTTGTTCAAGG
ATGTGATCGACCAGAGCGGCGAGGACATCTTTGACGACGTGCCAGATTTTCACCGCCAGGTGAAAGCGCGTCTGCTCAAGCTAGG
TCGCACTTCGCAACTCATCCGCGAAACGACGTTGGCACCCGACAAATTCCTAAATAACGCGGGCTATCCAAAGCGTGGGTTGCAG
GATCCGGCGACAGTGGCGTGGAATCTGGCAACTGGACTTTACTACAAAACCCAACCCTTGCCGCCGTGGAAACTCGCGCATGTCA
GGCCGGGCGTTTGTTACATCGGACTTGTTTTCAAGATGATTCCGAATGATCCAAAGGAACATGCCTGCTGTGCGGCGCAGATGTT
TCTTAATGAGAGCGACGCCGTTGTTTTCAGGGGCGCAAATGGCCCGTGGAAAACCGACGACTTTGAATTCCACCTTCAACCCAAA
GAGGCGCAAAGCCTGATTGCCAAAGTGCTCAAAACCTTCGAGGAGAAGCACGGTGTGCCACCAAAGGAATTTTTCATCCACGGGT
GCACAACCTTCAACGAGGATGAATGGAAAGCCTTCAAAAAGGCCACGCCGAAGGGCACCAATCTTGTCGGCGTCCGCATCAAGGA
AACCAAAGGGGAATCCAAGCTGTTCCGTGATGGTGATTATCCGGTAATGAGGGGAACGGCCATCATTCTTGATCACCGAAACGCC
TTGCTGTGGACGAATGGATTTGTGCCACGGCTGGACACCTATATTGGGCCTGAGACGCCAAACCCGCTTTTGATAACCGTTCTGC
GTAGTACGGGTCGGCGACCTAACATTCGCACCGTTCTTGCTGACATCATGGGCCTTACCAAGATCAACTACAACGCCTGCAACTA
CAATGACGGATTGCCCGTCACGATCCGCTTTGCGAGCAAGGTGGGCGATGTGCTGACGATGGGTTCGGCACGCGACGCAGACAAA
CAGCCCCTGAAGTTCTACGTCTAG
In some cases, a nuclease can be from one or more CRISPR systems, or a variant or derivative thereof. A nuclease from a CRISPR system can be a Cas protein.
In S. pyogenes, Cas9 can generate a blunt-ended double-stranded break from about 1 bp to about 10 bp upstream of the protospacer-adjacent motif (PAM) via a process mediated by two catalytic domains in the protein: an HNH domain that cleaves the complementary strand of the DNA and a RuvC-like domain that cleaves the non-complementary strand. In some cases the double-stranded break is at about 3 bp upstream of the PAM. See Jinke et al., Science 337, 816-821 (2012) hereby incorporated by reference in its entirety. Cas9 proteins are known to exist in many Type II CRISPR systems including the following as identified in the supplementary information to Makarova et al., Nature Reviews, Microbiology, Vol. 9. June 2011, pp. 467-477: Methanococcus maripaludis C7: Corynebacterium diphtheriae; Corynebacterium efficiens YS-314; Corynebacterium glutamicum ATCC 13032 Kitasato; Corynebacterium glutamicum ATCC 13032 Bielefeld; Corynebacterium glutamicum R; Corynebacterium kroppenstedtii DSM 44385; Mycobacterium abscessus ATCC 19977; Nocardia farcinica IFM10152; Rhodococcus erythropolis PR4; Rhodococcus jastii RHA1; Rhodococcus opacus B4 uid36573; Acidothermus cellulolyticus 11B; Arthrobacter chlorophenolicus A6; Kribbella flavida DSM 17836 uid43465; Thermomonospora curvata DSM 43183; Bifidobacterium dentium Bd1; Bifidobacterium longum DJO10A; Slackia heliotrinireducens DSM 20476; Persephonella marina EX H1; Bacteroides fragilis NCTC 9434; Capnocytophaga ochracea DSM 7271; Flavobacterium psychrophilum JIP02 86; Akkermansia muciniphila ATCC BAA835; Roseiflexus castenholzii DSM 13941; Roseiflexus RS1; Synechocystis PCC6803; Elusimicrobium minutum Pei191; uncultured Termite group I bacterium phylotype Rs D17; Fibrobacter succinogenes S85; Bacillus cervus ATCC 10987; Listeria innocua; Lactobacillus casei; Lactobacillus rhamnosus GG; Lactobacillus salivarius UCC118; Streptococcus agalactiae A909: Streptococcus agalactiae NEM316; Streptococcus agalactiae 2603; Streptococcus dysgalactiae equisimilis GGS 124; Streptococcus equi zooepidemicus MGCS10565; Streptococcus gallolyticus UCN34 uid46061: Streptococcus gordonii Challis subst CH1: Streptococcus mutans NN2025 uid46353; Streptococcus mutans; Streptococcus pyogenes M1 GAS; Streptococcus pyogenes MGAS5005; Streptococcus pyogenes MGAS2096; Streptococcus pyogenes MGAS9429; Streptococcus pyogenes MGAS10270: Streptococcus pyogenes MGAS6180; Streptococcus pyogenes MGAS315; Streptococcus pyogenes SSI-1; Streptococcus pyogenes MGAS10750; Streptococcus pyogenes NZ131; Streptococcus thermophiles CNRZ1066; Streptococcus thermophiles LMD-9; Streptococcus thermophiles LMG 18311; Clostridium botulinum A3 Loch Maree; Clostridium botulinum B Eklund 171B; Clostridium botulinum Ba4 657; Clostridium botulinum F Langeland; Clostridium cellulolyticum H10: Finegoldia magna ATCC 29328; Eubacterium rectale ATCC 33656; Mycoplasma gallisepticum; Mycoplasma mobile 163K; Mycoplasma penetrans; Mycoplasma synoviae 53; Streptobacillus moniliformis DSM 12112; Bradyrhizobium BTAi1; Nitrobacter hamburgensis X14; Rhodopseudomonas palustris BisB 18; Rhodopseudomonas palustris B is B5; Parvibaculum lavamentivorans DS-1; Dinoroseobacter shibae DFL 12; Gluconacetobacter diazotrophicus Pal 5 FAPERJ; Gluconacetobacter diazotrophicus Pal 5 JGI; Azospirillum BS10 uid46085: Rhodospirillum rubrum ATCC 11170; Diaphorobacter TPSY uid29975; Verminephrobacter eiseniae EF01-2: Neisseria meningitides 053442: Neisseria meningitides alpha 14; Neisseria meningitides 72491; Desulfovibrio salexigens DSM 2638; Campylobacter jejuni doylei 269 97; Campylobacter jejuni 81116; Campylobacter jejuni; Campylobacter lari RM2100; Helicobacter hepaticus; Wolinella succinogenes; Tolumonas auensis DSM 9187; Pseudoalteromonas atlantica T6c; Shewanella pealeana ATCC 700345: Legionella pneumophila Paris; Actinobacillus succinogenes 130Z; Pasteurella multocida; Francisella tularensis novicida U112; Francisella tularensis holarctica; Francisella tularensis FSC 198; Francisella tularensis tularensis; Francisella tularensis WY96-3418; and Treponema denticola ATCC 35405. Accordingly, aspects of the present disclosure are directed to a Cas9 protein present in a Type II CRISPR system that are used in combination with the disclosed gene editing system. In some cases, a Cas can be used as a module in the RNase-H like domain containing peptide complex.
Non-limiting examples of Cas proteins can include Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9 (also known as Csn1 or Csx12), Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, Cas9HiFi, xCas9, CasX, CasY, CasRX, homologues thereof, or modified versions thereof. In some cases, alternatives to Cas can be utilized. For example, in some cases, a Cpf1 endonuclease can be used. Cpf1 can be phylogenetically close to bacterial and archaea Argonauts. For example, at a C-terminus of Cpf1 it may align with an Argonaute. A C terminus of Cpf1 can comprise a PIWI domain. In some cases, a catalytically dead Cas protein (e.g., dCas9) may also be used. A Cas can be partially catalytically dead. A Cas protein can have DNA or RNA cleavage activity. A CRISPR enzyme can direct cleavage of one or both strands at a target sequence, such as within a gene sequence and/or within a complement of a gene sequence. For example, a CRISPR enzyme can direct cleavage of one or both strands within or within about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, 100, 200, 500, or more base pairs from the first or last nucleotide of a protospacer adjacent motif (PAM) sequence. In some cases a Cas protein can be a high fidelity Cas protein such as Cas9HiFi. In some cases, a Cas can be a partially dead Cas such as a nickase.
TABLE 4
Streptococcus pyogenes Cas9 (SpCas9)
SEQ
ID NO Sequence 5′ to 3′
58 ATGGACTATAAGGACCACGACGGAGACTACAAGGATCATGATA
TTGATTACAAAGACGATGACGATAAGATGGCCCCAAAGAAGAA
GCGGAAGGTCGGTATCCACGGAGTCCCAGCAGCCGACAAGAAG
TACAGCATCGGCCTGGACATCGGCACCAACTCTGTGGGCTGGG
CCGTGATCACCGACG
In some cases, a Cas9 can be utilized. A Cas9 can refer to a polypeptide with at least or at least about 50%, 60%, 70%, 80%, 90%, 100% sequence identity and/or sequence similarity to a wild type exemplary Cas9 polypeptide (e.g., Cas9 from S. pyogenes). Cas9 can refer to a polypeptide with at most or at most about 50%, 60%, 70%, 80%, 90%, 100% sequence identity and/or sequence similarity to a wild type exemplary Cas9 polypeptide (e.g., from S. pyogenes). Cas9 can refer to the wild type or a modified form of the Cas9 protein that can comprise an amino acid change such as a deletion, insertion, substitution, variant, mutation, fusion, chimera, or any combination thereof. Cas9 can refer to a polypeptide with at least or at least about 50%, 60%, 70%, 80%, 90%, 100% sequence identity and/or sequence similarity to SEQ ID NO: 58.
While S. pyogenes Cas9 (SpCas9), Table 4, can be used as a CRISPR endonuclease for genome engineering, in some cases it will not be the best endonuclease for every target excision site. For example, the PAM sequence for SpCas9 (5′ NGG 3′) is abundant throughout the human genome, but a NGG sequence may not be positioned correctly to target a desired gene for modification. In some cases, a different endonuclease can be used to target certain genomic targets. In some cases, synthetic SpCas9-derived variants with non-NGG PAM sequences can be used. Additionally, other Cas9 orthologues from various species have been identified and these “non-SpCas9s” bind a variety of PAM sequences that could also be useful for the present invention. For example, the relatively large size of SpCas9 (approximately 4 kb coding sequence) means that plasmids carrying the SpCas9 cDNA cannot be efficiently expressed in a cell. Conversely, the coding sequence for Staphylococcus aureus Cas9 (SaCas9) is approximately 1 kilo base shorter than SpCas9, possibly allowing it to be efficiently expressed in a cell. Similar to SpCas9, the SaCas9 endonuclease is capable of modifying target genes in mammalian cells in vitro and in mice in vivo.
Alternatives to S. pyogenes Cas9 can include RNA-guided endonucleases from the Cpf1 family that display cleavage activity in mammalian cells. Unlike Cas9 nucleases, the result of Cpf1-mediated DNA cleavage is a double-strand break with a short 3′ overhang. Cpf1's staggered cleavage pattern can open up the possibility of directional gene transfer, analogous to traditional restriction enzyme cloning, which can increase the efficiency of gene editing. Like the Cas9 variants and orthologues described above, Cpf1 can also expand the number of sites that can be targeted by CRISPR to AT-rich regions or AT-rich genomes that lack the NGG PAM sites favored by SpCas9. In some cases, a nuclease may comprise a polynucleic acid-unwinding agent, such as a helicase. In other cases, a nuclease may not contain a DNA-unwinding agent. A nuclease that can unwind a polynucleic acid can be Cas or Cpf1.
In some cases, a nuclease can function in a transposon/transposase system. Transposable elements can be natural, non-viral gene delivery vehicles capable of mediating stable genomic integration and/or disruption. A transposon/transposase can be PiggyBac. PiggyBac can be made up of both a transposon cassette and a transposase. A PiggyBac, system transposon can modify a genome at a ‘TTAA’ site.
A nuclease can be codon optimized for expression in particular cells, such as eukaryotic cells. A polynucleotide encoding an endonuclease (e.g., an Argonaute) can be codon optimized for expression in particular cells, such as eukaryotic cells. This type of optimization can entail the mutation of foreign-derived (e.g., recombinant) nucleic acids to mimic the codon preferences of the intended host organism or cell while encoding the same protein.
Transposases may be symmetrically coordinated and exchange roles to alternately activate water and a 3′-OH for successive strand cleavage and transfer by a ping-pong mechanism.
In some embodiments. RNase-H specifically recognizes an A form RNA strand and a B form DNA strand.
A nuclease can bind and/or modify (e.g., cleave, methylate, demethylate, etc.) a target nucleic acid and/or a polypeptide associated with target nucleic acid. As described in further detail below, in some cases, a subject nuclease can have enzymatic activity that modifies target nucleic acid. Enzymatic activity may refer to nuclease activity, methyltransferase activity, demethylase activity. DNA repair activity. DNA damage activity, deamination activity, dismutase activity, alkylation activity, depurination activity, oxidation activity, pyrimidine dimer forming activity, integrase activity, transposase activity, recombinase activity, polymerase activity, ligase activity, helicase activity, photolyase activity or glycosylase activity. In other cases, a subject nuclease can have enzymatic activity that modifies a polypeptide associated with a target nucleic acid.
In some embodiments, in addition to or as a substitute for nucleic acid-cleaving activity, the compositions, polypeptides, methods, and systems described herein can also have a “pasting” function. Accordingly, the compositions, polypeptides, methods, and systems can be used to insert a nucleic acid into a target sequence in addition to or instead of cleaving the target nucleic acid. Such exemplary nucleic acid-insertion activities include, but are not limited to, integrase, flippase, transponase, and recombinase activity. Thus, exemplary polypeptides having such function (nucleic acid-insertion polypeptides) include integrases, recombinases, and flippases. These nucleic acid-insertion polypeptides can, for example, insert a nucleic acid sequence at a site that has been cleaved by a polypeptide of the present disclosure.
In some cases, an Argonaute nuclease, CRISPR nuclease, or RNase-H like nuclease can contain a nuclear localization sequence (NLS). A nuclear localization sequence can be from SV40. An NLS can be from at least one of: SV40, nucleoplasmin, importin alpha, C-myc, EGL-13, TUS, BORG, hnRNPA1, Mata2, or PY-NLS. An NLS can be on a C-terminus or an N-terminus of a nuclease polypeptide or nucleic acid. In some cases, a nuclease may contain from about 1 to about 10 NLS sequences. A nuclease can contain 1, 2, 3, 4, 5, 6.7, 8, 9, or up to 10 NLS sequences. A nuclease may contain a SV40 and nucleoplasmin NLS sequence. In some cases, an NLS can be from Simian Vacuolating Virus 40.
Unwinding Agents
In some cases, a nucleic acid unwinding agent may be utilized. A nucleic acid unwinding agent may be a polynucleic acid, protein, drug, or system that unwinds a nucleic acid. A nucleic acid unwinding agent can be energy. A nucleic acid unwinding agent can provide energy or heat. Unwinding can refer to the unwinding of a double helix (e.g., of DNA) as well as to unwinding a double-stranded nucleic acid to convert it to a single-stranded nucleic acid or to unwinding DNA from histones. In some embodiments, an unwinding agent is a helicase. In some embodiments, helicases are enzymes that bind nucleic acid or nucleic acid protein complexes. In some embodiments, a helicase is a DNA helicase. In some embodiments, a helicase is an RNA helicase. In some embodiments, a helicase unwinds a polynucleic acid at any position. In some cases, a position that is unwound is found within an immune checkpoint gene. In some cases, a position of a nucleic acid that is unwound encodes a gene involved in disease. In some embodiments, an unwinding agent is an ATPase, helicase, synthetic associated helicase, or topoisomerase.
In some embodiments, a nucleic acid unwinding agent functions by breaking hydrogen bonds between nucleotide base pairs in double-stranded DNA or RNA. In some cases, unwinding a nucleic acid (e.g., by breaking a hydrogen bond) requires energy. To break hydrogen bonds, nucleic acid unwinding agents can use energy stored in ATP. In some embodiments, a nucleic acid unwinding agent includes an ATPase. For example, a polypeptide with nucleic acid unwinding activity can comprise or be fused to an ATPase. In some embodiments, an ATPase is added to a cellular system.
In some embodiments, a nucleic acid unwinding agent is a polypeptide. For example, a nucleic acid unwinding peptide can be of prokaryotic origin, archaeal origin, or eukaryotic origin. In some embodiments, a nucleic acid unwinding polypeptide comprises a helicase domain, a topoisomerase domain, a Cas protein domain e.g., a Cas protein domain selected from the group consisting of: Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4. Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, Cas9HiFi, xCas9, CasX, CasY, CasRX or a catalytically dead nucleic acid unwinding domain such as a dCas domain (e.g., a dCas9 domain).
In some embodiments, a nucleic acid unwinding agent is a small molecule. For example, a small molecule nucleic acid unwinding agent can unwind a nucleic acid through intercalation, groove binding or covalent binding to the nucleic acid, or a combination thereof. Exemplary small molecule nucleic acid unwinding agents include, but are not limited to, 9-aminoacridine, quinacrine, chloroquine, acriflavin, amsacrine, (Z)-3-(acridin-9-ylamino)-2-(5-chloro-1,3-benzoxazol-2-yl)prop-2-enal, small molecules that can stabilize quadruplex structures, quarfloxin, quindoline, quinoline-based triazine compounds, BRACO-19, acridines, pyridostatin, and derivatives thereof.
In some embodiments, a polynucleic acid is unwound in a physical manner. A physical manner can include addition of heat or shearing for example. In some cases, a polynucleic acid such as DNA or RNA can be exposed to heat for nucleic acid unwinding. A DNA or RNA may denature at temperatures from about 50° C. to about 15° C. DNA or RNA denatures from about 50° C. to 60° C., from about 60° C. to about 70° C., from about 70° C. to about 80° C., from about 80° C. to about 90° C., from about 90 CC to about 100° C., from about 100° C. to about 110° C., from about 110° C. to about 120° C., from about 120° C. to about 130° C., from about 130° C. to about 140° C., from about 140° C. to about 150° C.
In some cases, a polynucleic acid can be denatured via changes in pH. For example, sodium hydroxide (NaOH) can be used to denature a polynucleic acid by increasing a pH to about 25 to about 29. In some cases, a polynucleic acid can be denatured via the addition of a salt.
In some cases, the disclosed editing system utilizing an unwinding agent can reduce a thermodynamic energetic requirement by about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 40%, 50%, or up to about 60% as compared to a system that does not employ the disclosed unwinding agent. In some cases, the disclosed editing system utilizing an unwinding agent can reduce an immune response to the unwinding agent by about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 40%, 50%, or up to about 60% as compared to a system that does not employ the disclosed unwinding agent. In some cases, an unwinding agent can be harvested from bacteria that are endogenously present in the human body to prevent eliciting an immune response.
Regulatory Domain Polypeptide (RDP)
In some cases, a regulatory domain polypeptide can be part of a nucleic acid editing system. An RDP can regulate a level of an activity, such as editing, of a nucleic acid editing system. Non-limiting examples of RDPs can include recombinases, epigenetic modulators, germ cell repair domains, or DNA repair proteins. In some cases, an RDP can be mined by screening for co-localized DNA repair proteins in a region comprising an RNase-H like domain containing polypeptide.
Exemplary recombinases that can be used as RDPs include Cre, Hin, Tre, or FLP recombinases. In some cases, recombinases involved in homologous recombination can be utilized. For example an RDP can be RadA, Rad51, RecA, Dmc1, or UvsX.
An epigenetic modulator can be a protein that can modify an epigenome directly through DNA methylation, post-translational modification of chromatin, or by altering a structure of chromatin.
Exemplary germ cell repair domains can include ATM, ATR, or DNA-PK to name a few. A germ cell repair domain can repair DNA damage though a variety of mechanisms such as nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), DNA double strand break repair (DSBR), and post replication repair (PRR).
An RDP can be a tunable component of a nucleic acid editing system. For example, an RDP can be swapped in the editing system to achieve a particular outcome. In some cases, an RDP can be selected based on a cell to be targeted, a level of editing efficiency that is sought, or in order to reduce off-target effects of a nucleic acid editing system. A dialing up or a tuning can enhance a parameter (efficiency, safety, speed, or accuracy) of a genomic break repair by about 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or up to about 100% as compared to a comparable gene editing system. A dialing down or a tuning can be performed by interchanging a domain such as an RDP to achieve a different effect during a genomic modification. For example, a different effect may be a skewing towards a particular genomic break repair, a recombination, an epigenetic modulation, or a high fidelity repair. In some cases, an RDP may be used to enhance a transgene insertion into a genomic break. In some cases, interchanging a module of a gene editing system can allow for HDR of a double strand break as opposed to NHEJ or MMEJ. Use of a gene editing system disclosed herein can allow for preferential HDR of a double strand break over that of comparable or alternate gene editing systems. In some cases, an HDR repair can preferentially occur in a population of cells from about 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70% 80% 90%, 95%, or up to about (10% over that which occurs in a comparable gene editing system without said RDP.
In some cases, the disclosed editing system utilizing an RDP can reduce a thermodynamic energetic requirement by about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 40%, 50%, or up to about 60% as compared to a system that does not employ the disclosed RDP. In some cases, the disclosed editing system utilizing an RDP can reduce an immune response to the RDP by about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 40%, 50%, or up to about 60% as compared to a system that does not employ the disclosed RDP. In some cases, an RDP can be harvested from bacteria that are endogenously present in the human body to prevent eliciting an immune response.
Guiding Polynucleic Acid
A guiding polynucleic acid can direct a gene editing system comprising an RHDC polypeptide-encoded protein to a genomic location. In some cases, a guiding polynucleic acid can be a DNA. In other cases, a guiding polynucleic acid can be RNA. A guiding polynucleic acid can be a combination of DNA and RNA. A guiding polynucleic acid can be single stranded, double stranded, or a combination thereof. A guiding polynucleic acid can be at least or at least about 5, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30 or more nucleotides long. A guiding polynucleotide can be at most or at most about 5, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30 or more nucleotides long. A guiding polynucleotide can be about 5, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30 or more nucleotides long. In some cases, a guiding polynucleic acid may be truncated, such as in Table 22. Truncated guiding polynucleic acids can be utilized to determine a minimum binding length.
A guiding polynucleic acid can be a guide RNA (i.e., “gRNA”) that can associate with and direct an RHDC polypeptide to a specific target sequence within a target nucleic acid by virtue of hybridization to a target site of the target nucleic acid. Similarly a guiding polynucleic acid can be a guide RNA (i.e., “gDNA”) that can associate with and direct an RHDC polypeptide to a specific target sequence within a target nucleic acid by virtue of hybridization to a target site of the target nucleic acid. In some cases, a guiding polynucleic acid can hybridize with a mismatch between a guiding polynucleic acid and a target nucleic acid. A guiding polynucleic acid can comprise at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 25, 30, 35, or up to 40 mismatches when hybridized to a target nucleic acid. In some cases, a guiding polynucleic acid can tolerate mismatches in a recruiting domain, for example at g6, g7, and g8. In some cases, a guiding polynucleic acid can contain mismatches in a stabilization domain. A stabilization domain can be adjacent to a 3′ end of a guiding molecule. For example, positions g6-g16, such as g6, g7, g8, g9, g10, g11, g12, g13, g14, g15, and g16 or any combination thereof, can be mismatched in 16 nucleotide long guide molecules. Mismatches in a recruiting domain can have mismatches preferably in positions g6, g7, and/or g8.
A method disclosed herein also can comprise introducing into a cell or embryo at least one guide RNA or nucleic acid, e.g., DNA encoding at least one guide RNA. A guide RNA can interact with a RNA-guided endonuclease to direct the endonuclease to a specific target site, at which site the 5′ end of the guide RNA base pairs with a specific protospacer sequence in a chromosomal sequence.
A guide RNA can comprise two RNAs, e.g., CRISPR RNA (crRNA) and transactivating crRNA (tracrRNA). A guide RNA can sometimes comprise a single-guide RNA (sgRNA) formed by fusion of a portion (e.g., a functional portion) of crRNA and tracrRNA. A guide RNA can also be a dual RNA comprising a crRNA and a tracrRNA. A guide RNA can comprise a crRNA and lack a tracrRNA. Furthermore, a crRNA can hybridize with a target DNA or protospacer sequence.
As discussed above, a guide RNA can be an expression product. For example, a DNA that encodes a guide RNA can be a vector comprising a sequence coding for the guide RNA. A guide RNA can be transferred into a cell or organism by transfecting the cell or organism with an isolated guide RNA or plasmid DNA comprising a sequence coding for the guide RNA and a promoter. A guide RNA can also be transferred into a cell or organism in other way, such as using virus-mediated gene delivery.
A guiding polynucleic acid can be isolated. For example, a guide RNA can be transfected in the form of an isolated RNA into a cell or organism. A guide RNA can be prepared by in vitro transcription using any in vitro transcription system. A guide RNA can be transferred to a cell in the form of isolated RNA rather than in the form of plasmid comprising encoding sequence for a guide RNA.
A guide RNA can comprise a DNA-targeting segment and a protein binding segment. A DNA-targeting segment (or DNA-targeting sequence, or spacer sequence) comprises a nucleotide sequence that can be complementary to a specific sequence within a target DNA (e.g., a protospacer). A protein-binding segment (or protein-binding sequence) can interact with a site-directed modifying polypeptide, e.g. an RNA-guided endonuclease such as a Cas protein. By “segment” it is meant a segment/section/region of a molecule, e.g., a contiguous stretch of nucleotides in RNA. A segment can also mean a region/section of a complex such that a segment can comprise regions of more than one molecule. For example, in some cases a protein-binding segment of a DNA-targeting RNA is one RNA molecule and the protein-binding segment therefore comprises a region of that RNA molecule. In other cases, the protein-binding segment of a DNA-targeting RNA comprises two separate molecules that are hybridized along a region of complementarity.
A guiding polynucleic acid can comprise two separate polynucleic acid molecules or a single polynucleic acid molecule. An exemplary single molecule guiding polynucleic acid (e.g., guide RNA) comprises both a DNA-targeting segment and a protein-binding segment.
In some cases, an RHDC polypeptide or portion thereof can form a complex with a guiding polynucleic acid. A guiding polynucleic acid can provide target specificity to a complex by comprising a nucleotide sequence that can be complementary to a sequence of a target nucleic acid. In some cases, a target nucleic acid can comprise at least a portion of a gene. In some cases, a target nucleic acid can be within an exon of a gene. In other cases, a target nucleic acid can be within an intron of a gene.
A guiding polynucleic acid can complex with an RHDC polypeptide to provide the RHDC polypeptide site-specific activity. In other words, an RHDC polypeptide can be guided to a target site within a single stranded target nucleic acid sequence e.g. a single stranded region of a double stranded nucleic acid, a chromosomal sequence or an extrachromosomal sequence, e.g. an episomal sequence, a minicircle sequence, a mitochondrial sequence, a chloroplast sequence, an ssRNA, an ssDNA, etc. by virtue of its association with a guiding polynucleic acid.
In some cases a guiding polynucleic acid can comprise one or more modifications (e.g., a base modification, a backbone modification), to provide the nucleic acid with a new or enhanced feature (e.g., improved stability). A guiding polynucleic acid can comprise a nucleic acid affinity tag. A nucleoside can be a base-sugar combination. A base portion of the nucleoside can be a heterocyclic base. The two most common classes of such heterocyclic bases can be purines and pyrimidines. Nucleotides can be nucleosides that further include a phosphate group covalently linked to a sugar portion of a nucleoside. For those nucleosides that include a pentofuranosyl sugar, a phosphate group can be linked to the 2′, the 3′, or the 5′ hydroxyl moiety of a sugar. In forming guiding polynucleic acids, a phosphate group can covalently link adjacent nucleosides to one another to form a linear polymeric compound. In addition, linear compounds may have internal nucleotide base complementarity and may therefore fold in a manner as to produce a fully or partially double-stranded compound. Within guiding polynucleic acids, a phosphate groups can commonly be referred to as forming a internucleoside backbone of a guiding polynucleic acid. The linkage or backbone of the guiding polynucleic acid can be a 3′ to 5′ phosphodiester linkage. In some cases, a guiding polynucleic acid can comprise nucleoside analogs, which can be oxy- or deoxy-analogues of a naturally-occurring DNA and RNA nucleosides deoxycytidine, deoxyuridine, deoxyadenosine, deoxyguanosine and thymidine. A guiding polynucleic acid can also include a universal base, such as deoxyinosine, or 5-nitroindole. A guiding polynucleic acid can comprise a modified backbone and/or modified internucleoside linkages. Modified backbones can include those that can retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone. Suitable modified guiding polynucleic acid backbones containing a phosphorus atom therein can include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates such as 3′-alkylene phosphonates, 5′-alkylene phosphonates, chiral phosphonates, phosphinates, phosphoramidates including 3′-amino phosphoramidate and aminoalkylphosphoramidates, phosphorodiamidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, selenophosphates, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs, and those having inverted polarity wherein one or more internucleotide linkages is a 3′ to 3′, a 5 to 5′ or a 2′ to 2′ linkage. Suitable guiding polynucleic acids having inverted polarity can comprise a single 3′ to 3′ linkage at the 3′-most internucleotide linkage (i.e. a single inverted nucleoside residue in which the nucleobase is missing or has a hydroxyl group in place thereof).
In some cases, a guiding polynucleic acid (e.g., a guide RNA) can also comprise a tail region at a 5′ or 3′ end that can be essentially single-stranded. For example, a tail region is sometimes not complementarity to any chromosomal sequence in a cell of interest and can sometimes not be complementary to the rest of a guide polynucleic acid. Further, the length of a tail region can vary. A tail region can be more than or more than about 4 nucleotides in length. For example, the length of a tail region can range from or from about 5 to from or from about 60 nucleotides in length.
In some cases, a guiding polynucleic acid can bind to a region of a genome adjacent to a protospacer adjacent motif (PAM). A guide nucleic acid can comprise a nucleotide sequence (e.g., a spacer), for example, at or near a 5′ end or 3′ end, that can hybridize to a sequence in a target nucleic acid (e.g., a protospacer). A spacer of a guide nucleic acid can interact with a target nucleic acid in a sequence-specific manner via hybridization (i.e., base pairing). A spacer sequence can hybridize to a target nucleic acid that is located 5′ or 3′ of a protospacer adjacent motif (PAM). The length of a spacer sequence can be at least or at least about 5, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30 or more nucleotides. The length of a spacer sequence can be at most or at most about 5, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30 or more nucleotides. In some cases, a guiding polynucleic acid can bind to a region from about 1 to about 20 base pairs adjacent to a PAM. In other cases, a guiding polynucleic acid can bind from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or up to 85 base pairs away from a PAM. Generally, a guiding polynucleic acid binding region can be designed to complement or substantially complement the target nucleic acid sequence or sequences. In some cases, a binding region of a guiding polynucleic acid can incorporate wobble or degenerate bases to bind multiple sequences. In some cases, the binding region can be altered to increase stability. For example, non-natural nucleotides can be incorporated to increase RNA resistance to degradation. In some cases, the binding region can be altered or designed to avoid or reduce secondary structure formation in the binding region. In some cases, the binding region can be designed to optimize G-C content. In some cases. G-C content is preferably between about 40% and about 60% (e.g., 40%, 45%, 50%, 55%, and 60%). In some cases, the binding region can contain modified nucleotides such as, without limitation, methylated or phosphorylated nucleotides.
In some cases, a guiding polynucleic acid can also comprise a double strand duplex region that can form a secondary structure. For example, a secondary structure formed by a guiding polynucleic acid can comprise a stem (or hairpin) and a loop. A length of a loop and a stem can vary. For example, a loop can range from about 3 to about 10 nucleotides in length, and a stem can range from about 6 to about 20 base pairs in length. A stem can comprise one or more bulges of 1 to about 10 nucleotides. The overall length of a second region can range from about 16 to about 60 nucleotides in length. For example, a loop can be or can be about 4 nucleotides in length and a stem can be or can be about 12 base pairs. In some cases, a 5′ stem-loop region can be between about 15 and about 50 nucleotides in length (e.g., about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or about 50 nucleotides in length). In some cases, a 5′ stem-loop region is between about 30-45 nucleotides in length (e.g., about 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 nucleotides in length). In some cases, a 5′ stem-loop region is at least about 31 nucleotides in length (e.g., at least about 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 nucleotides in length). In some cases, a 5′ stem-loop structure contains one or more loops or bulges, each loop or bulge of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides. In some cases, a 5′ stem-loop structure contains a stem of between about 10 and 30 complementary base pairs (e.g., 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 complementary base pairs). In some cases, a 5′ stem-loop structure can contain protein-binding, or small molecule-binding structures. In some cases, a 5′ stem-loop function (e.g., interacting or assembling with a guiding polynucleic acid-guided nuclease) can be conditionally activated by drugs, growth factors, small molecule ligands, or a protein that binds to the protein-binding structure of the 5′ stem-loop. In some cases, a 5′ stem-loop structure can contain non-natural nucleotides. For example, non-natural nucleotides can be incorporated to enhance protein-RNA interaction, protein DNA interaction, or to increase the thermal stability or resistance to degradation of the guiding polynucleic acid.
In some cases, a guiding polynucleic acid may have an intervening sequence between the 5′ and 3′ stem-loop structures that can be between about 10 and about 50 nucleotides in length (e.g., about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or about 50 nucleotides in length). In some cases, the intervening sequence is designed to be linear, unstructured, substantially linear, or substantially unstructured. In some embodiments, the intervening sequence can contain non-natural nucleotides. For example, non-natural nucleotides can be incorporated to enhance protein-RNA interaction or to increase the activity of the gRNA: nuclease complex. As another example, natural nucleotides can be incorporated to enhance the thermal stability or resistance to degradation of the gRNA. In some cases, a 3′ stem-loop structure can contain about 3, 4, 5, 6, 7, or 8 nucleotide loop and an about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotide or longer stem. In some cases, the 3′ stem-loop can contain a protein-binding, small molecule-binding, hormone-binding, or metabolite-binding structure that can conditionally stabilize the secondary and/or tertiary structure of the gRNA. In some embodiments, the 3′ stem-loop can contain non-natural nucleotides. For example, non-natural nucleotides can be incorporated to enhance protein-guiding nucleic acid interaction or to increase the activity of the guiding polynucleic acid: nuclease complex. As another example, natural nucleotides can be incorporated to enhance the thermal stability or resistance to degradation of the gRNA or gDNA.
In some cases, a guiding polynucleic acid can include a termination structure at its 3′ end. In some cases, a guiding polynucleic acid can include an additional 3′ hairpin structure, e.g., before the termination structure, that can interact with proteins, small-molecules, hormones, or the like, for stabilization or additional functionality, such as conditional stabilization or conditional regulation of a guiding polynucleic acid: nuclease assembly or activity. In some cases, a guiding polynucleic acid can be optimized to enhance stability, assembly, and/or expression. In some case, a guiding polynucleic acid can be optimized to enhance the activity of a guiding polynucleic acid: nuclease complex as compared to control or comparable guiding polynucleic acid: nuclease structures (gRNA, CRISPR RNP, unmodified gRNA, or unmodified guiding polynucleic acids). In some cases, a guiding polynucleic acid can be optimized for expression by substituting, deleting, or adding one or more nucleotides. In some cases, a nucleotide sequence that provides inefficient transcription from an encoding template nucleic acid can be deleted or substituted. For example, in some cases, a guiding polynucleic acid can be transcribed from a nucleic acid operably linked to an RNA polymerase III promoter. In some cases, a guiding polynucleic acid can be modified for increased stability. Stability can be enhanced by optimizing the stability of the guiding polynucleic acid: nuclease interaction, optimizing assembly of the guiding polynucleic acid: nuclease complex, removing or altering RNA or DNA destabilizing sequence elements, or adding RNA or DNA stabilizing sequence elements. In some embodiments, a guiding polynucleic acid can contain a 5′ stem-loop structure proximal to, or adjacent to, the binding region that interacts with the guiding polynucleic acid-guided nuclease. Optimization of the 5′ stem-loop structure can provide enhanced stability or assembly of the guiding polynucleic acid: nuclease complex. In some cases, the 5′ stem-loop structure is optimized by increasing the length of the stem portion of the stem-loop structure. For example, a 5′ stem-loop optimization can be combined with mutations for increased transcription to provide an optimized guiding polynucleic acid. For example, an A-U flip and an elongated stem loop can be combined to provide an optimized guiding polynucleic acid.
A double stranded-guiding polynucleic acid duplex region can comprise a protein-binding segment that can form a complex with an RNA or DNA-binding protein, such as an Argonaute protein, polypeptide, or functional portion thereof.
In some cases, a guiding polynucleic acid can comprise a modification. A modification can be a chemical modification. A modification can be selected from 5′adenylate, 5′ guanosine-triphosphate cap, 5′N7-Methylguanosine-triphosphate cap, 5′triphosphate cap, 3′phosphate, 3′thiophosphate, 5′phosphate, 5′thiophosphate, Cis-Syn thymidine dimer, trimers, C12 spacer. C3 spacer. C6 spacer, dSpacer, PC spacer, rSpacer, Spacer 18, Spacer 9,3′-3′ modifications, 5′-5′ modifications, abasic, acridine, azobenzene, biotin, biotin BB, biotin TEG, cholesteryl TEG, desthiobiotin TEG, DNP TEG, DNP-X, DOTA, dT-Biotin, dual biotin. PC biotin, psoralen C2, psoralen C6, TINA, 3′DABCYL, black hole quencher 1, black hole quencher 2, DABCYL SE, dT-DABCYL, IRDye QC-1, QSY-21, QSY-35, QSY-7, QSY-9, carboxyl linker, thiol linkers, 2′deoxyribonucleoside analog purine, 2′deoxyribonucleoside analog pyrimidine, ribonucleoside analog, 2′-O-methyl ribonucleoside analog, sugar modified analogs, wobble/universal bases, fluorescent dye label, 2′fluoro RNA, 2′O-methyl RNA, methylphosphonate, phosphodiester DNA, phosphodiester RNA, phosphothioate DNA, phosphorothioate RNA, UNA, pseudouridine-5′-triphosphate, 5-methylcytidine-5′-triphosphate, 2-O-methyl 3phosphorothioate or any combinations thereof. A modification can be a pseudouridine modification. In some cases, a modification cannot affect viability.
In some cases, a modification is a 2-O-methyl 3 phosphorothioate addition. A 2-O-methyl 3 phosphorothioate addition can be performed from 1 base to 150 bases. A 2-O-methyl 3 phosphorothioate addition can be performed from 1 base to 4 bases. A 2-O-methyl 3 phosphorothioate addition can be performed on 2 bases. A 2-O-methyl 3 phosphorothioate addition can be performed on 4 bases. A modification can also be a truncation. A truncation can be a 5 base truncation. Guiding polynucleic acids can be modified by methods known in the art. In some cases, the modifications can include, but are not limited to, the addition of one or more of the following sequence elements: a 5′ cap (e.g., a 7-methylguanylate cap); a 3′ polyadenylated tail; a riboswitch sequence; a stability control sequence; a hairpin; a subcellular localization sequence: a detection sequence or label: or a binding site for one or more proteins. Modifications can also include the introduction of non-natural nucleotides including, but not limited to, one or more of the following: fluorescent nucleotides and methylated nucleotides. In some embodiments, a guiding polynucleic acid can contain from 5′ to 3′: (i) a binding region of between about 10 and about 50 nucleotides; (ii) a 5′ hairpin region containing fewer than four consecutive uracil nucleotides, or a length of at least 31 nucleotides (e.g., from about 31 to about 41 nucleotides); (iii) a 3′ hairpin region; and (iv) a transcription termination sequence, wherein the small guide RNA is configured to form a complex with a guiding polynucleic acid-guided nuclease, the complex having increased stability or activity relative to an unmodified complex.
A guide RNA or guide DNA can target a nucleic acid sequence of or of about 20 nucleotides. A target nucleic acid can be less than or less than about 20 nucleotides. A target nucleic acid can be at least or at least about 5, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30 or more nucleotides. A target nucleic acid can be at most or at most about 5, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30 or more nucleotides. A target nucleic acid sequence can be or can be about 20 bases immediately 5′ of the first nucleotide of the PAM. A guide RNA or guide DNA can target a nucleic acid sequence comprising a gene or portion thereof.
A guide RNA or guide DNA can target a genomic sequence comprising a gene. A gene that can be targeted can be involved in a disease. A disease can be a cancer, a cardiovascular condition, a reproductive condition, a neurological disease, an immunological disease, an organ condition, degeneration, an ocular condition, diabetes, a vascular condition, or a gastrointestinal condition.
A gene that can be disrupted can be a member of a family of genes. For example, a gene that can be disrupted can improve therapeutic potential of cancer immunotherapy. A gene that can be disrupted can ameliorate one or more symptoms or complications associated with human genetic diseases.
A gene that can be disrupted can be involved in attenuating TCR signaling, functional avidity, or immunity to cancer. In some cases, a gene to be disrupted is upregulated when a TCR is stimulated. A gene can be involved in inhibiting cellular expansion, functional avidity, or cytokine polyfunctionality. A gene can be involved in negatively regulating cellular cytokine production. For example, a gene can be involved in inhibiting production of effector cytokines. IFN-gamma and/or TNF for example. A gene can also be involved in inhibiting expression of supportive cytokines such as IL-2 after TCR stimulation.
A disease can be a neoplasia. Genes associated with neoplasia can be: PTEN; ATM; ATR; EGFR; ERBB2; ERBB3; ERBB4; Notch1; Notch2; Notch3; Notch4; AKT; AKT2; AKT3; HIF; HIF1a; HIF3a; Met; HRG; Bcl2; PPAR alpha; PPAR gamma; WT1 (Wilms Tumor); FGF Receptor Family members (5 members: 1, 2, 3, 4, 5); CDKN2a; APC; RB (retinoblastoma); MEN1; VHL; BRCA1; BRCA2; AR (Androgen Receptor); TSG101; IGF; IGF Receptor; Igf1 (4 variants); Igf2 (3 variants): Igf 1 Receptor; Igf 2 Receptor; Bax; Bcl2: caspases family (9 members: 1, 2, 3, 4, 6, 7, 8, 9, 12); Kras; Apc. A disease can be age-related macular degeneration. Genes associated with macular degeneration can be: Abcr; Ccl2; Cc2; cp (ceruloplasmin); Timp3; cathepsinD; Vidir; Ccr2. A disease can be schizophrenia. Genes associated with schizophrenia can be: Neuregulin1 (Nrg1); Erb4 (receptor for Neuregulin); Complexin1 (Cptx1); Tph1 Tryptophan hydroxylase; Tph2 Tryptophan hydroxylase 2; Neurexin 1; GSK3; GSK3a; GSK3b. A disorder can be associated with a gene such as: 5-HTT (Slc6a4): COMT; DRD (Drd1a); SLC6A3; DAOA; DTNBP1; Dao (Dao1). A disease can be a trinucleotide repeat disorder. A trinucleotide repeat disorder can be associated with genes such as: HTT (Huntington's Dx): SBMA/SMAX1/AR (Kennedy's Dx); FXN/X25 (Friedrich's Ataxia); ATX3 (Machado-Joseph's Dx); ATXN1 and ATXN2 (spinocerebellar ataxias); DMPK (myotonic dystrophy); Atrophin-1 and Atn1 (DRPLA Dx); CBP (Creb-BP—global instability); VLDLR (Alzheimer's); Aixn7; Atxn10. A disease can be fragile X syndrome. Genes associated with fragile X syndrome can be: FMR2; FXR1; FXR2; mGLUR5. A disease can be secretase related with associated genes selected from: APH-1 (alpha and beta); Presenilin (Psen1); nicastrin, (Ncstn); PEN-2; Nos1; Parp1; Nat1; Nat2. A disease can be a prion related disorder with relevant genes being selected from: Prp. A disease can be ALS with relevant genes being: SOD1; ALS2; STEX; FUS; TARDBP; VEGF (VEGF-a; VEGF-b; VEGF-c). A disease can be drug addiction with relevant genes being; Prkce (alcohol): Drd2; Drd4; ABAT (alcohol); GRIA2; Grm5; Grin1; Htr1b; Grin2a; Drd3; Pdyn; Gria1 (alcohol). A disease can be autism with relevant genes being selected from: Mecp2; BZRAP1; MDGA2; Sema5A; Neurexin 1; Fragile X (FMR2 (AFF2); FXR1; FXR2; Mglur5). A disease can be Alzheimer's disease with relevant genes being selected from: E1; CHIP; UCH; UBB; Tau; LRP; PICALM; Clusterin; PS1; SORL1; CR1; Vldlr; Uba1; Uba3; CHIP28 (Aqp1, Aquaporin 1); Uchl1; Uchl3; APP. A disease can be inflammation with relevant genes being selected from: IL-10; IL-1 (IL-1a; IL-1b); IL-13; IL-17 (IL-17a (CTLA8); IL-17b; IL-17c; IL-17d; IL-17f); Il-23; Cx3cr1; ptpn22; TNFa; NOD2/CARD15 for IBD; IL-6; IL-12 (IL-12a; IL-12b); CTLA4; Cx3c11. A disease can be Parkinson's disease with relevant genes being selected from: x-Synuclein; DJ-1; LRRK2; Parkin; PINK1. A disease can be a blood and coagulation disorders: Anemia (CDAN1, CDA1, RPS19, DBA, PKLR, PK1, NT5C3, UMPH1, PSN1, RHAG, RH50A, NRAMP2, SPTB, ALAS2, ANH1, ASB, ABCB7, ABC7, ASAT); Bare lymphocyte syndrome (TAPBP, TPSN, TAP2, ABCB3, PSF2, RING11, MHC2TA, C2TA, RFX5, RFXAP, RFX5), Bleeding disorders (TBXA2R, P2RX1, P2X1): Factor H and factor H-like 1 (HF1, CFH, HUS); Factor V and factor VIII (MCFD2); Factor VII deficiency (F7); Factor X deficiency (F10); Factor XI deficiency (F11); Factor XII deficiency (F12, HAF); Factor XIIIA deficiency (F13A1, F13A); Factor XIIIB deficiency (F13B); Fanconi anemia (FANCA, FACA, FA1, FA, FAA, FAAP95, FAAP90, FLJ34064, FANCB, FANCC, FACC, BRCA2, FANCD1, FANCD2, FANCD, FACD, FAD, FANCE, FACE, FANCF, XRCC9, FANCG, BRIP1, BACH1, FANCJ, PHF9, FANCL, FANCM, KIAA159); Hemophagocytic lymphohistiocytosis disorders (PRF1, HPLH2. UNC13D, MUNC13-4. HPLH3, HLH3, FHL3); Hemophilia A (F8, FSC, HEMA); Hemophilia B (F9, HEMB), Hemorrhagic disorders (PI, ATT, F5); Leukocyde deficiencies and disorders (ITGB2, CD18, LCAMB, LAD, EIF2B1, EIF2BA, EIF2B2, EIF2B3, EIF2B5, LVWM, CACH, CLE, EIF2B4); Sickle cell anemia (HBB); Thalassemia (HBA2, HBB, HBD, LCRB, HBA1). Cell dysregulation and oncology diseases and disorders: B-cell non-Hodgkin lymphoma (BCL7A, BCL7); Leukemia (TAL1 TCL5, SCL, TAL2, FLT3, NBS1, NBS, ZNFN1A1, IK1, LYF1, HOXD4, HOX4B, BCR, CML, PHL, ALL, ARNT, KRAS2, RASK2, GMPS, AF10, ARHGEF12, LARG, KTAA0382, CALM, CLTH, CEBPA, CEBP, CHIC2, BTL, FLT3, KIT, PBT, LPP, NPM1, NUP214, D9S46E, CAN, CAIN, RUNX1, CBFA2, AML, WHSCIL1, NSD3, FLT3, AF1Q, NPM1, NUMA1, ZNF145, PLZF, PML, MYL, STAT5B, AF10, CALM, CLTH, ARL11, ARLTS1, P2RX7, P2X7, BCR, CML, PHL, ALL, GRAF, NF1, VRNF, WSS, NFNS, PTPN11, PTP2C, SHP2, NS1, BCL2, CCND1, PRAD1, BCL1, TCRA, GATA1, GF1, ERYF1, NFE1, ABL1, NQO1, DIA4, NMOR1, NUP214, D9S46E, CAN, CAIN). A disease can be an inflammation and/or an immune related diseases and disorders: AIDS (KIR3DL1, NKAT3, NKB1, AMB11, KIR3DS1, IFNG, CXCL12, SDF1); Autoimmune lymphoproliferative syndrome (TNFRSF6, APT1, FAS, CD95, ALPS1A); Combined immunodeficiency, (IL2RG, SCIDX1, SCIDX, IMD4); HIV-1 (CCLS, SCYA5, D17S136E, TCP228), HIV susceptibility or infection (IL10, CSIF, CMKBR2, CCR2, CMKBR5, CCCKR5 (CCR5)); Immunodeficiencies (CD3E, CD3G, AICDA, AID, HIGM2, TNFRSF5, CD40, UNG, DGU, HIGM4, TNFSF5, CD40LG, HIGM1, IGM, FOXP3, IPEX, AIID, XPTD, PIDX, TNFRSF14B, TACI); Inflammation (IL-10, IL-1 (IL-1a, IL-1b), IL-13, IL-17 (IL-17a (CTLA8), IL-17b, IL-17c, IL-17d, IL-17f), 11-23, Cx3cr1, ptpn22, TNFa, NOD2/CARD15 for IBD, IL-6, IL-12 (IL-12a, IL-12b), CTLA4, Cx3c11); Severe combined immunodeficiencies (SCIDs)(JAK3, JAKL, DCLRE1C, ARTEMIS, SCIDA, RAG1, RAG2, ADA, PTPRC, CD45, LCA, IL7R, CD3D, T3D, IL2RG, SCIDX1, SCIDX, IMD4). A disease can be metabolic, liver, kidney and protein diseases and disorders: Amyloid neuropathy (TTR, PALB); Amyloidosis (APOA1, APP, AAA, CVAP, AD1, GSN, FGA, LYZ, TTR, PALB); Cirrhosis (KRT18, KRT8, CIRH1A, NAIC, TEX292, KIAA1988); Cystic fibrosis (CFTR, ABCC7, CF, MRP7); Glycogen storage diseases (SLC2A2, GLUT2, G6PC, G6PT, G6PT1, GAA, LAMP2, LAMPB, AGL, GDE, GBE1, GYS2, PYGL, PFKM); Hepatic adenoma, 142330 (TCF1, HNF1A, MODY3), Hepatic failure, early onset, and neurologic disorder (SCOD1, SCO1), Hepatic lipase deficiency (LIPC), Hepatoblastoma, cancer and carcinomas (CTNNB1, PDGFRL, PDGRL, PRLTS, AXIN1, AXIN, CTNNB1, TP53, PS3, LFS1, IGF2R, MPRI, MET, CASP8, MCH5; Medullary cystic kidney disease (UMOD, HNFJ, FJHN, MCKD2, ADMCKD2); Phenylketonuria (PAH, PKU1, QDPR, DHPR, PTS); Polycystic kidney and hepatic disease (FCYT, PKHD1, ARPKD, PKD1, PKD2, PKD4, PKDTS, PRKCSH, G19P1, PCLD, SEC63). A disease can be muscular/skeletal diseases and disorders: Becker muscular dystrophy (DMD, BMD, MYF6), Duchenne Muscular Dystrophy (DMD, BMD); Emery-Dreifuss muscular dystrophy (LMNA, LMN1, EMD2, FPLD, CMD1A, HGPS, LGMD1B, LMNA, LMN1, EMD2, FPLD, CMD1A); Facioscapulohumeral muscular dystrophy (FSHMD1A, FSHD1A); Muscular dystrophy (FKRP, MDC1C, LGMD21, LAMA2, LAMM, LARGE, KIAA060K), MDC1D, FCMD, TTID, MYOT, CAPN3, CANP3, DYSF, LGMD2B, SGCG, LGMD2C, DMDA1, SCO3, SGCA, ADL, DAG2, LGMD2D, DMDA2, SGCB, LGMD2E, SGCD, SGD, LGMD2F, CMD1L, TCAP, LGMD2G, CMD1N, TRIM32, HT2A, LGMD2H, FKRP, MDC1C, LGMD21, TTN, CMD1G, TMD, LGMD2J, POMT1, CAV3, LGMD1C, SEPN1, SELN, RSMD1, PLEC1, PLTN, EBS1); Osteopetrosis (LRP5, BMND1, LRP7, LR3, OPPG, VBCH2, CLCN7, CLC7, OPTA2, OSTM1, GL, TCIRG1, TIRC7, OCt16, OPTB1); Muscular atrophy (VAPB, VAPC, ALS8, SMN1, SMA1, SMA2, SMA3, SMA4, BSCL2, SPG17, GARS, SMAD1, CMT2D, HEXB, IGHMBP2, SMUBP2, CATF1, SMARD1). A disease can be neurological and neuronal diseases and disorders: ALS (SOD1, ALS2, STEX, FUS, TARDBP, VEGF (VEGF-a, VEGF-b, VEGF-c); Alzheimer disease (APP, AAA, CVAP, AD1, APOE, AD2, PSEN2, AD4, STM2, APBB2, FE65L1, NOS3, PLAU, URK, ACE, DCP1, ACE1, MPO, PACIP1, PAXIP1L, PTIP, A2M, BLMH, BMH, PSEN1, AD3); Autism (Mecp2, BZRAP1, MDGA2, Sema5A, Neurexin 1, GLO1, MECP2, RTT, PPMX, MRX16, MRX79, NLGN3, NLGN4, KIAA1260, AUTSX2); Fragile X Syndrome (FMR2, FXR1, FXR2, mGLUR5); Huntington's disease and disease like disorders (HD, IT15, PRNP, PRIP, JPH3, JP3, HDL2, TBP, SCA17); Parkinson disease (NR4A2, NURR1, NOT, TINUR, SNCAIP, TBP, SCA17, SNCA, NACP, PARK1, PARK4, DJ1, PARK7, LRRK2, PARK8, PINK1, PARK6, UCHL1, PARK5, SNCA, NACP, PARK1, PARK4, PRKN, PARK2, PDJ, DBH, NDUFV2); Rett syndrome (MECP2, RTT, PPMX, MRX16, MRX79, CDKL5, STK9, MECP2, RTT, PPMX, MRX16, MRX79, x-Synuclein. DJ-1); Schizophrenia (Neuregulin1 (Nrg1), Erb4 (receptor for Neuregulin), Complexin1 (Cp1x1), Tph1 Tryptophan hydroxylase, Tph2, Tryptophan hydroxylase 2, Neurexin 1, GSK3, GSK3a, GSK3b, 5-HTT (Slc6a4), COMT, DRD (Drd1a), SLC6A3, DAOA, DTNBP1, Dao (Dao1)); Secretase Related Disorders (APH-1 (alpha and beta), Presenilin (Psen1), nicastrin, (Ncstn), PEN-2, Nos1, Parp1, Nat1, Nat2); Trinucleotide Repeat Disorders (HTT (Huntington's Dx), SBMA/SMAX1/AR (Kennedy's Dx), FXN/X25 (Friedrich's Ataxia), ATX3 (Machado-Joseph's Dx), ATXN1 and ATXN2 (spinocerebellar ataxias), DMPK (myotonic dystrophy), Atrophin-1 and Atn1 (DRPLA Dx), CBP (Creb-BP—global instability), VLDLR (Alzheimer's), Atxn7, Atxn10). A disease can be an Ocular disease and/or disorder: Age-related macular degeneration (Abcr, Ccl2, Cc2, cp (ceruloplasmin), Timp3, cathepsinD, Vidlr, Ccr2); Cataract (CRYAA, CRYA1, CRYBB2, CRYB2, PITX3, BFSP2, CP49, CP47, CRYAA, CRYA1, PAX6, AN2, MGDA, CRYBA1, CRYB1, CRYGC, CRYG3, CCL, LIM2, MP19, CRYGD, CRYG4, BFSP2, CP49, CP47, HSF4, CTM, HSF4, CTM, MIP, AQP0, CRYAB, CRYA2, CTPP2, CRYBB1, CRYGD, CRYG4, CRYBB2, CRYB2. CRYGC, CRYG3, CCL, CRYAA, CRYA1, GJA8, CX50, CAE1, GJA3, CX46, CZP3, CAE3, CCM1, CAM, KRIT1); Corneal clouding and dystrophy (APOA1, TGFB1, CSD2, CDGG1, CSD, BIGH3, CDG2, TACSTD2, TROP2, M1S1, VSX1, RINX, PPCD, PPD, KTCN, COL8A2, FECD, PPCD2, PIP5K3, CFD); Cornea plana congenital (KERA, CNA2); Glaucoma (MYOC, TIGR, GLC1A, JOAG, GPOA, OPTN, GLC1E, FIP2, HYPL, NRP, CYP1B1, GLC3A, OPA1, NTG, NPG, CYP1B1, GLC3A); Leber congenital amaurosis (CRB1, RP12, CRX, CORD2, CRD, RPGRIP1, LCA6, CORD9, RPE65, RP20, AIPL1, LCA4, GUCY2D, GUC2D, LCA1, CORD6, RDH12, LCA3); Macular dystrophy (ELOVL4, ADMD, STGD2, STGD3, RDS, RP7, PRPH2, PRPH, AVMD, AOFMD, VMD2).
In some cases a disease that can be treated with the disclosed editing system can be associated with a cellular condition. For example, genes associated with cellular performance may be disrupted with the disclosed editing system: PI3K/AKT Signaling: PRKCE; ITGAM; TTGA5; IRAK1; PRKAA2; EIF2AK2; PTEN; ETF4E; PRKCZ; GRK6; MAPK1; TSC1; PLK1; AKT2; IKBKB; PIK3CA; CDK8; CDKN1B; NFKB2; BCL2; PIK3CB; PPP2R1A; MAPK8; BCL2L1; MAPK3; TSC2; ITGA1; KRAS; EIF4EBP1; RELA; PRKCD; NOS3; PRKAA1; MAPK9; CDK2; PPP2CA; PIM1; ITGB7; YWHAZ; ILK; TPS3; RAF1; IKBKG; RELB; DYRK1A; CDKN1A; ITOB1; MAP2K2; JAK1; AKT1; JAK2; PIK3R1; CHUK; PDPK1; PPP2R5C; CTNNB1; MAP2K1; NFKB1; PAK3; ITGB3; CCND1; GSK3A; FRAP1; SFN; ITGA2; TTK; CSNK1A1; BRAF; GSK3B; AKT3; FOXO1; SGK; HSP90AA1; RPS6KB1. For example, ERK/MAPK Signaling: PRKCE; ITGAM; ITGA5; HSPB1; IRAK1; PRKAA2; EIF2AK2; RAC1; RAP1A; TLN1; E1F4E; ELK1; GRK6; MAPK1; RAC2; PLK1; AKT2; PIK3CA; CDK8; CREB1; PRKC1; PTK2; FOS; RPS6KA4; PTK3CB; PPP2R1A; PIK3C3; MAPK8; MAPK3; ITGA1; ETS; KRAS; MYCN; EIF4EBP1; PPARG; PRKCD; PRKAA1; MAPK9; SRC; CDK2; PPP2CA; PIM1; PIK3C2A; ITGB7; YWHAZ; PPP1CC; KSR1; PXN; RAF1; FYN; DYRK1A; ITGB1; MAP2K2; PAK4; PIK3R1; STAT3; PPP2R5C; MAP2K1; PAK3; ITGB3; ESR1; ITGA2; MYC; TTK; CSNK1A1; CRKL; BRAF; ATF4; PRKCA; SRF; STAT1; SGK. Glucocorticoid Receptor Signaling: RAC1; TAF4B; EP300; SMAD2; TRAF6; PCAF; ELK1; MAPK1; SMAD3; AKT2; IKBKB; NCOR2; UBE2I; PTK3CA; CREB1; FOS; HSPA5; NFKB2; BCL2; MAP3K14; STAT5B; PIK3CB; PIK3C3; MAPK8; BCL2L1; MAPK3; TSC22D3; MAPK10; NRIP1; KRAS; MAPK13; RELA; STAT5A; MAPK9; NOS2A; PBX1; NR3C1; PIK3C2A; CDKN1C; TRAF2; SERPINE1; NCOA3; MAPK14; TNF; RAF1; IKBKG; MAP3K7; CREBBP; CDKN1A; MAP2K2; JAK1; IL8; NCOA2; AKT1; JAK2; PIK3R1; CHUK; STAT3; MAP2K1; NFKB1; TGFBR1; ESR1; SMAD4; CEBPB; JUN; AR; AKT3; CCL2; MMP1; STAT1; IL6; HSP90AA1. Axonal Guidance Signaling: PRKCE; ITGAM; ROCK1; ITGA5; CXCR4; ADAM12; IGF1; RAC1; RAP1A; EIF4E; PRKCZ; NRP1; NTRK2; ARHGEF7; SMO; ROCK2; MAPK1; PGF; RAC2; PTPN11; GNAS; AKT2; PIK3CA; ERBB2; PRKCE; PTK2; CFL1; GNAQ; PIK3CB; CXCL12; PIK3C3; WNT11; PRKD1; GNB2L1; ABL1; MAPK3; ITGA1; KRAS; RHOA; PRKCD; PIK3C2A; ITGB7; GL12; PXN; VASP; RAF1; FYN; ITGB1; MAP2K2; PAK4; ADAM17; AKT1; PIK3R1; GLI1; WNTSA; ADAM10; MAP2K1; PAK3; ITGB3; CDC42; VEGFA; ITGA2; EPHA8; CRKL; RND1; GSK3B; AKT3; PRKCA. Ephrin Receptor Signaling: PRKCE; ITGAM; ROCK1; ITGA5; CXCR4; IRAK1; PRKAA2; E1F2AK2; RAC1; RAP1A; GRK6; ROCK2; MAPK1; PGF; RAC2; PTPN11; GNAS; PLK1; AKT2; DOK1; CDK8; CREB1; PTK2; CFL1; GNAQ; MAP3K14; CXCL12; MAPK8; GNB2L1; ABL1; MAPK3; ITGA1; KRAS; RHOA; PRKCD; PRKAA1; MAPK9; SRC; CDK2; PIM1; ITGB7; PXN; RAF1; FYN; DYRK1A; ITGB1; MAP2K2; PAK4, AKT1; JAK2; STAT3; ADAM10; MAP2K; PAK3; ITGB3; CDC42; VEGFA; ITGA2; EPHA8; TTK; CSNK1A1; CRKL; BRAF; PTPN13; ATF4; AKT3; SGK. Actin Cytoskeleton Signaling: ACTN4; PRKCE; ITGAM; ROCK1; TTGA5; IRAK1; PRKAA2; EIF2AK2; RAC1; INS; ARHGEF7; GRK6; ROCK2; MAPK1; RAC2; PLK1; AKT2; PIK3CA; CDK8; PTK2; CFL1; PIK3CB; MYH9; DIAPH1; PIK3C3; MAPK8; F2R; MAPK3; SLC9A1; ITGA1; KRAS; RHOA; PRKCD; PRKAA1; MAPK9; CDK2; PIM1; PIK3C2A; ITGB7; PPP1CC; PXN; VIL2; RAF1; GSN; DYRK1A; ITGB1; MAP2K2; PAK4; PIP5K1A; PIK3R1; MAP2K1; PAK3; ITGB3; CDC42; APC; ITGA2; TTK; CSNK1A1; CRKL; BRAF; VAV3; SGK. Huntington's Disease Signaling: PRKCE; IGF1; EP300; RCOR1; PRKCZ; HDAC4; TGM2; MAPK1; CAPNS1; AKT2; EGFR; NCOR2; SP1; CAPN2; PIK3CA; HDAC5; CREB1; PRKC1; HSPA5; REST; GNAQ; PIK3CB; PIK3C3; MAPK8; IGF1R; PRKD1; GNB2L1; BCL2L1; CAPN1; MAPK3; CASP8; HDAC2; HDAC7A; PRKCD; HDAC11; MAPK9; HDAC9; PIK3C2A; HDAC3; TP53; CASP9; CREBBP; AKT1 PIK3R1; PDPK1; CASP1; APAF1; FRAP1; CASP2; JUN; BAX; ATF4; AKT3; PRKCA; CLTC; SGK; HDAC6; CASP3. Apoptosis Signaling: PRKCE; ROCK1; BID; IRAK1; PRKAA2; E1F2AK2; BAK1; BIRC4; GRK6; MAPK1; CAPNS1; PLK1; AKT2; IKBKB; CAPN2; CDK8; FAS; NFKB2; BCL2; MAP3K14; MAPK8; BCL2L1; CAPN1; MAPK3; CASP8; KRAS; RELA; PRKCD; PRKAA1; MAPK9; CDK2; PIM1; TPS3; TNF; RAF1; IKBKG; RELB; CASP9; DYRK1A; MAP2K2; CHUK; APAF1; MAP2K; NFKB1; PAK3; LMNA; CASP2; BIRC2; TTK; CSNK1A 1; BRAF; BAX; PRKCA; SGK; CASP3; BIRC3; PARP1. B Cell Receptor Signaling: RAC1; PTEN; LYN; ELK1; MAPK1; RAC2; PTPN11; AKT2; IKBKB; PIK3CA; CREB1; SYK; NFKB2; CAMK2A; MAP3K14; PIK3CB; PIK3C3; MAPK8; BCL2L1; ABL1; MAPK3; ETS1; KRAS; MAPK13; RELA; PTPN6; MAPK9; EGR1; PIK3C2A; BTK; MAPK14; RAF1; IKBKG; RELB; MAP3K7; MAP2K2; AKT1; PIK3R1; CHUK; MAP2K1; NFKB1; CDC42; GSK3A; FRAP1; BCL6; BCL10; JUN; GSK3B; ATF4; AKT3; VAV3; RPS6KB1. Leukocyte Extravasation Signaling: ACTN4; CD44; PRKCE; ITGAM; ROCK1; CXCR4; CYBA; RAC1; RAP1A; PRKCZ; ROCK2; RAC2; PTPN11; MMP14; PIK3CA; PRKC1; PTK2; PIK3CB; CXCL12; PIK3C3; MAPK8; PRKD1; ABL1; MAPK10; CYBB; MAPK13; RHOA; PRKCD; MAPK9; SRC; PIK3C2A; BTK; MAPK14; NOX1; PXN; VIL2; VASP; ITGB1; MAP2K2; CTNND1; PIK3R1; CTNNB1; CLDN1; CDC42; F11R; ITK; CRKL; VAV3; CTTN; PRKCA; MMP1; MMP9. Integrin Signaling: ACTN4; ITGAM; ROCK1; ITGA5; RAC1; PTEN; RAP1A; TLN1; ARHGEF7; MAPK1; RAC2; CAPNS1; AKT2; CAPN2; PIK3CA; PTK2; PIK3CB; PIK3C3; MAPK8; CAV1; CAPN1; ABL1; MAPK3; ITGA1; KRAS; RHOA; SRC; PIK3C2A; ITGB7; PPP1CC; ILK; PXN; VASP; RAF1; FYN; ITGB1; MAP2K2; PAK4; AKT1; PK3R1; TNK2; MAP2K1; PAK3; ITGB3; CDC42; RND3; ITGA2; CRKL; BRAF; GSK3B; AKT3. Acute Phase Response Signaling: IRAK1; SOD2; MYD88; TRAF6; ELK1; MAPK1; PTPN1; AKT2; IKBKB; PIK3CA; FOS; NFKB2; MAP3K14; PIK3CB; MAPK8; RIPK1; MAPK3; IL6ST; KRAS; MAPK13; IL6R; RELA; SOCS1; MAPK9; FTL; NR3C1; TRAF2; SERPINE1; MAPK14; TNF; RAF1; PDK1; IKBKG; RELB; MAP3K7; MAP2K2; AKT1; JAK2; PIK3R; CHUK; STAT3; MAP2K1; NFKB1; FRAP1; CEBPB; JUN; AKT3; IL1R1; IL6. PTEN Signaling: ITGAM; ITGA5; RAC1; PTEN; PRKCZ; BCL2L11; MAPK1; RAC2; AKT2; EGFR; IKBKB; CBL; PIK3CA; CDKN1B; PTK2; NFKB2; BCL2; PIK3CB; BCL2L1; MAPK3; ITGA1; KRAS; ITGB7; ILK; PDGFRB; INSR; RAF1; IKBKG; CASP9; CDKN1A; ITGB1; MAP2K2; AKT1; PIK3R1; CHUK; PDGFRA; PDPK1; MAP2K1; NFKB1; ITGB3; CDC42; CCND1; GSK3A; ITGA2; GSK3B; AKT3; FOXO1; CASP3; RPS6KB1. p53 Signaling: PTEN; EP300; BBC3; PCAF; FASN; BRCA1; GADD45A; BIRC5; AKT2; PIK3CA; CHEK1; TP53INP1; BCL2; PIK3CB; PIK3C3; MAPK8; THBS1; ATR; BCL2L1; E2F1; PMAIP1; CHEK2; TNFRSF10B; TP73; RB1; HDAC9; CDK2; PIK3C2A; MAPK14; TP53; LRDD; CDKN1A; HIPK2; AKT1; PIK3R1; RRM2B; APAF1; CTNNB1; SIRT1; CCND1; PRKDC; ATM; SFN; CDKN2A; JUN; SNAI2; GSK3B; BAX; AKT3. Aryl Hydrocarbon Receptor Signaling: HSPB1; EP300; FASN; TGM2; RXRA; MAPK1; NQO1; NCOR2; SP1; ARNT; CDKN1B; FOS; CHEK1; SMARCA4; NFKB2; MAPK8; ALDH1A1; ATR; E2F1; MAPK3; NRIP1; CHEK2; RELA; TP73; GSTP1; RB1; SRC; CDK2; AHR; NFE2L2; NCOA3; TPS3; TNF; CDKN1A; NCOA2; APAF1; NFKB1; CCND1; ATM; ESR1; CDKN2A; MYC; JUN; ESR2; BAX; IL6; CYP1B1; HSP90AA1. Xenobiotic Metabolism Signaling: PRKCE; EP300; PRKCZ; RXRA; MAPK1; NQO1; NCOR2; PIK3CA; ARNT; PRKCI; NFKB2; CAMK2A; PIK3CB; PPP2R1A; PIK3C3; MAPK8; PRKD1; ALDH1A1; MAPK3; NRIP1; KRAS; MAPK13; PRKCD; GSTP1; MAPK9; NOS2A; ABCB1; AHR; PPP2CA; FTL; NFE2L2; PIK3C2A; PPARGC1A; MAPK14; TNF; RAF1; CREBBP; MAP2K2; PIK3R1; PPP2R5C; MAP2K1; NFKB1; KEAP1; PRKCA; ETF2AK3; IL6; CYP1B1; HSP90AA1. SAPK/JNK Signaling: PRKCE; IRAK1; PRKAA2; EIF2AK2; RAC1; ELK1; GRK6; MAPK1; GADD45A; RAC2; PLK1; AKT2; PIK3CA; FADD; CDK8; PIK3CB; PIK3C3; MAPK8; RIPK1; GNB2L1; IRS1; MAPK3; MAPK10; DAXX; KRAS; PRKCD; PRKAA1; MAPK9; CDK2; PIM1; PIK3C2A; TRAF2; TP53; LCK; MAP3K7; DYRK1A; MAP2K2; PIK3R1; MAP2K1; PAK3; CDC42; JUN; TTK; CSNK1A1; CRKL; BRAF; SGK. PPAr/RXR Signaling: PRKAA2; EP300; INS; SMAD2; TRAF6; PPARA; FASN; RXRA; MAPK1; SMAD3; GNAS; IKBKB; NCOR2; ABCA1; GNAQ; NFKB2; MAP3K14; STAT5B; MAPK8; IRS1; MAPK3; KRAS; RELA; PRKAA1; PPARGC1A; NCOA3; MAPK14; INSR; RAF1; IKBKG; RELB; MAP3K7; CREBBP; MAP2K2; JAK2; CHUK; MAP2K1; NFKB1; TGFBR1; SMAD4; JUN; IL1R1; PRKCA; IL6; HSP90AA1; AD1POQ. NF-KB Signaling: IRAK1; EIF2AK2; EP300; INS; MYD88; PRKCZ; TRAF6; TBK1; AKT2; EGFR; IKBKB; PIK3CA; BTRC; NFKB2; MAP3K14; PIK3CB; PIK3C3; MAPK8; RIPK1; HDAC2; KRAS; RELA; PIK3C2A; TRAF2; TLR4; PDGFRB; TNF; INSR; LCK; IKBKG; RELB; MAP3K7; CREBBP; AKT1; PIK3R1; CHUK; PDGFRA; NFKB1; TLR2; BCL10; GSK3B; AKT3; TNFAIP3; IL1R1. Neuregulin Signaling: ERBB4; PRKCE; ITGAM; ITGA5; PTEN; PRKCZ; ELK1; MAPK1; PTPN11; AKT2; EGFR; ERBB2; PRKC1: CDKN1B; STAT5B; PRKD1; MAPK3; ITGA1; KRAS; PRKCD; STAT5A; SRC; ITGB7; RAF1; ITGB1; MAP2K2; ADAM17; AKT1; PIK3R1; PDPK1; MAP2K1; ITGB3; EREG; FRAP1; PSEN1; ITGA2; MYC; NRG1; CRKL; AKT3; PRKCA; HSP90AA1; RPS6KB1. Wnt & Beta catenin Signaling: CD44; EP300; LRP6; DVL3; CSNK1E; GJA1; SMO; AKT2; PIN1; CDH1; BTRC; GNAQ; MARK2; PPP2R1A; WNT11; SRC; DKK1; PPP2CA; SOX6; SFRP2; ILK; LEF1; SOX9; TP53; MAP3K7; CREBBP; TCF7L2; AKT1; PPP2R5C; WNTSA; LRP5; CTNNB1; TGFBR1; CCND1; GSK3A; DVL1; APC; CDKN2A; MYC; CSNK1A1; GSK3B; AKT3; SOX2. Insulin Receptor Signaling: PTEN; INS; EIF4E; PTPN1; PRKCZ; MAPK1; TSC1; PTPN11; AKT2; CBL; PIK3CA; PRKC1; PIK3CB; PIK3C3; MAPK8; IRS1; MAPK3; TSC2; KRAS; EIF4EBP1; SLC2A4; PIK3C2A; PPP1CC; INSR; RAF1; FYN; MAP2K2; JAK1; AKT1; JAK2; PIK3R1; PDPK1; MAP2K1; GSK3A; FRAP1; CRKL; GSK3B; AKT3; FOXO1; SGK; RPS6KB1. IL-6 Signaling: HSPB1; TRAF6; MAPKAPK2; ELK1; MAPK1; PTPN11; IKBKB; FOS; NFKB2; MAP3K14; MAPK8; MAPK3; MAPK10; IL6ST; KRAS; MAPK13; IL6R; RELA; SOCS1; MAPK9; ABCB1; TRAF2; MAPK14; TNF; RAF1; IKBKG; RELB; MAP3K7; MAP2K2; IL8; JAK2; CHUK; STAT3; MAP2K1; NFKB1; CEBPB; JUN; IL1R1; SRF; IL6. Hepatic Cholestasis: PRKCE; IRAK1; INS; MYD88; PRKCZ; TRAF6; PPARA; RXRA; IKBKB; PRKC1; NFKB2; MAP3K14; MAPK8; PRKD1; MAPK10; RELA; PRKCD; MAPK9; ABCB1; TRAF2; TLR4; TNF; INSR; IKBKG; RELB; MAP3K7; ILS; CHUK; NR1H2; TJP2; NFKB1; ESR1; SREBF1; FGFR4; JUN; IL1R1; PRKCA; IL6. IGF-1 Signaling: IGF1; PRKCZ; ELK1; MAPK1; PTPN1; NEDD4; AKT2; PIK3CA; PRKC1; PTK2; FOS; PIK3CB; PIK3C3; MAPK8; IGF1R; IRS1; MAPK3; IGFBP7; KRAS; PIK3C2A; YWHAZ; PXN; RAF1; CASP9; MAP2K2; AKT1; PIK3R1; PDPK1; MAP2K1; IGFBP2; SFN; JUN; CYR61; AKT3; FOXO1; SRF; CTGF; RPS6KB1. NRF2-mediated Oxidative Stress Response: PRKCE; EP300; SOD2; PRKCZ; MAPK1; SQSTM1; NQO1; PIK3CA; PRKC1; FOS; PIK3CB; PIK3C3; MAPK8; PRKD1; MAPK3; KRAS; PRKCD; GSTP1; MAPK9; FTL; NFE2L2; PIK3C2A; MAPK14; RAF1; MAP3K7; CREBBP; MAP2K2; AKT1; PIK3R1; MAP2K1; PPIB; JUN; KEAP1; GSK3B; ATF4; PRKCA; EIF2AK3; HSP90AA1. Hepatic Fibrosis/Hepatic Stellate Cell Activation: EDN1; IGF1; KDR; FLT1; SMAD2; FGFR1; MET; PGF; SMAD3; EGFR; FAS; CSF1; NFKB2; BCL2; MYH9; IGF1R; IL6R; RELA; TLR4; PDGFRB; TNF; RELB; IL8; PDGFRA; NFKB1; TGFBR1; SMAD4; VEGFA; BAX; IL1R1; CCL2; HGF; MMP1; STAT; IL6; CTGF; MMP9. PPAR Signaling: EP300; INS; TRAF6; PPARA; RXRA; MAPK1; IKBKB; NCOR2; FOS; NFKB2; MAP3K14; STAT5B; MAPK3; NRIP1; KRAS; PPARG; RELA; STAT5A; TRAF2; PPARGC1A; PDGFRB; TNF; INSR; RAF; IKBKG; RELB; MAP3K7; CREBBP; MAP2K2; CHUK; PDGFRA; MAP2K1; NFKB1; JUN; IL1R1; HSP90AA1. Fc Epsilon RI Signaling: PRKCE; RAC1; PRKCZ; LYN; MAPK1; RAC2; PTPN11; AKT2; PIK3CA; SYK; PRKC1; PIK3CB; PIK3C3; MAPK8; PRKD1; MAPK3; MAPK10; KRAS; MAPK13; PRKCD; MAPK9; PIK3C2A; BTK; MAPK14; TNF; RAF1; FYN; MAP2K2; AKT1; PIK3R1; PDPK1; MAP2K1; AKT3; VAV3; PRKCA. G-Protein Coupled Receptor Signaling: PRKCE; RAP1A; RGS16; MAPK1; GNAS; AKT2; IKBKB; PIK3CA; CREB1; GNAQ; NFKB2; CAMK2A; PIK3CB; PIK3C3; MAPK3; KRAS; RELA; SRC; PIK3C2A; RAF1; IKBKG; RELB; FYN; MAP2K2; AKT1; PIK3R1; CHUK; PDPK1; STAT3; MAP2K1; NFKB1; BRAF; ATF4; AKT3; PRKCA, Inositol Phosphate Metabolism: PRKCE; IRAK1; PRKAA2; EIF2AK2; PTEN; GRK6; MAPK1; PLK1; AKT2; PIK3CA; CDK8; PIK3CB; PIK3C3; MAPK8; MAPK3; PRKCD; PRKAA1; MAPK9; CDK2; PIM1; PIK3C2A; DYRK1A; MAP2K2; PIP5K1A; PIK3R1; MAP2K1; PAK3; ATM; TTK; CSNK1A1; BRAF; SGK. PDGF Signaling: EIF2AK2; ELK1; ABL2; MAPK1; PIK3CA; FOS; PIK3CB; PIK3C3; MAPK8; CAV1; ABL1; MAPK3; KRAS; SRC; PIK3C2A; PDGFRB; RAF1; MAP2K2; JAK1; JAK2; PIK3R1; PDGFRA; STAT3; SPHK1; MAP2K1; MYC; JUN; CRKL; PRKCA; SRF; STAT1; SPHK2. VEGF Signaling: ACTN4; ROCK1; KDR; FLT1; ROCK2; MAPK1; PGF; AKT2; PIK3CA; ARNT; PTK2; BCL2; PIK3CB; PIK3C3; BCL2L1; MAPK3; KRAS; HIF1A; NOS3; PIK3C2A; PXN; RAF1; MAP2K2; ELAVL1; AKT1; PIK3R1; MAP2K1; SFN; VEGFA; AKT3; FOXO1; PRKCA. Natural Killer Cell Signaling: PRKCE; RAC1; PRKCZ; MAPK1; RAC2; PTPN11; KIR2DL3; AKT2; PIK3CA; SYK; PRKC1; PIK3CB; PTK3C3; PRKD1; MAPK3; KRAS; PRKCD; PTPN6; PIK3C2A; LCK; RAF1; FYN; MAP2K2; PAK4; AKT1; PIK3R1; MAP2K1; PAK3; AKT3; VAV3; PRKCA. Cell Cycle: G/S Checkpoint Regulation: HDAC4; SMAD3; SUV39H1; HDAC5; CDKN1B; BTRC; ATR; ABL1; E2F1; HDAC2; HDAC7A; RB1; HDAC11; HDAC9; CDK2; E2F2; HDAC3; TP53; CDKN1A; CCND1; E2F4; ATM; RBL2; SMAD4; CDKN2A; MYC; NRG1; GSK3B; RBL1; HDAC6. T Cell Receptor Signaling: RAC1; ELK1; MAPK1; IKBKB; CBL; PIK3CA; FOS; NFKB2; PIK3CB; PIK3C3; MAPK8; MAPK3; KRAS; RELA, PIK3C2A; BTK; LCK; RAF1; IKBKG; RELB, FYN; MAP2K2; PTK3R1; CHUK; MAP2K1; NFKB1; ITK; BCL10; JUN; VAV3. Death Receptor Signaling: CRADD; HSPB1; BID; BIRC4; TBK1; IKBKB; FADD; FAS; NFKB2; BCL2; MAP3K14; MAPK8; RIPK1; CASP8; DAXX; TNFRSF10B; RELA; TRAF2; TNF; IKBKG; RELB; CASP9; CHUK; APAF1; NFKB1; CASP2; BIRC2; CASP3; BIRC3. FGF Signaling: RAC1; FGFR1; MET; MAPKAPK2; MAPK1; PTPN11; AKT2; PIK3CA; CREB1; PIK3CB; PIK3C3; MAPK8; MAPK3; MAPK13; PTPN6; PIK3C2A; MAPK14; RAF1; AKT1; PIK3R1; STAT3; MAP2K1; FGFR4; CRKL; ATF4; AKT3; PRKCA; HGF. GM-CSF Signaling: LYN; ELK1; MAPK1; PTPN11; AKT2; PIK3CA; CAMK2A; STAT5B; PIK3CB; PIK3C3; GNB2L1; BCL2L1; MAPK3; ETS1; KRAS; RUNX1; PIM1; PIK3C2A; RAF1; MAP2K2; AKT1; JAK2; PIK3R1; STAT3; MAP2K1; CCND1; AKT3; STAT1. Amyotrophic Lateral Sclerosis Signaling: BID; IGF1; RAC1; BIRC4; PGF; CAPNS1; CAPN2; PIK3CA; BCL2; PIK3CB; PIK3C3; BCL2L1; CAPN1; PIK3C2A; TP53; CASP9; PIK3R1; RAB5A; CASP1; APAF1; VEGFA; BIRC2; BAX; AKT3; CASP3; BIRC3. JAK/Stat Signaling: PTPN1; MAPK1; PTPN11; AKT2; PIK3CA; STAT5B; PIK3CB; PIK3C3; MAPK3; KRAS; SOCS1; STAT5A; PTPN6; PIK3C2A; RAF1; CDKN1A; MAP2K2; JAK1; AKT1; JAK2; PIK3R1; STAT3; MAP2K1; FRAP1; AKT3; STAT1. Nicotinate and Nicotinamide Metabolism; PRKCE; IRAK1; PRKAA2; EIF2AK2; GRK6; MAPK1; PLK1; AKT2; CDK8; MAPK8; MAPK3; PRKCD; PRKAA1; PBEF1; MAPK9; CDK2; PIM1; DYRK1A; MAP2K2; MAP2K1; PAK3; NT5E; TTK; CSNK1A1; BRAF; SGK. Chemokine Signaling: CXCR4; ROCK2; MAPK1; PTK2; FOS; CFL1; GNAQ; CAMK2A; CXCL12; MAPK8; MAPK3; KRAS; MAPK13; RHOA; CCR3; SRC; PPP1CC; MAPK14; NOX1; RAF1; MAP2K2; MAP2K1; JUN; CCL2; PRKCA. IL-2 Signaling: ELK1; MAPK1; PTPN11; AKT2; PIK3CA; SYK; FOS; STAT5B; PIK3CB; PIK3C3; MAPK8; MAPK3; KRAS; SOCS1; STAT5A; PIK3C2A; LCK; RAF); MAP2K2; JAK1; AKT1; PIK3R1; MAP2K1; JUN; AKT3. Synaptic Long Term Depression: PRKCE; IGF1; PRKCZ; PRDX6; LYN; MAPK1; GNAS; PRKCI; GNAQ; PPP2R1A; IGF1R; PRKD1; MAPK3; KRAS; GRN; PRKCD; NOS3; NOS2A; PPP2CA; YWHAZ; RAF1; MAP2K2; PPP2R5C; MAP2K1; PRKCA. Estrogen Receptor Signaling: TAF4B; EP300; CARM1; PCAF; MAPK1; NCOR2; SMARCA4; MAPK3; NRIP1; KRAS; SRC; NR3C1; HDAC3; PPARGC1A; RBM9; NCOA3; RAF1; CREBBP; MAP2K2; NCOA2; MAP2K1; PRKDC; ESR1; ESR2. Protein Ubiquitination Pathway: TRAF6; SMURF1; BIRC4; BRCA1; UCHL1; NEDD4; CBL; UBE21; BTRC; HSPA5; USP7; USP10; FBXW7; USP9X; STUB1; USP22; B2M; BIRC2; PARK2; USP8; USP1; VHL; HSP90AA1; BIRC3. IL-10 Signaling: TRAF6; CCR1; ELK1; IKBKB; SP1; FOS; NFKB2; MAP3K14; MAPK8; MAPK13; RELA; MAPK14; TNF; IKBKG; RELB; MAP3K7; JAK1; CHUK; STAT3; NFKB1; JUN; IL1R1; IL6. VDR/RXR Activation: PRKCE; EP300; PRKCZ; RXRA; GADD45A; HES1; NCOR2; SP1; PRKC1; CDKN1B; PRKD1; PRKCD; RUNX2; KLF4; YY1; NCOA3; CDKN1A; NCOA2; SPP1; LRP5; CEBPB; FOXO1; PRKCA. TGF-beta Signaling: EP300; SMAD2; SMURF1; MAPK1; SMAD3; SMAD1; FOS; MAPK8; MAPK3; KRAS; MAPK9; RUNX2; SERPINE1; RAF; MAP3K7; CREBBP; MAP2K2; MAP2K1; TGFBR1; SMAD4; JUN; SMAD5. Toll-like Receptor Signaling: IRAK1; ETF2AK2; MYD88; TRAF6; PPARA; ELK1; IKBKB; FOS; NFKB2; MAP3K14; MAPK8; MAPK13; RELA; TLR4; MAPK14; IKBKG; RELB; MAP3K7; CHUK; NFKB1; TLR2; JUN. p38 MAPK Signaling: HSPB1; IRAK1; TRAF6; MAPKAPK2; ELK1; FADD; FAS; CREB1; DDIT3; RPS6KA4; DAXX; MAPK13; TRAF2; MAPK14; TNF; MAP3K7; TGFBR1; MYC; ATF4; IL1R1; SRF; STAT1. Neurotrophin/TRK Signaling: NTRK2; MAPK1; PTPN11; PIK3CA; CREB1; FOS; PIK3CB; PIK3C3; MAPK8; MAPK3; KRAS; PTK3C2A; RAF1; MAP2K2; AKT1; PIK3R1; PDPK1; MAP2K; CDC42; JUN; ATF4. FXR/RXR Activation: INS; PPARA; FASN; RXRA; AKT2; SDC1; MAPK8; APOB; MAPK10; PPARG; MTTP; MAPK9; PPARGC1A; TNF; CREBBP; AKT1; SREBF1; FGFR4; AKT3; FOXO1. Synaptic Long Term Potentiation: PRKCE; RAP1A; EP300; PRKCZ; MAPK1; CREB1; PRKCZ; GNAQ; CAMK2A; PRKD1; MAPK3; KRAS; PRKCD; PPP1 CC; RAF1; CREBBP; MAP2K2; MAP2K1; ATF4; PRKCA. Calcium Signaling: RAP1A; EP300; HDAC4; MAPK1; HDAC5; CREB1; CAMK2A; MYH9; MAPK3; HDAC2; HDAC7A; HDAC11; HDAC9; HDAC3; CREBBP; CALR; CAMKK2; ATF4; HDAC6. EGF Signaling: ELK1; MAPK1; EGFR; PIK3CA; FOS; PIK3CB; PIK3C3; MAPK8; MAPK3; PIK3C2A; RAF1; JAK1; PIK3R1; STAT3; MAP2K1; JUN; PRKCA; SRF; STAT1. Hypoxia Signaling in the Cardiovascular System: EDN1; PTEN; EP300; NQO1; UBE2I; CREB1; ARNT; HIF1A; SLC2A4; NOS3; TP53; LDHA; AKT1; ATM; VEGFA; JUN; ATF4; VHL; HSP90AA1. LPS/IL-1 Mediated Inhibition of RXR Function LXR/RXR Activation: IRAK1; MYD88; TRAF6; PPARA; RXRA; ABCA1, MAPK8; ALDH1A1; GSTP1; MAPK9; ABCB1; TRAF2; TLR4; TNF; MAP3K7; NR1H2; SREBF1; JUN; IL1R1 FASN; RXRA; NCOR2; ABCA1; NFKB2; IRF3; RELA; NOS2A; TLR4; TNF; RELB; LDLR; NR1H2; NFKB1; SREBF1; IL1R1; CCL2; IL6; MMP9. Amyloid Processing: PRKCE; CSNK1E; MAPK1; CAPNS1; AKT2; CAPN2; CAPN1; MAPK3; MAPK13; MAPT; MAPK14; AKT1; PSEN1; CSNK1A1; GSK3B; AKT3; APP. IL-4 Signaling: AKT2; PIK3CA; PIK3CB; PIK3C3; IRS1; KRAS; SOCS1; PTPN6; NR3C1; PIK3C2A; JAK1; AKT1; JAK2; PIK3R1; FRAP1; AKT3; RPS6KB1, Cell Cycle: G2/M DNA Damage Checkpoint Regulation: EP300; PCAF; BRCA1; GADD45A; PLK1; BTRC; CHEK1; ATR; CHEK2; YWHAZ; TP53; CDKN1A; PRKDC; ATM; SFN; CDKN2A. Nitric Oxide Signaling in the Cardiovascular System: KDR; FLT1; PGF; AKT2; PIK3CA; PIK3CB; PIK3C3; CAV1; PRKCD; NOS3; PIK3C2A; AKT1; PIK3R1; VEGFA; AKT3; HSP90AA1. Purine Metabolism: NME2; SMARCA4; MYH9; RRM2; ADAR; EIF2AK4; PKM2; ENTPD1; RAD51; RRM28; TJP2; RAD51C; NT5E; POLD1; NME1. cAMP-mediated Signaling: RAP1A; MAPK1; GNAS; CREB1; CAMK2A; MAPK3; SRC; RAF1; MAP2K2; STAT3; MAP2K1; BRAF; ATF4. Mitochondrial Dysfunction Notch Signaling: SOD2; MAPK8; CASP8; MAPK10; MAPK9; CASP9; PARK7; PSEN1; PARK2; APP; CASP3 HES1; JAG1; NUMB; NOTCH4; ADAM17; NOTCH2; PSEN1; NOTCH3; NOTCH1; DLL4. Endoplasmic Reticulum Stress Pathway: HSPA5; MAPK8; XBP1; TRAF2; ATF6; CASP9; ATF4; EIF2AK3; CASP3. Pyrimidine Metabolism: NME2; AICDA; RRM2; EIF2AK4; ENTPD1; RRM2B; NT5E; POLD1; NME1. Parkinson's Signaling: UCHL1; MAPK8; MAPK13; MAPK14; CASP9; PARK7; PARK2; CASP3. Cardiac & Beta Adrenergic Signaling: GNAS; GNAQ; PPP2R1A; GNB2L1; PPP2CA; PPP1CC; PPP2R5C. Glycolysis' Gluconeogenesis: HK2; GCK; GPI; ALDH1A 1; PKM2; LDHA; HK1. Interferon Signaling: IRF1; SOCS1; JAK1; JAK2; IFITM1; STAT1; IFIT3. Sonic Hedgehog Signaling: ARRB2; SMO; GL12; DYRK1A; GLI1; GSK3B; DYRK1B. Glycerophospholipid Metabolism: PLD1; GRN; GPAM; YWHAZ; SPHK1; SPHK2. Phospholipid Degradation: PRDX6; PLD1; GRN; YWHAZ; SPHK1; SPHK2. Tryptophan Metabolism: SIAH2; PRMT5; NEDD4; ALDH1A1; CYP1B1; SIAH1. Lysine Degradation: SUV39H1; EHMT2; NSD1; SETD7; PPP2R5C. Nucleotide Excision Repair Pathway: ERCC5; ERCC4; XPA; XPC; ERCC1. Starch and Sucrose Metabolism: UCHL1; HK2; GCK; GPI; HK1. Aminosugars Metabolism: NQO1; HK2; GCK; HK1. Arachidonic Acid Metabolism: PRDX6; GRN; YWHAZ; CYP1B1. Circadian Rhythm Signaling: CSNK1E; CREB1: ATF4; NR1D1. Coagulation System: BDKRB1; F2R; SERPINE1; F3. Dopamine Receptor Signaling: PPP2R1A; PPP2CA; PPP1CC; PPP2R5C. Glutathione Metabolism: IDH2; GSTP1; ANPEP; IDH1. Glycerolipid Metabolism: ALDH1A1; GPAM; SPHK1; SPHK2. Linoleic Acid Metabolism: PRDX6; GRN; YWHAZ; CYP1B1. Methionine Metabolism: DNMT1; DNMT3B; AHCY; DNMT3A. Pyruvate Metabolism: GLO1; ALDH1 A1; PKM2; LDHA. Arginine and Proline Metabolism: ALDH1A1; NOS3; NOS2A. Eicosanoid Signaling: PRDX6; GRN; YWHAZ. Fructose and Mannose Metabolism: HK2; GCK; HK1. Galactose Metabolism: HK2; GCK; HK1. Stilbene. Coumarine and Lignin Biosynthesis: PRDX6; PRDX1; TYR. Antigen Presentation Pathway: CALR; B2M. Biosynthesis or Steroids: NQO1; DHCR7. Butanoate Metabolism: ALDH1A1; NLGN1. Citrate Cycle: IDH2; IDH1. Fatty Acid Metabolism: ALDH1A1; CYP1B1. Glycerophospholipid Metabolism: PRDX6; CHKA. Histidine Metabolism: PRMT5; ALDH1A1. Inositol Metabolism: ERO1L; APEX1. Metabolism of Xenobiotics by Cytochrome p450: GSTP1; CYP1B1. Methane Metabolism: PRDX6; PRDX1. Phenylalanine Metabolism: PRDX6; PRDX1. Propanoate Metabolism: ALDH1A1; LDHA. Selenoamino Acid Metabolism: PRMT5; AHCY. Sphingolipid Metabolism: SPHK1; SPHK2. Aminophosphonate Metabolism: PRMT5. Androgen and Estrogen Metabolism: PRMT5. Ascorbate and Aldarate Metabolism: ALDH1A1. Bile Acid Biosynthesis: ALDH1A1. Cysteine Metabolism: LDHA. Fatty Acid Biosynthesis: FASN. Glutamate Receptor Signaling: GNB2L1. NRF2-mediated Oxidative Stress Response: PRDX1. Pentose Phosphate Pathway: GPI. Pentose and Glucuronate Interconversions: UCHL1. Retinol Metabolism: ALDH1A1. Riboflavin Metabolism: TYR. Tyrosine Metabolism: PRMT5, TYR. Ubiquinone Biosynthesis: PRMT5. Valine, Leucine and Isoleucine Degradation: ALDH1A1. Glycine, Serine and Threonine Metabolism: CHKA. Lysine Degradation: ALDH1A1. Pain/Taste: TRPM5; TRPA1. Pain: TRPM7; TRPC5; TRPC6; TRPC1; Cnr1; cnr2; Grk2; Trpa1; Pome: Cgrp; Crf; Pka; Era; Nr2b; TRPM5; Prkaea; Prkacb; Prkar1a; Prkar2a. Mitochondrial Function: AIF; CytC; SMAC (Diablo); Aifm-1; Aifm-2. Developmental Neurology: BMP-4; Chordin (Chrd); Noggin (Nog); WNT (Wnt2; Wnt2b; Wnt3a; Wnt4; Wnt5a; Wnt6; Wnt7b; Wnt8b; Wnt9a; Wnt9b; Wnt10a; Wnt10b; Wnt16); beta-catenin; Dkk-1; Frizzled related proteins; Otx-2; Gbx2; FGF-8; Reelin: Dab1; unc-86 (Pou4f1 or Brn3a); Numb; Reln
In some cases, an editing system can be used to improve an immune cell performance. Examples of genes involved in cancer or tumor suppression may include ATM (ataxia telangiectasia mutated), ATR (ataxia telangiectasia and Rad3 related). EGFR (epidermal growth factor receptor), ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2), ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3), ERBB4 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 4), Notch 1, Notch2, Notch 3, or Notch 4, for example. A gene and protein associated with a secretase disorder may also be disrupted or introduced and can include PSENEN (presenilin enhancer 2 homolog (C. elegans)), CTSB (cathepsin B), PSEN1 (presenilin 1), APP (amyloid beta (A4) precursor protein). APH1B (anterior pharynx defective 1 homolog B (C. elegans)), PSEN2 (presenilin 2 (Alzheimer disease 4)), or BACE1 (beta-site APP-cleaving enzyme 1). It is contemplated that genetic homologues (e.g., any mammalian version of the gene) of the genes within this applications are covered. For example, genes that can be targeted can further include CD27, CD40, CD122, OX40, GITR, CD137, CD28, ICOS, A2AR, B7-H3, B7-H4, BTLA, CTLA-4, IDO, KIR, LAG3, PD-1, TIM-3, VISTA, HPRT, CCR5, AAVS SITE (e.g. AAVS1, AAVS2, ETC.), PPP1R12C, TRAC, TCRB, or CISH. Therefore, it is contemplated that any one of the aforementioned gene that exhibits or exhibits about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity (at the nucleic acid or protein level) can be disrupted. It is also contemplated that any of the aforementioned genes that exhibits or exhibits about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity (at the nucleic acid or protein level) can be disrupted. Some genetic homologues are known in the art, however, in some cases, homologues are unknown. However, homologous genes between mammals can be found by comparing nucleic acid (DNA or RNA) sequences or protein sequences using publically available databases such as NCBI BLAST. Also disclosed herein can be non-human gene equivalents of any one of the aforementioned genes. A non-human equivalent of any of the aforementioned genes can be disrupted with the gene editing system disclosed herein.
A guide RNA can be introduced into a cell or embryo as an RNA molecule. For example, a RNA molecule can be transcribed in vitro and/or can be chemically synthesized. A guide RNA can then be introduced into a cell or embryo as an RNA molecule. A guide RNA can also be introduced into a cell or embryo in the form of a non-RNA nucleic acid molecule, e.g., DNA molecule. For example, a DNA encoding a guide RNA can be operably linked to promoter control sequence for expression of the guide RNA in a cell or embryo of interest. A RNA coding sequence can be operably linked to a promoter sequence that is recognized by RNA polymerase III (Pol III).
A nucleic acid encoding a guide RNA or guide DNA can be linear. A nucleic acid encoding a guide RNA or guide DNA can also be circular. A nucleic acid encoding a guiding polynucleic acid can also be part of a vector. Some examples of vectors can include plasmid vectors, phagemids, cosmids, artificial/mini-chromosomes, transposons, and viral vectors. For example, a DNA encoding a RNA-guided endonuclease is present in a plasmid vector. Other non-limiting examples of suitable plasmid vectors include pUC, pBR322, pET, pBluescript, and variants thereof. Further, a vector can comprise additional expression control sequences (e.g., enhancer sequences. Kozak sequences, polyadenylation sequences, transcriptional termination sequences, etc.), selectable marker sequences (e.g., antibiotic resistance genes), origins of replication, and the like.
Suitable methods for introduction of the guiding polynucleic acid, protein, or guiding polynucleic acid: nuclease complex are known in the art and include, for example, electroporation: calcium phosphate precipitation: or PEI, PEG, DEAE, nanoparticle, or liposome mediated transformation. Other suitable transfection methods include direct micro-injection. In some cases, the guiding polynucleic acid and nuclease are introduced separately and the guiding polynucleic acid: nuclease complexes are formed in a cell. In other cases, a guiding polynucleic acid: nuclease complex can be formed and then introduced into a cell. In some cases, multiple, differentially labeled, guiding polynucleic acid: nuclease complexes, each directed to a different genomic targets are formed and then introduced into a cell. When both a nucleic acid guided nuclease and a guide polynucleic acid are introduced into a cell, each can be part of a separate molecule (e.g., one vector containing fusion protein coding sequence and a second vector containing guide polynucleic acid coding sequence) or both can be part of a same molecule (e.g., one vector containing coding (and regulatory) sequence for both a fusion protein and a guiding polynucleic acid). In some cases, a nuclease can be pre-complexed with a guiding polynucleic acid. A complex can be a ribonucleoprotein (RNP) complex.
In some cases, a GUIDE-Seq analysis can be performed to determine the specificity of engineered guiding polynucleic acids. The general mechanism and protocol of GUIDE-Seq profiling of off-target cleavage by CRISPR system nucleases is discussed in Tsai. S. et al., “GUIDE-Seq enables genome-wide profiling of off-target cleavage by CRISPR system nucleases,” Nature, 33: 187-197 (2015).
A guiding polynucleic acid can be introduced at any functional concentration. For example, a guiding polynucleic acid can be introduced to a cell at 10 micrograms. In other cases, a guiding polynucleic acid can be introduced from 0.5 micrograms to 100 micrograms. A gRNA can be introduced from 0.5, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 micrograms.
A sequence of a guiding polynucleic acid need not be 100% complementary to that of its target nucleic acid to be specifically hybridizable or hybridizable. Moreover, a guiding polynucleic acid may hybridize over one or more segments such that intervening or adjacent segments are not involved in the hybridization event (e.g., a loop structure or hairpin structure). For example, a polynucleotide can comprise 60% or more, 65% or more, 70% or more, 75% or more. 80% or more. 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5%, or 100% sequence complementarity to a target region within the target nucleic acid sequence to which it will hybridize. For example, an antisense nucleic acid in which 18 of 20 nucleotides of the antisense compound are complementary to a target region, and would therefore specifically hybridize, would represent 90 percent complementarity. In this example, the remaining non-complementary nucleotides may be clustered or interspersed with complementary nucleotides and need not be contiguous to each other or to complementary nucleotides. Percent complementarity between particular stretches of nucleic acid sequences within nucleic acids can be determined using any convenient method. Exemplary methods include BLAST programs (basic local alignment search tools) and PowerBLAST programs (Altschul et al., J. Mol. Biol., 1990, 215, 403-410; Zhang and Madden, Genome Res., 1997, 7, 649-656) or by using the Gap program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, Madison Wis.), using default settings, which uses the algorithm of Smith and Waterman (Adv. Appl. Math., 1981, 2, 482-489).
A guiding polynucleic acid can target a gene or portion thereof. In some cases, a cell that is modified can comprise one or more suppressed, disrupted, or knocked out genes and one or more transgenes, such as a receptor.
Methods and compositions described herein can be used to target a gene from a mammal. A gene that can be targeted can be from any organ or tissue. A gene that can be targeted can be from skin, eyes, heart, liver, lung, kidney, reproductive tract, brain, to name a few. A gene that can be targeted can also be from a number of conditions and diseases
In some cases, a disruption can result in a reduction of copy number of genomic transcript of a disrupted gene or portion thereof. For example, a target gene that can be disrupted can have reduced transcript quantities compared to the same target gene in an undisrupted cell. A disruption can result in disruption results in less than 145 copies/μL, 140 copies/μL, 135 copies/μL, 130 copies/μL, 125 copies/μL, 120 copies/μL, 115 copies/μL, 110 copies/μL, 105 copies/μL, 100 copies/μL, 95 copies/μL, 190 copies/μL, 185 copies/μL, 80 copies/μL, 75 copies/μL, 70 copies/μL, 65 copies/μL, 60 copies/μL, 55 copies/μL, 50 copies/μL, 45 copies/μL, 40 copies/μL, 35 copies/μL, 30 copies/μL, 25 copies/μL, 20 copies/μL, 15 copies/μL, 10 copies/μL, 5 copies/μL, 1 copies/μL, or 0.05 copies/μL. In some cases, a disruption can result in less than 100 copies/μL.
One or more genes in a cell can be knocked out or disrupted using any method. For example, knocking out one or more genes can comprise deleting one or more genes from a genome of a cell. Knocking out can also comprise removing all or a part of a gene sequence from a cell. It is also contemplated that knocking out can comprise replacing all or a part of a gene in a genome of a cell with one or more nucleotides. Knocking out one or more genes can also comprise inserting a sequence in one or more genes thereby disrupting expression of the one or more genes. For example, inserting a sequence can generate a stop codon in the middle of one or more genes. Inserting a sequence can also shift the open reading frame of one or more genes.
An animal or cell may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more disrupted genomic sequences encoding a protein associated with a disease and zero. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more genomically integrated sequences encoding a protein associated with a disease.
Delivery into a Cell The RHDC and nucleic acid unwinding agents, polynucleotides encoding the same, and/or any transgene polynucleotides and compositions comprising the polypeptides and/or polynucleotides described herein can be delivered to a target cell by any suitable means.
Suitable cells can include but are not limited to eukaryotic and prokaryotic cells and/or cell lines. A suitable cell can be a human primary cell.
A primary cell can be taken directly from living tissue (i.e. biopsy material) and established for growth in vitro, that have undergone very few population doublings and are therefore more representative of the main functional components and characteristics of tissues from which they are derived from, in comparison to continuous tumorigenic or artificially immortalized cell lines.
A primary cell can be acquired from a variety of sources such as an organ, vasculature, buffy coat, whole blood, apheresis, plasma, bone marrow, tumor, cell-bank, cryopreservation bank, or a blood sample. A primary cell can be a stem cell. A suitable cell that can be edited with a genomic editing system comprising an Ranse-H like domain can be epithelial cells, fibroblast cells, neural cells, kertinocytes, hematopoietic cells, melanocytes, chondrocytes, lymphocytes (B, NK, and T), macrophages, monocytes, mononuclear cells, cardiac muscle cells, other muscle cells, granulosa cells, cumulus cells, epidermal cells, endothelial cells, pancreatic islet cells, blood cells, blood precursor cells, bone cells, bone precursor cells, neuronal stem cells, primordial stem cells, hepatocytes, keratinocytes, umbilical vein endothelial cells, aortic endothelial cells, microvascular endothelial cells, fibroblasts, liver stellate cells, aortic smooth muscle cells, cardiac myocytes, neurons, Kupffer cells, smooth muscle cells, Schwann cells, and epithelial cells, erythrocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils, adipocytes, chondrocytes, pancreatic islet cells, thyroid cells, parathyroid cells, parotid cells, tumor cells, glial cells, astrocytes, red blood cells, white blood cells, macrophages, epithelial cells, somatic cells, pituitary cells, adrenal cells, hair cells, bladder cells, kidney cells, retinal cells, rod cells, cone cells, heart cells, pacemaker cells, spleen cells, antigen presenting cells, memory cells, T cells, B cells, plasma cells, muscle cells, ovarian cells, uterine cells, prostate cells, vaginal epithelial cells, sperm cells, testicular cells, germ cells, egg cells, leydig cells, peritubular cells, sertoli cells, lutein cells, cervical cells, endometrial cells, mammary cells, follicle cells, mucous cells, ciliated cells, nonkeratinized epithelial cells, keratinized epithelial cells, lung cells, goblet cells, columnar epithelial cells, dopaminergic cells, squamous epithelial cells, osteocytes, osteoblasts, osteoclasts, dopaminergic cells, embryonic stem cells, fibroblasts and fetal fibroblasts. Further, the one or more cells can be pancreatic islet cells and/or cell clusters or the like, including, but not limited to pancreatic α cells, pancreatic β cells, pancreatic δ cells, pancreatic F cells (e.g., PP cells), or pancreatic c cells. In one instance, the one or more cells can be pancreatic a cells. In another instance, the one or more cells can be pancreatic β cells.
A human primary cell can be an immune cell. An immune cell can be a T cell, B cell, NK cell, and/or TIL. Non-limiting examples of such cells or cell lines generated from such cells include COS. CHO (e.g., CHO-S, CHO-K1, CHO-DG44, CHO-DUXB11, CHO-DUKX, CHOK1SV), VERO, MDCK, W138, V79, B14AF28-G3, BHK, HaK, NSO, SP2/0-Ag14, HeLa, HEK293 (e.g., HEK293-F, HEK293-H, HEK293-T), and perC6 cells as well as insect cells such as Spodoptera frugiperda (S), or fungal cells such as Saccharomyces, Pichia and Schizosaccharomyces. In some cases, a cell line can be a CHO-K1. MDCK or HEK293 cell line. In some cases, suitable primary cells include peripheral blood mononuclear cells (PBMC), peripheral blood lymphocytes (PBL), and other blood cell subsets such as, but not limited to, T cell, a natural killer cell, a monocyte, a natural killer T cell, a monocyte-precursor cell, a hematopoietic stem cell or a non-pluripotent stem cell. In some cases, the cell can be any immune cells including any T-cell such as tumor infiltrating cells (TILs), such as CD3+ T-cells, CD4+ T-cells, CD8+ T-cells, or any other type of T-cell. The T cell can also include memory T cells, memory stem T cells, or effector T cells. The T cells can also be selected from a bulk population, for example, selecting T cells from whole blood. The T cells can also be expanded from a bulk population. The T cells can also be skewed towards particular populations and phenotypes. For example, the T cells can be skewed to phenotypically comprise, CD45RO(−), CCR7(+), CD45RA(+), CD62L(+), CD27(+), CD28-+) and/or IL-7Rα(+). Suitable cells can be selected that comprise one of more markers selected from a list comprising: CD45RO(−), CCR7(+). CD45RA(+), CD62L(+), CD27(+), CD28(+) and/or IL-7Rα(+). Suitable cells also include stem cells such as, by way of example, embryonic stem cells, induced pluripotent stem cells, hematopoietic stem cells, neuronal stem cells and mesenchymal stem cells. Suitable cells can comprise any number of primary cells, such as human cells, non-human cells, and/or mouse cells. Suitable cells can be progenitor cells. Suitable cells can be derived from the subject to be treated (e.g., subject). Suitable cells can be derived from a human donor. Suitable cells can be stem memory TSCM cells comprised of CD45RO (−), CCR7(+). CD45RA (+), CD62L+(L-selectin), CD27+, CD28+ and IL-7Rα+, stem memory cells can also express CD95, IL-2Rβ, CXCR3, and LFA-1, and show numerous functional attributes distinctive of stem memory cells. Suitable cells can be central memory TCM cells comprising L-selectin and CCR7, central memory cells can secrete, for example, IL-2, but not IFNγ or IL-4. Suitable cells can also be effector memory TEM cells comprising L-selectin or CCR7 and produce, for example, effector cytokines such as IFNγ and IL-4.
In some cases, modified cells can be a stem memory TSCM cell comprised of CD45RO(−). CCR7(+), CD45RA (+), CD62L+(L-selectin), CD27+. CD28+ and IL-7Rα+, stem memory cells can also express CD95, IL-2Rβ, CXCR3, and LFA-1, and show numerous functional attributes distinctive of stem memory cells. Engineered cells, such as RHDC polypeptide modified cells can also be central memory TCM cells comprising L-selectin and CCR7, where the central memory cells can secrete, for example, IL-2, but not IFNγ or IL-4. Engineered cells can also be effector memory Tim cells comprising L-selectin or CCR7 and produce, for example, effector cytokines such as IFNγ and IL-4. In some cases a population of cells can be introduced to a subject. For example, a population of cells can be a combination of T cells and NK cells. In other cases, a population can be a combination of naïve cells and effector cells.
A method of attaining suitable cells, such as human primary cells, can comprise selecting cells. In some cases, a cell can comprise a marker that can be selected for the cell. For example, such marker can comprise GFP, a resistance gene, a cell surface marker, an endogenous tag. Cells can be selected using any endogenous marker. Suitable cells can be selected using any technology. Such technology can comprise flow cytometry and/or magnetic columns. The selected cells can then be infused into a subject. The selected cells can also be expanded to large numbers. The selected cells can be expanded prior to infusion.
In some cases, a suitable cell can be a recombinant cell. A recombinant cell can be an immortalized cell line. A cell line can be: CHO-K1 cells; HEK293 cells: Caco2 cells: U2-OS cells: NIH 3T3 cells: NSO cells; SP2 cells; CHO-S cells: DG44 cells; K-562 cells. U-937 cells: MRC5 cells; IMR90 cells; Jurkat cells; HepG2 cells: HeLa cells; HT-1080 cells: HCT-1 16 cells: Hu-h7 cells; Huvec cells; Molt 4 cells. All these cell lines can be modified by the method described herein to provide cell line models to produce, express, quantify, detect, study a gene or a protein of interest; these models can also be used to screen biologically active molecules of interest in research and production and various fields such as chemical, biofuels, therapeutics and agronomy as non-limiting examples.
The genomic editing system as described herein can be delivered using vectors, for example containing sequences encoding one or more of the proteins. In some cases, a system as described herein can be delivered absent a viral vector. In some cases, a system as described herein can be delivered absent a viral vector, for example, when the system is greater than one kilobase, without affecting cellular viability. Transgenes encoding polynucleotides can be similarly delivered. Any vector systems can be used including, but not limited to, plasmid vectors, retroviral vectors, lentiviral vectors, adenovirus vectors, poxvirus vectors: herpesvirus vectors and adeno-associated virus vectors, etc. Furthermore, any of these vectors can comprise one or more transcription factor, nuclease, and/or transgene. Thus, when one or more CRISPR, TALEN, transposon-based, ZFN, meganuclease, or Mega-TAL molecules and/or transgenes are introduced into the cell, CRISPR. TALEN, transposon-based, ZFN, meganuclease, or Mega-TAL molecules and/or transgenes can be carried on the same vector or on different vectors. When multiple vectors are used, each vector can comprise a sequence encoding one or multiple CRISPR, TALEN, transposon-based, ZFN, meganuclease, or Mega-TAL molecules and/or transgenes.
Conventional viral and non-viral based gene transfer methods can be used to introduce nucleic acids encoding engineered CRISPR, TALEN, transposon-based, ZFN, meganuclease, or Mega-TAL molecules and/or transgenes in cells (e.g., mammalian cells) and target tissues. Such methods can also be used to administer nucleic acids encoding CRISPR, TALEN, transposon-based, ZFN, meganuclease, or Mega-TAL molecules and/or transgenes to cells in vitro. In some examples, nucleic acids encoding CRISPR, TALEN, transposon-based, ZFN, meganuclease, or Mega-TAL molecules and/or transgenes can be administered for in vivo or ex vivo immunotherapy uses. Non-viral vector delivery systems can include DNA plasmids, naked nucleic acid, and nucleic acid complexed with a delivery vehicle such as a liposome or poloxamer. Viral vector delivery systems can include DNA and RNA viruses, which have either episomal or integrated genomes after delivery to the cell.
Methods of non-viral delivery of nucleic acids include electroporation, lipofection, nucleofection, gold nanoparticle delivery, microinjection, biolistics, virosomes, liposomes, immunoliposomes, polycation or lipid: nucleic acid conjugates, naked DNA, mRNA, artificial virions, and agent-enhanced uptake of DNA. Sonoporation using, e.g., the Sonitron 2000 system (Rich-Mar) can also be used for delivery of nucleic acids. Additional exemplary nucleic acid delivery systems include those provided by AMAXA® Biosystems (Cologne, Germany). Life Technologies (Frederick, Md.). MAXCYTE, Inc. (Rockville, Md.). BTX Molecular Delivery Systems (Holliston, Mass.) and Copernicus Therapeutics Inc. (see for example U.S. Pat. No. 6,008,336). Lipofection reagents are sold commercially (e.g., TRANSFECTAM® and LIPOFECTIN®). Delivery can be to cells (ex vivo administration) or target tissues (in vivo administration). Additional methods of delivery include the use of packaging the nucleic acids to be delivered into EnGeneIC delivery vehicles (EDVs). These EDVs are specifically delivered to target tissues using bispecific antibodies where one arm of the antibody has specificity for the target tissue and the other has specificity for the EDV. The antibody brings the EDVs to the target cell surface and then the EDV is brought into the cell by endocytosis.
Vectors including viral and non-viral vectors containing nucleic acids encoding engineered CRISPR, TALEN, transposon-based, ZFN, meganuclease, or Mega-TAL molecules, transposon and/or transgenes can also be administered directly to an organism for transduction of cells in vivo. Alternatively, naked DNA or mRNA can be administered. Administration is by any of the routes normally used for introducing a molecule into ultimate contact with blood or tissue cells including, but not limited to, injection, infusion, topical application and electroporation. More than one route can be used to administer a particular composition. Pharmaceutically acceptable carriers are determined in part by the particular composition being administered, as well as by the particular method used to administer the composition.
In some cases, a vector encoding for an exogenous transgene can be shuttled to a cellular nuclease. For example, a vector can contain a nuclear localization sequence (NLS). An NLS can be from Simian Vacuolating Virus 40. A vector can also be shuttled by a protein or protein complex. In some cases, Cas9 can be used as a means to shuttle a minicircle vector. A Cas can comprise one or more NLS. In some cases, a vector can be pre-complexed with a Cas protein prior to electroporation. A Cas protein that can be used for shuttling can be a nuclease-deficient Cas9 (dCas9) protein. A Cas protein that can be used for shuttling can be a nuclease-competent Cas9. In some cases, Cas protein can be pre-mixed with a guide RNA and a vector or plasmid encoding an exogenous transgene.
Vectors can be delivered in vivo by administration to an individual subject, typically by systemic administration (e.g., intravenous, intraperitoneal, intramuscular, subdermal, or intracranial infusion) or topical application, as described below. Alternatively, vectors can be delivered to cells ex vivo, such as cells explanted from an individual subject (e.g., lymphocytes. T cells, bone marrow aspirates, tissue biopsy), followed by reimplantation of the cells into a subject, usually after selection for cells which have incorporated the vector. Prior to or after selection, the cells can be expanded.
A cell can be transfected with a mutant or chimeric adeno-associated viral vector encoding an exogenous transgene and an editing system comprising an RNase-H like domain containing protein. An AAV vector concentration can be from 0.5 nanograms to 50 micrograms. In some cases, the amount of nucleic acid (e.g., ssDNA, dsDNA, RNA) that can be introduced into the cell by electroporation can be varied to optimize transfection efficiency and/or cell viability. In some cases, less than about 100 picograms of nucleic acid can be added to each cell sample (e.g., one or more cells being electroporated). In some cases, at least about 100 picograms, at least about 200 picograms, at least about 300 picograms, at least about 400 picograms, at least about 500 picograms, at least about 600 picograms, at least about 700 picograms, at least about 800 picograms, at least about 900 picograms, at least about 1 microgram, at least about 1.5 micrograms, at least about 2 micrograms, at least about 2.5 micrograms, at least about 3 micrograms, at least about 3.5 micrograms, at least about 4 micrograms, at least about 4.5 micrograms, at least about 5 micrograms, at least about 5.5 micrograms, at least about 6 micrograms, at least about 6.5 micrograms, at least about 7 micrograms, at least about 7.5 micrograms, at least about 8 micrograms, at least about 8.5 micrograms, at least about 9 micrograms, at least about 9.5 micrograms, at least about 10 micrograms, at least about 11 micrograms, at least about 12 micrograms, at least about 13 micrograms, at least about 14 micrograms, at least about 15 micrograms, at least about 20 micrograms, at least about 25 micrograms, at least about 30 micrograms, at least about 35 micrograms, at least about 40 micrograms, at least about 45 micrograms, or at least about 50 micrograms, of nucleic acid can be added to each cell sample (e.g., one or more cells being electroporated). For example, 1 microgram of dsDNA can be added to each cell sample for electroporation. In some cases, the amount of nucleic acid (e.g., dsDNA) required for optimal transfection efficiency and/or cell viability can be specific to the cell type. In some cases, the amount of nucleic acid (e.g., dsDNA) used for each sample can directly correspond to the transfection efficiency and/or cell viability.
The transfection efficiency of cells with any of the nucleic acid delivery platforms described herein, for example, nucleofection or electroporation, can be or can be about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more than 99.9%.
Vectors, plasmids, and genomic editing systems described herein can be delivered by any suitable method, including transfection, electroporation, liposome delivery, membrane fusion techniques, high velocity DNA-coated pellets, viral infection and protoplast fusion. The methods used to construct any embodiment of this invention are known to those with skill in nucleic acid manipulation and include genetic engineering, recombinant engineering, and synthetic techniques. See, e.g., Sambrook et al, Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Press. Cold Spring Harbor, N.Y. Electroporation using, for example, the Neon® Transfection System (ThermoFisher Scientific) or the AMAXA® Nucleofector (AMAXA® Biosystems) can also be used for delivery of nucleic acids into a cell. Electroporation parameters can be adjusted to optimize transfection efficiency and/or cell viability. Electroporation devices can have multiple electrical wave form pulse settings such as exponential decay, time constant and square wave. Every cell type has a unique optimal Field Strength (E) that is dependent on the pulse parameters applied (e.g., voltage, capacitance and resistance). Application of optimal field strength causes electropermeabilization through induction of transmembrane voltage, which allows nucleic acids to pass through the cell membrane. In some cases, the electroporation pulse voltage, the electroporation pulse width, number of pulses, cell density, and tip type can be adjusted to optimize transfection efficiency and/or cell viability.
In some cases, electroporation pulse voltage can be varied to optimize transfection efficiency and/or cell viability. In some cases, the electroporation voltage can be less than about 500 volts. In some cases, the electroporation voltage can be at least about 500 volts, at least about 600 volts, at least about 700 volts, at least about 800 volts, at least about 900 volts, at least about 1000 volts, at least about 1100 volts, at least about 1200 volts, at least about 1300 volts, at least about 1400 volts, at least about 1500 volts, at least about 1600 volts, at least about 1700 volts, at least about 1800 volts, at least about 1900 volts, at least about 2000 volts, at least about 2100 volts, at least about 2200 volts, at least about 2300 volts, at least about 2400 volts, at least about 2500 volts, at least about 2600 volts, at least about 2700 volts, at least about 2800 volts, at least about 2900 volts, or at least about 3000 volts. In some cases, the electroporation pulse voltage required for optimal transfection efficiency and/or cell viability can be specific to the cell type. For example, an electroporation voltage of 1900 volts can optimal (e.g., provide the highest viability and/or transfection efficiency) for macrophage cells. In another example, an electroporation voltage of about 1350 volts can optimal (e.g., provide the highest viability and/or transfection efficiency) for Jurkat cells or primary human cells such as T cells. In some cases, a range of electroporation voltages can be optimal for a given cell type. For example, an electroporation voltage between about 1000 volts and about 1300 volts can optimal (e.g., provide the highest viability and/or transfection efficiency) for human 578T cells.
In some cases, electroporation pulse width can be varied to optimize transfection efficiency and/or cell viability. In some cases, the electroporation pulse width can be less than about 5 milliseconds. In some cases, the electroporation width can be at least about 5 milliseconds, at least about 6 milliseconds, at least about 7 milliseconds, at least about 8 milliseconds, at least about 9 milliseconds, at least about 10 milliseconds, at least about 11 milliseconds, at least about 12 milliseconds, at least about 13 milliseconds, at least about 14 milliseconds, at least about 15 milliseconds, at least about 16 milliseconds, at least about 17 milliseconds, at least about 18 milliseconds, at least about 19 milliseconds, at least about 20 milliseconds, at least about 21 milliseconds, at least about 22 milliseconds, at least about 23 milliseconds, at least about 24 milliseconds, at least about 25 milliseconds, at least about 26 milliseconds, at least about 27 milliseconds, at least about 28 milliseconds, at least about 29 milliseconds, at least about 30 milliseconds, at least about 31 milliseconds, at least about 32 milliseconds, at least about 33 milliseconds, at least about 34 milliseconds, at least about 35 milliseconds, at least about 36 milliseconds, at least about 37 milliseconds, at least about 38 milliseconds, at least about 39 milliseconds, at least about 40 milliseconds, at least about 41 milliseconds, at least about 42 milliseconds, at least about 43 milliseconds, at least about 44 milliseconds, at least about 45 milliseconds, at least about 46 milliseconds, at least about 47 milliseconds, at least about 48 milliseconds, at least about 49 milliseconds, or at least about 50 milliseconds. In some cases, the electroporation pulse width required for optimal transfection efficiency and/or cell viability can be specific to the cell type. For example, an electroporation pulse width of 30 milliseconds can optimal (e.g., provide the highest viability and/or transfection efficiency) for macrophage cells. In another example, an electroporation width of about 10 milliseconds can optimal (e.g., provide the highest viability and/or transfection efficiency) for Jurkat cells. In some cases, a range of electroporation widths can be optimal for a given cell type. For example, an electroporation width between about 20 milliseconds and about 30 milliseconds can optimal (e.g., provide the highest viability and/or transfection efficiency) for human 578T cells.
In some cases, the number of electroporation pulses can be varied to optimize transfection efficiency and/or cell viability. In some cases, electroporation can comprise a single pulse. In some cases, electroporation can comprise more than one pulse. In some cases, electroporation can comprise 2 pulses, 3 pulses, 4 pulses, 5 pulses 6 pulses, 7 pulses, 8 pulses. 9 pulses, or 10 or more pulses. In some cases, the number of electroporation pulses required for optimal transfection efficiency and/or cell viability can be specific to the cell type. For example, electroporation with a single pulse can be optimal (e.g., provide the highest viability and/or transfection efficiency) for macrophage cells. In another example, electroporation with a 3 pulses can be optimal (e.g., provide the highest viability and/or transfection efficiency) for primary cells. In some cases, a range of electroporation widths can be optimal for a given cell type. For example, electroporation with between about 1 to about 3 pulses can be optimal (e.g., provide the highest viability and/or transfection efficiency) for human cells.
In some cases, the starting cell density for electroporation can be varied to optimize transfection efficiency and/or cell viability. In some cases, the starting cell density for electroporation can be less than about 1×105 cells. In some cases, the starting cell density for electroporation can be at least about 1×105 cells, at least about 2×105 cells, at least about 3×105 cells, at least about 4×105 cells, at least about 5×105 cells, at least about 6×105 cells, at least about 7×105 cells, at least about 8×105 cells, at least about 9×105 cells, at least about 1×106 cells, at least about 1.5×106 cells, at least about 2×106 cells, at least about 2.5×106 cells, at least about 3×106 cells, at least about 3.5×106 cells, at least about 4×106 cells, at least about 4.5×106 cells, at least about 5×106 cells, at least about 5.5×106 cells, at least about 6×106 cells, at least about 6.5×106 cells, at least about 7×106 cells, at least about 7.5×106 cells, at least about 8×106 cells, at least about 8.5×106 cells, at least about 9×106 cells, at least about 9.5×106 cells, at least about 1×107 cells, at least about 1.2×107 cells, at least about 1.4×107 cells, at least about 1.6×107 cells, at least about 1.8×107 cells, at least about 2×107 cells, at least about 2.2×107 cells, at least about 2.4×107 cells, at least about 2.6×107 cells, at least about 2.8×107 cells, at least about 3×107 cells, at least about 3.2×107 cells, at least about 3.4×107 cells, at least about 3.6×107 cells, at least about 3.8×107 cells, at least about 4×107 cells, at least about 4.2×107 cells, at least about 4.4×107 cells, at least about 4.6×107 cells, at least about 4.8×107 cells, or at least about 5×107 cells. In some cases, the starting cell density for electroporation required for optimal transfection efficiency and/or cell viability can be specific to the cell type. For example, a starting cell density for electroporation of 1.5×106 cells can optimal (e.g., provide the highest viability and/or transfection efficiency) for macrophage cells. In another example, a starting cell density for electroporation of 5×106 cells can optimal (e.g., provide the highest viability and/or transfection efficiency) for human cells. In some cases, a range of starting cell densities for electroporation can be optimal for a given cell type. For example, a starting cell density for electroporation between of 3.6×106 and 5×107 cells can optimal (e.g., provide the highest viability and/or transfection efficiency) for human cells such as T cells.
In some cases, a guiding polynucleic acid and nuclease can be introduced into cells as a complex. A complex can be a ribonuclear protein complex (RNP). Introduction of an RNP complex can be timed. In some cases, a cell can be synchronized with other cells at G1, S, and/or M phases of the cell cycle prior to introduction of a guiding polynucleic acid and nuclease. In some cases, an RNP complex can be delivered at a cell phase such that HDR, MMEJ, or NHEJ can be enhanced. In some cases an RNP complex can facilitate homology directed repair.
Non-homologous end joining (NHEJ) and Homology-directed repair (HDR) can be quantified using a variety of methods.
In some cases, a percent of NHEJ, HDR, or a combination of both can be determined by co-delivering the gene editing molecules, for example a guiding polynucleic acid and an RNase H like domain containing polypeptide, with a donor DNA template that encodes a promoterless GFP into cells. After about 72 hrs., flow cytometry can be performed to quantify the total cell number (NTotal), GFP-positive cell number (NGFP+), and GFP-negative cell number (NGFP−). Among the GFP negative cells, next-generation sequencing can be performed to identify cells without mutations (NGFP−0), and with mutations (NGFP−1). HDR efficiency can be calculated as NGFP+/NTotal×100%, and NHEJ efficiency will be calculated as NGFP−1/NTotal×100%.
In some cases, activity of a DNA editing system may be assayed using a cell expressing a reporter protein or containing a reporter gene. For example, a reporter protein may be engineered to contain an obstruction, such as a stop codon, a frameshift mutation, a spacer, a linker, or a transcriptional terminator; the DNA editing system may then be used to remove the obstruction and the resultant functional reporter protein may be detected. In some cases, the obstruction may be designed such that a specific sequence modification is required to restore functionality of the reporter protein. In other cases, the obstruction may be designed such that any insertion or deletion which results in a frame shift of one or two bases may be sufficient to restore functionality of the reporter protein. Examples of reporter proteins include colorimetric enzymes, metabolic enzymes, fluorescent proteins, enzymes and transporters associated with antibiotic resistance, and luminescent enzymes. Examples of such reporter proteins include β-galactosidase, Chloramphenicol acetyltransferase, Green fluorescent protein, Red fluorescent protein, luciferase, and renilla. Different detection methods may be used for different reporter proteins. For example, the reporter protein may affect cell viability, cell growth, fluorescence, luminescence, or expression of a detectable product. In some cases, the reporter protein may be detected using a colorimetric assay. In some cases, the reporter protein may be a fluorescent protein, and DNA editing may be assayed by measuring the degree of fluorescence in treated cells, or the number of treated cells with at least a threshold level of fluorescence. In some cases, transcript levels of a reporter gene may be assessed. In other cases, a reporter gene may be assessed by sequencing. In some cases, an assay for measuring DNA editing may use a split fluorescence protein system, such as the self-complementing split GFP1-10/11 systems, in which two fragments (G1-10 and G11) of the GFP protein which can associate by themselves to form a functional GFP signal are linked using a frameshifting linker. Insertions or deletions within the frameshifting linker can restore the frame of the G11 fragment allowing the two fragments to form a functional GFP signal. An example of such an assay is shown in Example 12, and FIGS. 18-25 and FIG. 27-32. As seen in FIG. 32A and FIG. 32B Ago51 and Ago89 both resulted in ˜1.2% of cells showing GFP fluorescence, a level 2 fold higher than seen in the no Ago control condition (0.6%), indicating successful DNA editing at a level of double that seen at baseline. In some cases, Ago proteins as described herein may result in at least about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.5%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, 95%, 97%, 98%, or 99% of cells exhibiting restored activity of a reporter protein. In some cases. Ago proteins as described herein may result in at least about 1% to 99%, 1% to 10%, 1% to 5%, 1% to 2%, 5% to 50%, 10% to 80%, 10% to 50%, 30% to 70%, or 50% to 80% of cells exhibiting restored activity of a reporter protein. In some cases, Ago proteins as described herein may result in at least about a 1.5 fold, 2 fold, 3 fold, 4 fold, 5 fold, 6 fold, 7 fold, 8 fold, 9 fold, 10 fold, 15 fold, 20 fold, 25 fold, 30 fold, 40 fold, 50 fold, 60 fold, 70 fold, 80 fold, 90 fold, or 100 fold increase in the percentage of cells with restored activity of a reporter as compared to baseline. In some cases, Ago proteins as described herein may result in at least about a 1.2 fold to 10 fold, 1.5 fold to 10 fold, 2 fold to 10 fold, 2 fold to 5 fold, 2 fold to 20 fold, 3 fold to 5 fold, 4 fold to 10 fold, 5 fold to 20 fold, 10 fold to 100 fold, 10 fold to 50 fold or 1.2 fold to 100 fold increase in the percentage of cells with restored activity of a reporter as compared to baseline.
The percent occurrence of a genomic break repair utilizing HDR over NHEJ or MMEJ can be or can be about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more than 99.9% of cells that are contacted with a genomic editing system comprising an RNase-H like domain. The percent occurrence of a genomic break repair utilizing NHEJ over HDR or MMEJ can be or can be about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more than 99.9% of cells that are contacted with a genomic editing system comprising an RNase-H like domain. The percent occurrence of a genomic break repair utilizing MMEJ over HDR or NHEJ can be or can be about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or more than 99.9% of cells that are contacted with a genomic editing system comprising an RNase-H like domain.
Integration of an exogenous polynucleic acid, such as a TCR, can be measured using any technique. For example, integration can be measured by flow cytometry, surveyor nuclease assay, tracking of indels by decomposition (TIDE), junction PCR, or any combination thereof. In other cases, transgene integration can be measured by PCR. A TIDE analysis can also be performed on engineered cells. Ex vivo cell transfection can also be used for diagnostics, research, or for gene therapy (e.g., via re-infusion of the transfected cells into the host organism). In some cases, cells are isolated from the subject organism, transfected with a nucleic acid (e.g., gene or cDNA), and re-infused back into the subject organism (e.g., subject).
The amount of RHDC polypeptide-containing modified cells that can be necessary to be therapeutically effective in a subject can vary depending on the viability of the cells, and the efficiency with which the cells have been genetically modified (e.g., the efficiency with which a transgene has been integrated into one or more cells). In some cases, the product (e.g., multiplication) of the viability of cells post genetic modification and the efficiency of integration of a transgene can correspond to the therapeutic aliquot of cells available for administration to a subject. In some cases, an increase in the viability of cells post genetic modification can correspond to a decrease in the amount of cells that are necessary for administration to be therapeutically effective in a subject. In some cases, an increase in the efficiency with which a transgene has been integrated into one or more cells can correspond to a decrease in the amount of cells that are necessary for administration to be therapeutically effective in a subject. In some cases, determining an amount of cells that are necessary to be therapeutically effective can comprise determining a function corresponding to a change in the viability of cells over time. In some cases, determining an amount of cells that are necessary to be therapeutically effective can comprise determining a function corresponding to a change in the efficiency with which a transgene can be integrated into one or more cells with respect to time dependent variables (e.g., cell culture time, electroporation time, cell stimulation time).
As described herein, viral particles, such as AAV, can be used to deliver a viral vector comprising a gene of interest or a transgene, such as an exogenous TCR, into a cell ex vivo or in vivo. In some embodiments, a mutated or chimeric adeno-associated viral vector as disclosed herein can be measured as pfu (plaque forming units). In some cases, the pfu of recombinant virus or mutated or chimeric adeno-associated viral vector of the compositions and methods of the disclosure can be about 108 to about 5×1010 pfu. In some cases, recombinant viruses of this disclosure are at least about 1×108, 2×108, 3×108, 4×108, 5×108, 6×108, 7×108, 8×108, 9−108, 1×109, 2×109, 3×109, 4×109, 5×109, 6×109, 7×109, 8×109, 9×109, 1×1010, 2×1010, 3×1010, 4×1010, and 5×1010 pfu. In some cases, recombinant viruses of this disclosure are at most about 1×108, 2×108, 3×108, 4×108, 5×108, 6×108, 7×108, 8×108, 9×108, 1×109, 2×109, 3×109, 4×109, 5×109, 6×109, 7×109, 8×109, 9×109, 1×1010, 2×1010, 3×1010, 4×1010, and 5×1010 pfu. In some aspects, a mutated or chimeric adeno-associated viral vector of the disclosure can be measured as vector genomes. In some cases, recombinant viruses of this disclosure are 1×1010 to 3×1012 vector genomes, or 1×109 to 3×1013 vector genomes, or 1×108 to 3×1014 vector genomes, or at least about 1×101, 1×102, 1×103, 1×104, 1×105, 1×106, 1×107, 1×108, 1×109, 1×1010, 1×1011, 1×1012, 1×1013, 1×1014, 1×1015, 1×1016, 1×1017, and 1×1018 vector genomes, or are 1×108 to 3×1014 vector genomes, or are at most about 1×101, 1×102, 1×103, 1×104, 1×105, 1×106, 1×107, 1×108, 1×109, 1×1010, 1×1011, 1×1012, 1×1013, 1×1014, 1×1015, 1×1016, 1×1017, and 1×1018 vector genomes.
In some cases, a mutated or chimeric adeno-associated viral vector of the disclosure can be measured using multiplicity of infection (MOI). In some cases, MOI can refer to the ratio, or multiple of vector or viral genomes to the cells to which the nucleic can be delivered. In some cases, the MOI can be 1×106 GC/mL. In some cases, the MOI can be 1×105 GC/mL to 1×107 GC/mL. In some cases, the MOI can be 1×104 GC/mL to 1×108 GC/mL. In some cases, recombinant viruses of the disclosure are at least about 1×101 GC/mL, 1×102 GC/mL, 1×103 GC/mL, 1×104 GC/mL, 1×105 GC/mL, 1×106 GC/mL, 1×107 GC/mL, 1×108 GC/mL, 1×109 GC/mL, 1×1010 GC/mL, 1×1011 GC/mL, 1×1012 GC/mL, 1×1013 GC/mL, 1×1014 GC/mL, 1×1015 GC/mL, 1×1016 GC/mL, 1×1017 GC/mL, and 1×1018 GC/mL MOI. In some cases, a mutated or chimeric adeno-associated viruses of this disclosure are from about 1×108 GC/mL to about 3×1014 GC/mL MOI, or are at most about 1×101 GC/mL, 1×102 GC/mL, 1×103 GC/mL, 1×104 GC/mL, 1×105 GC/mL, 1×106 GC/mL, 1×107 GC/mL, 1×108 GC/mL, 1×109 GC/mL, 1×1010 GC/mL, 1×1011 GC/mL, 1×1012 GC/mL, 1×1013 GC/mL, 1×1014 GC/mL, 1×1015 GC/mL, 1×1016 GC/mL, 1×1017 GC/mL, and 1×1018 GC/mL MOI.
In some aspects, a non-viral vector or nucleic acid can be delivered without the use of a mutated or chimeric adeno-associated viral vector and can be measured according to the quantity of nucleic acid. Generally, any suitable amount of nucleic acid can be used with the compositions and methods of this disclosure. In some cases, nucleic acid can be at least about 1 pg, 10 pg, 100 pg, 1 pg, 10 pg, 100 pg, 200 pg, 300 pg, 400 pg, 500 pg, 600 pg, 700 pg, 800 pg, 900 pg, 1 μg, 10 μg, 100 μg, 200 μg, 300 μg, 400 μg, 500 μg, 600 μg, 700 μg, 800 μg, 900 μg, 1 ng, 10 ng, 100 ng, 200 ng, 300 ng, 400 ng, 500 ng, 600 ng, 700 ng, 800 ng, 900 ng, 1 mg, 10 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1 g, 2 g, 3 g, 4 g, or 5 g. In some cases, nucleic acid can be at most about 1 pg, 10 pg, 100 pg, 1 pg, 10 pg, 100 pg, 200 pg, 300 pg, 400 pg, 500 pg, 600 pg, 700 pg, 800 pg, 900 pg, 1 μg, 10 μg, 100 μg, 200 μg, 300 μg, 400 μg, 500 μg, 600 μg, 700 μg, 800 μg, 900 μg, 1 ng, 10 ng, 100 ng, 200 ng, 300 ng, 400 ng, 500 ng, 600 ng, 700 ng, 800 ng, 900 ng, 1 mg, 10 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1 g, 2 g, 3 g, 4 g, or 5 g.
Cells (e.g., engineered cells or engineered primary Cells) before, after, and/or during transplantation can be functional. For example, transplanted cells can be functional for at least or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 6, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, or 100 days after transplantation. Transplanted cells can be functional for at least or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months after transplantation. Transplanted cells can be functional for at least or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30 years after transplantation. In some cases, transplanted cells can be functional for up to the lifetime of a recipient.
Further, transplanted cells can function at 100% of its normal intended operation. Transplanted cells can also function 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% of its normal intended operation.
Transplanted cells can also function over 100% of its normal intended operation. For example, transplanted cells can function 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1000 or more % of its normal intended operation.
One or more cytokines can be introduced with cells of the invention. Cytokines can be utilized to boost cytotoxic T lymphocytes (including adoptively transferred tumor-specific cytotoxic T lymphocytes) to expand within a tumor microenvironment. In some cases, IL-2 can be used to facilitate expansion of the cells described herein. Cytokines such as IL-15 can also be employed. Other relevant cytokines in the field of immunotherapy can also be utilized, such as IL-2, IL-7, IL-12, IL-15, IL-21, or any combination thereof.
In some cases, IL-2 can be administered beginning within 24 hours of cell infusion and continuing for up to about 4 days (maximum 12 doses). In some cases, IL-2 can be administered for up to about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 days after an initial administration. Doses of IL-2 can be administered every eight hours. In some cases. IL-2 can be administered from about every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 hours after an initial administration. In some cases, IL-2 dosing can be stopped if toxicities are detected. In some cases, doses can be delayed or stopped if subjects reach Grade 3 or 4 toxicity due to aldesleukin except for the reversible Grade 3 toxicities common to Aldesleukin such as diarrhea, nausea, vomiting, hypotension, skin changes, anorexia, mucositis, dysphagia, or constitutional symptoms and laboratory changes. In some cases, if these toxicities can be easily reversed within 24 hours by supportive measures, then additional doses can be given. In addition, dosing can be held or stopped at the discretion of a treating physician.
Pharmaceutical Compositions and Formulations The compositions described throughout can be formulation into a pharmaceutical medicament and be used to treat a human or mammal, in need thereof, diagnosed with a disease, e.g., cancer. These medicaments can be co-administered with one or more T cells (e.g., engineered T cells) to a human or mammal, together with one or more chemotherapeutic agent or chemotherapeutic compound. The application also provides materials and methods comprising modified polynucleotides and methods of using such polynucleotides for ameliorating one or more symptoms or complications associated with human genetic diseases.
A chemotherapeutic agent can be a chemical compound useful in the treatment of cancer. The chemotherapeutic cancer agents that can be used in combination with the disclosed T cell include, but are not limited to, mitotic inhibitors (vinca alkaloids). These include vincristine, vinblastine, vindesine and Navelbine™ (vinorelbine, 5′-noranhydroblastine). In yet other cases, chemotherapeutic cancer agents include topoisomerase I inhibitors, such as camptothecin compounds. As used herein. “camptothecin compounds” include Camptosar™ (irinotecan HCL). Hycamtin™ (topotecan HCL) and other compounds derived from camptothecin and its analogues. Another category of chemotherapeutic cancer agents that can be used in the methods and compositions disclosed herein can be podophyllotoxin derivatives, such as etoposide, teniposide and mitopodozide. The present disclosure further encompasses other chemotherapeutic cancer agents known as alkylating agents, which alkylate the genetic material in tumor cells. These include without limitation cisplatin, cyclophosphamide, nitrogen mustard, trimethylene thiophosphoramide, carmustine, busulfan, chlorambucil, belustine, uracil mustard, chlomaphazin, and dacarbazine. The disclosure encompasses antimetabolites as chemotherapeutic agents. Examples of these types of agents include cytosine arabinoside, fluorouracil, methotrexate, mercaptopurine, azathioprime, and procarbazine. An additional category of chemotherapeutic cancer agents that can be used in the methods and compositions disclosed herein includes antibiotics. Examples include without limitation doxorubicin, bleomycin, dactinomycin, daunorubicin, mithramycin, mitomycin, mytomycin C, and daunomycin. There are numerous liposomal formulations commercially available for these compounds. The present disclosure further encompasses other chemotherapeutic cancer agents including without limitation anti-tumor antibodies, dacarbazine, azacytidine, amsacrine, melphalan, ifosfamide and mitoxantrone.
A patient may be infused with as many cells that can be generated for them. In some cases, cells that are infused into a patient are not all engineered. In some cases, a subject may receive a percentage of engineered cells in a total population of cells that can be introduced. For example, at least 90% of cells that can be introduced into a patient can be engineered. In other instances, at least 40% of cells that are introduced into a patient can be engineered. For example, a patient may receive any number of engineered cells, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% of the total introduced population.
The disclosed cell herein can be administered in combination with other anti-tumor agents, including cytotoxic/antineoplastic agents and anti-angiogenic agents. Cytotoxic/anti-neoplastic agents can be defined as agents who attack and kill cancer cells.
Anti-angiogenic agents can also be used. Suitable anti-angiogenic agents for use in the disclosed methods and compositions include anti-VEGF antibodies, including humanized and chimeric antibodies, anti-VEGF aptamers and antisense oligonucleotides. Other inhibitors of angiogenesis include angiostatin, endostatin, interferons, interleukin 1 (including α and β) interleukin 12, retinoic acid, and tissue inhibitors of metalloproteinase-1 and -2. (TIMP-1 and -2). Small molecules, including topoisomerases such as razoxane, a topoisomerase II inhibitor with anti-angiogenic activity, can also be used.
In some cases, for example, in the compositions, formulations and methods of treatment, the unit dosage of the composition or formulation administered can be 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 mg. In some cases, the total amount of the composition or formulation administered can be 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 0.5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100 g.
In some cases, the present invention provides a pharmaceutical composition comprising a cell can be administered either alone or together with a pharmaceutically acceptable carrier or excipient, by any routes, and such administration can be carried out in both single and multiple dosages. More particularly, the pharmaceutical composition can be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hand candies, powders, sprays, aqueous suspensions, injectable solutions, elixirs, syrups, and the like. Such carriers include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc. Moreover, such oral pharmaceutical formulations can be suitably sweetened and/or flavored by means of various agents of the type commonly employed for such purposes.
In some cases a carrier can be water, saline, ethanol, glycerol, lactose, sucrose, calcium phosphate, gelatin, dextran, agar, pectin, peanut oil, sesame oil, etc., a diluent, a pharmaceutically-acceptable carrier (e.g., phosphate-buffered saline), a pharmaceutically-acceptable excipient, an adjuvant to enhance antigenicity, an immunostimulatory compound or molecule, and/or other compounds known in the art. The adjuvant herein may contain a suspension of minerals (alum, aluminum hydroxide, aluminum phosphate) on which antigen is adsorbed: or water-in-oil emulsion in which antigen solution is emulsified in oil (MF-59, Freund's incomplete adjuvant), sometimes with the inclusion of killed mycobacteria (Freund's complete adjuvant) to further enhance antigenicity (inhibits degradation of antigen and/or causes influx of macrophages). Adjuvants also include immunostimulatory molecules, such as cytokines, costimulatory molecules, and for example, immunostimulatory DNA or RNA molecules, such as CpG oligonucleotides. Such a dosage formulation is readily ascertainable by one skilled in the art. A dosage may further contain one or more pharmaceutically acceptable salts such as, for example, a mineral acid salt such as a hydrochloride, a hydrobromide, a phosphate, a sulfate, etc.; and the salts of organic acids such as acetates, propionates, malonates, benzoates, etc. Additionally, auxiliary substances, such as wetting or emulsifying agents, pH buffering substances, gels or gelling materials, flavorings, colorants, microspheres, polymers, suspension agents, etc. may also be present herein. In addition, one or more other conventional pharmaceutical ingredients, such as preservatives, humectants, suspending agents, surfactants, antioxidants, anticaking agents, fillers, chelating agents, coating agents, chemical stabilizers, etc. may also be present, especially if the dosage form is a reconstitutable form. Suitable exemplary ingredients include microcrystalline cellulose, carboxymethylcellulose sodium, polysorbate 80, phenyl ethyl alcohol, chlorobutanol, potassium sorbate, sorbic acid, sulfur dioxide, propyl gallate, the parabens, ethyl vanillin, glycerin, phenol, parachlorophenol, gelatin, albumin and a combination thereof. A thorough discussion of pharmaceutically acceptable excipients is available in Remington's pharmaceutical sciences (Mack Pub. Co., N.J. 1991) which is incorporated by reference herein.
Cells can be extracted from a human as described herein. Cells can be genetically altered ex vivo and used accordingly. These cells can be used for cell-based therapies. These cells can be used to treat disease in a recipient (e.g., a human). For example, these cells can be used to treat cancer.
Described herein is a method of treating a disease (e.g., cancer) in a recipient comprising transplanting to the recipient one or more cells (including organs and/or tissues) comprising engineered cells. Cells prepared by intracellular genomic transplant can be used to treat cancer.
Described herein is a method of treating a disease (e.g., cancer) in a recipient comprising transplanting to the recipient one or more Argonaute modified cells (including organs and/or tissues). Generally, modified cells described herein can be expanded by contact with a surface having attached thereto an agent that can stimulate a CD3 TCR complex associated signal and a ligand that can stimulate a co-stimulatory molecule on the surface of the T cells. In particular, cell populations can be stimulated in vitro such as by contact with an anti-CD3 antibody or antigen-binding fragment thereof, or an anti-CD2 antibody immobilized on a surface, or by contact with a protein kinase C activator (e.g., bryostatin) sometimes in conjunction with a calcium ionophore. For co-stimulation of an accessory molecule on the surface of modified cells, a ligand that binds the accessory molecule can be used. For example, a population of cells can be contacted with an anti-CD3 antibody and an anti-CD28 antibody, under conditions that can stimulate proliferation of the T cells. In some cases, 4-1BB can be used to stimulate cells. For example, cells can be stimulated with 4-1BB and IL-21 or another cytokine. In some cases 5×1010 cells will be administered to a subject. In other cases, 5×1011 cells will be administered to a subject.
In some embodiments, about 5×1010 cells are administered to a subject. In some embodiments, about 5×1010 cells represent the median amount of cells administered to a subject. In some embodiments, about 5×1010 cells are necessary to affect a therapeutic response in a subject. In some embodiments, at least about at least about 1×107 cells, at least about 2×107 cells, at least about 3×107 cells, at least about 4×107 cells, at least about 5×107 cells, at least about 6×107 cells, at least about 6×107 cells, at least about 8×107 cells, at least about 9×107 cells, at least about 1×108 cells, at least about 2×108 cells, at least about 3×108 cells, at least about 4×108 cells, at least about 5×108 cells, at least about 6×108 cells, at least about 6×108 cells, at least about 8×108 cells, at least about 9×108 cells, at least about 1×109 cells, at least about 2×109 cells, at least about 3×109 cells, at least about 4×109 cells, at least about 5×109 cells, at least about 6×109 cells, at least about 6×109 cells, at least about 8×109 cells, at least about 9×109 cells, at least about 1×1010 cells, at least about 2×1010 cells, at least about 3×1010 cells, at least about 4×1010 cells, at least about 5×1010 cells, at least about 6×1010 cells, at least about 6×1010 cells, at least about 8×1010 cells, at least about 9×1010 cells, at least about 1×1011 cells, at least about 2×1011 cells, at least about 3×1011 cells, at least about 4×1011 cells, at least about 5×1011 cells, at least about 6×1011 cells, at least about 6×1011 cells, at least about 8×1011 cells, at least about 9×1011 cells, or at least about 1×1012 cells. For example, about 5×1010 cells can be administered to a subject. In another example, starting with 3×106 cells, the cells can be expanded to about 5×1010 cells and administered to a subject. In some cases, cells are expanded to sufficient numbers for therapy. For example, 5×107 cells can undergo rapid expansion to generate sufficient numbers for therapeutic use. In some cases, sufficient numbers for therapeutic use can be 5×1010. Any number of cells can be infused for therapeutic use. For example, a subject can be infused with a number of cells between 1×106 to 5×1012 inclusive. A subject can be infused with as many cells that can be generated for them. In some cases, cells that are infused into a subject are not all engineered. For example, at least 90% of cells that are infused into a subject can be engineered. In other instances, at least 40% of cells that are infused into a subject can be engineered.
In some embodiments, a method of the present disclosure comprises calculating and/or administering to a subject an amount of modified cells necessary to affect a therapeutic response in the subject. In some embodiments, calculating the amount of engineered cells necessary to affect a therapeutic response comprises the viability of the cells and/or the efficiency with which a transgene has been integrated into the genome of a cell. In some embodiments, in order to affect a therapeutic response in a subject, modified cells that can be administered to a subject can be viable. In some embodiments, in order to effect a therapeutic response in a subject, at least about 95%, at least about 90%, at least about 85%, at least about 80%, at least about 75%, at least about 70%, at least about 65%, at least about 60%, at least about 55%, at least about 50%, at least about 45%, at least about 40%, at least about 35%, at least about 30%, at least about 25%, at least about 20%, at least about 15%, at least about 10% of the cells are viable cells. In some embodiments, in order to affect a therapeutic response in a subject, the RHDC polypeptide modified cells administered to a subject can be cells that have had one or more transgenes successfully integrated into the genome of the cell. In some embodiments, in order to effect a therapeutic response in a subject, at least about 95%, at least about 90%, at least about 85%, at least about 80%, at least about 75%, at least about 70%, at least about 65%, at least about 60%, at least about 55%, at least about 50%, at least about 45%, at least about 40%, at least about 35%, at least about 30%, at least about 25%, at least about 20%, at least about 15%, at least about 10% of the cells have had one or more transgenes successfully integrated into the genome of the cell.
The methods disclosed herein can be used for treating or preventing disease including, but not limited to, cancer, cardiovascular diseases, lung diseases, liver diseases, skin diseases, or neurological diseases by administering to a subject in need thereof RNase-H like domain containing peptide modified cells.
Transplanting can be by any type of transplanting. Sites can include, but not limited to, liver subcapsular space, splenic subcapsular space, renal subcapsular space, omentum, gastric or intestinal submucosa, vascular segment of small intestine, venous sac, testis, brain, spleen, or cornea. For example, transplanting can be subcapsular transplanting. Transplanting can also be intramuscular transplanting. Transplanting can be intraportal transplanting.
Transplanting can be of one or more cells from a human. For example, the one or more cells can be from an organ, which can be a brain, heart, lungs, eye, stomach, pancreas, kidneys, liver, intestines, uterus, bladder, skin, hair, nails, ears, glands, nose, mouth, lips, spleen, gums, teeth, tongue, salivary glands, tonsils, pharynx, esophagus, large intestine, small intestine, rectum, anus, thyroid gland, thymus gland, bones, cartilage, tendons, ligaments, suprarenal capsule, skeletal muscles, smooth muscles, blood vessels, blood, spinal cord, trachea, ureters, urethra, hypothalamus, pituitary, pylorus, adrenal glands, ovaries, oviducts, uterus, vagina, mammary glands, testes, seminal vesicles, penis, lymph, lymph nodes or lymph vessels. The one or more cells can also be from a brain, heart, liver, skin, intestine, lung, kidney, eye, small bowel, or pancreas. The one or more cells can be from a pancreas, kidney, eye, liver, small bowel, lung, or heart. The one or more cells can be from a pancreas. The one or more cells can be pancreatic islet cells, for example, pancreatic β cells. The one or more cells can be any blood cells, such as peripheral blood mononuclear cell (PBMC), lymphocytes, monocytes or macrophages. The one or more cells can be any immune cells such as lymphocytes, B cells, or T cells.
The method disclosed herein can also comprise transplanting one or more cells (e.g., autologous cells or allogeneic cells), wherein the one or more cells can be can be any types of cells. For example, the one or more cells can be epithelial cells, fibroblast cells, neural cells, keratinocytes, hematopoietic cells, melanocytes, chondrocytes, lymphocytes (B and T), macrophages, monocytes, mononuclear cells, cardiac muscle cells, other muscle cells, granulosa cells, cumulus cells, epidermal cells, endothelial cells, pancreatic islet cells, blood cells, blood precursor cells, bone cells, bone precursor cells, neuronal stem cells, primordial stem cells, hepatocytes, keratinocytes, umbilical vein endothelial cells, aortic endothelial cells, microvascular endothelial cells, fibroblasts, liver stellate cells, aortic smooth muscle cells, cardiac myocytes, neurons, Kupffer cells, smooth muscle cells, Schwann cells, and epithelial cells, erythrocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils, adipocytes, chondrocytes, pancreatic islet cells, thyroid cells, parathyroid cells, parotid cells, tumor cells, glial cells, astrocytes, red blood cells, white blood cells, macrophages, epithelial cells, somatic cells, pituitary cells, adrenal cells, hair cells, bladder cells, kidney cells, retinal cells, rod cells, cone cells, heart cells, pacemaker cells, spleen cells, antigen presenting cells, memory cells, T cells, B cells, plasma cells, muscle cells, ovarian cells, uterine cells, prostate cells, vaginal epithelial cells, sperm cells, testicular cells, germ cells, egg cells, leydig cells, peritubular cells, sertoli cells, lutein cells, cervical cells, endometrial cells, mammary cells, follicle cells, mucous cells, ciliated cells, nonkeratinized epithelial cells, keratinized epithelial cells, lung cells, goblet cells, columnar epithelial cells, dopaminergic cells, squamous epithelial cells, osteocytes, osteoblasts, osteoclasts, dopaminergic cells, embryonic stem cells, fibroblasts and fetal fibroblasts. Further, the one or more cells can be pancreatic islet cells and/or cell clusters or the like, including, but not limited to pancreatic α cells, pancreatic β cells, pancreatic δ cells, pancreatic F cells (e.g., PP cells), or pancreatic s cells. In one instance, the one or more cells can be pancreatic α cells. In another instance, the one or more cells can be pancreatic β cells.
A donor can be at any stage of development including, but not limited to, fetal, neonatal, young and adult. For example, donor T cells can be isolated from an adult human. Donor human T cells can be under the age of 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 year(s). For example, T cells can be isolated from a human under the age of 6 years. T cells can also be isolated from a human under the age of 3 years. A donor can be older than 10 years.
Kits Disclosed herein can be kits comprising compositions. Disclosed herein can also be kits for the treatment or prevention of a cancer, pathogen infection, immune disorder or allogenic transplant. In one embodiment, a kit can include a therapeutic or prophylactic composition containing an effective amount of a composition of nuclease modified cells in unit dosage form. In some embodiments, a kit comprises a sterile container which can contain a therapeutic composition of engineered T cells; such containers can be boxes, ampules, bottles, vials, tubes, bags, pouches, blister-packs, or other suitable container forms known in the art. Such containers can be made of plastic, glass, laminated paper, metal foil, or other materials suitable for holding medicaments. In some cases, RHDC polypeptide modified cells can be provided together with instructions for administering the cells to a subject having or at risk of developing a cancer, pathogen infection, immune disorder or allogeneic transplant. Instructions can generally include information about the use of the composition for the treatment or prevention of cancer, pathogen infection, immune disorder or allogeneic transplant. In some cases, a kit can include from about 1×104 cells to about 1×1012 cells. In some cases a kit can include at least about 1×105 cells, at least about 1×104 cells, at least about 1×107 cells, at least about 4×107 cells, at least about 5×107 cells, at least about 6×107 cells, at least about 6×107 cells, at least about 8×107 cells, at least about 9×107 cells, at least about 1×108 cells, at least about 2×108 cells, at least about 3×108 cells, at least about 4×108 cells, at least about 5×108 cells, at least about 6×108 cells, at least about 6×108 cells, at least about 8×108 cells, at least about 9×108 cells, at least about 1×109 cells, at least about 2×109 cells, at least about 3×109 cells, at least about 4×109 cells, at least about 5×109 cells, at least about 6×109 cells, at least about 6×109 cells, at least about 8×109 cells, at least about 9×109 cells, at least about 1×1010 cells, at least about 2×1010 cells, at least about 3×1010 cells, at least about 4×1010 cells, at least about 5×1010 cells, at least about 6×1010 cells, at least about 6×1010 cells, at least about 8×1010 cells, at least about 9×1010 cells, at least about 1×1011 cells, at least about 2×1011 cells, at least about 3×1011 cells, at least about 4×1011 cells, at least about 5×1011 cells, at least about 6×1011 cells, at least about 6×1011 cells, at least about 8×1011 cells, at least about 9×1011 cells, or at least about 1×1012 cells. For example, about 5×1010 cells can be included in a kit. In another example, a kit can include 3×106 cells; the cells can be expanded to about 5×1010 cells and administered to a subject.
In some cases, a kit can include allogenic cells. In some cases, a kit can include cells that can comprise a genomic modification. In some cases, a kit can comprise “off-the-shelf” cells. In some cases, a kit can include cells that can be expanded for clinical use. In some cases, a kit can contain contents for a research purpose.
In some cases, the instructions include at least one of the following: description of the therapeutic agent: dosage schedule and administration for treatment or prevention of a neoplasia, pathogen infection, immune disorder or allogeneic transplant or symptoms thereof; precautions; warnings; indications: counter-indications; overdosage information; adverse reactions; animal pharmacology; clinical studies; and/or references. The instructions can be printed directly on the container (when present), or as a label applied to the container, or as a separate sheet, pamphlet, card, or folder supplied in or with the container. In some cases, instructions provide procedures for administering nuclease modified cells at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or up to 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days after administering a chemotherapeutic agent. In some cases, instructions provide procedures for administering engineered cells at least 24 hours after administering a chemotherapeutic agent. Nuclease modified cells can be formulated for intravenous injection. Nuclease modified cells can be formulated for infusion. In some cases a kit can contain products at a pediatric dosage.
Further uses of the methods, compositions, or kits described herein can include one or more of the following: genome editing, transcriptional or epigenetic regulation, genome imaging, copy number analysis, analysis of living cells, detection of highly repetitive genome sequence or structure, detection of complex genome sequences or structures, detection of gene duplication or rearrangement, enhanced FISH labeling, unwinding of target nucleic acid, large scale diagnostics of diseases and genetic disorders related to genome deletion, duplication, and rearrangement, use of an RNA oligo chip with multiple unique gRNAs or gDNAs for high-throughput imaging and/or diagnostics, multicolor differential detection of target sequences, identification or diagnosis of diseases of unknown cause or origin, and 4-dimensional (e.g., time-lapse) or 5-dimensional (e.g., multicolor time-lapse) imaging of cells (e.g., live cells), tissues, or organisms.
EXAMPLES Example 1: Nuclease Mining Pipeline 1 An NCBI RefSeq database was used to search the WIPI location of various PIWI sequences using TBlastN. Sequences that were analyzed had WIPI 1 hit+/−10 kb. Amino acid sequences were predicted using GeneMarS for relevant hits. Relevant hits were grouped into protein families, secondary structure and functional enrichment of adjacent regions. Protein family hits were analyzed against the CDD database. Secondary structures were analyzed. Functional enrichment analysis reviewed adjacent regions for domains involved in defense, stress response Cas system, DNA repair, or toxin defense, FIG. 2
Pipeline 2 An NCBI RefSeq database was used to search the WIPI location of various PIWI sequences using TBlastN. Sequences that were analyzed had WIPI 1 hit+/−10 kb. Amino acid sequences were predicted using GeneMarS for relevant hits. Relevant hits were analyzed using amino acids in ORFs using RPS-BLAST against the CDD database. Candidate Argonaute sequences were identified.
Results
Argonaute was encoded in ˜65% of the sequence eukaryotic genomes dispersed over at least four of the five eukaryotic supergroups. In contrast, a position-specific iterative basic local alignment search tool (PSI-BLAST) search of the RefSeq database (November 2013) using representative PIWI domain sequences as queries shows that Ago proteins are encoded in ˜32% and ˜9% of the available archaeal and bacterial genomes, respectively, and in 17 of 37 prokaryotic phyla. Similarly to most prokaryotic defense genes42, pAgo shows a patchy distribution, with at most 70% representation in any bacterial or archaeal phylum.
TABLE 10
Nuclease origin summary
Number of Species Number of Hits
Bacteria 1300 (of 45,031) 1363
Archaea 83 (of 1,012) 87
Eukaryote 1392 6693
TABLE 11
Taxonomic Distribution
Count
Acidobacteria 5
Actinobacteria 44
Aquificae 1
Bacteroidetes 60
Balneolaeota 1
Chlorobi 1
Chloroflexi 9
Cyanobacteria 48
Deinococcus-Thermus 16
Firmicutes 62
Nitrospirae 2
Planctomycetes 13
Proteobacteria 504
Spirochaetes 3
Verrucomicrobia 6
TABLE 12
Taxonomic Distribution
Taxonomy Count
Alphaproteobacteria 244
Betaproteobacteria 95
Deltaproteobacteria 8
Gammaproteobacteria 151
Zetaproteobacteria 2
Example 2: Identifying Suitable Nucleases A suitable nuclease is identified by secondary structural alignment to an RNase-H protein from individual genome sequences or gene assemblies from metagenomics. RNase-H1, RNase-H11, RVE/Transp, Argonaute, Prp8, RuvC, RuvC, RuvX, RNaseT, and DNAPolII were aligned, and alignment results revealed that these proteins share secondary structural homology. Structural alignments confirm the presence of a nuclease domain.
Example 3: RNase-H-Like Domain-Containing (RHDC) Polypeptide Constructs An RNase-H-like domain-containing (RHDC) polypeptide (e.g., an Argonaute protein) is fused to a nucleic acid unwinding polypeptide (e.g., a helicase domain) via a designed or screened peptide linker sequence, utilizing PCR techniques, molecular cloning or recombinant DNA techniques. The resulting fusion polypeptide is isolated and purified.
Example 4: Synthetic Helicase-Argonaute Fusion Constructs A catalytically dead Cas9 (e.g., dCas9), is guided to a target sequence by a single guide RNA (sgRNA). To achieve genomic disruption, dCas9 can be used by itself (whereby it represses transcription through steric hindrance) or as a helicase. DCas9 when fused to an RHDC polypeptide, or functional portion thereof, allows for a two-step genome editing system whereby dCas9 is first directed to the target sequence where it unwinds the double strand helix at a targeted site within the target sequence and in a second step, the RHDC executes a genomic break at the unwound target sequence.
Example 5: Genomic Engineering Using RNase-H-Like Domain-Containing (RHDC) Polypeptide Constructs Neon Transfection of T Cells
Unstimulated or stimulated T cells are electroporated using the Neon Transfection System (10 uL Kit, Invitrogen, Life Technologies). Cells are counted and resuspended at a density of 2×105 cells in 10 uL of T buffer. 1 ug of Argonaute-helicase construct or mRNA and 1 ug of gRNA targeting a target gene (e.g., an immune checkpoint gene) plasmid or mRNA are added to the cell mixture. Cells are electroporated at 1400 V, 10 ms, 3 pulses. After transfection, cells are plated in a 200 uL culturing media in a 48 well plate.
Flow Cytometry
Electroporated T cells are analyzed by flow cytometry 24-48 hours post transfection for expression of the disrupted target gene. Cells are prepped by washing with chilled 1×PBS with 0.5% FBS and stained with APC anti-human CD3ε (eBiosciences, San Diego) and Fixable Viability Dye eFlour 780 (eBiosciences, San Diego). The following mAbs and reagents are used with the indicated specificity and the appropriate isotype controls. From BD Biosciences: APC-conjugated anti-CD3 (555335). FITC-anti-CD8 (555366), PE-anti-CD8 (555635), PE-anti-CD28 (561793), PE-anti-CD107a (555801), and PE-anti-β-2 microglobulin (551337), FITC-anti-HLA-1 (555552), APC-anti-CD137 (550890). From Biolegend: APC-anti-PD1 (114102), APC-anti-PDL1 (329702), FITC-anti-CD45RO (304204), APC-anti-CD62L (304814). From Beckman Coulter: PE-anti-Vb13.1 (IM2021U). Data are acquired on a FACS Accuri (BD Biosciences) using CellQuest version 3.3 (BD Biosciences) and analyzed by FCS Express version 3.0) (De Novo Software) or FlowJo version 7.6.1 (Tree Star. Inc.).
Measuring Allele Modification Frequencies Using T7E1 Assay, TIDE, and Sequencing of PCR Fragments
The level of genomic disruption of a target gene in T cells is determined by a T7E1 Nuclease assay (NEB). The percent target disruption is quantified by densitometry. PCR products are ligated to TOPO cloning vector (Invitrogen) then transformed in E. coli. A single clone is picked and sequenced to calculate the indels and insertions. PD1 disruption is confirmed by Sanger sequencing. The PCR primers used for the amplification of the target locus are as follows: PD1 forward, 5′-GTAATAAAATGCTCAGCACAGAATA-3′(SEQ ID NO: 382): PD1 reverse, 5′ GAGAAAAATATCACCAGCTCATCT-3′ (SEQ ID NO: 383). For analyzing allele modification frequencies using TIDE (Tracking of Indels by Decomposition), the purified PCR products are Sanger-sequenced using both PCR primers and each sequence chromatogram is analyzed with the online TIDE software. Analyses are performed using a reference sequence from a Cas9 mock-transfected sample. Parameters are set to the default maximum indel size of 10 nucleotides and the decomposition window to cover the largest possible window with high quality traces. All TIDE analyses below the detection sensitivity of 1.5% are set to 0%.
ELISA Assays Target cells are washed and suspended at 1×106 cells/mL in R10 medium. Next, 100 μL of each target cell type is added in triplicate to a 96-well round-bottom plate (Corning). Effector T cells are washed and resuspended at 1×106 cells/mL in R 10 medium, and then 100 μL of T cells are combined with the target cells in the indicated wells. The plates are incubated at 37° C. for 18 to 24 hours. After the incubation, the supernatant is harvested and subjected to an ELISA (eBioscience).
IFNγ ELISpot RNase-H-like domain-containing (RHDC) fusion construct-edited T cells are plated in ELISpot plates (R&D Systems) at the concentration of 2×104 cells per well with irradiated allogenic PBMCs. Another experiment is performed by co-culturing of allogenic PBMCs with irradiated edited T cells. Cells were incubated for 18 hours at a stimulator-to-responder ratio of 1:1. Experiments are performed according to the manufacturer's instructions. The spots are automatically quantified using an ELISpot plate reader for scanning and analyzing.
Example 6: Detection of Genomic Disruption at the Protein Level To determine whether observed knockout frequencies at the genetic level correlate with loss of protein; the expression of target protein after knockout is assessed. Peripheral blood (PB) T-cells and TILs are re-stimulated at day 14 post-electroporation using plate bound anti-CD3 and soluble anti-CD28 antibody and assessed the loss of target gene by Coomassie Blue stained gel.
Example 7: RHDC Gene Cutting Assay Gene Editing Reporter System: The RHDC gene cutting assay is a highly sensitive gain-of-function mammalian gene editing reporter system, FIG. 9. Transient plasmid DNA, FIG. 10, was transfected into HEK293T QMS cells in wells of a 24-well plate. All plasmids were prepared from E. coli stellar cell using endotoxin-free DNA preparation kit. In summary, 5×104 cells were plated in 0.5 ml complete DMEM growth medium per well in a 6-well plate. Cell cultures were incubated under 37° C. for approximately 24-36 hours before transfection. Cells were about 60-70% confluent prior to transfection.
A: Immediately before transfection the TransIT-LT1 Reagent: DNA complex was made Table 13.
TABLE 13
TransIT-LT1 Reagent: DNA complex recipe
Recipe in 24 well plate
Opt 50 ul
TransIt reagent 1.5 ul
pX459-cymR-94 plasmid, FIG. 11 0.5-1 ug
The Reagent: DNA complex was generated by: Warming the TransIT-LT1 Reagent to room temperature and vortexing gently before use. 50 μL of Opti-MEM 1 Reduced-Serum Medium was placed in a sterile 1.5 ml tube. 1 μg plasmid DNA was added followed by pipetting to mix completely. 1.5 μL TransIT-LT1 Reagent was added to the DNA mixture and pipetted gently. A 30 min incubation was finally performed.
B: Complexes were Distributed to Cells in Complete Growth Medium
The TransIT-LT1 Reagent: DNA complexes were added drop-wise to different areas of the wells. The plate was gently rocked back-and-forth and from side-to-side to evenly distribute the TransIT-LT1 Reagent: DNA complexes. The mixture was incubated under 37° C. Cells were passaged as necessary.
C: Flow Cytometry Analysis of Transfected Cells
Transfected cells were trypsinized utilizing 0.25% Trypsin. The cells were spun down at 500 g for 5 minutes and resuspended in DPBS with 5% FBS and 0.5m EDTA and passed through the top-filter of 5 ml FACS tubes. Cells were analyzed using a Beckman CytoFlex flow cytometer at Day 3, Day 6 and Day 10.
RHDC Gene Editing in HEK293T
Transient plasmid DNA. FIG. 10, was transfected into HEK293T QMS cells in wells of a 24-well plate. All plasmids were prepared from E. coli stellar cell using endotoxin-free DNA preparation kit. In summary, 5×104 cells were plated in 0.5 ml complete DMEM growth medium per well in a 6-well plate. Cell cultures were incubated under 37° C. for approximately 24-36 hours before transfection. Cells were about 60-70% confluent prior to transfection.
A: Immediately Before Transfection the Gene Cutting Mixture was Generated
TABLE 14
Recipe for Argonaute gene editing in HEK293T assay
Recipe in 24well Note
Ago plasmid DNA 0.5 ug in pMAXGFP or pHR backbone
sgDNA-F ODN 250 ng 5′ phosphate
sgDNA-R ODN 250 ng 5′ phosphate
Opt-MEM 150 ul —
TransIt reagent 4.5 ul —
dCas9 plasmid 0.5 ug pSLQ1339
sgCymR plasmid 0.2 ug in pSLQ1371 backbone
B: Complexes were Distributed to Cells in Complete Growth Medium
The mixture was added drop-wise to different areas of the wells. The plate was gently rocked back-and-forth and from side-to-side to evenly distribute the mixture. The mixture was incubated under 37° C. Cells were passaged as necessary.
C: Flow Cytometry Analysis of Transfected Cells
Transfected cells were trypsinized utilizing 0.25% Trypsin. The cells were spun down at 500 g for 5 minutes and resuspended in DPBS with 5% FBS and 0.5m EDTA and passed through the top-filter of 5 ml FACS tubes. Cells were analyzed using a Beckman CytoFlex flow cytometer at Day 3, Day 6 and Day 10.
TABLE 15
Gene Cutting Assay Comparison
Ago only assay Ago + dCas9 helper system assay
Treatment1 Ago plasmid + sgDNA Ago plasmid + sgDNA ODN + dCas9
ODN plasmid + sgCymR
Treatment2 Ago plasmid dCas9 plasmid + sgCymR
Treatment3 sgDNA ODN —
Control1 pX459-sgCymR94 pX459-sgCymR94
Control2 cumate 30 uM cumate 30 uM
Control3 HEK293T QMS cell only HEK293T QMS cell only
Example 8: Genomic Thermodynamic Calculation of an Assembled Genetic Editing Molecule Measurement of energy of a genomic editing system of Assembled Genetic Editing Molecule (AGEM) can be calculated by considering the amount of ATP, ADP, and percentage of modified DNA.
AGEM is a modular system comprising an RNase H-like domain-containing (RHDC) polypeptide, a nucleic acid unwinding polypeptide, and an optional regulatory domain polypeptide (RDP), FIG. 34. The energy cost of a genetic thermodynamic reaction can be measured in a biochemical system, by providing finite amount of ATP into the reaction. At the end of the reaction, a quantification of the amount of DNA that is properly modified and the amount of ATP and ADP remaining in the reaction can be analyzed by calculating ([ATP]-[ADP])/[modified DNA], FIG. 33. This formula can estimate how much energy per editing reaction is expended. The exact energy cost per editing event will differ as the modules of the editing system can be interchanged. For example, an RHDC can be interchanged to any nuclease domain (from a CRISPR system. Argonaute system, meganuclease, Zinc Finger nuclease (ZFN), TALEN, or any restriction enzyme system) without affecting the nucleic acid unwinding agent or RDP function.
A measurement of a genomic thermodynamic reaction of a genome editing molecule can be determined by taking dsDNA that is 100 bp in length which contains a perfect matching sequence for the guiding polynucleic acid (gDNA or gRNA) into the reaction. 1 uM of gene editing molecules are added and 1 uM of guide DNA or guide RNA is added such that a ratio is: gene editor: target DNA=1:1, 10:1 (10 uM) ATP is supplemented into the reaction. The reaction will be performed for 1 hour. At the end of the reaction, stop buffer is added to the reaction (e.g., MOPS). The amount of remaining ATP is measured by a standard ATP assay based on phosphorylation of glycerol to generate a product that is easily quantifiable by colorimetric (OD=570 nm) or fluorometric (Ex/Em=535/587 nm) assays. The amount of target DNA that is modified is quantified by a T7 Endonuclease I assay, which recognizes and cleaves non-perfectly matching DNA (the edited DNA) followed by polyacrylamide gel electrophoresis. The total energy consumed by the gene editing molecule is calculated by ([ATP]-[ATP]remaining/[Edited DNA].
Example 9: Helicases that Co-Localize with Argonauts and their Optimized Nucleic Acid Sequences The sequences described in Table 16 are optimized to remove any known restriction enzyme recognition sites, cryptic gene expression regulatory sites, sequences that are predicted to sequester transcription or translation, repetitive sequences that are more than 10 bp. The optimization doesn't change protein peptide sequences, and is purely based on the redundancy of codon usage for using different triplets of nucleotides to encode the same amino acid.
TABLE 16
Nucleotide sequences for Optimized Ago Helicases
SEQ
ID NO Sequence
59 ATGCCCAAAAAGAAAAGGAAAGTGGAAGACCCAAAAAAGAAAAGAAAAGTCGGATCCGGATCCATGTCTATCTTCGCAAATTC
ATTTGAAATTGAGGTTCCCACACTGCCCGCCGAAATATATAAGATCGATCCACAGCCGTCCGAGAGCGACCCCTGGAGGGCAC
TGGATTCCTATGAGGAAAGCATAGAACGGACTTGCCGCGGTAGCGCCCACCGCATTAAAAATTCTGGTGACTGGGCCATCTTG
TCCATCGCTGCCACGGATAGTCAAGATGAGCTTCAGGGGCCAGACGGGACCCGCCTGGTTAGGACTAGCGAGACCACAGTGGG
GGGTGAGAACGGAAGATACCAAAGCGCCGTGAAACAAGCCCTCCGCAACAGCCTCGAGTGGTTCGTAACAAACCACCTCGACT
TTTGGGAGAGGGGGAATAGCCAGGCATTCTACGAATGGGACCCAAGCAATACAGTGGGAATGTATGACGCCTATCACGGCTAC
AAAGCTACCATTGATTATAACGATGGGTACTATCTGACAGTGGACTCTACCGTGAAGTTTATTAGCTCCAAATCCATCAACGA
GTACCTGTCAGAGCTCGGGCGAGACGTAGTGAAGACTCGCTTCTTCGACAGGTATTGCACACTGATGTCAGACAGCCGCCCCA
GCGTTGAGCTCGTATCCCTGGCAGAGGATTTGACGGTGAGTGACAAGACCATGAACTTCGGTGGGAAGGAGATGTCCGTGATT
GACTATATCAAATCTGACGACAAGTACTCTCAGGAGGCATTCGATGCTATTGACCCTGATGAGCCGCTTGCCCGCGTTAGATT
CCCGTGGAGCGATGACCCAGTTGATACAGCCCCGTCACTGCTGCACCCTCTCCCTAACGGTATCGAACCTAAAATGACCGGTT
ATGCCGCCAGAAGTGCCGACGAACGGTGGCGCGACACCGAACGCTTTGCTAAGCGGATTGATTACGTTCAGGTGTTTGACGAA
CAGTGTAACGTCTCCGATGAACCAAGAAGGGGCGGTTCTGTCCACGATTATCCGTCTCTCAAGTTCGGCGGCACCGAAGTTCT
TAACCTGGGGCAGCAGAATCCACTCAATACCGACCAGACCGTGAATAGACAGAATTGGAGGTATCTGGTGCGCGACTTCCTGG
AGGAGTACGGACCAGCTGTGAGACAACGGGGCGCTGCCCAGATTGATGTTGTTCATCCGGACGGTCGAAGCGATATGGCAGCA
GAGCTCTTTGCCAATCTGTCTAAATACCTGGAGAATTTTGTGGGGATTACGGTGCGGGACCAGCCCGGTATTGTGTCCCATAG
CGACTACCAGAAGCTGCGAGAATGGAGAGAACGGCACGCTGAGGATAGCGATGGAATCTTGGTACTTCAGGAGGACGGTTCAG
ATAGGTACCTTGACATCGTGGCGGAGCTGGAGGGGAACCCTACACAGGGGATTACCGTTGGAACATATGAATCATCACTTAGG
AGCAGTGGGTTCGATGACAGCATGTATAATATTGCCTGTGGGCTCGCCACCAAAATGGGAGTCAGACCTTTTCTGCTCGATCA
ACCTCTGAATGCCGATCTGTTTCTCGGTATGTCAGTGACCGGAGACGAAGTCAACAACGCCACAGCTGTTTTGGTGTCCGGAG
AGGATGGGGACTTGATTGGCCAGACCCAGACGAATCTGGCCACCGGCAGTAGCACTGTGACAGGAAAGGATGTTGCAGCTAGG
ATCGTTAGGCAGCAGATCAGTGCCGCCATCGACAGAAATCAACTTGGATACGTAGGAAGCTTGACAATTCATCGGAATGGTCA
GTTTGGGGACGGCGAGCTGGAGGGCATCAGAGAGGGCATCGCTGAACTCCAGTCCTCCGGTGATCTCAACGAAGAGTTGACTT
GGCAAGCCATTGAAATATCTGATGGCAGCAGCCATAGACTGTACACTGATGACTCCGGAAGTATGGTGCAGACGGGCAGTGTG
ATGCCACTCGACGATAAGAGCGTTACAGTGGTTACTTTCGGCTCCCCACACATCCATCAGGCAACCCCTGACCCACTTTATTG
CACCATTGCTGACGGAGAGGGAGAAACTGATATCAACCTGATCGGCACTGACATTCTGTCCTTGTCCTTTTTGAATTGGGGCT
CCCCAATGATGAAGATGAAGCAACCACTGACCACATACTTGCCAGCCGAGATGCATGACATTCTGTCAACCGGAACTCAACTG
AATCACCCTCCTTTTTAGTAA
60 ATGCCTAAAAAAAAACGGAAGGTTGAGGATCCGAAAAAAAAGCGAAAGGTGGGCAGCGGCTCTATGAGCGATTTTGACCCTAA
TGAGAAACAGGGAAGACTGATCGAGAGCACCGATGGCTTGCACCTTGTTGATGCAGGAGCAGGTACCGGCAAAACTTTCACTG
TAACACGGAGATACGCCACAATTGTCGAACAGTCTGACGTGGATCCTGCTGATATTCTCTTGGTGACTTTCACAAACAATGCC
GCCGCCGAGATGAAAGAGAGAATTGTGTCCCAGTCCGAATATGGGATGCGGGAGCTTACCGACGCTCCTATTCAGACCTTCCA
CTCCCTGGCAAACGACCTGTTGGAGGAGCATGGGCACGCTGTGCCTACGTATCTCGGTATAGATGATAGGATCACAGGGTCTA
CACAGATCCTGGAGGATGAGCTTGTCGAGGAGGCACTGTTTGACGAATTCATAGGGCAGTTCATGGACACTAACCCAGAGTAT
AACAGTTTCTTCACTGCTATCAGTGATACTACGGAACTCCTGGACCTGATCAAGGAGCTGGCAGCTAAAGGTGTTTTCCCCAC
CGCCAAAGGCTGGTACAGGGACGGTGAATCCCACCTGGACGGCGACTTCGAGGCTTTTGAAGACCTCTTCGAAGAAATAAATG
AACCAAGAAACGGCGGGTCCAAGCAGTCTAGACTCAGGGCCAAACTGAATAAGTACGGAGAGAATAAAGCTTATCTGCCCGAG
GCACCAGAGAGATGGGAAATCAGAGACGGCGGCAAACAGGTCCCAGATACCGTGGCTAGGCGCGTTTTCGAGGAAGACAGGGA
GGAGTTGAAGACATTCATTCACGACATGTACCACGCTTATCTTTCCTTCGCTCTGAGGAGAAATTACCTCAATTTCTCTTTCT
TGCAGCTGTTCGCTTTTGTACTGCTGTGTGAGGACCACGAACTGCGGGAGGAGCTGGGCTATGAATATGTAATGGTAGATGAG
TTCCAGGACAGTAGCGAGATCCAGTTTAAGCTCACTCTGCTGTTGGCAGGTACCAACAATATCTGTGTGGTAGGGGATTGGAA
GCAGTCCATATATTCATTCCAATACGCCGACGTCGATAACATAAGGGAATTTGAAACTCGCCTGGAACGCTTTACTACAGAAC
TTAATAATGACTATGACAGGATCCAGTACCCCACAACTCCCGTGACCAAGCTGGAACTGGACACAAACTACCGGTCAACCCAG
TCAGTACTGGACTTTACGGAACACGCACTGACGACACCTGCCACATCCAGCGAGTCAGTTGATGTGGATGCCGTGAGGGAGAA
GATTACCTCCTTGACCGCTGACGCTGATTACGATAACAGTATCATCGAAGCTATCAGATCCGATAAAGAGCACGAGGCCATTT
TGACGAAAATCGATGAAATCACCGGAAATGAAAGCTATGCTGTCGAGAAGGACGGGGAACTTAGAGCCCCCACCTATTCAGAT
ATCGCCGTGGTAACACGCACTAGGGATTTTGGCAGAGACTTGTTGGATGTTGCAGAGGAATGTGGCCTTCCTATGGCTTATGA
GGGCGGGATCGAGGTCTTTAGAACCGACGCGGCAAAACTGCTGCTGGCTTGGTTCAGGATACTCGAGCGAGACGCTGATCGAG
GGTGGGCTTTGGTACTCGAGGAAGCGGGATATACTATAGACGAGAGCAAAGCCGTGCTGAAGAACGAGGCCTACCCAGAGATG
ATGATAGGCTTCAGAGAGGAGCTTAGGAAGCTGGAGACCTTCGGAGGGGTTGCGCGCCGGGTGTTCGAGCGGTATGGCTGTGA
AGGTCCTACCGCTGATGTGGTCCTCCATACTGTGCAGTCTGTGTATGAGGCGACCACACTGACTCGCGGGGACCTGATCCGGT
TCATAGAAGACGCCATTGAGTCCGGAAGCACACACGAAGTCCAGGCCGGCGCAGGTACTAACAGTGTCACAGTTCAGACTATT
CACGCAACCAAAGGCCTCGAGTACCCAATCGTGATTCTGGCGAACATGAACACCAATAAGTTTCCATCCAGTGGTGGATCCGG
CACCGATATCTCATACGACGATCCCATCGGTTTGAGAAGACGCAAACTGTACAGTGAGGTTGCCCATGGGGTCCCATACGTGT
ATGACAATTGGAAACTGGACGTGCTGAGACGCTGTCTGCCCCGCGAATATGACGAGGAGAGGAGGCTCCTGTACGTTGCTATT
ACACGGGCTGAAAACCACGTGGTTTTCACTGCTGGTGAGAATCCTAACACTTTCCTCGAAGAACTGCCTGTGGATGTCGAAGC
GGTCAATCCGGACTTGTCAAGTTTCACACCTGAACCGGTCGACGAGAGCCCATTCGAGGTCGAGATCTCTGCCTCAGAAGGGT
CTCCGCGCTTTTCCCCTCATACGTTTATCGATGACGCTGTGTTTGACGACGGAACAGGGGGAAGAGGTATGGAGTTCGGTTCT
CAGGTGCACGACTTCGCTGAGGCATATGTGCTTGGGGAAGATGTCACCAGTTCCTCCCCTTAGTAA
61 ATGCCAAAGAAGAAGAGGAAAGTGGAAGACCCAAAAAAGAAAAGGAAAGTGGGATCAGGCTCTATGCACGATGATCACGACAC
CGACCACTCCCAGACTGACCTGACAACTAACCCCAAGGACAACTCTAACAACGGGGATATTGACATCGAGACTGACATTCTCC
AGCTTACAGGGGAGGACCTCGAATCTACCTACCCTAACAATCGGTACTTCGGGCAGGTTCACGAAAACTTCGAAATACCCGCT
AGAGAAGAGCAGACAGTTCCCGCTGGCGACGTGCTTCCTCCTAAAATTGCGCAAAACCTGGAGTTCAACCCCTGGTCCCATCA
GGCGGAAGCCTTGCAGGTTCTGGATCGGGGCGACAACGTCTGTGTGGCCACCTCAACTTCTAGTGGAAAGACCTTGGTGTACG
GTCTGCATATCGCCAGACAGTATTTGGAAGACCCCGAAACACGCAGCCTGATTGTCTACCCTACTAAGGCTCTGTCTAGAGAC
CAAGAGCAGGAATTGAACGAATTCCTGCGAAACACGTTGGGGCTCGACATTTCCGTTGGCGTGTACGATGGGGACACCAAATC
AGAAGAGAAGAGCCGGATCAGGGATGAATGCAACGTGGTGATAACCAACTTTGTGGGCCTCAATCAGTATCTGGAAAGCCACC
ACCTGTGGGCAGACTTCCACAGCAACTGTAGTCTGGTTGTTATTGACGAAGCGCATATGTGGACCGGCCTCGGAGGTATGCAT
GTAGCCTGGATTTTGAGGCGAGCCCAGCGGATAATTGACTACTATGGAGGCGATCCACAGTATGTGCTCACTACCGCAACGAT
TGGCAACCCAACAGAACACGCATTGGCTCTCACAGGCGAGCCGGCTGCGGTCGTCGACGAGGATGGAAGCCCACGCGGAATTC
GGCATCTTGTTTTTTGGGACCCACCAATGAGCGGGGATGACGGATTCACTGATGATATAGACTCCCCAGCTCTGTCCAAGCGA
CCAGCAACAGTGGAGGCACCTGAAGTTTGGGCTCATATGTGTCAGAAGAACGTTCAAAGCCTCCTGTTTTGTGACAGCAGGAA
GCTGACAGAGTTGAGCGTGAATAGGGCGAAGAGATTTATATCAGATCCTAAAAATCGGTATCAAGGACGGCCAGACCTTGCTT
CATATCATGCTGGACATGGAAAGCAATCCCGGAGAGGGACAGAATACCAGCTTAAGGAAGGCCAACTCGACGGGGTGTCAACG
ACATCTGCCTTGGAAGTCGGCATTAATATCGGGGGGGTCGACGGCACCGTCTTGATGGGTTATCCTGGGTCTCGACAATCATT
CTGGCAGCGCATCGGGCGGAGCGGTAGGGGGACAAGAGACGCGCTGTCTGTTTTCGTGCCCTCCCACTCAACCTTGGATCAGT
ATATCCTGAGACACCCAGAATATGTCCTGGAAGAGGATCACGAGTCTGCCGTAGTGGATTTGGACAACAACCCAGTTTATTTG
CAGCAGTTGAATTGCGCAGCCCAGGAATTGCCCCTGACACGGGATGACGCTGAAGACTTCGGAGGGGAAGAACGCTTGGAGCG
GGCAGTCGAATATGGCAGGAGAAAGGGTGACCTTGAGGGCTCCCTGGACAGTGGAGTTATGTACGCACACCGCGATCGGCCTC
AGGACGCAATCTCCCTTTATAGCTCAGGAGGTAACACCTTCGACGTGCGACTGGCAGGTGATGGATCTATTGATCATCAGCCC
ATCGGGAGGGACAGGGCATATCGCGATTATCACGAGGGGGCCACAGTGCTTCACCAGGGCGAGCAGTACCAGGTGGTTGAACT
GAGGGAGGACATACCCCAACCTTACATTTCACTTGAAAAAGCGAATGTGAGTTATTACACCCAGTCACAAGGACAGGTAAATA
TATATGACACTGTTGTGGAAGATAGTAGAGAGGTAGGGCCGTTTACGCTTAACTGGGGATACGGGACAGTTTCTATCCACTAT
TCCACTTACCTCAAGCGAGAGATTGGATCTGGCGATGTGTTGGAGCTTGGGAACGAGACCGGGGTGCCTCCGCTCGAGATGAG
AACCCAGCTGTGCTGGGCCGAAACCCCTAATGACATCGAGAGAGCCATGTTGAACAAGCATAGTGAGTATCATAACCCCGAGT
GTATTAACCTCCCACCTCGGCTGCACGGCTATCTCGGAGGTATTCATGCTGTTGAGCACGCTATGATCGCCGTCTCTCCACTC
GAGTTGAAAGTGGATGGCGGAGATATCGGCGGCCTGGCGACAAACCGCCTGCCCGGCAATCCTGACAAGTCAGGGTGGTTCAT
CTATGATGGAATCGAAGGAGGATTGGGGTTCTCTAGGAGTATTTATGAGCACTTTGAAGATGTCGCTCGAAGAGCTCATGATC
TGATTGTTGACTGTTCATGTGGTCGGGACGAGGGATGCCCAGCATGCACAATGGATGATCGCTGCGGCAATGATAATAGGCCA
CTGTATTCACCAGCTGCCGCCGACGTGATTGAGCATCTGCTCGGCGATCAAGAGGAGGACGACCTGAACGAGCACCTCCCCGA
GACAGGGTCTGAAGTAACTCCTGTGGAGGAACAACGCCCACCTGCATCAATATCTTAGTAA
62 ATGCCCAAAAAGAAGAGAAAAGTGGAGGATCCAAAGAAGAAAAGGAAGGTGGGGTCCGGGAGCATGTCCGAGCTGGAGACTAA
CATCTTCCCGATTACTAACCTGCACGAGTTGGAGTCCCGCTTTAGGCTGTACAGGGTTAGAGGGTTGAGCATTAATCAGGAAG
AATACGATCCCAATACCCAGACCTTGGTTCGGAAACTTAGTTACAGTATGAGGTCACCGGTTGCCGTAATCCTCAGAAACAGC
GACCCGTTCCTTGCCCTGCCTATCGATGCTCCAGAACCGATCTCCCCCTATCCACTTGTGCGAGCTACCGCCGTTTTCGAGAA
AACGGATGAAGTCTTTACGTTGGATTACGAAAGCCCTACTCCTGAAACTGATGCACTGAGGATCCGCTTTCTTCAATTCATAA
TTCAAGGAGCTCTTTTCAGGAATCCCAGTCTGTGGCAGCCCTCAGCAGGGACACCCTTTTTCGAAAGGAGCCCGGTCCTGGAG
AAGGCAGGGATTTGCGCATACCGGGGCTTCAGTGTACGGGTCGTCCCCATTGAGGGGGGTAAGCTGGGGATATGCGTTGATGT
CAAGCACAGATATGTGTCTAAGAACCCCATAGAAGCCAATATTAAGCGGGAAGAGTTTCGAAAGTACAAAAATGGCCGATGTA
TTTACCACTATGGACACAACTGGTATGAGATTAAGCTTCAGGACCATACTGGGTTGAGCGTTTCCGAACAAATGATTTCAAAT
GGCACCGCCAAGCCAATTTCCCTGTACCAGTTCATCATGAACAATGCTCCTAAGCCTCTCCCTCGCGAAGTGATAGACATGCC
CCCAGACTCTCCCGCCGTCAAGTACATGACCTCTCGCGATGAGGTCAGATATGTACCATCTATTCTCTGTTACCCAGTGTTCG
ACACATCAGACCCACGCGTGAAACCTACCCATCGCGGTACCATCCTGCTGCCCAATGTAAGGAGACAGTACATTCATAATTTT
GTGAATTCCCACCTGACGGACGTGAGAAGCAAGGATATGGCCATCAGGATCAGCTCTAAGCCAGTGATCGCCCCCACAAAAAT
CTTCTTGCCCCCAGATCTGGCGTTTGGTAACAACACCGTGTTCAGCGTCCGGGGTACTCCCGGGACGACCTACGTGAGCCTGG
AGCAGCTCGGCCAGACAAGGATTTCAGCTCTCTTCAACCAGAAAATTGGGCCCTACGATAGTAGACCTCTCGACAGGCAGTAT
ATGATACTTCCCAAGTCCGTCTGGGACTCACACGGGCCCGTCTTCCTGAACGACTTTAAGAAGATTATGAATGAACTGTACTT
GCACGAACTTCCTTATAACCCTATTGTGGTGACCTATAATGATCTGAGTGCTAAGACTTACGCGCTGCAGGGGAGGGCAATTC
TCGACGCCGTCGATAGCGAATTGAGGGAGCCAGGCTACGGCGTCGTCATGATACATGAAACAGTGGATAGAAGAAATCGCCAG
CATGATCAACTGGCCGCCATGGTTATGAGAGAACTTAGGAACCGGAGGCTGTACGTGAGCGTGATCCACACTACAGTGACCAA
AGACTGTTACCAGCTGCCTCAAAACGCTCCGATAGGCAAGGCCTACTGCCCTGTGGCCGGAAAGCAGGGTAAACTGAACGGCT
ATCTGAGGAATGTGGCCATAACAAAAGTTCTCCTCACAAACGAGCGCTGGCCTTTTGTTATAAGTACCCCACTTCATGCCGAC
TTCACCGTGGCCTTCGACGTGCAGCTGAATACCGCCTGCTTCACATTTATCGGGAAGAGCGGGAGTGACATCCGGACAGTTCT
CAAGACCAGCAACCAAAAAGAGCGGTTGAGTAAGGCTCAGGTGCGGCAAACACTGTTGGAGGTGCTGCGCCAGGAGGTCGGCT
TTGGAAGGCGCACCATGCAGACTATAGTGGTTCAACGAGACGGCAAGCTGTTTGCTAGCGAGATCGCAGGGGCGAAAGATGCC
ATCGAAATTGTTAAAAAAGAGGGCATTCTGCCCAGCGACGTCTCTCTGAACTTCATTGAAATCCCTAAGAGCAGCGTGGCTCC
TTTTCGACTGTTCGATTCCTCTCCTCGGCCGGGACAGCCAGAAATGGCTAACAACCCACGGATAGGATCATACTTCATTGCCA
CAAACTACGACGGCTACATCTGTACAACAGGGAAGGAATTTTATCATCCTGGAACCGCTAATCCACTCCATGTCAAGTATATC
GAAGGTAATATGCCTTTCGAGAAGATTCTTGAGGACGTGTACGCATTGACATGTCTCGCGCTGACCCGCCCCGAGGACTGCAC
TCGCGAGCCATTCACAATGAAACTCGCCGACATCCGACTGCGGGAACACGCAGGAGGGTACGATGAAGACGCGCTGGCCTACG
ATGACGAAAACGAAAATGACGAGGATAATGAAAATGAGTAGTAA
63 ATGCCAAAGAAGAAGCGCAAAGTCGAAGACCCAAAGAAGAAAAGGAAAGTAGGTTCAGGCTCCATGACGTTCACCGAATACAA
GACGGTGGAAAAAGAGATCCTGGATTGTCTGCAAACTGCGGAGCTTGGCTGGAGGTATGAACCGGGGGATGAAGTGACACTTA
AGTACCGGGGCGGGGATGAGCAAGAGATGCTCCTTATACCCATACTGCGAGAGAAGCTGAAGGAACTGAACCATGGAGTGATC
ACCGATGACGAGCGGGCCAATATTATTATTCAGAAGCTGAGGGCCTTGAAAGACAACCAAGAGTGGATTAAATGGATCAGAGG
GGAGAAAACCTACAAGTTCAGCCAGGATGAACCAAGCAGGAATATAAACCTCATTGACTACACAGGTGTGGGCAACAACGACT
TCCTTGCTAGCAACCAGGTTTGGATTCAGGGAATCGAGCACAGGAGACCGGATATCCTGCTCTTCGTAAACGGAATTCCCGTG
GTGGACATCGAGGCAAAGACTGCCTCTCACGGCCATATTGATTGGGCTGAAGGCGCCAAGCAGACGGGGAGATATGACAAAGA
AATACCCAATCTCTACTACTCCAACTGTTTCTGTGCCGGAGTGAATGAGCTGCGAATGAAGTATGGTATTCCTGGAGAACGAC
TCCAATACTGGCAGCAGTGGAGAGACCCTTACCCACACACCCACATTCCTAGTTTTGACGAGATGAAGTGTACAATCTATGGT
CTTTTCGACCGGACCAATTTGCTTGATATTATTCAGAACTTCATTGTCTTCGAAACTGAACAGAGCAAGACTATCAAGAAAAT
AGCTAGATACCAGCAATTCCGCGCCGCCAATAAAATCGTGGCTAGAGCACTCAACCTTGATCAGGAAAGTGGTCAACGGCGGG
GCATCGTGTGGCATACACAGGGCAGCGGGAAGTCATTGACAATGTTGTTTGCCGCCCGAAAGTTGTGGAATGACTCCAAACTT
AAGCAACCCACTATCATTATTGTGGTGGATCGGGAGCAGCTGCAGGATCAAATGATCGGTGAGTTGTTCAAGACCAATTCAGA
AAACGTCGCCGTAGCCGTCTCCATCCAAGACCTGCGCCGACTCGTTGCAGAGGGCGACGGTTACCGGGGCATCATCGTGACCA
TAGTAAACAAATTCGAGGGCATGCAGATCGAAATCAGCAAACGCGCTAACATAGTCATGCTCGTGGATGAAGCTCATAGGACC
CAGTACGGCGATCTCGGGATCTTCATGCGGTCAGCGATGCCCAATGCAAGTCTTTTCGGGCTGACGGGAACACCTCTCGAACT
CGACGATCGGAATACACCCAGAGCGTTTGGCCGCAAACTCGGGGAAGACAGATTCGAAAGGTACATGGACAGGTATTCAATCG
AGGATTCCCTTAGAGACGGCGCCACGCGCCCTATCCATTACGAGGTCCGCGCGACCGATTGGACGGTCGCTTACACAGACCTT
GACAAAAAATTTGAGGCTTTGTTCGCTGATCGCTCTCCTGAGGAACGAAAAGCGCTGATGGGCGAGGCTAAACTCGACGCCAT
CCTGAAACACCCTAAACGGATAGCACAGGTGGCCAATGATATTGCTAATCATTTCATCGAACACATAAGACCGAACGGATTTA
AGGCAATGGTTGTGTGCAGGGATAAAGAGATGTGCGCGCTCTACAAAACTGCTCTGGATCAGCTGCTGGCACCGGAAGTGAGC
CTGATCATCATCAGCGAGGACCCCACTCATGACGTCGACAGTATCAAACCGTACTACCTTGGAGACACACAAAGAAGAAATGC
CGTCGACGACTTCAAGAACCCTGCCCCCAAATCCCAAGAAGAAAGGGATAACCCCGATAACAGATTTAAAAGGGTGGAGATAC
TGATCGTGTGTGATATGCTGCTCACCGGATTCGACGCCCCGATACTGCAGGTCATGTACCTCGATAAGTCCATGAGAGATCAT
ACCCTTCTGCAGGCTATCGCCAGGGTAAATCGCCCATACTCTGAGTTGAAGGAGTTCGGGCTGATCCTGGACTATTTTGGGAT
GTTCGAGAAACTGAATGACGCACTCAACTACGATAAAAACGAGCTTGGGGAAGTGGCCTTTCCTTACGGTAAATTCAGGGATA
TGTTCAGAACCAATATAACGGAATTGCTGGACCTCTTCATCGGGATCCCACACGATGGCTCCCACCAGAGTGCAATGCGCGTT
CTGATTATGTTGAACGACAACGATGAGAAACGCGAACAGTTCGAGAAGCTGTTCCGCAATGTTAGGGTGCTTTTCGAGACTCT
GCAGCCAGACGAATTCTTGCGAGACTTTCTCTATGATTATGAGTGGCTGTGCAAACTGTACATGATCTACCTTAAAAAGTTCT
ATCCAGCAGAGCACTTTGAGATAAGCGAGGAGGACGGGGCAAAGACCAGACAGCTCATTCGAGAGCACGTGGATGTTAAGGAG
ATCGAGGAGGAGTTCCCGACCTACAAGCTGGATGAAAACTACTTGACTAAAATAAAAGATATGAATCCCAATGCCAAAGCACT
GGACATCGAGGCAATGTTGGACGCTGAGATTAGGATCAGGCTGGATGAGGACGAAGACGTGCGCCCACTGTCTGAGCGCCTTA
AGCATATAATTGAGCAGAAGCGGGCAGGAACTCTCGCAGGGATAACTCTGCTTAAAGAGCTGGAGGATTTGACAAAGCAGGTG
GTCGATGTAATCCAAGAAACCCAGCGACCTGTGGTGGACTCTATTGCAAAGGAGGTCGCGAAGCGCGTACCGAATATCCCGCA
GGGCGAAGCAATGGCTGTTGCCCAGGCTATCATAGCTAAGGCTAAGGAGAAATGCTTCGAGAACTGGTTCTTGCAGAACTATA
TGGACACTGAGCTGTACCGCGAGTTCACCATTTTGCTTGCAACACAGTTCAAGAATCTGCAGCTGCACGGTGCAGGCAAAGAT
TTCGTAGAGAGGTGTATACGCCTCTTGAAAAAGGCGAGGTTTGCCGGAAAGGATAAGTAGTAA
64 ATGCCAAAGAAAAAGCGGAAGGTCGAGGACCCTAAGAAAAAGAGAAAAGTGGGCTCCGGGTCAATGAACATTATTCTTGATAA
GTCTGTAGAGCTGTTGTTCGTCTTCATTTGTAAAACAGTGATTTTTATCAACTATTACACACGCAACTACTATTGCGTTTACC
CTATTACCACCGATCTGCAGATAAATGTTGTCAACAATATGGAAGAGAACTGGCATTACACAAATTCCTTTCTTATCAATAAG
CATTTTATCGATATTGTGTCTAAAAACTGTGTTCGGATTGTGTGTAAGATCAATTACTTGGATAAAAAGGAGGATATCGAGAA
GCTCCTGCACTCCATCGCTGCCACCCTGGGCGGAGTCTACATCGAGGATTACAATCCCTTGAAGAATGAGTTTAGCTTTTACA
TATGGAAGAGAATCCTGAATAAAAAGATCAAGGATCTGAAAAGCGAGGAGCTGGAAAAACGGATGGAAGATCTGGGCATTAAA
GACATAAAAAATAAGACCCTTCTCGATTACGTTACTAAAAAGTACGAGAATGAAATCAACTTTAAGATCATTAACGAGGAAAA
AGTCAATTGGAACGAGCTTAACTATGAGATCAAGGAGAAGATTGTGCTTGGAGCCATAAAGGCACACCCAGCGATCCGCAAAC
TCATTGAGTACAAAGAGGAAGAACTGTTGGAGGACATTGGGCAGAAGATCCTCACTTATTTCACCATCACCGTCGAATCCGAC
GAAAATGAGAATTATTTCCTGGTGGTCATGCCCAAACATCGGATCATTAGCTCCGAGACTATCTATGAAATGCTGAAGTCAAA
CAAAATTGACATTAATAAGCTGAAGCGGGACCTGCTCGGGGGCAGCGTCTTCATAACAACATCCCGGAAGGGCGTTCGGCGGA
AAAAGGTGAAGATTAAAAAGATTATCAGCCCCAAGGAGCGCGAGTATCGGAAGTACGTTGAAATCATTAATAACTACTACAAG
GAGAAGGGTATTCCTATCAAGGTCGGGGGTGAAGACATCCACTGTTATATTCTCATCGGAGAAGAGAAGATTGATGTTTACCA
CACTAAGAATGCACTGCTGTACAAAGGTATCGACGAAAAAACCCAGAAAATTATACTGGATAAAGGCAAGTTTCTGCACGAGC
TCGAAACCGCAAAGCAGATTCTGAGCAAATACGGCAATCTGATTGACTTCGACGGTGAGTTCTCTAATATCCTCACTAAGGAC
GGCTACGTGATGACACAGCTGTCTACCGTGCCCAAAATAAATATCAAGCTGAGAACTAAAAATGGCATCAAAACCTACAATTA
TCTGAAACTGATGTATCTCTTTGATTGGATTTTCAATAAAACCCTGAACGACCGGGAAATTTTCCTCCCGCTTGTGATTCCCC
CAATGTTGAAAGAAAAGGAGAAAATAGGCATTTATATCTTTTATTCCAACATCTCCGATGTGGAGCTGAACTTCATTAAAGAC
ATTTTCCGGAAGCTCTCAATCCTGCACAAACTGGATAAAAACATACCAAAGATTGAAATTAAACTCGAAAAGGAAATTGATTT
CGAGGATTACGCTAACTCTCGGGCGATTATTACCCAAACTGTGCTGAATAATTCTGAGGAGAAAGAACAGCCCTTCCTCATCT
GTATCTCTCCAAAGCTGCCAAACAACGAGTTTGACGAGCTGAAATCACACCTGTTCTCATACCAACAAACTACTTTCCATCAA
TTCATGTATCCTTTCAATCTGAAAAGATGCTTGAACGACGACGACTTTAAAAAACCCTTCATTAATTCAATCCTTTCTCAGTT
CTTTCACAAGATGGGCATGTACCTGTTTAGTTTCTCCGAAGAGCTGGGAGACTACGACTTCATCATTGGGTACGACATCACGA
AGGAAAAAGACGAAAATGATAAGATCAAGGGTATCGGGGGATCAGCTATCATCTACAACAGCCATGGCCACGTAATCACCACC
GTGACCTTCGAGGACGTACACACCTCCAGCGAGATAGCTAGGTATGAGAAGCTCTTTGCAAAGGTGTATAGCGAACTGGTTCC
CCACCTGAACTTGAATAATAAGAGGAAGATAAAAATACTTCTGTTGAAAGACGGCAGAATCTTTAAGAAGGAGTTGGAGAAAT
TGTCTCTTATCAGCAAGAAGTATGGGTTTGAGATAATTTACATCGACGTGCGCAAAAGCACTAAGCTGCGCTTTTTCGACATC
AAATCTAAAAAAGCTGTACCCGAAGGTAAGAACGCATATACCAAATTCGGTCGAGCCTATTATGTGAGTAGTCACTACTATAA
AAGGTTCCTGAAGCAGCCCATCAAGATTGTCGAGAAGTACAGGATCGATGACGGTTCTTACAAGGGAGTGAAAATAGAGGAAA
AGGATATAAAGCAGCTGATTCTTCTCACAAAAATCAATTTTAGTCAGCTGATGCCCGATAAAATGAAGCTGCCAGCCCCAGTC
CACTACGCTCATAAACATGTCAATGCGGTGCGAAGAGGCTGGAAGGTGGATGATAAGACTATCCTCCGGAATGGATGTCTGCC
TACTATCTAGTAA
65 ATGCCCAAAAAGAAACGGAAGGTGGAAGATCCCAAAAAGAAACGCAAAGTCGGAAGCGGGTCCATGGACTTGAATGAGTTCAT
GGAGATCATCCACCCAATGCTGCCTTCCGGCGGGCTGGATGAAAACCAGATGAACGTGGTGATACATGGCCAGGGACCATTGT
GGGTGATTGCCGGGCCTGGAAGCGGCAAGACCGAAACCCTGGTGATCCGGACTCTGAAACTGATATTCGTGGACAACGTGAAT
CCAAAGAGTATTGTTATTACAACGTTTACAGAGAAGGCGGCCAAGAATATAAAGGACAGAATCAGCAACTACGCCTACCTGAT
CTATCAAAAGTACCCAGAACTGCAGCGGAACCTGGACGTTAATGATATCTACATAGGTACTTTGCACTCCCTGTGCAACCAGA
TCATGCTGGAGTACAGATACCCAGGGTATGAGAATTATAGGCTCATGGATGATATTGAACAATACCTGTTCGTCCATGAGCAC
AGCGACGCTGTAAAGCATCATCACAAATACCAGGATATGTGGAATCACTTTAAATACTTGGAAAACAAATGGAACCGCAGTTT
CAACTCCAGATGGGGGAGAACCCAGGTGGCCACAACCCTCTTTAACCGGATCGTGGAGTACCTCATAGACATAGAGGAACTTA
AGCAGAGCGATGAGAAGTGGGCTGTGCAGCTCGCAGACGCTTATGAGAACTACGTCCAGCTGCTGGAAATCCACCATAGGTGC
GACTTTTCCCATCTCCAGAAGAAATTTCTGGAATTCCTGAACACGAAACTGGGCGAGTTGTTCATTAAAGGGGATGGTTCTCT
GAGACACCCTGGGATTTCCCACGTACTGGTCGACGAGTATCAAGATACGAACCCCATCCAGGAAGCCATTTACTTCAAAATGG
CCGAGAATACCCATAACCTGTGTGTAGTAGGAGATGACGACCAGGCGCTCTATCGATTCAGAGGCGGAACTGTGGAATGTATG
GTAAATTTCGGGAATGCTTGTCACCGCGAATGGGGCATTACCCTCGAACGGGTGAATACGGTCTTTCTGAACAATAACTATCG
GTCCCATAGGGAAATAGTTAATTACTGTAACAAGTTTATAACTTCTTTCCCTGTGATGCAGAAGATCGGAGCCAGAGTGAAGG
ATAAACCTGAACTTAACCCCAAGTCCGATATTTCTGGCAATTACCCCGCAGTTGCCTACATTACAGGGCGGACCATTGAGGAG
ACAGCAAATAATTTTGCCAATTTCGTCAGGTACCTCCTGGACGAAGGCGTGGTGTCCAAGCCATCCGACTGTGCGCTCCTTAT
GAAATCTGTGCGCGAAAATCGCAATTGGGCGGAGCCCTTCAAGAAGGCTCTGAACAAGGTCGGGATCGAAGTATACAACCCTA
GATCCAGGAAATTTCTCGAGCAGGAGGAAGTGATGGCCGCACTTGGAGCTTTTATCACCATTATTGACCCCAAGCAGAATGCG
CTCAGGAAGGTTTGCAACGAAAACATACAGAGACTGGTGAATCGCTGGGTGGACACATACAGGAATGTGGCATCCGAGAGCCC
GGAACTGCGAAAGTACGTGGACTGTTCTATCAAGAGCATCGCCAAACGAAATCTGGGTGAAAGGCTGAATATTAATATTAGCG
AGATCTTGTACAGGATACTCGCCCACCCCCCCTTTTCCGATTGGCTGGACGACCCGGAGCGAAGCTATAGGCTTGGGAAACTC
ACCCAGCTGTTCGAGAAGTATTCTTCCATCCCCTACGATACCCCAGGGTCTACACGAGGACTCCTTAAAATGTCATCTAAGAA
TAACGGAGAAATTAGTTTCCGCTGGAGACAAAATTTTTATAATTCTTTTATTGGACTGCTCAGTACTGAAGGGCTGAACGATC
CTGAGGATGAGGAAATTATCTGTCCTCCAGATCGCCTGCCGATTATGACCATCCATCAAGCCAAAGGTTTGGAGTTCCCCTTT
GTCTTCGTGTATGGCTTGCGGTTGAAGGGAGACAAGCCAAATGAGTCCGCAATTATAGAGGAAGACTTGTACAAGTATAGGAA
AATCAAGTATAGTATCAACTTTACCCCACTGGAAAGAACGCAGCAAGACCTGATCCGACTGTACTATGTTGCCTATTCAAGGG
CTAAGTATGCTCTGATTCACCTTGTACCAAGAAATCATATGGGGTCAAAGGGCTTCGGGTTTATTGGAAATAACTTTAGCCTC
TTCTCTGCTATCGTGAAAAAAATCTAGTAA
66 ATGCCCAAAAAGAAGCGCAAAGTGGAAGATCCTAAGAAAAAAAGAAAAGTTGGCTCCGGATCTATGCCAGTGTATCTTAACCG
GTTCCTTTTGGACCACCTGACCTCACCTCTGTCATTGCCTGCCTTTCGAGTTGAACTTGATCCCCCTCCATCAAAGGACGAAG
TCCACCCCCTGCTGGCGCTGGTTGGACGCGAAGCCGGTGGGTTGGTGCGGTTTCAGAACAGGCTCATCGGCTGGGAAGCACCG
CGGGCACTCGAGGGACAGGTGCGGCGGGGTAAGCAGTCTTACAGACTTGTGCCCCTGGGAAGACAAGCACTGAACCTGCGCAA
GCCAGAGGAACGACAGGCTCTGGAGAATCTCTATCGGATTAGACTCGAGAATATCCTGAAAGCTTTGGCCAAGCGCCACCGGG
CCAGGGTGGAGCGCCGGGGCAATGGACTGTTCCTTTGGCGGCCCGAAAATCCCCGAGAAGAAAAAGAGGGGTGGCACTTGTAC
AGAGGATCCCTGTATCGCATCCATCTTTACCCAGATGGCGAAGTGATCCTCGAGGTGGATGTCCAACACCGCTTCCAGCCCAC
CTTGCACTTGGAGGAGTGGCTTCAGCGGGGTTACCCTTTGCCACGCCGAGTTACAAACGCATATGAAGATGAGAAAGAGTGGG
CTCTTCTGGGGATCGAGGAAGGGAAGGACCCACGCAGTTTTCTCCTTGATGGTGGGGAGTCCCTGTTGGATTACCACCGAAAA
AAGGGCCGGCTGGCCGAAGGACAGGATCCAGGCAGAGTTGTATGGGTCGCCCGAGGAAAGGAACGAGAACGCATCCCACACCT
GTCTGTCCTGTTGAAGCCAGTGATTACTATGGAACTGCTGGCGGAGGTGGCTGAAGTGACCCAGGAAGCTCTCCCTGCCCTGC
AGCTGGAGCCGGAGGAACGACTCAAAGACATCAGGCGATTCGCTGAGCCCGTCTTGCAGGCTTTCGGAAAGCGCGAGACTGCT
AAGCCGCTTGAGGGTCGGGCCCAAAGGCTTCCAAGACCATCCCTTCTCGCACGGGGAAAAAAGCGAGTCGGCAAGGTAGCGGA
CGTGCTGGAAAAGGGAGCATTGAGCCCAGGGGAAACCCGACTCGCCCTTCTTGCATGGGAAGGCGACGGGAAGGCTAAAGGGG
GACTCGCCTATCTCGAGGAGCGCCTGCAGGGCGTGGGCTCAGCCAGCGGAATCAAACTGGAGTTGAAAAGAAGATTTCTCCCT
AGAGGGGACAACCTGGAGATGGCCCAAGTCTTTGAGGAACTGTCCCAAGAGGGTGTCGGAGCCGGGCTGTTGCTCACTCCCAG
GCTCACCGAAGGCGAAAGACGAGAGCTGAAGAATACGGCCGCCTCACACGGTCTGGCACTTCAGCTCCTTAATCCATTTGACC
CTGGAGATATCTACAGAGTTAACAACGCTCTGCTCGGCTTTCTTGCAAAGGCGGGCTGGCTGTTCCTCAGGCTGGAGGGGACA
TACCCTGCAGATCTGGTGGTGGCCTACGATGCAGGGGGGGAGTCCCTGAGGTTTGGCGGGGCGTGTTTTGCACACCTGACAGA
CGGTACACATCTGGGTTTTAGCCTCCCGGCCGCCCAAGGAGGCGAACGGATGGCTGAGGAAGTCGCTTGGGAACTCCTTCGCC
CTCTGTTGCTGAGATACAGGAAGGCGAAGGGACAGACTCCTGGCCGGATCTTCCTGCTGCGGGACGGCAAAATCCAGAAAGAA
GAGTTTCGAAAGGTTGAGGAAGAGTTGCGAAAAAGGAATATTCCATATGCACTCTTCTCTGTTAGGAAGACAGGAGCTCCACG
GCTCTTCAGCAAGAATGGACCCCTTGGGGACGGCCTTTTCCTGAGGCTTCCAGAGGAGGAGGGTGGATTCCTGCTCCTGAGCG
CCGAAGGCGGGAAGGGCACGCCTAGGCCTGTGAAATACGTCCTGGAAGCTGGAGAAGTAGACCTTA/TCTGGAGGAAGCAGCT
AGGCAGTTGTATCACCTGTCCCGCATATACCCGGGCTCAGGATATCGGTTTCCCAGACTGCCCGCGCCCCTCCATATGGTTGA
TAGGATGGTGAGGGAAGTGGCGAGACTGGGCGGGTCCCACAACCTGCGGCTGAAAGAGGAACAGCTCTTCTTTCTGTAGTAA
67 ATGCCAAAGAAGAAAAGGAAAGTGGAAGACCCGAAGAAGAAGCGCAAGGTCGGCTCTGGGAGCATGCATCCTGAGGGAGCAGA
CCTGATCCAAAGAAACCGGGCAGTGCACCGAATGCTTGTGGATGGCGTGACTGTGGAGTATAGGACCTCCGAGGGGGCAATCC
GGGGGGCCCAGGCGCGGGTCATAGACTTCGATGATCCAGAAAATAATGATTGGTTGGCAGTTAACCAGTTTACTGTGGTGGAG
AATCGCCATCGGCGCCGCCCAGATGTCGTCCTTTTCGTCAATGGGCTGCCACTCGCAGTGATTGAATTTAAGAACCCAACCGA
TAAAAAGGCAACAATATGGAGTGCATACAGGCAATTGCAAACATACAAAGCCGAGATCCCCTCCCTGCTCGTGTATAATGAGG
CCCTGGTGATTTCCGATGGATTGGAGGCAAGGATCGGCACGCTGACCGCAGACAGAGACCGATTCATGCCCTGGAGGACAATC
ACAGGCGAAGATGTGGCCCCAGCCGAGATGCCCCAACTCGAGGTCCTGTTGAAGGGAGTGTTCGAACGGCGAAGATTTCTGGA
GCTGGTGCGCGGCTTTGTCGTTTTTGAAGACGAAGGGGGGGGTAAACTGGCCAAAAAGATGGCCGGGTACCACCAGTTCCATG
CTGTGAGAGTGGCCGTCGAAGAGACACTGCGGGCAGCCGCCAGATATGAGGCAGGACGCCAACCTGGGGGAAAACCCGGCGAC
CGAAGAATAGGGGTCGTCTGGCATACCCAGGGCTCCGGCAAAAGCTTGACCATGGTGTTTTACGCCGGCCGCATAATTAGGCA
TCCCCGAATGGAAAACCCAACTATCGTGGTACTCACAGATCGCAATGATTTGGACGGACAGTTGTTTGGTGTCTTCTCTCGGT
GCCGCGAACTTCTCGGGCAAGATCCTATCCAGGCCGAAAGCCGCGCCCACCTGCGGGAGTTGCTTCAGGGGCGGCAAAGTGGA
GGAGTGATTTTCACCACAATTCAAAAATTCCTCCCAGAGGAGAAGGGGGATCGATACCCACAGCTGTCTGATAGGCGCAATAT
CGTTGTTATCGCCGACGAGGCACACAGGAGTCAGTATGATTTCATTGACGGTTTCGCTAGACATATGAGGGATGCCCTGCCGA
ATGCTAGCTTCATAGGCTTCACAGGCACACCTCTCGAGCTGGATGATAGAAACACCCGCTCAGTGTTCGGAGATTACATTAGC
ATATACGACATACAAAGAGCAGTGCTTGACGGCGCTACCGTGCCAATCTACTATGAGTCAAGACTCGCCAAACTGGACCTTCC
TGAGGAACTGAAGCCAAAAGTGGATGAGGAATTTGAGGAAGTGACCGAATCCGAGGAAGTCGAGCGAAAAGAGCGCCTGAAGA
CAAAGTGGGCCCAGCTGGAAGCGGTAGTAGGGGCGGAAAAACGGCTGAGACTGGTGGCCCAGGACATTGTGACTGATTTCGAG
CAACGCCTGGAAGCTCTGGACGGAAAAGCCATGATTGTATGTATGTCCCGGAGGATTTGTGTTGAGCTCTATAACGAAATTGT
TAGACTGCGCCCAGCCTGGCATAACGATGGGGATGATAAAGGCGTGATCAAAGTGGTGATGACCGGAAGCGCCTCAGATCCAG
TTGAATGGCAGTCCCATATTCGGAACAAACAGAGACGGGAATTCCTGGCCAAAAAGCGCTTTCGCGACCCTGCTGACCCCTTT
AAGCTGGTCATTGTGCGCGACATGTGGCTCACCGGGTTCGATTGCCCTTCCCTTCACACTATGTACCTGGACAAACCGATGAG
GGCTCACGGCCTCATGCAGGCCATTGCCAGAGTCAACCGGGTGTTTAGGGACAAACCTGGTGGCCTGGTGGTCGATTATCTGG
GACTCGCTCACGAACTGAAAGCCGCACTGGCCACCTATACGGAGTCTGGCGGAACAGGGCGAACAGCCATAGATCAATCTGAA
GCTGTCGCCGTGATGGAAGAGAAATACGAAATCTGCCGAAACCTGTTTCACGGCTTTGACTGGTCCCTGTGGAAAACTGGCAG
ACCCGAAGAAAGACTCGCCCTGCTTCCAGCCGCCCAGGAGCATATTCTCGCGCAGGAGAACGGGAAAGAGCGCCTCCTGCAGG
CCGTGAGTGAGCTGTCTAGAGCGTTTGCCCTTGCTCTGCCTCACGAAAAGGCACTGGCCATCCGGGACGACGTCGCATTTTTT
CAGGCCGTTAGGGCCGCCCTCGCAAAACGCGCCAGCTCTGAAGAGAGGACCGAAGAAGACTTGGATCACGCCATCAGACAGAT
TGTTTCTAGAGCTCTGATGCCCGAGGGGGTAGTAGATTTGTTCGCTGCCGCCGGCCTCAAGAAGCCGGACATCAGCATTCTGT
CCGAGGAATTTCTGGCCGAGGTCAGAGGAATGCCTCAGCGGAATCTGGCTGTGGAGCTGCTCCGAAAACTGCTGGAGGGCGAG
ATAAAGACGCGGCGCAAGAAGAACGTCGTCCAAGCGCGCTCTTTTGCCGAAATGCTGGAGCAAGCCATTAGAAGATATCAGAA
TCGGGCCGTTGAAGCGGCTCAGGTGATCGAGGAATTGATCGCGCTCGCACGGGAAATGCGGGAGGCAGACAGGCGAGGACAGG
CTCTGGGCCTTAGTGAAGAAGAGTTGGCCTTTTACGATGCATTGGAGACCAACGACAGTGCTGTGAAGGTTCTCGGCGAGCCA
ACTCTTCGCGAGATTGCAAGGGAACTCGTGGATACTGTCAGAAGAAACGTGACAATCGACTGGACCGAGCGAGAAAATGTGAG
AGCCCATCTGAGGCGCTTGGTGAAGAGGGTCTTGCGCAAGTATGGATACCCACCCGATAAGCAGGAGAGGGCAACCCAGACTG
TGCTCGAGCAGGCAGAGGTACTCTCAGAGCAGTGGGCCGCCTAGTAA
TABLE 17
Argonaute nucleotide sequences containing 2X Nuclear localization sequence (NLS) from
Simian Vacuolating Virus 40
SEQ
ID NO Sequence
68 ATGCCAAAGAAAAAGAGGAAAGTCGAGGATCCGAAGAAGAAACGGAAGGTGGGTTCCGGTTCTATGCCTTCAGCTCAACGGTGCAT
CTGGGAGTGGAAGAGGGATATCTTCGTGACCAAGAATCCGACGCTCCGGGAGTCCGTGGATGAACTTAGCTTGCCAGGGACCAGGC
GCATCGTACAGGGATGGATCGACCAGCAAGCCCAATACCCGGAAGATGGGTCAGCAGACGAATATAGCTTTTATGCCGAAGAGTGC
TACCCAACCTCTCATGACCGGCGAGCGTTCTTCCATCGCTTCATTGCCGAGGCGAGACCGCATATCGGCTACAAGCTGGTTGCGCA
GTTGGCAGAAGCAGGGTTCTTGAGAACCATTTGGACGACCAACTTTGACGGACTGGTTAGCAGAGCGTGCACAGCGGCTAACGTCG
TGTGCGTGGAAGTGGGCATGGACACACCCCACAGGGCCTCACGACCGCAAGGGGATGACGAAGTCAGACTGGTGTCCCTCCACGGT
GACTTTAGGTATGACCTGCTGAAGAACACCGCCAATGAGCTGCGCGAGCAGGATTTGGCCCTTAGGGAGGAACTGCTGCACGAACT
CAAAGACTACGACCTGGTGGTCATCGGATATTCAGGGCGGGACGACAGCCTTATGCAAGTGCTCTCTGCTGCCTACAGCGACCGCG
CATCTTGTAGGCTCTACTGGTGCGGGTTTGGCGCGGAACCAGCACCGGAAGTGAGGCACCTTATTAAGAGCATCGACCCAGCCCGA
GAGAGCGCGTTCTACGTGGATACCGCCGGATTTGACGACGTAATGAGCAGGCTTGCACTCAGGCGACTGAGCGGTGAAAGCCTCGA
AAGGGCCCAGAAGCTCATAGAAAGCGTCACCCCGGTTGCTGGCAAAAAGATGGCCTTTAGTGTTCCACCATTGGCCCCTAGCGCCT
TGGTGAAGGGTAATGCCTACCGATTGACCTGTCCGGCAAACGTCTTGAAACTTGATATCGAACTTCCCGAGCACGGTTCCTGGCGC
GATTGGCTGTCCGAACGAATGACTCCAGAAAGGGGGCAGGCCGTTGTGTTCGAGAAGGGAGCACTGGTTTTGGCCGACATGGCGGT
TACCGCTAAAGTTTTCGATGGATTTCTTAGGGTGAGCCCGACACGGGTGGAGATAAGTGACGAGAACATCATCGCTGACGGCCGGA
TCGCCAGTCTTTACCGACGAGCTCTCGTGAGCAGTGCCGCAAAAGCGCTCCAGATCCAAACCGACCACAGGAGGAGGATATGGGAG
CCCGTGCACTATGATACAAGGCAACTCGACGATGTGACGTACCGCGTGCATCGAGCCGTCTCCCTGACGATAGTAGGGATAGAGGG
AGTGCCCCATGTGGTGCTGATGCCAGAGGTCGTCGCATCTACGTTGGCGGGCGACCTTGCGCCGGTTGACAGTCAAAAGACTCTCC
GCAATGCCATTTACGGGTTCCAACATAACGATAAGTTTGATGCCGACCTCAGCTATTGGACCCACCGCCTTGTTGAGAAGGAGCTG
GCTTCCAGCGGCGAGGGCGTTTTCGTATTGAGCAAAGTGCCACTTTATGCGGGCCTGGCACAAAAAGGTAAAGCTCCTCTCCCACA
CAGGTTTGCACGCCACGCTAAACAGCATGGAATTATTGTGCCCGACGCACCGCTTGTTTTCAGCGCCAAGGTTGGCTCTGGAGAGG
TACGAAACCCCAATCCGCTGCATGGGCTGGTGCAAAACCGGCCATGGGACCACTCTCTTACGGCGTCTGGTTTGTGTCCGAGTACA
GATGCTAGCGTGATCTGCCCCGCAGACGCTGCTCCGAGGTTTGAGAGATTCCTCCAATCTATGCAGGAGGTAGCAAGACCAAGCCA
GAGCGAGAGGGACTATTTGCATGATTTTCCCGGCTTCCCTGCGGCCTTTGGACTGCCACTCCGAATGCCCGTGAGAGGGGACGCAA
ACTGGATTACCATCGACGACGGAGTGAGCACCGATGCCCTGACAGGGGCTAAGCAACTGGCGCACCGAGTGTGCCAAGCACTCGAC
CACCTCCGCAGAGCAAGGCCCTCTGACACGGCGATCGTGTTCGTTCCCAGGAGATGGGAACCATATAAGGTAGTGGACACGCAGCA
CGAAAGATTCAATTTCCACGATTACATTAAGGCCTACGCGGCCAGGCACAGTCAGAGCACGCAGTTCGTCAGAGAAGAGACCATCC
AAAGCCAATACGTGTGTAGGGTCCGGTGGTGGTTGAGTTTGGCACTGTATGTTAAGGCTATGCGGACCCCCTGGCGGCTGGATGCG
CTTGATGAGAATACGGCTTTTGTTGGTATAGGGTACTCCCTGGACGCAGAGGCAGGGAGGGGCAACCATGTACTGCTCGGCTGCAG
CCACCTGTATTCTGCGAGGGGTGAGGGATTGCAGTTTAGGCTGGGCCGAATCGAGAATCCCGTGGTGCGAGGAAGGAACCCCTTCA
TGAGCGAGGACGACGCAAGGAGGACCGGAGACACCATCCGGCAGCTTTTCTACGATAGCAAAATGCATATTCCGACAAGGGTGGTG
ATACACAAGAGGACAAGGTTCACTGACGAGGAGCAGAGGGGGTTGGTACAAGGATTGGACGGTGTGAGGAATATCGAGCTGATAGA
GATCAACCAGGAAGAGAGCTTGCGATATCTCAGCAGCCAGATGAAGGACGGCAGATTTGAGATCGACAAGTTCCCCCTGTTCAGGG
GTACCACAATAGTTGAGTCAGATGACACTGCATTGCTGTGGGTGCATGGAGCCACACCCAGCGCCGTGAACAAGTACTGGAGGTAC
TACCAGGGGAAGCGCCGCATTCCGGCGCCATTGAGGATTCGAAGGTTCCTCGGGCAAAGCGACGTAGTGCAGATCGCGACCGAGAT
CTTGGGACTGTCTAAAATGAACTGGAATACGCTTGACTACTATTCAAGGATGCCTGCGACTCTGGATTCTGCAGGCAGTATTGCCA
AGTTCGGGTCATATCTTGATGGGTTTACGAGCGCACCCTATGATTACAGACTTCTGATCTAGTAA
69 ATGCCTAAAAAGAAAAGGAAGGTAGAGGACCCCAAGAAAAAGCGCAAAGTAGGGAGCGGTAGCATGAACTATACCGCTGCTAACAC
AGCGAACTTCCCGATATTTCTGAGCGAAATAAGCTTTCTCACAACCAATAACATTTGCTTGAACTGTTTCAAGCTTAACTACCAGG
TAACGAGGAAGATCGGTAACCGATTTTCATGGCAGTTCAGCAGGAAATTCCCCGACGTTGTAGTGATATTCGAAGACAACTGCTTC
TGGGTCCTGGCAAAGGACGAGAAGTTCTTCCCCTCACCACAACAGTGGAAGGAAGCACTTAGCGATATCCAGGAGGTTCTTAGAGA
GGACATCGGGGACCACTACTACAGCATCTATTGGCTTAAAGACTTTCAAATAAAGGCCCTGGTGACCGCCCAACTGGCGGTGAGGA
TACTCAAGATTTTCGGCAAATTTAGCTACCCAATCGTCTTTCCCAAGGATAGCCAGATATCAGAAAATCAAGTGCAGGTCAGGCGC
GAAGTTGACTTTTGGGCCGAGATCATCAATGACACCAACCCCGCAATCTGTCTGACCGTGGATAGTAGCATTGTGTACAGTGGCGA
CCTTGAACAGTTTTACGAAAACCACCCCTACAGGCAAGACGCCGCTAAGCTGCTGGTGGGACTGAAGGTGAAGACCATCGAAACCA
ATGGCACCGCGAAGATCATACGGATCGCCGGTACCATAGGCGAGCGCAGAGAAGACTTGCTGAAGAAGGCCACAGGCTCAATGTCA
CGACGGAAACTGGAGGAAGCCCATCTCGAACAACCCGTCGTCGCAGTCCAGTTCGGAAAGAACCCCCAGGAGTACATATACCCGCT
TGCGGCCCTTAAACCTAGCGTGACCGACGAAGATGAGAGCCTCTTCCAGGTCAACCACGGAGACTTGTTGAAGGAGACCAAGATCC
TGTATGCGGAGAGGCAGGAGCTTCTGAAGCTGTACAAGCAGGAGGCCCAGAAAACCCTGAACAACTTTGGGTTCCAGTTGAGGGAG
AGGTCCATCAATTCTCAGGAATATCCTGAGGTGTTTTGGACTCCCAGCATCAGCCTGGAGCAAACCCCAATCTTGTTTGGCAAGGG
GGAGCGAGGTGAAAAAAGAGAGATTTTGAAGGGCCTGAGCAAAGGCGGAGTGTACAAAAGGCACAGGGAATACGTGGACACAGCTC
GCAAAATTCGCCTGGCCATACTTAAGCCCGCTAACCTCCGCGTGGGCGACTTTCGGGAGCAACTTGAGAAGCGATTGAAGCTTTAT
AAGTTTGAGACAATTCTGCCACCGGAGAACCAAATTAACTTCAGTGTCGAAGGCGAAGGTTCCGAAAAGAGGGCCCGATTGGAAGA
AGCGGTCGACAGACTCATAAGGGGGGAGATCCCCGTAGACATTGCACTGGTGTTCCTCCCGCAGAGCGATAGGAATGCAGACAACA
CCGAGGAGGGAAGCCTTTACAGTTGGATCAAGAGAAAATTCCTCGATAGGGGCGTGATTACACAGATGATTTATGAGAAAACGCTT
AACAATAAGTCACAGTACAACAACATCCTGAACCAGGTGGTGCCGGGGATTCTTGCGAAGCTGGGAAACCTGCCATACGTTCTTGC
AGAGCCGCTTGAGATAGCCGACTACTTCATAGGCCTGGATGTGGGGCGGATGCCAAAGAAGAATCTTCCGGGGAGCCTCAACGTGT
GCGCGTCTGTCAGGCTCTATGGCAAGCAAGGCGAGTTCGTGCGCTGCCGCGTCGAGGACAGCTTGACCGAGGGCGAAGAGATTCCC
CAGCGGATCCTGGAAAATTGCCTGCCCCAAGCAGAACTTAAAAACCAAACTGTCCTTATCTACAGAGATGGTAAATTCCAGGGAAA
GGAGGTGGATAACCTTTTGGCTAGGGCTCGCGCAATCAATGCCAAGTTCATACTGGTTGAGTGCTACAAGACCGGTATCCCCCGAC
TGTATAACTTCGAGCAAAAACAGATCAACGCACCCTCCAAGGGGCTGGCACTCGCGTTGAGCAACCGAGAGGTGATCTTGATTACG
AGCCAAGTGAGCGAGAAGATAGGCGTTCCTCGGCCACTTAGACTCAAAGTGAATGAGCTGGGTGAACAGGTGAACCTGAAGCAGCT
GGTCGATACCACTCTTAAACTCACGCTGCTCCACTATGGGTCTCTGAAAGACCCACGGCTGCCTATTCCCCTGTACGGTGCCGACA
TCATAGCCTATCGGCGGCTGCAAGGAATCTACCCATCCCTTCTCGAGGATGATTGTCAGTTCTGGCTGTAGTAA
70 ATGCCGAAGAAAAAGCGCAAGGTAGAAGACCCTAAAAAGAAGCGGAAAGTTGGCAGCGGGTCAATGAACACGCCTTTGACGCATTA
CGTGCTCACCGAGTGGGAATCCGATACAAATACTAATGTATTGCACATCCACCTGTACACCCTCCCCGTTAGGAACGTGTTCGAGC
AGCACAAGGAGAACGGTAACGCATGTTTCGATCTTCGCAAGCTGAATAGGAGTCTGATCATCGACTTCTACGACCAATATATCGTG
AGCTGGCAGCCTATAGAAAACTGGGGCGAGTACACCTTCACCCAGCACGAATACCGCAGTATAAACCCAACAATACTGGCCGAGAG
GGCCATCCTCGAACGACTCCTCTTGCGGACAATCGAAAGCGTCCAGCCCAAGAAGGAGATCGCAGCTGGTTCCCGCAAGTTTACCT
GGCTGAAGGCAGAGAAGGTCGTGGAGAACATTAGCATCCACAGGGTAATCCAGTGCGACGTAACCGTGGACTACGCCGGCAAGATC
TCTGTGGGCTTTGACCTCAATCACAGCTATAGGACAAATGAGAGCGTGTACGACCTCATGAAGTCTAACGCCATCTTTAAGGGAGA
CCGCGTGATAGACATTTACAATAACCTGCACTACGAGTTTGTAGAGATTTCCAACTCCACAATAAATGACTCCATCCCCGAGCTCA
ACCAAAGTGTCGTCAACTACTTTACGAAGGAGCGAAAGCAAGCATGGAAAGTGGATAAGCTGGAACAGAGCATGCCAGTCGTGTAC
CTCAAGGCATTCAACGGCAGTAGGATTGCATACGCGCCTGCGATGCTCCAAAAAGAGCTGACCTTTGAGAGTCTCCCGACCAACGT
AGTACGGCAGACGTCAGAAATATTCAAGCAAAATGCCAATCAGAAAATCAAGACCTTGCTGGATGAAATCCAAAAGATTCTTGCCC
GCACCGACAAGATCAAATTCAACAAGCAGAAGCTGTTGGTTCAGCAGGCCGGCTACGAGATACTTGAACTGTCCAACCCAAACCTC
CAGTTTGGGAAGAACGTTACTCAGACGCAACTGAAGTATGGACTGGATAAAGGCGGAGTTGTGGCCTCCAAGCCGCTCAGCATCAA
TCTTCTGGTCTACCCGGAACTTATAGACACCAAGCTCGATGTGATCAACGATTTCAATGACAAACTGAACGCTTTGTCCCACAAAT
GGGGCGTGCCCCTGAGTATCCTGAAGAAGTCTGGAGCGTACCGCAACAGACCCATTGATTTCACTAACCCCCACCAGCTCGCGATT
CTGTTGAAGGAACTGACCAAGAACCTTTTCCAGGAACTCACGCTTGTGATAATACCGGAAAAGATCAGCGGCATGTGGTACGATCT
GGTTAAAAAGGAATTTGGCGGCAATAGCAGTGTTCCGACGCAATTTATCACCATCGAGACACTTCAGAAGGCAAACGACTATATTC
TGGGGAACCTGCTCCTTGGCCTCTATAGCAAGTCCGGCATCCAACCATGGATTCTTAATAGCCCCCTTAGCTCCGACTGCTTCATC
GGTCTGGACGTATCACATGAGGCGGGTCGCCACAGCACCGGGATAGTCCAAGTCGTAGGAAAGGACGGGCGCGTGTTGTCATCCAA
GGCGAATACGAGCAATGAAGCCGGCGAGAAGATCCGCCACGAGACCATGTGCCAAATAGTGTATAGCGCCATCGACCAGTACCAGC
AACACTACAACGAGAGGCCTAAGCACGTGACCTTCCACCGCGACGGTTTTTGCAGGGAGGACCTGCTGTCACTCGACGAGGTGATG
AACTCCCTGGATGTCCAGTACGACATGGTGGAGATCATCAAAAAAACCAATCGGCGAATGGCACTGACCGTCGGCAAACAAGGATG
GGAAACCAAGCCAGGACTGTGCTACCTGAAGGACGAGAGCGCCTATCTGATCGCCACCAATCCGCACCCGAGGGTGGGCACCGCGC
AACCCATCAAGATTATCAAGAAGAAGGGGAGCCTCCCTATCGAGGCCATTATACAGGACATCTACCACCTGAGCTTCATGCATATC
GGCTCACTGCTTAAGTGCCGACTCCCCATCACAACTTATTACGCCGATCTGTCTAGCACCTTCTTTAACCGCCAATGGCTTCCGAT
CGATAGTGGCGAGGCCCTTCACTTCGTGTAGTAA
71 ATGCCGAAAAAGAAGCGGAAAGTTGAGGACCCCAAGAAAAAGCGCAAGGTGGGCAGCGGCTCCATGCTTATCTGGCAATTCAAGAG
AATGCTCTACTGCCAGGCCAACAACATCAAAGAGGAAAAATTCAAAGACCTGGAGAGCGAGCGAAATCAAAACACTATCCAGAGCT
ATTTTGACCTGAAGGGCGGCTATCCGGAAAGATATAGCCAGGAGGAATACTCCGCTTATTTCGAGCATTGCTTCCCGAAGTCTATC
AACCGGAAGTATTTCATGCAGAAAATAGTAGAGGGCCGAAATCCGAGCATAGGTCACAAGTGTTTGGGTGCCCTGTTCGACTGCAA
AAAGGTAAACCACATCTGGACAACCAACTTCGACGAGCTCATCGAGAATGGGATTAAAAGCGTCAACAATGCCAGCAGCTTCGAGG
TCATTAGTATCGACAATCAGAGGCAGCTGGCCAACCTCAACAACTACCCAAGGGTGGTAAAACTTCACGGCGACTACAGGTACGAC
AAGCTCCAAAATACCGTTGACGAACTGCAGACGCTGGAGAAGGACCTCCATAAGTACTTCGCCGATGTGCAAAGCAAGACCGGCTT
GATTGTGATAGGCTACGGCGGAAACGACCAGAGCATCATGTCCGCCTTTGAAAAGACTTTGGAGGCCGACAACCCGTTCCCGTTTG
GGCTTTACTGGTGCGTGAGGACGGGCCAGAAAACCAACAAGAAGGTAATCGAATTCATAGAGAAGGTTCACCAGAAGAACAAGGAA
AAGCTTGCTGCGTTCATCGAAATCGACTCTTTTGACGATTTTCTTTATGAGCTGTATAAGACGAACAACCTTGCCAACGATCACAT
TGAAAATATCGCCAAAAGCCGCTTCGAAAAAAGGAAGGCTTTTACAGCCCCCCAGATCGGCACCTCCTTTACGCCTATAAAGCTTA
ACGCCATAAAGGCCAAGACTTACCCGAAAAGCATCTATTCCTTTAAAACTGACCTCAAGGGGGGCAAGGATGACTGGGATAAACTC
AGGGAAATCATTAAGGACCAACCGGTGAGCGCGGCTCTGACCAATGAAAACACGGTCGCCTTCGCAAGTGTCAACGACATCAAGAA
ACTCTTCTCACACACACTGAAGTCAGAGATCACCACCGTGGACATAGATGACAAGTTGATCTATCGGCAGGAGTCTTTCTACCTGG
GCATGCTTTACGATCTGATAGAGCACAACCTCCTGAAGAAGTTCAAGTTGGAGAAAGTGCCCAACAATAGGCTCCGCAAGTATTAT
AGCAAAAACTACAAGCTGAATACCGAGGAGCTTCAGAAGTCCAAGATCAAGACCAGCCTGTCCGTCTACGAAGCGTTCGAGATTCA
AATAGAATTCCACAATAAAGAGCTGTTCCTCATTATCCTTCCGTCCATCCACATAGACGACAAAGCCGGGCTGAGCCGATTTGAGA
AACAGGAGATAGCCAATAAGATCATAAGCAAAAGGTGGAACCGCATGGTTAACAACCAGCTTAGGTTCTGGCTGGGGCTCCTTAAG
AACGATAACACTAACATAGAGTTCAGCATCGACAGTTTCAAGATTGATTTGGAAGAAAAGTTCTCCGGCGTCGGGAGCTTTACATC
CTCTTACTACATCTTTAAGGGCGCGTTTATTTCCAACGAACCCAAGCTTAGCTTCCATATCTCCGACAGCAATTACAAAACAGTGC
ACCCCCTGAAAGGCCTCAAGAACTTCGGTCCACTGGATTACTCATTTGAAAGCAAACAGACCAATCAGCAGGCTATTAAACTTGGT
ATAATCACTCCGATCAGCGGCATGCAACGGATACTCAAACACCTGAACGAACTTAATAACGAGATCCGCGCAGCTACGGAAAAGGA
GTACCTGACCGATTATTACCCCTTTAGCAACATCTACAAGAGATACCTTGACATCCCGCAGAATAAGGATAGTAAATTCTTGGAAC
TCGTGAATGAAGCCGAAGTGAACAAACTGAACCACCTCGAGTTTTATGACTTCCTCAAACGCAAAATTGATTACTTCTATACAATT
AGGGGCGAGTTCGACGTGCTTGTGTTGTATTTTCCCAAAGGCTGGACTAAGTTCCGCGAGCTGAAAAATGACAGTGTCTACTTTGA
TCTGCACGACTCCATCAAGCTGTACTGTGCTAAGAAGAATATCAAGATCCAATTCGTGGAAGATAAGAGTATAGACTACCTCGACC
CGGCCAAGGTTAAATGGTGGTTGAGCCTCGGCTTGTATGTCAAAGCGAACGGGCTGCCCTGGCGGAACGTGGTCGTAAACGAAAGC
ACCGCGTTTGTCGGGCTCGACTTCGCGGTCCAGCGAATAAACAACAGTAACAAGTACGTGCTGGGTAGCTCACAGATCTTCGACAG
CTCCGGACAAGGACTCAGGTTTCTGTTGCAGCCCATCGAACACCCTGTGTTTATCGGTAAAAACCCCTTCATGAGCAAGGAAGATG
CGCGACGGATGATTCTTAAATTGAAGGAAGCGTATTTTAGGATTGACGGTAACTCCAAGCTGGAAAAACTGGTGGTGCACAAAGTA
CTGCATTACACAAATGATGAGATGACCGGCATTTCCGAGGCGCTGGAAGGTATTGAGAACATTGAGCTTCTGCAAATACAGAAGTA
TAGTAAGTGGAGGGCAATTAGAGGGGACATCGATCGGTATACGGGAAAGGTGAAGACCGACCCGCACAATTTCCCGATCCAACGGG
GGACAGTGATCCAGCTCGACGACTTCTCTTTCCTTCTGTGGACACATGGAAGTGTACAGGAAGACGACGTGGCTGGTAGGCACATG
AATTACTACCAGGGTAAGCGCGGGATTCCCGCACCACTTCTCATACGGAGGTTTCGCGGCACCGATCCGATTGAAATGACCGTGCG
AGACATCCTGTCACTCACCAAGATGAACTGGAACGGAGGCGAACTTTACAAGACTCTGCCGGTGACCCTGGATTTCTCTAAACGGC
TTTCTAAGTATGCGAAGCAGGCAGAGACCCTCCAGGCAATACCCTACGACTTTCGGTTCTTCATGTAGTAA
72 ATGCCCAAGAAAAAGCGAAAGGTAGAGGACCCCAAAAAGAAACGCAAAGTGGGCTCCGGAAGCCTGAAGCTGAACCACTTCCCCCT
TAATCCCGACCTCCCCCTGTACATCACAGAATATGCCCACCGGAACCCGCGAGCGTTGCTCGGATTCGTTAGGGGCCAAGGTTTCT
GGGCGCAACAGGTCGGAGAACAGGTACAAGTGTACCACGGTAGACCGCAGCCCACGTTCAGGGGAGTTCAGGTGATCAGCCATACC
AGGTTGGACCCCGACCATCCGGCTTTTGACCAAGGCGTTTTGAGCCTCATCCGACAAGCACTGGTGAGGGCGGGATACGTGCTGAC
CTACAGGGAGAGGATGGCTATTCATCCCAGACTGGAGAGGGTTGTGCTGAGACCCCCGGACCGGCACCCAGCAGAGTTGACCGTCC
ATGCACATCTGCGATGGGAATGGGAGCTTGAAAGGCACAGCGGACAACGCTGGCTGGTTCTTCGACCCGGCAGGCGACATCTGAGC
GCCCTTCCATGGCCCGCAGAAGCAGTACAAATGTGGTCCGCCGCTCTTCCGGCCACCTGCCAGAAGCTGCACGCCCTTTGTCTGGA
CCGAGGCCAACAGATGGCCCTTTTGCGGCAAGAGGACGGCTGGCACTTCGCCAATCCCGGTGCTGCCACTCAAGGAAGGTGGCACC
TGTCCTTTAGCCCCCAGGCCCTTCACGAGCTGGGACTGGCACAGGCTGCGCACCATGCGGCTGCATTTAGGTGGGACGAGGTACAG
CGACTCGTGCAACTGACTGACCTGTGGAAGCCCTTCGTGACCTCTCTGGAGCCCCTTGAGGTAGCTGCCCCCATCATTGCCGGGAA
AAGGCTGAGGTTTGGACGGGGTCTTGGCCGCGATGTCACGGAGGTGCACAAGCGAGGTATCCTGGAACCACCCCCACTGCCCGTGC
GACTGGCTGTCGTGTCTCCCCATCTTCCTGATGAGCACGCGAACGCCCAGTTGAGGCGGGAGTTGCTTGCTCACCTCCTCCCGCGA
CACCAAGTACTGAGATCAGCGGAGAGCCGGCAAGGCCTCCACGAGCACCTGAGGAGGCAAGATCAGGACGATACCCTGTATACCTT
TTGGTCAGGCGGCGAGTACAGGAAGCTGGGCTTGCCCCCCTTCGATCTCGCACGAGGCCTGCACACCTACGACCCAGCTAGCGGCC
AGCTGCAACAACCGGCTGCCCTGGCACCAGCACCCGCGCAGGCCACGCAAGCGGGTAGGCAGCTGATAGCCCTGGTGGTGTTGCCC
GACGACCTGACGCGGTCTGTCCGGGACACCCTGTTTCAGCAGCTCCAGCAGTTGGGCCTTAGGTGTCTGTTTAGTGTGAGCAGGAC
CCTGCTGCACCGACCACGCACAGAGTATATGGCATGGGTAAACATGGCCGTCAAGTTGGCTAGGACTGCAGGGGCCGTGCCTTGGG
ACCTGGCAGACCTGCCCGGTGTCACCGAGCAGACGTTTTTCGTAGGCGTTGATCTGGGGCATGACCACACCCACCAACAGTCCCTC
CCGGCCTTCACCCTGCACGACCATAGGGGACGCCCTCTTCAAAGCTGGACGCCTCCCCGACGCACCAATAATGAGAGGCTGTCATT
GGCCGAGCTTAAGAAGGGGTTGCATAGGCTTCTTGCACGCAGGAGCGTGGACCAAGTGATCGTGCATCGAGACGGCCGATTCCTTG
CTGGCGAGGTGGACGACTTCACTCTGGCGTTGCATGATCTCGGCATCCCGCAGTTTAGCTTGTTGGCAATCAAAAAAAGCAACCAC
AGCGTGGCGGTGCAAGCAGAGGAAGGATCCGTGCTTAGCCTGGACGAACGACGATGCCTTCTTGTTACTAATACCCAAGCCGCGCT
TCCGCGGCCCACGGAGTTGGAACTGGTCCATAGCGACAGGCTTAGTTTGGCGACCCTGACCGAACAAGTATTCTGGCTGACCCGCG
TCTTCATGAACAACGCGCAGCATGCGGGCAGCGATCCAGCCACCATCGAATGGGCCAACGGCATAGCCAGGACTGGACAGCGAGTG
CCCCTGGCCGGGTGGCGGCTGTAGTAA
73 ATGCCAAAGAAGAAGCGAAAAGTGGAGGACCCTAAGAAAAAAAGAAAGGTGGGCTCAGGGAGCATGGAGGCGTACATAACGGAGAT
GGTGTCCAGGGAGAGGGCCAACGAGCTGGAGGTTTACGTGTACGTGTTTCCACGGAAGCAATCCGACAACAACTACGAGGGTGTGT
ATCACATAATGAGGGCGTGGCAACGGGCTAATGACCTGCCTCTGGCGTATAATCAACATACGATCATGGCATTTTCCCCCGTGAGG
CATATGTGTGGCTACACGCCGATGGAGACGCAGAAACGCCATATTAACATTGACTCCCCATTCGAGAGAGCCCTGCTGGAGCGACT
GATAAAGAACAGCCTGATTTTTACAGCCGAGCGCCATTTGCATGCCAAGCGGGTAGGCCATGCGCTTCGGCTGAACCAGGTGCAGC
AAATCCGGCAGGTGATCATCTATGAGGCCATCGAGCTCTATGTAAATATCATTGAGAATAGAATAAGCATCGGCTTTCACCTCACC
CACCAGTTCGAGTACGTATACACTCTCCAGAGCATGATAGAACAGGGAAAAACAATCAGACCTGGAATGCGCGTCGTGCATTCTAA
CGGAAGGCAGCATTATACCTACACCGTGGAGAACGTAGCAACATATGGGGTGACCGACAGATGCCCGCTGCTGCAGACCAGCATTT
ACCAATACTACGTCGAAAAAGGCGCGCAGCACATTTTGCGCACCTTCACCCGATCCACCAGGGTGATCCACGTAAGAACGAAAGAG
CAGAGGTTGAGCTACGCGGCGACACTCCTGAAACCGCTGTGTACTTTTGAGACCATGCAACCCCAGGACGTGCTCAATGTCAGCAA
GTGCATCAAACTTAGCGCGAGCAAACGAATGAAATGTACTTACAGGTGGATTCAGCAACTCCGGGCACAGTACCGACACCTGACCT
TTGCGCCGAACCCCTTCACGATCGCCCAGAATGGCTATAAACTTGATCAGCTCAGCACCCCCAAGGTGCACTTCCACAGAGACTAC
GCCACCGTCGTGAGCGGAATGAAGACCGGCAAGCTTTACAAAGGCGGTAATATCAAGATCAGCGTGCTCTTCGACGAGGACTTTTA
CTTGAAACACCACATCACCAAGAAGGACATATATCAATTCATTGCAGTCCTGCAGAAAATCGCCATCGCACAAGGCGTGAACATGA
CCATAAGCACGAGCACCAAGTCCATTACGGGCAAGTTCACGGACGACTTTTTCCACCACTTCACCGAGGAGGTCGAAGCACTGCAG
CCCATCTTCGCGCAAACCACAGTTCTGGCATTCATTACCAGTACCCACCTGAGCAACAAGAAAACCAGGAGTTACCAGCTGCTGAA
ACAGTACTTCGGCGGCAAGTGGGACATTGCCTCTCAAGTCATCACGGAGAAGACGATTGAGGCGTTCCAAAAAATCTTGCACAAGC
ACGGCCTGAAGAATTTCTACCCCAATGACGAACAGCACTGTCTCCGCGTGATCGATGTCCTCAAGAATGAGAGCTTCTACTACACG
GTCATGAACATCCTCTTGGGAGTATATGTGAAAAGCGGCATCCAGCCCTGGATCCTTGCTAATACAACCCACTCAGACTGCTTCAT
CGGCATCGACGTTAGCCACGAGAACGGAAACTCTGCGGCTGGGATGATGAATGTTATCGGCAGCCAGGGCCACCTTATCCAACAGG
CGCCCCTGAACGGCATATTGGCGGGAGAAAAGATTGACGACACCCTGCTCGCAAACTTGCTTAAACAAATGATTAAGGCATACCAC
ACCCAGTTCCAGCGCTTTCCCAAGCATATAACAATCCACAGGGACGGCTTTTGGAGAGAACACACTGCACTGGTCGAGAAGATCAT
GAGCCACTATGAGATTACCTACGACATCGTCGAGATCATCAAAAAGCCTAATAGGAGGATGGCTTTCTTCAACAGCGTGGACAACA
CCTTTAGCACCAGGCAGGGGACAGTGTACCAACGGGGCAACGAAGCCTTTCTGTGCGCCACTAACCCTCAGCAGAAAGTGGGCATG
GCACAACCAATCAAAATACATCAGGTGACCAAGACCCTGCCCTTCTCACACATCATAGAAGATGTCTACAACCTCAGCTTCCTTCA
TATTCACGCTATGAATAAGATGCGACTGCCGGCCACCATACATTATGCCGACCTGTCTGCCACCGCTTACCAGAGGGGCCAAGTGA
TGCCCAGGAGCGGTAACCAGACAAATCTGCCTTTCGTGTAGTAA
74 ATGCCTAAAAAGAAACGCAAGGTAGAGGATCCCAAGAAGAAAAGGAAGGTGGGGAGCGGGAGCGTTCACGCATTGCTCGCTCTGCT
CGCGAACCGAGCCGGTGGAAGGACCGCCAGAATGGGAGACAGCTTGCTCACGTGGAGCCCTCCTGAGTCTCTGCTGCTTGAAGGGA
CCCTGAGCTGGCGCGGCAACACCTACACATACCGGCTTCGCCCACTGGCGAGAAGGGTGCTCAACCCTAGGAATCCCAGTGAGAGA
GACGCCTTGTCCGCGTTGGCGCGACGACTCCTCCGAGAAGTGCTTGAGCAATTCAGGCGCGAGGGGTTTTGGGTTGAAGGTTGGGC
CTTTTACAGGAAGGAGCACGCACGGGGTCCCGGGTGGCGCGTGCTGAAAGGTGCGGCGCTGGATCTGTGGGTTTCAGCCGAGGGGG
CCATGGTATTGGAGGTGGATCCGACTTATCGAATCCTGTGTGACATGACACTCGAGGCGTGGCTTGCACAGGGACATCCACCCCCG
AAACGCGTCAAGAACGCGTACAACGACAGGACATGGGAACTCCTGGGTCTGGGTGAGGAGGACCCGCAAGGCATTCTTTTGCCAGG
CGGGCTGAACCTCGTCGAGTACCACGCTAGTAAGGGCAGAATCAGAGACGGCGGGTGGGGTCGGGTTGCGTGGGTGGCAAATCCTA
AAGACGCCAAAGAGAAGATCCCGCATTTGACGAGCTTGTTGATCCCCGTCTTGACCCTGGAAGACCTGCATGAAGAGGGGGGCTCT
AACTTGGCCCTCTCCATCCCGTGGAATCAAAGGCAAGAGGAAACCCTTAAAGTGGCCCTGTCCGTGGCTCGCCGACTCGGCGTCGA
ACACCCCAAGCCCGTCGAGGCCAAAGCCTGGAGGATGAGGATGCCAGAGCTTCGCGCACGACGCAGGGTGGGTAAGCCAGCGGACG
CCCTTAGAGTGGGGCTGTACCGGGCTCAAGAGACTACCCTCGCACTGCTTCGGCTCGATGGCGGCAGAGGATGGCCTGACTTTCTG
CTTAAAGCATTGGAGAACGCTTTTAGGGCCAGCCAGGCTAGGCTTCATGTTAGGGAAATCCACGCGGATCCTAGCCAGCCCCTTGC
ATTTAGAGAAGCCTTGGAAGAAGCGAAAGAAGCAGGTGTGCAGGCTGTCCTCGTACTCACCCCCCCACTGAGTTGGGAGGAGCGAC
ACCGCTTGAAAGCACTGTTCCTCAAAGAAGGACTCCCAAGTCAACTTCTGAACGTCCCCATACAGAGGGAGGAAAGGCATCGGTTG
GAAAACGCCCTGCTCGGGCTCCTGGCGAAAGCGGGTCTCCAAGTAGTCGCCCTTGAGGGCGCATACCCTGCTGATTTGACAGTTGG
ATTTGATGCCGGAGGCCGCAAGTCCTTTAGGTTCGGAGGTGCCGCATGTGCTGTCGGCTCCGACGGAGGTCACTTGCTGTGGAGTC
TGCCGGAAGCCCAAGCGGGCGAACGGATACCAGGCGAAGTAGTTTGGGACCTGTTGGAGGAGGCGTTGCTGGTGTTTAAGAGAAAA
AGAGGGCGGTTGCCCAGCCGGGTGCTTCTGCTGAGGGATGGCAGGCTTCCCAAGGACGAGTTCACCCTGGCACTTGCAAAGCTGAG
GCAGCTCGGCATTGGCTTCGACCTCGTGTCCGTAAGGAAGAGTGGAGGCGGAAGGATTTATCCGACCCGGGGAAGATTGCTTGACG
GCCTTCTGGTGCCCGTTGAAGAGAGGACTTTTTTGCTCCTGACGGTGCATAGGGAGTTCAGAGGCACCCCACGGCCCCTCAAATTG
GTACACGAAGAAGGTGAGACACCTCTGGAGGCTCTCGCAGAGCAGATCTACCACCTGACGAGGCTGTATCCTGCATCAGGTTTCGC
ATTTCCCAGACTGCCCGCACCCCTGCACTTGGCAGATAGGCTCGTGAAAGAGGTGGGCCGATTGGGCGTGAGGCATCTCAAGGAAG
TAGACAGGGAAAAGCTGTTCTTTGTATAGTAA
75 ATGCCTAAGAAGAAGCGAAAAGTGGAAGACCCAAAAAAGAAAAGGAAGGTGGGTAGCGGCAGCATGAACGCCGTGACCGTGGGCAG
CACCCCAAGCGCCCAGGTACTCGTCGGTGTTCAGCCATACGACGAAACCACCCTGGAGAGCCTGAGAAGTAAACACCGCGGAGACT
ATCTCTTTAAAAGGGGGGGAGAGAACGGCGATAGCATACTTGCTGTGGCCCTGAAACCGAGTCTGCCGGTCATCGGAGCAACCGAG
GAGGATGTAATTCTTGCCGAGAGCCCATGGTTGTTGGCTCCACTTGCCTTGGAGACTTTGCTGCAATGCTTCGTGAGGCTTCAAAG
GCCCATCCTGAAAGCTAGGCATCCCCTGAGAGTGCTCTCACAAAAACCGGCAAATCTTTTCCCAGCCGATGCGGGGGTCCCCCAGT
GGCTGCAGAGGAGACTGGTGCTGGAATTCGACACGCGCACTGTTAGGGACAGGTCAGACGCTGCCTCTGTCGTGCTGGCATGTGGC
GTGAGGACTCGGAATTTGATTGATGCCGACTGCGCGACACTGATAGCAGCCGGTGTCCCCCTTGTGAATCGATACGTGGTGACGAG
GCACCCTGCGGATGATCCCCGAGTGCAGGGCTATTTGAGGCTCGCCGGGAGGGTGACCAGGATAGATGGCCCCAACCTGTACTTGG
AGGATCATGGCGATGGAGCAGCTGTGATCAAGGCCTCCATGGCCTATCTGGAGCCCAGGAGGGAGAACGTGATTTGGTGTGCCCAC
CATTTGCTGGGGAGAAATGCGGATAGAGTACTGGCGGAAGCGGATAACGCAGCCGCAAAGCACTTGAGCGGTCCCGAACGATTGGC
CGTAGTGAAGAAGACTTTCGACTACCTTAGGAGCCAGAACATCGAGCTTGCGCCTGGAGTGCCCCTCACTCTGGGTAACGTTGTGG
GGAATGACAAGGGTTCTTGGATCTTCCGGACGGAAACTCTGCCCAAGCCCCACCTGGTGTTCGACCCGAGCGGGACCCGGATCGAT
AGGTGGAATGAGAGGGGATTGGACGCTCACGGGCCCTATGATCAAAGGACCTTCACCCCTAAACAACTGAGGATTGCCGTCATATG
TCAACTGCCCTACGAAGGCCAGGTCGATGCGTTCCTGGCAAAATTTCTCGACGGCCTTCCAGACGTGAAGACCGGCTACGGGGACC
GGGCCAGGGCGCCTTATGCCAAGGGGTTCATCAGGAGGTACGGTCTGGAGAAGCCCAAGGTGAGCACCTTCGCAACAAAAGGCGCT
ACTGCTAAGGACTATGCCGCTGCATGTAGGGCGGCTGTGGAGGACGCAACCGCAAGCGGCTTCGAGTGGAATCTGGCTATCGTGCA
GATCGACAAGGATTTCAAGGAGCTGAGTGACGTGGAGAATCCCTACTTCACCACCAAGGCCCTGCTGCTGAAGCATCGGGTGCCCG
TCCAAGAGGTGACGCTGGAGACGATGAGGTTGGCAGACGAACAGCTGGTGTACGTGTTGAACAACATGAGCGTAGCCACCTACGCC
AAAGTGGGCGGTACTCCCTGGCTCTTGAAAGCGCAACCAACCGTGGCCCATGAGTTGGTAGTTGGAATCGGAAGCCAGACTTTTAG
TGCCTCAAGGCTGGGTGAGAAAGAGAGGGTTGTAGGCCTTACCACCGTGTTCTCCTCCGACGGGAAATACCTGCTGGACGACCGGA
CTAGCGCCGTTGATTACGACAACTATAGCGAAGAGCTGTTTAAGAGCTTGTCCCGGTCAATAGAATCAGTAAGGATCGCCGATAAC
TGGCGAAGTACGGACAGTGTCAGGCTGATTTTCCATGTTTTCAAGCAGATGGCGGACGAGGAAGCCGACGCGGTTGACAAGTTGGT
GCAAAAGCTGGGTTTGGCACAGGTTAAGTTCGCGTTTCTGCACATCGTGGATGACCACCCATTCGCCCTGTTTGACGAGAAGAACA
TAGGTACAAAGACATGGGGTGGGATATTCAAGGGCGTCTTGGCACCGGAAAGGGGCCTCGCGGTAAACCTCTCTGGGGCCGAAACC
CTGTTGTGCTTCACAGGCGGCAGGGAACTGAAACAGGCGAAGGATGGCCTGCCCGTGCCTAGTCTGCTGCGACTGCACCACAGGAG
TACGTTCAGGGACATGACCTACCTGACGGGGCAAGCCTTCAACTTCAGCTGTCACACCTGGCGCATGTTCACACCCGCTCCTGTTC
CCATCACAATACATTACAGCGAGCTGATGGCGCGACTCCTTACGGGCCTCAGGCACGTCCCGGATTGGGATCCAGACACAATGCTG
ACCCCCATCAGTCGAACCCGGTGGTTCCTGTAGTAA
76 ATGCCCAAGAAGAAAAGGAAGGTAGAGGATCCAAAGAAAAAGCGGAAGGTTGGAAGTGGAAGCCTCCCCATCGTCCTGAACGCCTT
CCCACTTAAAGTACCCGAACTGGAGCTGGAAGTTAGGCAAATACCGTACGATAAAGAGACGCTTGACGGCCTCAGGGCTGCGCACA
AGGCCACCCACGCTTTCCGCAGGCAGGGCGACAACATACTGATTTTTTCCGGTGATGGCACATTTCCCGCGTCTGGGACGCCTCAA
ACTATTGCACTGAAGGACAATTTCGGCGTGTTCTACAGCCTCGTGAAGGATGGTCTTATCCGCCACCTTGCGGGGCTCGGGAGGAA
TCCCAGCGGGTTCAACCCCATAGAGTTGGTGTCCGCAAAACCCGAAGACAACCTGCTGGTCCCCATACTCGGCGATGCGTATCCTT
TTAAGGTGTGCGCGAAATACAGCATTGACACCAGAACCGTGCTGGGGCACCCATGTCTGGTGATCGATTGCACGACCAGGAGGGTG
TTGAAGGAAAATGGCTTGTTCTTTTTGAACGCTGGGTTCGACCTCGCGGGCAGGTACGTGGTGACGGAGCAAGATGACGGGTACAG
GAAATTGCTCGGCAGCGTGAGCGGCTGTAAGGGTGAAACGCTGTACGTGACTAGGCCCGATGGCCAAGTGGTGCAGGCCGAGGCTA
AAAACGTGTACCTGGAGGCATCCCGCACAAATTTCGACGACTATATTCTGCACACCCACAGGGCTCAGAAGGACGCGATCGTTGAA
CGAATCAGACAGTCCGTTTCCGTGTTTAATGGGGGCGAAAATAAGAAAGCCCGAATCGACACGCTGAAGAAGTATATCCAGTCCAA
AACCATTCCCTTGATCGACGGCACCAGGATTGAGATCCAAGATTCCCCTAACATACAGAAAGACTGCGGCCAGATGCAAAAACCGG
TATTCGTCTTTAACGACAACGGCGAGGCGGACTGGGCGGAGAAGGGGCTGACCCAATCTGGGCCGTACACCAAGAGGACCTTCGAC
AGGAATGACCCCTCCATTTGCGTGATCTGCGCCCAACATGACAAGGGACGCGTTGAGCAGTTCGTCAGGAAGTTGCTTAAGGGCAT
TCCAAACTCCAAATACTTCAGCAACGGTCTCGAGGGGAAGTTTACCCTGGGCACTAGCAGGGTAGAAGTGTTCGCGACCGCTACTG
ACAGCGTAGACGCCTACAAGAACGCTATTGAAGCCGCAATACGGAAGAAGGCCGACGACGGCGGCAGGTGGGACCTGGCCCTGGTT
CAAGTGAGGCAGAGCTTTAAGAAGTTGAAAGTGACCGAGAACCCCTACTACCTTGGCAAAAGTCTGTTCTTCCTCCACCAGGTGCC
CGTCCAGGACTTTACCATTGAGCTGTTGGCTCAGTCCGACTACTCCCTCGGCTACTCTCTGAATAACATGGCCCTTGCATGCTACG
CGAAGATGGGCGGTGTGCCCTGGCTGCTTAAATCTTCACCCACCCTCAGCCATGAGCTTGTGATAGGCATCGGCTCCGCCAACATC
GGCCAGGAGAGAGGAGCTGATAATCAGAGAATTATGGGCATCACCACTGTGTTCAGCGGAGACGGCAGCTATATCGTGAGCAATAC
ATCTAAGGCTGTTGTCCCCGAAGCTTACTGCGAGGCCCTTACCGCCGTACTTGGCGAAACCATCGAAAAGATTCAGAAGAGGATGA
ACTGGCAGAAGGGCGATACCATCAGATTGATCTTCCACGCTCAGGTCAAGAAATTCAACAAGGAGGAAATCGAAGCGGTCAGAGCC
GTCATTGAGAAATATCGGGAATACCAGATCGAGTACACTTTTCTGAAGATAAGCGAAAACCACGGGCTTCACATGTTCGATAGTGC
AACCGCAGGGGTGCAAAAGGGCCGACTTGCCCCTCCGAGGGGGAAGACGTTCAAGCTGAGCAAACATGAGATGCTGGTTTATCTGA
TAGGGCAGAGGGAGCTGCGGCAAGACACCGATGGTCATCCCAGGGGCGTCATCCTTGATGTTCACAAGGACAGTACATTCAAAGAC
ATCACCTACCTTTCAGCCCAGCTCTACTCATTTGCCAGCCACAGCTGGCGCTCTTACTTTCCCAACCCTATGCCAGTAACCATTTC
ATACAGCGATCTGATCGCTCGAAACCTTGGTTGGCTGAACCAACTGCCCGGGTGGAACGACTCCGTGATGATCGGAAAGATCGGGC
AAAGCCAGTGGTTCCTGTAGTAA
77 ATGCCGAAGAAGAAACGAAAGGTTGAGGACCCCAAAAAGAAAAGGAAGGTGGGGAGCGGCAGCATGAATAACATACCCATCAGGCT
GAACTTTTTCGCCCTGAAGAACCAGAACATTAGCTTCAGGATCTACAGGCAGGACTTCAACGGCCAGAAAAAACAGGACGGGTACT
ACAGGACCAAGCTGCCCATCAACGACTCTTCTGACACCTACGCGGAGTACTGGGTGACAACCCAGCCCAAGGATGGCTTCGAGAGG
GTGTACTGCCTGGGTTCCTCAAACCCTAAGCTCACCGTCCGAATCATGTGGGAGAGCTTCCTGGATAGGGTCCAGAAGTCCCTGAG
CTCCGACGAATATATCCTTTACGGTAACGGATTTAGCCGGAAGGTCGCCGTGATCATCGGCAGGCACAGGGAGGGCAATGAGGTGA
TCCAGATAGAGCCCTATTACCTGAAGGCCGAGAAGAAGTTCGGCTTTCTGGTGGACTTCGCATTTAAGAAGGCCAAGGACGTGCCC
TATAGCATCAGGGTTCAGCAGCTGAGCCTGTCACTGAACAAGTATGGGAAGAGCAACGCCGACTACTATAGCGACAAGCTGGATAA
GATAAAGTTCTTTATGCAGAAGTTTAAGCAGAGGCTTTTCCCATTTAGCTTGGATAACGAGGATTACGACATCGAGAACGAGCTGT
ATCTGATGAGGAGCTACCCGCTCAAGATGAAGACCTACATATTCTCTAATGGCAAGGAAAGCAACAGCCAGGTGCAGGGTCTCAAA
ACCTACGGACCGCTGGCGAATCTCGATAAGGAGCCACTGTTCGTGTTCATGTTCGAGTCCCAGGACAGGAACGAGGCCCTGGAGCT
CTATTCTAGCCTGCTGGGCAAGACGTACACCAACATATTTGCTGGCATGGAGAGCGTGTACAAAATCAAACTCGCAAAAGAGAATG
TGAAGCACATCATCATCCCCAGCCTTACCAAGGAGGGTCTGCAAGTGGTGGAGCAAGAGCTGCAAACTATCGTGGAGAGTCATCAG
GACAAGAAGGTGATTGGGATATTTGTAATGAATGAAAAGGTGCCCTCATCCATCACCGGTTTCAGCCCCTACCACTACGTCAAGTA
CATCTTCACAGAGAAACGCATTCCCCTCCAGACAGTGAGGTGCGAGAGGATCGCTGCCAGGGATGGCCTCAAATGGAGCGTTGGCA
ACATCGGCCTCCAAATTTTCGCTAAATTGGGCGGCATCCCCTGGAAAGTCAAGCCGAGTAACGATAAGTGCATCATTTTTGGCCTG
GGCTGCGCCCACAAAAAAGACGAACTGGGAAACATTAACAAATACTTCGCCTACAGCGTGTGCATGGACAGCAGCGGCATTTACCG
AAAGATTAATGTGCTCGGCGATGCAAAGGAGCGCACTGATTACATCCTTCAACTGCGGGAGAACATCAAAAGCGTGATAAGCGAGA
ATCTGGACGGGAGCATTGAAAAGTGCGTGATTCACCTGCCCTTCAAAATTAAGAACGACGAGATCAGGTACATAAAATCCAGCGTG
CAGGAGATCGCGCACCTGTATTCCGACATAGAATTTCAATTTATCAAGATCAACACGGACAACAAGTTTTTCGGATACGCTGAAAA
CAACAGCAAGGTACCCTACGAGAGCAGCTACATACAACTGAGCAGCAACGAGTTCCTGGTGTGGTTCGAAGGCCTGCAGTACGGGA
AGGAGCTGGTGAAGAAAAAGGTAGGTAACCCCGTGCACATTGAGTTCATGCAGATCGATGAGTTGGATCCCGAAAAGAAGCGGCGA
TATCTGCAGGATATCATAAACCTGAGCGGTGCCAACTGGCGAGGTTTTAACGCCAAACTGTCTCCAATCAGCATCTACTACCCCAA
CATCATAGCCAATTTCATTTCAGAGTTCAGGGAGTTCCAGCCCGAAGGCGACGTGGACCTGACCAACTTTTACATTCCCTGGTTCC
TGTAGTAA
78 ATGCCCAAGAAGAAGCGCAAAGTAGAGGACCCTAAGAAAAAACGCAAGGTCGGCAGTGGCAGCATGCATAACATCGAAATCAACAC
CTTCGTCAACAGCTTTGCCATTAAACCCAACAACTCCATGTCCTTCCTGCTCGGCGCAGGCGCGTCTATATCCTCCGGGATCCTGT
CTGGCGGACAGATGGTGTGGGACTTTAAACGGAACCTCTATTGTGCGTCCAAAAACATACGCACCAGCAATTTTCCCGATATGAGC
AAAAAGAATGCGCAGGACGAGATCCAACGCTTTTTTGATGGGCAGGCCGGAAATCCTAGCCTGTGGTCCTCCGAGGAGTATAGTTT
CTACTTCGAGAGGTGTTATCCGGCGAGGAAAGACAGGGAGCTGTACATACAGAACAAGGTACGAGACGTCAAGCCGTCATTGGGGT
ATCTCTGCCTCGGGGAATTGATCATACACGAGAAGATCGGTGTAGTATCAACCACAAACTTTGATGACCTGGTGTTGGCCGGCATC
CATTCAATAAGACCGGACCTGAGTGTGAAGACCATCAGCAGTGCCCTCAAAAATAGCACGGGATTCTTCGTGAACGACGGGTTCCC
GAACATCATTAAGCTGCACGGCGATTACTTGTACGATAAGCTGAAGAATACCGATAAGGAGCTGCAAAAGCTCGAGACGGAGATCA
GCGGAATTTTTCGAGATGCCGTCAAGAGTGGCGGGCTCATCGTACTTGGCTACGCCGGCAACGACAACAGCGTGATGAGCGTCCTG
GAGGAGCTCGTAAGCTCCGGGCAAATCAGGTACGGCGTGTTCTGGTGCCAACCGAAGGGCTTCCCCCTGTCCAAGCGAGCGCGGGA
GTTTATTGAGAAGGCTTGCGCCTACAATGAGGAATCCGGGGTTGTCGAGATCAACAATTTTGACGACTTTATGTACCGCCTGTTCC
TTACACTCAACATCCAAAACTCATTTATCGACAGCATGTGGGAACAGAGCGGCATGAAGCAGCCGATCCTCTATGAGAATATCGGA
CGACACAAGTCCACCGCCGTGACGAACGCCCTGTGCGCCCTGCAGTACCCCCGAAAATGCTACGTCTTCAACGCGAATATATCAAG
CTGGAAGGAACTGCGCGAGACGATAAACGACACGTGCGTGGCAGTGCTGTATAAGGGCATGGTTTGGGCGCTGGGCAGCAAAGCAG
GCATCGTGCATGCGTTCGCCGGGAAGATCAATGGAGACATATACGAACTCGACATCCCGTTGTACATGATGAAACTCGAGGATTCT
GACATCCTGGGCATGTTTTACGACATCATAGGACGCGGCCTTCAGCGAAAGGGGCTGGTGAGCTACGGTAATAGGAAACATCACAA
ATACTTCAACCCCTCCAGCAAACGGTTCAAGAACGGTCAAAACATCTACGACGCGGTCAAGATATCACTGAGTTTCGTGGACGATC
AGCTCGTGCTCATCCTGCTGCCTACGGTGCATCTGCTGAAACGCGACGGGACGGAGCTGGAGAAATTTGACTACCAAAAATTGGTG
TCCCAGGAGATGGCAACACACTACAACAAAGTGGTGGACAGCGAGATAGAGATCTGGCTGAAATTCATCTCTAATAACGGCAAGAT
AATCTTTGAGCTGGGGAACGCAATACTGGAATTTAACAACGTCCGCATCCAGTACTCTGGTAACGGTAACCTCAGCAAGTGCTACC
AGGTGAGCGAGCCCGAGCTCACGTTCAGTTACGAAAAGGACAACTGCATCGCTACCAACCAACTGCGGGGTCTGATCAACTATGGA
CCCATAGAGACTTACGTGAACAAAGCCATCAGGTTGGCTGTACTCAGCCCTAAGGAGTGTGCCGCGGACATTTGGAAACACCTGCA
GAAGTTGAATGAGCATCACGTCACCTCCCTTATTCAGGATGCAAATTTTCTGCCGGAGTACACCGGCTTTCAGAACGTTTTTAGGT
GCAACCTTGACATTCCCAATGGGAACGATGTGCATAGGTTCAAAGGCTACAGTATAGACAAGGTCATGCAACTCAACGCAAAGAGC
TACTTTTACGGGATCTGCAAGTACATTGATGCATTCGAGACACAAAGGAGCCAATACGACCTCCTCGTCATCTATATACCTAAGCA
GTTGACCCACATCCGAGAGGCCAAGAATAACTTCGAATATTTCGACCTGCACGACAGCCTGAAGATTTATTGCGCTGGTAAAGGTA
TAGTCACGCAGATCATCGAGGAACACAGTGTTTATACTAACAATGACACCGCCAAGATCATATGGGGTCTCTCAACGGCCATATTC
ACCAAGACCGCCGGAAGGTTGTGGAAACCCAGACGCTATTCCATGAACACCGCTTACGTCGGCCTGTCATATGTGCAGAGCGTTAA
GAACAACGAGAAAGTCAGCATCGGTTGCAGTCAGCTGTTCGACGCCGAAGGCAATGGAATGAAGCTTTACCTGAGACCCTTGATGA
ACCCCCAGATAATTCAAAATAACCCTTTTATGCGGAGCGACGACGCTTGCAGGCTTATGTCAAACCTTAAGCGGATGTATGACGAC
AGTGTCCCGCTCTACAAACTGAATAGGATCGTGATCCACAAAACTACGTTCTTCACTAAAGAAGAGATGGAAGGCATCACCAAAGG
GCTGGCTGGAGTGGATGACATAGAGTTGCTCCAGATCCAGGAGTTCACAGCTTGGCGAGCAATACGCTTCGACTACGACAAGATCG
CACCGTTTCCGATACAGAGGGGCACAGTGATTCTGGGGTGGGGCCACTTTAGTTACTTGGATACCTGGAAGTGTACCACCTAGTAA
79 ATGCCTAAGAAAAAGCGAAAGGTCGAGGATCCAAAGAAGAAACGGAAGGTGGGCAGCGGCTCCATGCAAGAACACCTGAAGACGAA
CATACTGAACTTTAAATGGCCCAACTCTGCTCCGACCATCTACCTGACATTGGAGGACATTGAGGGGAGCCACCCTATCCACAAAA
GCAAATTTTCTAGACAGATAAAAGAAGTGTTCCCCGACGCGGATTTGAGTAACAAGGACCAGATCTTTACGACATTCACGACCGAA
ATCCCAGACGCCCCAAGCATAAAACTGAACCTTGTGGACGGCCGAGAATTGCGGATCTATAAACAGTTCCTCAAGCACAAGCTGCG
GTCATATTTCAAATCTAAGGACTACATCGTGGTCAAGAATTTCGTGGGCGACGTTCAAGTGTGGATGCCGAGCAAAAAGGGTAACA
CCGCAGATTACAACCTGTACTATAAGTTTAGCTTTAAGATCCAATTTGCCAAACTGACGGACCTCCCCGAGCTGATCGTAAGCTAC
GATGGCACCTCCAAGGTGCTCACGACGTCCGTTAAGGACATCGAAGATTCAGAGCTCATCAAGCGATGCGTCTACGGCCAAAAGAC
GTTTAACTACCAAATGGACTTGGACACCGAAGAGAAGCAAGAGTTTTACAACGCGATACAGTTTGACCAGGCCTACCCAATTTTCA
ACCTTTCCCTGGCAAGGGCACTCGACATCCCCATAGAGGAGCCAATAAGGCCGATCAACAAATACCAAAAATACGTAGCCCTGATT
AACAATTTCGCAACTAATTACCTTTTCAAGGAGGACTTCAAGGTTATCTTCCCGTTTAAAACAGACACGTTCATCGACGTGCCTAT
AAATCGGATAAATCACATCGACCCCCAAGTCGGCCTGTTGGAATTCGGAAAAGATCAATATGGCAACAAGAAAACCCACCTGGTAC
CTAAAAAGGCAATGAACATCTTGAATCCATACCGGCGACCTAATAATCAGAACATCAAAATCTTTTTCATCTGTCACACAAGCCAC
AAAGACTCCGTGCTCAGCTTCTATCAGAATCTGAAGGAAGGAGTAAACACGGAGAAGAACTACTACAAAGGACTTGAAGCCTACGT
GAACATTAAGGCAAGTAGTAGCAAGGAGCATTTTATCGAGTTCACGAACGAGAATGACCCCATCCCGGAGATCGTGGAGAAGCTTG
AGAGCCTCACATTTGATCATGACAATGTTCTCTACGCGGCGTTCTATCTCTCCCCCTTCGACAAATTCACCCAGAATCCGGAGGAC
CGGGAAATTTACATCCAAATAAAGGAGTTGTTCCTGAACGAAGGTATCGTGACCCAAGTTGTCGATTACGAGAAAATGGTCGTCAA
TATCGAGAATCAGTATAACTTCCAGTTCAGCCTGCAAAACATGGCCCTCGCCATTCATGCTAAGCTGGGCGGTGCCCCGTGGAAGC
TGGCCGTGACCGACAAGAAGGAATTGGTCATCGGGGTTGGAGCGTTTACAAATCAAGGCGAGAACAGACGCTATATTGCTTCCGCC
TTCTCCTTTCAGAATAACGGCCTCTTCCGCAAGTTCGAGTACTTCGATCAAAGCGAGACCGACCTCCTGGCTGGCAGTATCTGCAA
AGCCATCCGCGACTTCACCAGCGTAGCGGAGGCAGATAAGGTCGTTATCCATTTCTATAAGGAGATGAGTTACGAGGAGCTTAAAC
CCATCATTCGGGGCATGCACACGCTTGGGCTGAAGATACCCCTTTACATACTTAACATAAACAAGACTGAAGCCGAGGATATTATC
GCCTACGACCTGAATTGGAACAAAAAGCTGATGCCCGTCAGCGGCACCTACATTCGCATCTCCGAAAATCATTTCCTGCTCTTCAA
TAACGCACGATATCCTAATTCCCAACGGTACGCCGACACGGATGGTTACCCGTTTCCCATTAAGATTAAGGTCAGCTCTCCGGACG
AGGATGCCTTTGAAGATGCAGATGTGGTCCTGGAGCTGCTTACTCAGGTTTATCAATTTAGTAGACTGTATTGGAAAAGTCTTCGC
CAACAAAATGTACCTATCACCATCAAGTACCCAGAGATGGTAGCCCAGATTGCCCCCCATTTCAACAACGGGGTGCCCGACGATGC
CAAGGATGCTCTGTGGTTCCTGTAGTAA
80 ATGCCTAAGAAAAAACGGAAAGTGGAGGATCCCAAAAAGAAGCGGAAGGTCGGCAGCGGCTCAATGGCCTATCCAATCGCTGACGA
CCGGCGAAAGTACTTCCACAGTCTTTTCGAGAACAAGGAGCCGTACATCGGATACAAGGCTCTGTGTCTGCTGGCCAAGAACGACA
TCATCAAGAGCGTGTGGACGACCAACTTTGACGGGTTGACTGTGCGGACCGCATTCCAAAGTAACTTGACCCCCATAGAAATAACC
CTCGACAACGCAGACAGACTGTTTAGGAACCAAAGCAAGAGAGAGCTGCTGAGCATATCACTTCATGGCGACTATAAGTATAGCAC
GCTGAAAAATACCGAGAAGGAGTTGGACTCACAGGACGGCACCTTCAGCGAGCATCTGGGTAACTATCACGTCGACAAGAACCTGA
TTGTGATAGGTTATTCAGGGCGCGACAAAAGTCTGATGAAATCCCTGAACGATGCATTCACCAAGAGGGGCACCGGCAGGCTGTAT
TGGTGCGGCTACGGTGACAAGATCAACACTGAGGTGGAAGAACTTATACGCAACGTACGAACCGCTGGAAGGGAAGCCTTCTACAT
ATCCACCGATGGTTTTGATAAGACGCTGATCGACCTTTCTAAAAGCGCTCTGGAGGACAACAGCATGAGCCTCGAAAGCCTTAATT
CCATCCTGAAACTGGCAAACAACGAGGAGCTCTCAAAGATCGAATTTAGCCAGAGCATCACCAGGACCGACAAATACCTGAAGAGT
AATCTGCACGCAATTGTGTTCCCCAAGGAGATATTCCAGTTTGAAGTCGAGTTTGGCGACAACAAGCCCTGGTCATTCCTTAAAGA
CAAAACTAACAACACCGACATATGCGCCATCCCCTTCAAGAGGAAGGTTTACGCCCTGGGCACGCTCAGCGGTATATCTAGCGTGT
TCAAAAACGTGCTCAAAAGCGAGATTAGGAGGGTACCAATCTCCAAGTTCGACATCGACAATGTGAGCAGCTTTAGGTCTCTCATG
ATCCAAACGGTGATCAAGCACTTTCTGTCATACGGAATCTTCGACAGCAACCTCAAGGACAAACTGTGGCTTAGAAATTCCGACAA
TTCCTTCGGGGACAAGAAAATACACAAGGCGATTTACCTCAGCTTCTACTTCGATAAGAGCAGCAAATTCGGCTACATTAGCTTCA
GCCCCAGCATACACATAACCTCCGATAACGAGATCAGCAAGGAGGTGAAACAAAGGATTAGCAAAGAGATCTTGGAAAAGCTCCGA
AACGATAAGTTTGACGAAATACTGGAGTACTGGAACACCATACTGTTCAATTACAAAAATCTTAAGTTCGAGTACCCCCTTAACAG
CGGGACCGGATTCGAGTTCCAAATAAGCCGAAACACTGCGTTTGCCGAAATCATGGTGCTGGACCCGAACTATCGAGTCTATAAAC
CAAGCGATTACAACAACAAGCTGACCCAGTTCAGAGGTGTGCAGTATCTGGAGCCGCAACTGATCTTTCAGAACTCACTGAGTAAC
TCCCACACCAAGGACTACCACCCCATGAGGGCGTTGACCAATAACAGGCCATACGACAACAACTTGAATGGCATCATCTATTCAAA
CGAGGTCAATTTGGCCGTGATTTGCGGGGAAAACTACTCCAAAAACCTCTACGACTTCCTGAACCAGCTTAACCTTAAACACCCCA
CAGACAACATCAACCCCGATTTCCTTATAGAATATCCTGGCTTCGCGAGCGCCTACAACCTCCCCATCAACATCCCATACTATGAG
GACGCGGACAAGTGGATTAACATAGATTTGGAGAAGAGCAACAAGTCCGACAGCGAGAACGCCATCATCGTTGCACGCCTCATCAC
AAGCAAAATCGAGCAGATCATAAACATACAGTCTCAGCACACCATCGTCATCTTCATCCCCAAAGAGTGGCAGGCCTTCGAGAGCT
TCCAGGAAAATGGCGAGGACTTCGACCTCCACGACTACATCAAGGCGTTTAGTGCATCCAAGGGCGTGAGCACCCAGCTCATCAGG
GAGGAGACACTGTCAGACAGGTTGAAATGCCAGGTCTACTGGTGGCTGTCTCTGAGTTTTTATGTAAAGTCTCTGCGCACGCCATG
GGTCTTGAATAATCAGGAGAAAAACACCGCCTACGCCGGCATAGGCTACAGCATTAAGAAGAACAGCAATGACACCGAGGTGGTGA
TCGGTTGCAGCCACATTTACGATTCTAATGGCCAGGGCCTGAAGTACAAGTTGAGTAAAGTAGATAATTACATCCTGGATAAGCAG
AGCAATCCCTTCATGAGCTATAATGACGCGTTTCAGTTCGGCGTGTCAATTAGGGAACTGTTCTACAATAGCCTGGACAGGCTCCC
CGAGAGGGTGGTTATCCATAAGCGGACCAAGTTTACGAACGACGAGATAAAAGGTATTACTGCCAGCCTCAACATGGCGGGGATTA
CCAAGATAGATCTCATTGAAATCAACTACGAGACGGAGGCTAGGTTTCTCTCCATGAACGTATTCAACGGCCTTCTGGGCATAGAC
AAATTCCCTATCAGTAGGGGTACCTGCATTATTACGAATAAGTACGAAGCCCTCCTTTGGACCCACGGCATCGTGCCCTCCGTGAA
GAATCCCATTCACAAGTATTACCTGGGCGGCAGGAGCATCCCAGCCCCGATCAAAATTACTAGGCATTACGGCGAGAGCGATCTGA
ATACTATTGCCATCGAGATCCTCGGCCTCACCAAAATGAATTGGAATAGCTTTGACCTTTACAGCAAGCTCCCTGCGACGATTAAC
TCCTCAAATCAGATAGCCCGGATCGGTAAGTTGCTGGCGCGCTTTGAGGGCAAGACCTATGATTATAGGCTCTTTATTTAGTAA
81 ATGCCCAAGAAGAAGCGAAAGGTAGAGGACCCAAAGAAAAAAAGGAAGGTGGGCTCCGGATCTCTGGACAGTTTCCACCTCGTGCA
GACAGAGAAAAAGGCCATCGCAATGCCAAAGCAGAAGCTTGCGGTTAATGCACTCCCCATTAGCCTGAAAGAGCAGGAGCAGCACA
AGCTGTTCTTTTTTAGCAAGGAAAAGCAGGGCGAGCGAGCCCCGCTCACCAGGAAAGAATATCCTGACAGCTTCGCCAAGAGGTAC
CCCAAGAGCTCCAAAGAGTACGACGTGCTGTACACGGACTTCACCCCAGAGCCAGCTGAGGATGGGTTTGAAATTGATATCGACCT
GGAGGAGGCACCTGGCCTTGCCAAGCACTACTTGCACAAAAGGATCTTTGAGGCCTTTAAGGGAGTAGCTGACTTCAGAAAGCGGG
ATTTCATCAACGGTGTGGAGCTTTGGTTCAGGGACAAACCCGCCGACGAAGTTAATTTCCGGGCCTACAAGAAGTTTAAGATTACC
ACCCGCAGAACTTGGTTCTCCGCAGGCTGGGCCCTGTTCATACAATACACCGGCCATTCCTTTATTCACCCGGTGGCGATCAATAG
CGAAGAGGCCGCAGTGGACACTACGGAACTCACGCGGGTTGCTTATAACCGACACATCTTCCACTACGAGGAGATCCCCGAAGACA
AACTGAGTGAGATAGATTTCAGTAAGATGTACCCCGTGGTGAACTTCAACATTAGGGATAAAATGCAGCAGTTCCCCGTTATCGAT
CCATTCAAAAACAAGGTCAAGGAATATGTCGACGAAATAGACAGGTTCAAGAACATGTATCTGATCGCGCCAGCGGTTGAGGAGGT
GCTTCCGTTTACTTTCAACGACGACAACTGGTGCGAGATCAAGATCGGCACCTACCATACCGTGCCCAATGCCGGTTCCAAATTGG
TTTTCCGCGATGGGCAAACCGAGATACACCCGTTCTACGGTATCAGGAACCACGGCCCTTTCATGCCCCCCAAACACAGCCACATA
AGGTTTTTGTTTATCATGAGCAAGAGGGACATCAAGGGCGCTGGTAAGCAATTCTATGAATACTTGAAGGGGGAGGTAAAAGGAGT
GGACGGGTTCAACAGGTATGCTAATATACCGTCATCCCTGAGGGGTGAGATGATCGAGTTTGAGAACGAGCAAAACCCCCTGCCGG
AGATTATCGACGGCTTGAACAACATGGAGCGAGAAGCGGGCGTGGCCTACTTCGCCTTCTATATCAGCCCCATCGACCGAGAAGTG
AGGAACAGGAAGGAGAGGTTGGTGTACTACAGGGTTAAGGAGGAGCTGCTGAAGAGAAAGATTGCCTCACAAGTGGTAGAAAGGAG
CACTATCGAGAAGGCCGACTTCCGCTACAGCATCCCCAACATCGCCGTTGCCACAGTGGCCAAGCTGGGAGGCATCCCGTGGAAGC
TTACTCAACCCCCAGAAGCAGAGCTGATCGTGGGCATAGGCGCATTCCAGCCACGCGAGTTCGACAAGCGATATCTGGGCAGCGCC
TTTTGCTTCCAAGGCGACGGAACCTTTAGCGGCCTGAGGTGTTTCACCAAGGACGAACCCCATATGCTTGCTGGCAGCATCAGGGA
AGCGGTTCAAAGGTACGCCGATGAAAACAGGCAAGTGGAACGGCTGGTTATCCATTTCTACAAAACCATGAGCTATGACGAGAGGA
AGCCGATCCTGGCCACCTTGAAAGAACTCGGCCTGGACATTCCCGTTGTGGTGGTCACTATCAACAAGACTGAATACGAGCAGACA
ATCCTCTTTGACCTGAATTCTAGCATGAGGCTGCCGCTGAGTGGTACCTATTTCAGCCAGCGCAGGGACGACATCCTGCTGAGCAA
CAACACCAGGTACCGCAAAGACAGCGAGGTGAAGAGGGGTTTCCCTTTTCCCGTGAGACTGCAGCTGTGGTGCTCCAAGGAGGGCC
TGCTGGACGACGAGGGTTTTAGGGAGCGACTGATCACCCAAGTGTATAGGTTTTCTCGGCTTTACTGGAAGAGCGTGTCTCAACAG
AATCTGCCCGTGACCATTAAGTATCCCGAGATGCTGGCCGAAAAGTTCCCATACTTTAACTCAAGGAGCCTTCCTAGCTTCGGCGA
AAAAAGCCTGTGGTTCTTGTAGTAA
82 ATGCCTAAGAAGAAGCGGAAGGTGGAAGACCCGAAGAAAAAACGAAAGGTGGGCTCCGGAAGCATGAACAACACCATAAACAAAAT
AGACTTCGGCGCGTTTCTGAGATCATTCAAGCAGAACCTGGACGGTAGCTTTTCTTTCCTTCTGGGAGCAGGCGCGAGTGTGAGCA
GCGGCGTACAGTCTGCAAGCGACTGCATTTGGGACTGGAAAAAAGACATTTTTCTGGCCCAAAACCTTCAATTTGAGGAGTTTCTG
GACATCCATAGTGACTTCTGTAAAGATAAAATCCAAAAGTGGTTGGATGAGCAGGGCGTGTTTCCCAAGCGAGACTCAGAGGAAGA
GTACGTGTTTTATGCCGAGAAAGCGTACCCAATGGAACAGGACAGGACCAAGTATTTCGAGAACCTTTGCGCGGACAAAACCCCCT
ACATAGGGTATAAACTGCTGATGCTGCTGAACAAATACGGAGTTCTGAAATCCGTGTGGACAACGAATTTTGACGGTCTGATAGAA
CGCGCAGCGCACCAAGCCGATCTGACGCCCATCGCCGTTACCCTCGACAACCCCGAAAGGATTAGCCGAAACGAGAGTAAATCTGA
GCTGCTCTACGTGGCACTCCACGGTGACTACAAGTATAGCAAGCTGAAGAACACAGCCCAAGAGCTGGACGCGCAAGAAATTCTCT
TCACCGAACGCCTGAAGTCTTACTTCATCGATAAGAATTTGGTGGTGATCGGTTACAGCGGTCGAGACAAAAGTTTGATGCACACC
TTGTGCGAGGCTTTTATGACGAAGGGGTGCGGTCGGCTTTACTGGTGCGGCTACGGTAACAAGATTACCTCTGAAGTGCAGAACTT
CCTCAACAGAATAAACGATTCAGGTAGGGAAGCCGTGTACGTGGACACCGATGGGTTCGATGCCACCCTCGTGTCTATTATGAAGT
TTTGCTACGAGGATCAATTCGACAAGAAAATCGAAATCGGCAAGTATCTCAAGGGCCTGTCAAGGGTGAAGCATATTATCCCTTTC
AGCGTTGAGAATACCACGTTCACCGGCTGCGCCAAGACCAACCTGTACCCCTTGATCATCCCCCAAGACATATTCCAGTTCGAGAT
AGAGAGCCCCGAAGGTAGCAGCAAATGGACCTTCATTAAAGAGAAGATTAAGGGCAAGGACATTATCGCTGCCCCTTACGAGAAAA
TAGTCTACGCATACGGGCTGCCAAACTCAATCTACAACGTATTCAGTAAGGAGCTGATCGGCGAGATCAAGAGGGTTCCCATCAGC
CTGAGTAACATCAAAGACAACAGCACCCTCAAGAATATCATCCTGAAGGTGCTGATATGTTCTCTGAGCAGTAACGCGGGACTCAG
GGCGAGTATGAGCAAGAAGATCATCTGGAATGAGAAAGAGAGGTTCCAGAGCAACGTTTTTAAGGCAATAAAGATCGACATCGTTT
TCATCAATAGCGAAAAGTACGCCCTCATCTCAATCACCCCTACCCTCTATTTCAACAAGGAGGGCAACTACACGACGCTGCAGAAG
CAGGAAATTACGCGGAGCTACATTGACAAGCTGTACAATAAGATTTATGAGGAAACCCTTTGTTACTGGGAGGCCATCCTGTTTAA
GCAGCAGACCAAGATCTGCTTCGACTACCCGCTCAATTCCGGGAACGGCTGTTTCTTCAAGGTTAGCTCTAACAGGGGCGAAGCCC
TGTTCAATAATCCGAATAAGCCGTACGTGATTACTAACGACATCATACTTAAACGCAAAATCTACGAAGGCATCATAATCGACGAG
CCCCTCCTGAACTTCTCAGGGTCAACCAGCGCCCACATCATTATGGACTCCAATCCGATGCGCGGTCTCAACAACAATAACCCATA
TGATCACTTCATTGCAAGCAAGTTTAGGGACGTTTCTATCCACATCGGAGTCGTGTGTCCCTGTACATATAGCGACAGGTTTTTTA
GCTTTCTGAACGAGCTGCAAAGTCCGATAAAGAATAACAATCCTAACTCAGACTACATCCAGAACTATAACGGATTCAGCCAGATA
TACGCAAGCATTCTTAATATCCCAGCGATCAACAGCCAATACTGGATCTCATGCCGCGAAGAGCAGGATAACAGCATCTCTTTGGC
TAGGAACCTGTGTAAATACGCGAACCAGATGGCCACTAACATGCCAGGTATAATAGTTACCTTCTTCATTCCTAACAGCTGGAGCA
ACCACAAGAGTTTCAAAGAATGTGGCGAGGTATTCGACCTCCACAGTTACATCAAGGCTTTCGCCGCACAGCACGGTTTTACAACC
CAAATCATTGAAGAGCGAACTCTCACAAATCTCTCCATGAAAAAGGAGATCTATTGGTGGCTGAGCCTGGCGTTCTTTGTAAAGGC
TATGCGAGTACCATGGACCCTGGCCAATCTGGACCAGAACACCGCCTTCGCCGGCATCGGCTACTCCCTGAGCAAAAAGCAAAGCG
GCAAATTCAATATCGTTATCGGCTGTAGCCATATCTATAATTCTGAGGGCCAAGGCCTGAGGTACAAGCTCTCAAAGATAGATAAT
CCAATCTTGGACCGGAAAAACAACCCGTACCTGACCTATAATGAGGCGTATAAGTTGGGCGTGAACATACAGAATCTGTTCATTCA
GAGCATGGACAAACTCCCGAAGCGAGTAGTGATCCACAAAAGGATCCCGTTCCTGGAGGACGAGATAAAGGGCATTACCGAGGCGT
TGGCCCAGGCCAACATCACGAATGTTGACCTCATCACTATCACGATCGAAAAGAACATCAGATGCCTGGATCAGTTCTTCTACAAT
GGTCAAGCCAAGAACAGCAACTTCCCACTGCATAGGGGCACCTGCATGAAGCTCAGTGATACCGAGTGTCTGTTGTGGACCCACGG
CGTGGTGGACTCAATTAAGGCGGGCAGGAACTACTACTCTGGTGGCAAGGGTATCCCCTCCCCCCTCCGCATATCAAAGTTTTACG
GCGCAGGCTCTATGAAGACTATATGCAACGAAATCCTGGGGTTCACAAAGATGAATTGGAATAGCTTTAACTTCTATACCAAGCTT
CCCGCGACCATCGACACCAGCAACACGCTGGCGCAAGTGGGGAACATGCTCGATAATTACAACGGTATTACATACGATTACAGGTA
TTTCATCTAGTAA
83 ATGCCCAAAAAGAAACGCAAGGTCGAGGACCCTAAGAAGAAGAGGAAAGTAGGGTCTGGCTCTATGCAACTGAACTATTTCCCCAT
CCAGTTTGACTTTTCTGACTACCAGGTCATCACGCAGCCCTACTCCGACGAGAGATTGAAAGAACTCAGGCAGGCCTACAACGCCA
GCTATTCCTTCTTTCGGGACGGCAACCTTATCGTAATTTCCAATAAAGAGGACGAGGAAAACCAATTGACGGGCAACGTCGAAAAC
CGCAGCGTGTTCGACGATGCCAAAGTTACCGCCAGCATGGTCAAGCATATATTCTTTAGGACGTTCAAGGACAGGTTCCAAGGCTT
CATCCCCGTGGACTTTTACCCCTTCCGATTCTACAGCAGACAAGAGAAGGACGACCTTATTCTGAACCACCTGCCCGAAAAACTTA
AGCATAAAATCGCCTTTAAGAAACTGATCGAGGTGCAGCTCAGGGAGACGAATCTTAATTCAACCCAGGGCTTTGCTTTCGTCGTC
TGCGGAGACGCTTCCCGGGTTGGACAATATCCTGGCCCCGAACGAGGACTTCGTTGGCCTTCTCAAGAGCATCAACGGCGAGACTG
CCATTGTGAGCACTAGCGAGGGTGCCCGCTCCTATTCACTGCAGGAGCTCTTCATTCGCAAGACTAAGCACAACATACAGGCGTAC
CTCAACTTCGCCACCGGGGAAAAAAAGTGCGACCAGATCCTTGCAGCCGTGTCCCAGGAACGAATCCGGAAGCAGAACCCCGTGAA
TCAATTCAGCGAGATATCCAACATCGCGAAGCATCTTTTTTCAGACAAAGGCAATCCAGTGCTGTTCCAGAATATGGATGGCTTTT
GTTTTAAAGTTGACACCACGCCGATGCAGGTACAAAACTCCATGAACCTGCAAACTCCCACGTTCATCTACGACCACGCGGGTACC
AAGACGAACACCCGCAACGCGGACCAGGGGCTGAGCTACTACGGCCCCTACGATAGCCTCACCTTCGACATTAAGAAGCCAAGAGT
TCTCTCTATCTGCCATAAGACCAACCGAGGCTCCTTTACGCGCTTCCTCCACGACCTCAAAGACGGGCTCCCCAATAGCAGCTGGT
TCAAGAAGGGCCTCCTGAAGAAGTACGAGCTTCAAGAGGTGAATTACCTCATCCAGGAGATCAGCGACTACAGGTTGGAGGACTAC
CTGGAAGTGATCTCAAACTACGATGATGAGAAGCCGCACCTGGCAATCATCGAAATTCCAGATAGGTTCAAAAAACTGTCCGACCG
GGACAACCCCTATTTCAAGATTAAGGCAAAGCTGCTGAGCCTTGAGATTCCCGTACAATTTGTGCGCAGCACGACTTTGAGCAGCT
ACAGCGAATACATACTTAATCCGCTTGCATTGCAAATCTATGCGAAACTCGGCGGCACGCCTTGGGTTCTTCCGGCCCAACGCTCC
GTTGACCGCGAAATCGTTATTGGCATAGGTCACTCATGGCTTCGGAGTGGCATGTATAAGGGTGCTGAAAACAGCAGGGTGGTCGG
CATTACTACGTTTATGTCTAGCGATGGCCAATACCTCCTGGGCGACAAGGTGAAAGACGTGCCTTACGAGTCTTACTTCGAGGAGT
TGCTGAAGAGTCTCAAAAGTAGCATAAGCAGACTCTCCGATGAGTATGCCTGGCAGGATGGCGACACAGTGCGCCTCATTTTCCAC
ATCTTCAAACCCATCAAGAACGTTGAGTTCGATGTCATTAGCCAGCTTGTGAAGGACATCAGCCAGTTCAACATAAAGTTCGCGTT
TGTGACCATTAGCAAGTCACACCCGTCTATTCTCTTTGACACGAGTCAGCAAGGCGAGAAAAAGTACGGCTCTAACCAGGTGATAG
GGCAGTACATCCCTCAGAGGGGTAGCAATATCTTCATAGATGACGAAACCAGCCTGGTGCAGATGCTGGGCGCCAGGGAACTTAAA
ACTGCCAAACACGGGATGAGCACCCCAATCCAAATCAAACTTAGGACACCGCAGGGTAACCATAACGACCAAGAACTGAAGGATTT
GATGTTTTACGATCTTAACTACATTACCCAGCAGATCTATAGTTTTACTTACTTGAGCTGGAGGAGCTTTTTGCCACGCGAGGAAC
CGGCCACAATGCTCTACTCCAACTTGATATCCCGACTTCTTGGGAAGATGAGGAGCATCCCTGAATGGGATGCGGATAAGCTCAAT
TATACCCTTAAAAGGAAGAAATGGTTCCTGTAGTAA
84 ATGCCCAAAAAGAAGCGGAAAGTCGAAGACCCCAAGAAGAAGAGAAAGGTGGGCTCCGGCAGCGTGGGCGACAAGACCTTCAGCTT
CAAGGTGTATAGGAAACTGAAACAGCAGAACGACACCAAGGAAGACGAGATATACCTTTACAATTTGCCCCAAGGCGAGACCCTGA
ATGATTACAAGCCATATTGGATCAGTTTTACCCCGAAGGACGGATTCGAAGAATACATCGCTAATTCTTACTTGAGCATCGGCCTG
TCAAAAAAGTACCTGTTCAATAGATTCGTGGAGACGCTCAGCAACTCAAAACTGCACTTCACCTACAAGGTCAAAAGGAAATTCAC
CGACTGGTACGTCGATTTCGTAATCGCGCAGTACAGCCAGGGAGACAGGATCATCTACATGAGCCCCTACTTCCTGGAAGAGCAAA
ACACCTACGGCTTCATCATCGACTTCAAGTTCAGCAAGAAGGATGGTATCCCCTTCGATAAGGAGGTGCAAAAGCTGTCCCTTTCA
CTGGATAGCAACGGCCGCAGCAACAAAAACTATTACTCTGACAAATTTAGGCTGGTGAACAATTTCATTAAGGAGATTTACACCTC
CATAAAGAACATCGGGACCAGTAATAATCCTATCACCATTTCCAGCAACCTCATAGAGACCACCGTGTTCCACCTGAACAAGAAAG
AGTACATCTTTAGCAATAACAACGTAAGCTCTAGCCAGTTCCAGGGCGTGAGGAATTTCGGTGTCTATAAGAATATCCCCCAGGAC
GTGATCTTCGCGTTCATATTCGAGGATAGGTTCAGGAGCTTCGCCAACGAGCTGTATCTGAGCCTTACCGGAAAATTGAACCCCGG
GACCTTTCCCGGACTGGAGCAGATGTTCGGCATCAGCATCAACACCAAAAACGTGAGACAGATCAAGTTGGAGAACTACTCTCTGG
ATTCAATGCTTAGGGTGGTGAATGACGTGAAGAGCTTGCAGGAGAACAATCCCGATAAGAAGATCGTGGGAATCTACGTGGAAGAC
TGCACCATCGACAGCGAGGACATCCCTGCGTCCAACAACTACTACTTTCTGAAGTATCACTTTATCAAAAATGACCTGCCACTGCA
GGTTGTGAATTATCGGAAGCTGGGCGAAAGGAATTCTCTGAAATGGAGTACCTCCAACCTGGCCCTGGCCATGTTCGCAAAGATGG
GCGGCATCCCCTGGGTCGTAAAACCGTCTAATAAGAACTGCTTGATTCTTGGCATCGGATCTAGTCATAAGATAAACCGGGAGACC
GGCGATATACTTAAATACTTTGCATACACCATATGTCTCGACTCCAGTGGCCTGTACAAGGCCCTTGAGGTGCTGGCCGACGAGGA
GAGCGAGGTGAGCTACCTTGAGAAGCTTACTGCCAATCTGGTCGCCATACTGAAGGAACAAAAGACCAATTACGGCACCTGTGTGC
TGCACCTGCCCTTCAAGATTAAGAAAAAAGAGGTAGCCGCCATTAGTGATGCCATAAAACAAATCAACGACATCGAGCTGGTGGTG
GTAAAGATCAATGTGGATAACAAGTATTTCGGATACTCCTTCCACAACACATTGGTGCCCTACGAGAGCAGCTTCGTGAAGCTTTC
TAAGGATGAGTATCTGGTGTGGTTCGAGGGCCTGCTGTACGGCAAAGAGATCGTAGATAAGAGGTTGAGCAACCCCGTGCACATCC
AATTCTTGAACATCACCAACAGGAAGAACTTCGATGAGCAGGCGTTTCTGCAGGACATTCTGAATTTGAGCGGAGCCAACTGGAGG
GGCTTCAACGCCAAAAGCATCCCTATCTCAATTTACTATTCTCAAATCATCGCGAGGTACACCGAGGCCTTCGAAAACATCGACGG
TTACAAGGAGGGTACTATCTCTAACGACAAACCCTGGTTCCTGTAGTAA
85 ATGCCGAAGAAAAAGCGAAAAGTGGAAGACCCCAAAAAGAAGCGGAAGGTGGGCAGCGGCAGCATGGACAATTTGGCTCTCTCTGC
GCTTCAGCTGGACAGTAGATTGGATCACTGTATGGTATATCAATACAGGATCGTGTACCATAAGTTCGACGAAACAGAGGCGGGTG
AAAAACTGGCAAGAAAGGCCGCCTACGAACTGTGGAAGGTAAACAACTTCGGACTGCTCACCAACCTGGGTGCCAGTAGCATCCTG
TCCCTTAAGAGCCTGAGTCAGCTGTCTATCGATTCACCGCTGTTGCAGGCAAGTTTGAAAGCTGACGGCCAGTTGGAGCTGGATTG
CGGTAACGAACAGCATCAGGAGGCGCTGCAGAGACTCGTGAACCAGGACATAAACAAAGCGGCTTGGAACCTCAAACAAGCGAGCG
AGGGGAAGCTTGATTGCCGAAAATCACCAGGCGGGCACGCCGAAATCTTCGAGCCAAGTCACAGTAGTCGGATCAAGGCCCACAGT
ACCTATTTGGATGCCTTCTGCACCGTAAGGCTGATTCCCGAAGTGCTGTCAGACGGGACAGTGCTGATAGGGTTGCATCTTAAGCA
CAGCCTGACCGCGAAGGCGGACATCTCTCTTCAGTGGGTCATTGATCATAGGCCCGATTGGCTGATATCCATAGAGAAGGTGCGCC
ACAGGTATTACGAGCCCGGCAAAGCACCCCTCGTTGCGGAGTTCGTGAAAGTCGATGATTCCATCAACGGATCATCCCTTCTCCCA
CACTTGGGCAAATCCCTTGTCGCTTACCACCAGGAGAAAGGGCTGCTTTCAGCCGGACAGCTCGCAGAGGCAGCCACCAGCTCACT
CATCAAAGTGCGCTACGGACAGAAGGAGGCAGACCACGTTGCTAGCTTGGTGGAACCCATGTTTGATTTCGATACTCTGTCAAAGA
TTGACAGCCCCTTCCTGAATAGGCTCGCCAAAGACCTGAAGTGGAGCTTGGACGATAGAATAAAGACAAGCGCGGAGATGGTCAAG
AGGCTCTACCTGCCCGGGTTTAATCGAAAGTTGGTACAAGTTGACTACCAGAATCTGAGCAGGAAGAGGTTCAACCACAACCTTAT
GCTCCAGTTCGCGGATGGGGCAAGGAGCGGCCATGAACAAGACGTCCTGAAATACAAGGCTTTCGCCGACATGACCAGGGCTAGGG
TAATCCCACTCGTGGTAGGAGAGAGGAACAACACCGAAAGCAATAGACAATTGCTCCGGAACGCCTATAACGCACTGAGGCAACTT
ACCAAGGCCGAATTGCCCCCCTTCACGTCATTTCCCCCCAGCATCGGAAACGCCGACGAGTTGGACGCACGGCTGCACAAGAAATG
TCCCGACAACGCCATCCTGCTTATCGGGCTCACAGAGAAGAGTGACAAAGCCGCGATCAGGGACACGCCGTTCAACTACGGCCTGG
CCACCCACTTCATGACGCTCGATCACAACCCCAACGTTTACCACACCTTCTACTTCAATAACGTCGCAGCGGCCCTGTTCTCCAAC
GCAGGAGCGCAACTGTGCGCCGTGAACGACATGCCCGGTGAGACTGAACTGTTTATCGGTCTGGACATGCGCCGCGTCAATGTAAG
GGCCCCACCTTTCGCATTCCTGTTTCTCAACTCTGCCGCGCAACTGGGCTGCCACCTGGCTCACAAGCAGCACCGCGACAAAATGC
AGGACGACGCrCTCAGCAATCTGCTCGAGAAGTCTCTCAAAACCTACCTGAGGAGCACCGACGGGCTTTTGCCAAGGAGGATAACT
CTCCACAGGGACGGCAGGTTTTACGAGAGCATCAATGTGATAGAACAGTTTGAGCAGAAGCACGGGGTCAAGCTCGATGTTCTGGA
AGTCTTGAAAAGCGGAGCCCCGGTGCTGTACCGGAGAGAACGCAGTGCGGACGGTAAGAAAGTTTTCAGCAACCCAGCGGTTGGCG
ATGCCGTCTTCCTTAGCGACAGGGACGTCATTCTTAGCACTTACAGCGGCGAGGAACTTGGGAAGTCATGGGCTAACAAGCTGAGT
GTGAGGCCACTTCGACTCCGAAAGAGATACGGCGAGACCGCATTGAGCGTGTTGGCCCATCAGGTGTTGGTCCTGTCTAGGATCCA
TGGGGCCAGCCTCTACCGACACCCCCGACTTCCGGTGACCACCCACCACGCGGACAGGTTCGCAACCTTGCGGCAAGATGCGTGCA
TAGACGCACTTAGTAAGATGGATAGACTGTGTCCGGTGTATCTGTAGTAA
86 ATGCCTAAGAAGAAGAGGAAAGTGGAGGATCCCAAAAACAAACGAAAGGTCGGCAGCGGTTCTATGAGCGAGCTGGAGACCAACAT
CTTCCCAATCACCAACTTGCATGAGCTTGAAAGCAGGTTCAGGTTGTATAGGGTGAGGGGCCTGAGCATCAACCAAGAGGAGTACG
ACCCCAACACCCAGACATTGGTGAGGAAGCTGAGCTACAGCATGAGGTCTCCCGTAGCTGTGATACTTAGGAACAGCGACCCGTTC
CTGGCTCTTCCAATCGACGCACCCGAGCCCATCTCTCCGTACCCGCTCGTGAGAGCCACTGCTGTGTTCGAGAAGACGGACGAGGT
ATTTACTCTCGATTACGAAAGCCCAACTCCCGAGACAGATGCGCTGCGAATAAGGTTCCTGCAATTTATCATCCAAGGCGCGCTGT
TTAGGAATCCCAGCCTGTGGCAGCCCTCAGCTGGCACCCCCTTCTTCGAGAGGAGCCCCGTGTTGGAGAAGGCCGGCATTTGCGCG
TACCGAGGCTTCTCAGTGCGAGTCGTGCCCATAGAAGGTGGTAAACTGGGAATCTGTGTGGACGTTAAGCACAGGTACGTCAGCAA
AAACCCCATCGAAGCAAACATCAAGCGCGAGGAATTCAGGAAATACAAGAACGGCAGGTGCATATACCACTACGGCCACAACTGGT
ACGAGATCAAGTTGCAAGACCACACTGGGCTGTCCGTGTCAGAGCAGATGATCAGCAACGGGACGGCCAAACCCATAAGCTTGTAT
CAGTTCATTATGAATAACGCGCCCAAGCCCCTGCCCAGGGAGGTCATAGACATGCCTCCCGACTCACCCGCAGTCAAATACATGAC
CAGCAGGGATGAGGTGCGCTACGTGCCCTCCATCCTTTGTTATCCGGTCTTTGACACCTCTGACCCCAGGGTGAAGCCGACGCATA
GGGGCACAATCCTCCTCCCTAACGTGAGGCGACAGTATATCCACAATTTCGTGAACTCACACCTGACCGATGTGCGATCCAAAGAC
ATGGCAATCCGAATCAGCAGCAAGCCAGTTATCGCCCCTACCAAGATTTTCCTGCCGCCTGACCTGGCATTCGGCAACAACACCGT
GTTCAGCGTAAGAGGCACACCCGGGACCACGTATGTTAGCCTGGAGCAGCTGGGCCAGACGCGGATAAGCGCCCTCTTCAATCAGA
AAATACGCCCTTATCACACCAGGCCCCTCGATACGCACTACATCATTCTCCCCAAAACCCTGTGCCACTCCCACGCGCCACTATTT
CTGAATGACTTTAAGAAAATCATGAACGAGCTGTACCTGCACGAACTGCCCTACAATCCCATCGTCGTGACCTACAACGACTTGAG
CGCCAAGACCTACGCCCTTCAGCCAAGGGCTATTCTGGACGCCGTGCACAGCCAACTCAGACAGCCGCGATACGGCGTGGTTATGA
TACACGAGACGGTGGACCGCCGGAATAGACAGCACGACCAGCTTGCCGCGATGGTGATGAGGGAGCTCCGGAACAGGAGGCTCTAT
GTCAGCGTCATCCATACCACCCTGACCAAGCACTGTTACCAATTGCCCCACAACCCCCCCATTGCCAAGGCCTACTGCCCGGTAGC
AGCCAACCAGGGCAAACTCAATGGCTACTTCAGCAACGTCGCCATTACCAACGTCCTTCTGACCAACGAGAGCTGGCCCTTCCTTA
TATCTACCCCGCTGCATCCCCACTTTACCGTTCCCTTCGACGTCCACCTTAACACCGCTTGCTTCACATTCATCGGCAAGAGCGCC
TCCGACATCCGGACCGTTTTCAAGACCAGTAACCAAAAGGAGAGGTTGAGCAAGCCACAAGTAAGGCAGACGCTCCTCGAAGTGCT
CCGCCAGGAGGTTGGCTTCGGTCGACGGACCATGCAGACCATAGTGGTTCAGAGGGATGGCAAATTGTTTGCCAGTGAGATCGCGG
GAGCAAAAGACGCTATAGAGATAGTGAAGAAAGAAGGCATCTTGCCCAGCGATGTGTCACTGAATTTCATCGAAATCCCCAAGAGC
AGCGTCGCCCCATTTAGGCTGTTCGATAGCAGCCCCAGGCCAGGGCAGCCTGAAATGGCGAACAACCCAAGAATCGGCTCCTACTT
CATCGCGACGAATTACGACGGTTACATTTGCACCACCGGCAAGGAGTTTTACCATCCCGGTACGGCAAATCCTCTCCACGTGAAGT
ACATCGAGGGAAATATGCCATTTGAGAAGATCCTGGAGGACGTGTACGCCTTGACTTGCTTGGCGTTGACCAGGCCCGAAGACTGC
ACAAGGGAACCCTTCACCATGAAACTGGCCGATATCCGACTGAGGGAACATGCCGGAGGCTACGACGAAGATGCATTGGCGTATGA
TGATGAAAATGAGAACGACGAGGATAACGAGAATGAATAGTAA
87 ATGCCGAAAAAAAAGCGCAAGGTGGAGGATCCAAAAAAGAAACGGAAAGTGGGATCTGGCTCCATGAACTACACAGAGGCCAAGAC
CGCCAATAGCCCCTTGTTCCTTAGCGAGATTAGTAGTTTGACACTTAAGAATAGCTGCCTGAATTGTTTTAAGCTGAACCATCAGG
TCACCCGGAAAATAGGCAACAGGTTCTCTTGGCAGTTCAGCCACAAGTTCCCTGACGTCGTGGTAGTGTTCGAGGACAATTGCTTT
TGGGTGCTGGCTAAAGATGAAAAGAGTTTGCCTAGTCCACAGCAGTGGAAGGAAGCACTGTCAGACATACAGGAAGTGCTGAGGGA
AGACATTGGGGACCACTACTACAGCATTCACTGGTTGAAAGACTTCCAGATAACCGCCCTGGTCACCGCGCAGCTGGCTGTGCGGA
TTTTGAAGATATTTGGGAAGTTTAGCTACCCGATCGTGTTCCCCAAGGACAGTCAGATCTCTGAAAACCAGGTGCAGGTGCGAAGG
GAAGTGGATTTCTGGGCTGAGATAATCAACGACACGGACCCAGCAATATGCCTGACGGTGGAAAGCAGCATCGTTTACTCTGGCGA
CTTGGAACAGTTTTACGAAAATCATCCGTACCGACAGGACGCCGTGAAACTTCTCGTAGGGCTGAAAGTGAAAACTATCGAAACCA
ACGGCATCGCGAAGATTATCAAAATTGCCGGGACCATCGGAGAAAAGCGGGAGGAACTGCTGACCAAGGCAACCGGGTCCATAAGC
AGGCGCAAATTGGAGGAGGCACACCTGGGCCAACCTGTGGTGGCCGTGCAGTTCGGCAAGAATCCGAGAGAATACATCTATCCCCT
TGCCGCGCTCAAACCGTGTATGACCGACAAAGACGAGAGCCTGTTTCAAGTGAACTATGGCGAGCTTCTGAAGAAGACTAAGATTT
TCTACGCCGAACGGCAGGAGTTGCTGAAATTGTATAAACAGGAGGCGCAGAAGACGCTGAACAACTTCGGCTTCCAGCTCCGGGAG
CGGTCAATCAATAGCAGGGAGAACCCCGACTTTTTCTGGACCCCCTCAATTTCCCTTGAACAAACGCCCATCTTGTTTGGCAAAGG
TGAGCGACCTGACAAACCACACACCTTCAAACCCTTCACCAAACCCCGCCTCTACAACACACATAGCCACTACGTCCACCCCCCCA
GAAAGATTAGGCTGGCCATCCTGAAGCCGGCCAATCTCAAGGTTGGCGATTTTAGGGAGCAGCTCGAGAAGCGACTGAAGCTCTAT
AAGTTCGAGACCATCCTTCCCCCCGAGAATCAAATCAATTTTAGCGTACAGGGCGTGGGCTATCAAAAACGACCCCGCTTGCAAGA
GGCCGTGGACCAACTCATTACGGGGCAGATACCCGTGGATATCGCTCTTGTCTTTCTTCCGCAGGAGCACCGAAACGCCGACAACA
CCCAGGAGGGGAGCCTTTACTCATGGATCAAGAAGAAGTTCCTTGACAGGGTTGTGATAACGCAAATGATCTATGAGAAAACGCTT
AACTATAAGAACAATTACAAGAACATCCTCGATCAGGTGGTGCCTGGAATCCTTGCGAAACTTGGTAATCTGCCTTACGTGCTCGC
AGAGCCACTGCAAATCGCCGACTACTTCATTGGCCTGGATGTGGGTCGCATGCCTAAGAAAAACCTCCCCGGGTCACTTAACGTGT
GCGCGTCCGTAAGGTTGTACGGGAAGCAGGGCGAGTTTGTGCGGTGCCGAGTCGAAGATAGTCTCACCGAAGGTGAAGAGATCCCC
CAGAGAATCCTGGAGAATTGTCTGCCCCAAGCCGAGTTGAAGAACCAGACCGTGCTGATATACAGGGACGGTAAGTTCCAGGGCAA
GGAGGTGGATAACTTGCTGGCCCGAGCCAGGGCCATTAAGAGCAAATTCATACTTGTCGAATGCTATAAAACGGGCATCCCCAGAC
TGTATAACTTCAAGCAAAAACAGATCGACGCGCCCAGTAAGGGCCTGGCGTTCGCTCTGAGTAACAGGGAGGTGATCCTGATCACG
TCCCAGGTTAGCGAAAAGATCGGCGTGCCGCGACCTCTGAGGCTTAAGGTACATGAGCTGGGAGAGCAGGTAAATCTGAAGCAACT
GGTGGACACCACACTCAAGCTGACCCTGCTCCACTATGGGTCTCTTAAGGACCCGAGGCTGCCCATCCCCCTTTACGGCGCTGACA
TCATCGCGTATAGGAGGTTGCAGGGAATATATCCCTCTTTGCTGGAGGACGATTGTCAGTTCTGGCTGTAGTAA
88 ATGCCAAAGAAAAAAAGGAAAGTCGAGGACCCCAAAAAGAAGCGAAAAGTGGGCAGCGGCTCCTTGGACAATTACATACTGACCGA
GTACAAGGCCGGCATCCACGCCAGCGAGATCAAGATACACATCTACCGGATGCCCGTCAAGGATCTTGAGAAAATCGACTATGAGT
ACGGGAAGTACACACGCGACCTCAGACAAAAAAACAGGAAGACGATATCCTTTTACCGCTCTCTGATCGGCAGCTTTGAGAAGCTC
ACCATCGTGCCCAAGGGATACGAGAAGTACGAGTATAGATCAATTAAACTCGACCAGAGTGAGGAGrCACTCCAGGAGAGGAAACT
GCTGGAGAGGCTGATCTTCGACGGCCTTAGGGACAGCAATAGGAACCACTTTATGAGCACCGAGCAGAGCATCATCGAGAAAGAGC
CCATCAAGTCCCTGAGCAAGTGCAAAATCCACCGGGGTATCTACATAGACATCACCGTGAAAGAGAAAGGCGACATCTTCATCGGT
TTCGAGCTGAAGCACTCCATCCAGAGCACCCACACGATTATCAAGGCTCTGAAGGAGAAGAAACTGAACAAGGGCGATAAGGTGTT
TGACTTTCTGAACAGCGCCCACTACGAGTTCGAGGGGATTAGCGACAAAACCATCAGCGACCCCCTTCCCGAACTGGGCAACAAGA
GCATTATCCAGCACTACAAAACGAAACCCAGCATCTACTGCCACCTCGTGAAAAAACCGAACATGCCCGCCATCCTGGTACGCAGC
AAGAGCGGCAAGGTGTATCCTTACCCCCCACAGCTGCTTAAGAAGGAGTGCCTGATGAAGGATGTGCCGGCTAAGGAGCACAGCTC
TATCAAGCTGAACCCCAACGATAAGATCAACTACAGCATTGAGATCATGAAGAGAATCATAGATGCGTTCGAGAACAGGTATTTCC
CCATCGGCTTTGAAAAGAACAACCTGAACATCGCCAAGCTCGGATACAGGAGGAGGCTGGTCCCGGATCCCCTGCTGAGGATTGGC
AACGGAGCCACCTGCAACCACAGAGACCTCAAGGGTGCCTTCCTTAGGCACAAGATTTATGACAGCGTGAGCTCCCCTATCTACTA
CCAGCTTCTGCTTGACCAACCCTTCGAAAGGGAGTGGCAGAAAAAGATGAGCGAAGCGTTCATTACGAAGATGGAAAACCGGAGCA
GGCAGTGGGGCATAAAGCTTCAGTGTACCGGGAACCAGATCCTCCCTACCTCTAACCCGTACGCGCTGAGACTGCATCTTAAGGAC
ATCAACCTGGATACCGACATCATTAGCGTGGTCCTGTTGGACGAGACCAAACAAGAAGGCGAGGAGGTTTACTCTACCATCAAAAA
AGAGCTGGGTGGCACCAGGGGCGCACATACCCAGGTAATCCTGATCGATAGCCTGAAGAACGAATACACTATCCCCCAGATACTGT
TGGGAATCTACACCAAGGCTGGATTGCAGCCCTGGGTCTTGCACCAGCCGTTGCACGCCGACTGCTACGTTGGCTACGACGTGAGC
CATGAAAATGGCAGGCACACCACTGGCATAGTGCAAGTGTTCGGCAAAGACGGGTCACAGATCTTCAGTCAGCCCATTAGCAGCGC
GGAGGCCGGAGAGAAGGTGTCAAAGGAGACCATTCAGACTATGGTGATACACGTTCTTTACTATTACCAGAAGAAAGTTGGCAAGA
TGCCACAGCACATTGTCTTCCACAGGGACGGCCGAGGATACGTAGAGGAGATAGACTGGATTAAAGACATATTGAGTAATAGGGAC
CTCACCAACGGCCAAAGCATCGCTTTCGATTACATCTCAGTGATCAAAGAGTGTGGTCGGCGCATGGCTTACTTTGACGACATAAA
GAAGAAGTATGTGAACGTGCCCGGGATTGCCTACCTGGACGACAACGCCCAAAAGGCCTATCTTTGCAGCACCAATCCATACGAAA
AAGTAGGGATGAGCAAACCTATTAAGATTGTGAAGAAGATTGGCGAGATGACCCTGGAGCAGATCGTAGAAGACATCTATCACCTG
AGTTTTATGAATATCGACACCGATAGGAAGGTGAGGCTGCCCGTGACTACCAATTACGCCGATAAGTCTTCAACGTTTTTCTCTCG
CGGCTATCTGTCATCACAAAAGAAAGGAATTGGCTTCGTATAGTAA
89 ATGCCGAAAAAGAAAAGGAAAGTGGAGGACCCCAAAAAAAAGCGGAAGGTCGGGAGTGGCTCCGTGGCCGCTTTGAAGCGCTACTT
TAATGACAAGAACCTGATCGTGATAGGCTACTCTGGCAGGGACAAGAGCCTGATGAGTGCGCTTACCGAGGCTTTCTCTGAGAAGG
GCTCTGGCCGCATCTACTGGTGCGGCTACGGCAGCCACATTTCCCCCGAGGTGGAAAGCTTGTTGAGGACCGCGCGAGAGGCAAAC
CGCGACGCCTACTATATCGACACCGATGGGTTCGACAAAACCATGTTCAGCCTGGTAATAAACTGCTTCCAGGCGGATATCGAAAA
GAAGAAAGAGATAATGAGCATCCTGGAGTCTGCTCCCGAGGACAACGATACCAGCCCGTTCTCAATTCACATCACCAGGACGGATA
AATACCTTAAGTCCAACCTCTACCCGATCATCTTTCCTAAGGAGCTGTTTCAGTTTGAGATAGAATATCATGAGGGCGAACGACCA
TGGACCCTGCTGAGAGAGATCACCAAAGACCAGAACATCATCGCCGTGCCCTACAAGCAAAAAGTCTACGCCTTGTCAACGGGATC
AGCTATCAACAACGTGTTTGGTAGCCGGTTGAAATCAGATATAGAGAGGATTCCCGTGTCTATGGATGACATTGAGCGCAAGTCTA
GTTACAGGGAGCTCTTCCTGAGGGCCACCCTTCAGTCTATAGCCATTATAAGGGGCCTGAACGTGGACATACGACACAATACCCTT
TGGCGGAGCGACATCTTTAGGAACGACAATGGCACCCTCATCCACGAAGCGATCGAGTGTTCCCTGGTGTTTGTGCCCCAACAGAA
GTATGCCCTGTTGAGCTTGAGGCCCACCATCTACATAGAGAACTCTCATACGGTTAGCAAGGAGAAAAAGCAGGAGTACGCCAGGA
TCTACCTGGATAAGATGTGGAATAAAGCGTACAGCACGAAGTTGGCCCAGTGGGAATCTATAATCTTTGGAGACACGAGGCTCGCC
TTCGAGGTGCCGCAAAATTCAGGATCCGGGTTTAAGTTTCTGATAAGCCACAACTGCGGCTTCAGCGAAATCCAGTATCAAGACAA
CACCGAAAGGGGATACAGTAGCAAGAGCTACGACAACAAGAGGACGATCTATAGGGGCTTGCAGCTGAAGGAACCCGAGCTGGAAT
TTGTCAATACGTTTGCAGACCGGCCCTTCCTGGACAGCAACCCCATGCGAGGCCTGAGCAATCACAGGCCGTACGACAGCTGGCAG
AAAGACGTTCTCTTGCAGAACGTGCGGTTGGGCGTGATTTGCCCGAACACGCACACCGACCGATTCCACTCTTTTCTGCAGCAGCT
TAACACCACAATTCAAGCCAATGACGATAGCGACTACATTCAGTCCTACACCGGTTTCCATAGCATTTACAAGACTCTGCTGGAAA
TCCCCGATAACGGGACCGACAAATGGATAAACATCGAGGATACCCCCAAGGACACCATCAGTCTGGTTCAGAGTATATGTCACCAA
GCGAACCGACTGGCCGACAAGTACCCGGGCATCGTGGTGGTGATTTTCATCCCCGCATTTTGGTCTATCCATCGACAGTTCAAACA
CAACGGGGAGAGCTTCGATTTGCACAACTACATCAAGGCCTACGCCGCACAACATAGCTTCACTACCCAAATCATTGAGGAAAAGA
CGCTGCGCGACCACATGGTCTGCGAAATTTGTTGGTGGCTGTCACTCGCACTGTTCGTTAAGGCTATGCGAATCCCGTGGGCACTG
GCCAATTTGGACTCTGACACCGCTTACGCGGGTATAGGGTACTCAGTGAAGACCAACAGCAAAGGCAACGTCGACATAGTGCTTGG
ATGTTCACATATATACAACGCAAAGGGCCAGGGTCTCAGATACAAACTCTCTAAGGTCGAGCAGCCCCAATTCGATGGCAAGAAAA
ATCCTTACCTTACGTATGAAGAGGCCTTCAAGTTTGGAATTACCATACGCGAGTTGTTCGTCAAAAGTATGGACCGGCTTCCCAGG
AGGGTTGTGATTCACAAGCGGACGCCGTTCAAAAAGGAGGAAATAGAGGGAATCACTCACGCGTTGACTCAGGCTGGCATTAAGGA
CATCGATCTCATTACGATCAATTACGAGTACGACGCCAAGTTCATAGCGCAGAAGGTATACTATGACAACATCAGCGACGATTCAT
ATCCCGTAAGTAGGGGCACCTGCATCAAATTGTCCAGCCGAAATGCGCTGCTGTGGACACACGGCGTGGTTCCCTCAATCCGGGAG
AGACGACGCTACTACCCCGGTGGGCGCTGTATTCCCGCACCCCTGAAGATAACAAAATACTACGGTAAAGGCGATCTTCCGACAAT
CGCCAGCGAGATTATTGGATTTACTAAGATGAATTGGAACAGTTTTAATCTGTACACGAAACTGCCCGCCACCATAGATACGAGCA
ATACATTGGCGCAGGTCGGCAATCTGTTGCATCAGTATAACGGCGCAACTTACGACTACCGATATTTCATCTAGTAA
90 ATGCCCAAGAAAAAAAGAAAGGTGGAAGACCCTAAGAAGAAGCGCAAAGTGGGATCCGGCTCTATGTTGGAGACGAATATCAGGGT
GGTGCGGCCTGGTCCGCAGCTGTGCGTTCCTGTACGCAGGGTGATCGTGTCCGGTCAAACCTTGGCTCCCGACCTCCTGGAGAGGC
TGTGTAACCTGCTGCGAAGGAGGTACGGCATTAGCGCCGCAAGAATACCGGGCTCCGTGAGCGAGCTGTTCGTTGCGACCGACCGG
CAGGTGGAGAAGGTGACACTGGAAGAAGATAACTGGCAACTGACCGCCGTGGACTCCAACGACCCTACTCGAATCATGTCCATCTC
TAACACGGACGATGAGAGCTTTATAAGCATCCTGATCGAACGCGCGCTCCTTGCCCAGATCGCCAGTCGAAGCCTCTTTTGGACCC
TCGACTCTCCTCGAATTTGGTATGAGAAGAACCCGTTCCAAAGGAATGAAGGCGTAGCCGTCTACCACAGGTACGAGGTGGATGCG
CTCCCCCTCGGCGACGCAGGCATTGGCATCTCAGTGGATGTTTCAACGGCCTTTTTTAGCGAGCACACCCTGGAGTACTACTTCGC
CCCCAACCTGATTAGCGGCGAGAGCAAGACGCGACAGGACGAATTCCACAAGTTCACCGGCCGACAAGCTGGTCAAAAGGGGACGC
TGCTTTACAATAACGGCAGGAGTAAGGTGAAGTGCTATTTCGAGAACAATAGGGTGGGCCTGACATGTGGCGCAACCGGCCAAATG
AAACTCGAGGGAATCACGTATCCCAGCCTGTACCACTACTATGCGAGCAAGTATAGCGCATTGCAGATCAACGAGAACGATGCCGC
AGTGCAAGTGTCTTTCCCTGGCTTGGACCGCCCAGTTCCGGTAGCCGCCAGGCTCCTGTCCCTCCGAGTGATGAACGACGACGTGC
CCGATGGTCTGAGCTCCGTCGACAAGATCCCTCCAAGGAACCGCAAGTACCTTATCGAGCAGTTTTGGAAGTGCCTGGAGCCGAGA
CCCTTCGGGAATGTGGCCCCTGGTGTCTTCGACGGCTTCTGGAGACCCAACAACGAAAGGGTGCATTACATCCAGCTGCCCGAGAT
TAACTTTGGACAAGGCCAAAAAGCAGAACCGCCTGACGTACGCTCCGTTGCATCCATCAAAAACTATTTTAGGCGACGACTGGAAT
TGCTGGGTCACGCGGGGTGTTACCACTTTCCGCCCTCAGCCCCCAGGACAATCTTCTGCGCCTACCCGCAGTCATTGGGTGAGGAG
ATCCCGGAAAAGTTGGTGAACGGGATCGTCAATGTGCTGAACAAGTGGACCGGCCTCAGCTTCTGTAGCAACCTGGTAAGCTACAG
CACGGCCAGCGAGGCGTACGGTAAATTGAGGAGGGCCGAGAGTGCCGGCGTGGTCCTGTTCATCTTGGACGAGGAGCCGGCAGTCT
ACTACGACGCGAGCTTCAATCTTGAGGGCTGGAGGGTAAAGCGCGTAACCGAGCCTGTGCTGCGCCAGCAGCATAAGTATCTGACC
AACGGCGTGTGGGACCGGAAGAGGCAAGAGTATAGTTTGGGGAGGGGGCAGAGTCGCTGGGAAAGCTTCATCAATTTGATCGGATT
GGACGTTATCCAGCAACTCGATGCCATTCCGTATAGGATCCCCAACATCGGCCCCTACGAAGGCCAGCTGATAATCGACGTGGGGC
ATGACAGGCAATTCTTCGCCGTGTCACTGCTTATTGTGAGATCAGAAGACAAAGTGCCCGCATTTAACATCAGCAGCCAGGTCCAG
CACAAGGCGGATCATAAGCACGAAAGCATTAACCCGGTGCTGTTGAAGGACACCATCATTAACGTGTTCAAGACCGCCAAACGGAG
GACTTTTGATCCTCTGACTAGCCTGTTGATCATGCGGGATGGCAACGTGCAGGGCAGCGAGATCGGCGGGATAGACAACGCCCTGG
TCGAACTTAGGCAACTTGGCATAATCTCCCCCGATGCGAGGCTGGACATCGTGGGCGTACACAAGGAATCTGTAAGCTCCATCAGG
CTCTGGGACGTTGACGTAAGGGGGGAGGTAAGCAACCCGATCGAGGGCACCGGTCTGTCAGTCAACTCATCTCTGTACCTGGTGGC
GTGCACAGGTGAGGCCACGCTGACCCAAGGCACCGCAGAGCCCGTGGCCATCGTCGCAAACAACAGGTGCCTGAGTATTGCCGATG
CAGCCCTGAGCGCCTTTCTGGCAGCCCAACTGAACTGGAGCAGCCCGGGAGTCGCCCAGCGCCTGCCCCTGCCTCTGAAAAGAACA
GATGAGGAACTTACCGCTAGGAGCGATCAAGAAATTAGGAGGATAAGGTAGTAA
91 ATGCCAAAGAAGAAACGAAAAGTGGAAGATCCCAAGAAAAAAAGGAAAGTTGGTAGCGGCAGTATGATAATGAGCCTGGAGAGCAA
TATCTTCACTTTTAGCAACCTCGGGACACTTACCACGCAGTACCGACTGTATGAGATCAGAGGCCTGCAGAAAAGGCACCAAGAGT
ACTACCAGAACAGGCAAATCCTGATCCACCGACTCTCCTACCTTCTGAAAAATGCCGTAACTATCATAGAGCGCGACGAGAAACTG
TACCTTGTTGTAGCTGCCGATGCCCCGGAACCACCCAATAGTTATCCCATCGTTAGGGGCGTCATCTACTTCAAGCCCACCGGCCA
GATTCTGACCCTGGACTACAGCCTCCGAACACCCCAGAACGAAGAGATCTGCCAGAGGTTCCTCCATTTCATGGTACAAAGTGCCC
TGTTTCAAAACGCGAATTTGTGGCAACCCAGCGCCGGAAAGGCTTTCTTCGAGAAAAAGCCCTCATTCGAGTTCGGATCAATTCTG
TTGTTTCAGGGATTTAGCGTTAGGCCCATATTCACCAAGGACAAGATCGGCCTGTGTGTAGACATCCACCATAAATTCGTCAGCAA
AGAACCCCTCCCTAGCTACCTGAACTTCAACGAGTTCCAAAAATACAGAGGCGTGTCATGCATCTACCATTTCGGCCACCAGTGGT
ACGAGATCCAACTCTCTGAACTCTCCGAGCTTAACGCGACGGAGGCAATGGTACCCATCGAGAATAAGTTCGTGACCCTTATTAAC
TACATCACCCAGCAAGCCAGGAAGCCCATCCCGGAAGAGCTGGCAAACGTGTCACAGGACGCAGCCGTCGTGCACTACTTTAACAA
TCAGAACCAGGACAGGATGGCGGTGACGAGTCTGTGCTATCAGGTTTACGACAACTCTTATCCAGAAATCCGAAAGTACCACCAGC
ACACCATTCTGAAGCCACACATCCGCCGCAGCGCGATCCACGGAATAGTGCAGAAGTATCTCGCGGAGCTCAGGTTCGGCGACATA
ACCCTGAAGGTATCAACTATCCCCGAGCTGGTGCCCCAGGAGATGTTCAACCTGCCCGACTATTGCTTCGGCAACGATTACAAACT
GAGCGTGAAAGGAAGCGAGGGCACAGCCCAGATTAGCCTCGACCAGGTCGGGAAGCAGCGCCTTGAGCTGCTGAGTAAGGCTGAAG
CTGGTATCTACGTGCAGGAAAAGTTCGACCGCCAATACATTCTCCTGCCCCAAACCGTGGGGGACAGCTTCGGGAGCCGGTTCATC
GACGACCTCAAGAAGACCGTGGACAAGCTGTACCCCGCTGGAGGAGGGTACGACCCGAAGATCATTTACTACCCCGACCGAGGTCT
CCGGACCTACATCGAGCAGGGTAGGGCTATACTGAAAACAGTTGAAGAGAACGAGCTGCAGCCCGGCTACGGTATCGTAATGCTTC
ATGACAGTCCGGATCGACTGCTCAGACAACACGACAAACTCGCAGCTCTGGTCATTAGGGAGCTGAAGGACTACGATCTGTACGTG
GCCGTCATCCACAGCAAGACCGGGAGGGAGTGCTATGAGTTGAGATATAACAACCAGGGCGAGCCCTTCTATGCAGTAATACATGA
AAAACGGGGGAAGCTCTACGGCTACATGAGAGGGGTGGCGCTCAATAAGGTGCTTCTCACCAACGAGAGGTGGCCCTTTGTGCTTT
CTACCCCCCTGAATGCGGACGTGGTGATCGGAATCGACGTCAAGCACCACACCGCCGGTTACATAGTCGTCAACAAGAACGGGAGC
AGGATCTGGACTCTGCCCACGATCACGAGCAAGCAGAAGGAGAGGCTGCCCAGTATCCAAATAAAGGCGAGCTTGATCGAGATCAT
CACTAAGGAGGCCGAGCAAACAGTAGATCAGCTGCACAACATAGTGATACATAGGGACGGACGAATACACGAAAGCGAGATCGAGG
GCGCCAAGCAGGCGATGGCCGAGTTGATTAGCAGGTGTACGCTGCCTGTGAACGCCACACTCACGATCCTGGAAGTGGCGAAGAGC
AGCCCCGTTAGCTTTAGGCTGTTTGATGTCTCCAATACCAATTCTAAGGACCCGTTTGTGCAAAACCCACAAGTCGGGTGCTACTA
CATTGCCAACAGCACTGACGCCTACCTGTGTAGCACGGGGAGGGCGTTTCTCAAGTTTGGCACCGTGAACCCCCTGCACATAAGGT
ATGTGGAAGGTACGCTCCCCCTTAAACTGTGTTTGGAAGACGTGTACTATCTGACAGCCCTGCCTTGGACGAAACCCGACGGGTGC
ATCAGGTACCCCATTACCGTAAAGATCAACGACAGGAGGCTTGGGGAGGACGCCAGTGAGTACGACGAAGACGCCCTGCGCTTCGA
GCTGTTCGAGTCTCTCGAGTCCGAGGATGACTTTGACGAGATGACCGACAGCGACTTTAATCAGGAGGAGACAATGGTGTAGTAA
92 ATGCCTAAGAAAAAAAGAAAAGTCGAGGATCCCAAGAAGAAGCGGAAGGTGGGGTCCGGGTCTATGCTCACACAAGAACAATTTAT
ACGCAACTTTAGCGTTATGGCCAATGGTGAAGTAGACTTCTTTCTTGGTGCCGGTGCATCTATTGCGAGTGGAATCCCAACTGGGG
GTGGCTTGATTTGGGAATTTAAGAGGACACTGTACTGTAGCGAGTGCGGCATCAGCGCCGAAAAGTACAAGGACCTGTCACTCCCA
AGCACGCGCAAAACGCTCCAGGACTACTTCGACATTAAAGGGTATTGCCCCAAACAATATGCGCCTGAGGAATACAGCTTCTATTT
CGAGCAATGTTACACCGATCCCATGGCCCGAAAGAGGTTCATCGAGAATATGGTTAGTGGGAGGGAGCCAAGTATAGGTTACCTTT
GTCTCGCGGAGGCCGTTATGCAAGGCAAAGTTAAAAACATTTGGACTACCAACTTCGATAGCCTTCTGGAGAATGCCCTCCATAGG
CTTTACCCCATGAACAACGTTTTGGTGTGCTCCGAGGCTAATAGAGGCAGTGTGTGCCTGCTCAACCCGACGTACCCAGTCATAGG
CAAGCTCCACGGCGACTATCGCTATGATTGGCTCAGGAACACCGAGGACGAATTGCAGCGACTCGAGACCAGCCTTAAAGGTTACG
CGTCCAGCCAACTTACAGGGAAACAACTCGTCGTTATAGGATATAGCGGGAACGATGAGAGCATTATCAGTTTCCTCAAGGATTGC
ATAGATAACCCGGCACTGCTTACCAAGGGTCTGCTGTGGGCTGTACGACGCGGTTCCTGGGTAAACCCGAGGGTTAATGAGCTGAT
AGAACGGGCGCACAAAATTGGGAAACCAGCCGACGTGATCGAGATCGATGGCTTCGACCAATTGATGTTCTCAATATACCAGATCC
AGAACTACCATAATGAGATTATCGACGGCCAAGGCAGGCTCCTCCAGGTCGGATCTGACATCCGCCTCACGGGGAAGCCCGTGGAC
AGCTTTGTCAAGCTGAACGCTTACAAGGCTGAGTACTGCCCCCTTTGTAACGTGTTCGAGACAGACATCACATCCTGGAAGGAACT
TCGGACCATAACCGGCAGCAGTGACATCATCGCCGGTCTGTTCTCCAAACATATCTATTCTCTGTCTTCCGCAGACAAATTGAAGA
CCGTGTTCAGCAAGCACTTTCTCTCTAGCATTAACAAGGAGGAGGCTCCCGAACGGGACATTCGACGGAACGAGAGTGTGTACATT
GGATTGATTTACCAGCTTATTAAGCGGACCCTGCTTTCAAAAGGGATGGTGTCCTTCGCTAAGAATAAGGTCTATAACCCCGACAG
CTGCCGCAGCGAGCAAGGCTACCAAGTTTTTGACGCCCTGGAGATCGCGGTCAGCTTCGTTGATGGAAACCTGTACCTGAATCTTA
TGCCCACGGTACATGTGAGAGGCTCAAATGGCGAGAGTCTCGACAAAGAGTCCTACCAAATACAAGTCAACCATGTGGTCAGCACA
ATCTACAATAAGCAATACAATGAGAAACTGCGGTTCTGGGAGAGCTTGTGTCTGGACAGTGGTAGAATAATCTTCGAGAACGACGG
CTTCAGCATATCATTTGTCGCTCCCGCTGTCTCCCTGGGCGGCAACAATCGAAGAGCTAAGTGGCTTTCCATGCCGTCCTGCAAGT
ATGACGAACCACTCATGTGCTTCTCAGACACTGACAAAAGCAAACGAGTTATTAACCAACTGAAGGGACTCTGCCAGTACGGGCCA
ATCGACTGCTCTTATATGCGGGATAGCACCACAAGGCCCAGCGTTAGGCTGGCCGTTCTGAGCCCGAACCAGGACATGGACCGAAT
TCTTGCACACCTCAATAAACTCAACACCCACGTCCAAAACAGGGGCAGCGATAATTTCCTGCCCCACTATGAGGGCTTTGAGCAAG
TTTACAGAAGGGCTCTGAGCGTCCCTACGAAGGAGCAGAGCAACATCTGCATCGGATACAACGTGAACGCCATCCTCAAAATGTCT
CCTGCAGAGTTTCTGGCTTTTATGAAGCGGGGTATAGAGAAATACTCCCTTCGGTCAAGCGATTTCGATATACTCGTTATTTACAT
CCCAGAGTCATTCGCGCATTTCCGGACAGCAACCGAAATTAGTAGCGACTACAATCTGCACGATGCGCTCAAACTGTATGCCACGG
ATAAGGGGATTATCCTTCAACTCATAGAGGAGAAATCTGTGAAGTCATACGACCCCTGCAAAGTAATGTGGGGCTTGTCCACCTCA
CTCTACGCGAAGGCGACAGGGGTACTTTGGCATCCAGAGGCAATTAGAAATGACACGGCCTACATAGGGATAAGCTACGCTTTCAG
CGAAGAGAAAAGGATTTGTATAGGCTGCAGTCAGCTGTTCGACTCAACCGGGACAGGTATTCGGATGGTCCTTAGAAAGATAAACA
ATCCGATATTTCTGGGGCGATCCAACCCCTACATGAGGGAAGACGACGCTCGAATTATGATGACCGAGCTCAGGGAGCAGTATTAC
CACAGCGCACCTGTGAATACTCTCAAGAGGGTCGTGATCCATAAGACCACGCCCTTCATACGGGATGAGATAGCCGGTATAATGCA
GGCATTTAACGGCATCGAGGTCGAGCTGGTTCAGATTCAAGACTATTGCTCTTGGAGAGGCATACGCTTCGGCGGTGAGCCTGGGA
AAACGGCGTTTGGGTTCCCGGTGAAGCGAGGTATGGCCGTAAAACTCGACCGAGAAAGCTTCCTGCTCTGGACCCACGGCTGCGTG
ATTCACCCGGAACTGTCAGGCACGCATAACTATTTCAAAGGTTCACGCGGTATCCCAGCACCCCTCCTGGTCCGCAGGTTTGCGGG
TAACGCAAGTGGCGACACATTGGCAAAAGAGATTCTGATGCTTACGAAGATGAACTGGAACTCCGGTGACAGTCTGTACAAAACCC
TTCCCGTGACCCTGGATTTTGCGAAAGTTCTCGCCCGCATGTCTAAGCAAGATGAGGCGATCTTTGATAAGGCGTACGACTTCAGG
TTTTTCATGTAGTAA
93 ATGCCGAAAAAGAAGCGGAAGGTTGAAGATCCAAAGAAGAAGAGGAAGGTGGGGTCTGGGTCAATGCTCCTTAATCATCTCCCAAT
CGAGTTCTCCAGCGCACAGTTCGCTGGACACGAAATTGCTTATGTCGACGGCGAGCAGTTGAGGTCCATACGACAGAGACTCACGC
GCACGCACTTCGTGTTGAGGGATGGGGACAATGTTCTGCTCTTCCCGTACGAACATGGAACCGCGACCGAGGGAACCAGGCGAACA
TTCGACACGGGCGTTAATTTCAGCGTAGCCAACGCCCTGGCGCGCAACGGCATGCTTCTGCGATTCTTCCAGCACTCTAGAAGTAT
TTCCGGCGTCCGACCGGTGAAATTTGTGAAAGACAACCAGAACCTGCTCACGGGTGACGTAGGCCGGTTGTTTGCTATATGTCCGG
AGTACAGTTTCGACATCCGACCCCTGGCACCTCAAGACGGCAGCCTTGTGAACGGGGTACTGGTAAACTTCTCAGCCCGATTTTTG
GTGAAGCCCTCCCTCGACGAATTGATTGCGCAGGGGCTCGACCCACGGGGCCTGTATGTTGTTAAAGAGGCAGAAAGAGAATCACC
CTACATCCTGCCGATGTTTAATCGGAGATTGGTAGGGCGGATCCAGGACGTGGTCGGAGGTATCGCCAAGCTGGTGGACGAGCGCG
AACAGGACCTCCCTGTACATGAACTTCATGTCGAGGCCAACCTGGTCAACTTCGAGAAAGTAGGCAGAGCACTGCTTGGCCGGGAT
TACGAGCGAGTGAGTCGACAAGTGCTTCCCACCCTCCATAAGGTGAGCGGCGCAGAGAAACAGCTCGATCGCTTGGTCCAGCTGCT
GACGAGCTTCAAAGACCTCCAGGGTGACATCCCGTGTTGCGACGGCCTGACCGTTAGACTGGCAGGCATACTTACAGATGTGCCCT
TCGGCAGTGAGGTGGGCCAATTCCGCAAATTGTCCGCGCCACAGTGCAGCCTCCGCCCAGGGGGAACTATTACGGTGCCGTGGCCC
GTGGACGGCAAACTCAATGCCAACGGCCCCTTTGATGCAGACGCCTTCAGCAGGAAGGAACCAACAATCGGCGTTCTGTTTCCGGA
GCAGCACAAGGGTAGTGTAGAAGAGCTGGCCGCTAAACTCAGAGACGGCGCACCGAGCGATGGAAAGTACCCAAGTCCATTTCCCC
AAGGAATGCCCCGGAAGTATAGACTTAGGAAGATGACATATGAGCTGACGCCCACGAAAGTTTCAGGGGACAGGGCCGCAGCCTAC
AAGAATGCCGCGCTTGCAGCCGCCCAACAAGAGCTTGATCTCGCTCTGGTGGTCATATCTGAATCAGATAAGGCGTTGCTTGGAGC
CGCCAGCCCCTACTACACTGCGAAAGCCACATTGATGAGCCAAGGCGTGCCGGTGCAGGCTATTACCATTGAGACTATCAACAGGC
TCAACCCCTACACCTTGAATAATCTGGCACTTTCCCTTTACGCAAAACTCGGCGGGATACCTTGGACCCTGTCAGTTCAACAGCGA
CTGGTCCACGAGATAATTGTAGGGATAGGGTCTGCGAGAGTGGGCTTCGACCGCCTCTCAGAGCGGGAGAGGCTTGTCGGCATCAC
GACCGTGTTCTCCGGGGACGGATCATACCTTCTTGGCAATGCAACGACGGAAGCCAGCAGTACCGAATATAGGTCTCGCCTTCTGG
AGAGCCTTAGGGCGACTTTGGCAGAGTTGCGAAGACGATTTGGCTGGCAGCGGGGAGATAAATTGAGGATTATCTTCCACCAAAGC
TATAAGCGGTACAAGGAGACCGAAGCAACCGCCGTTAGCGACCTCATCGCCGAACTTGATGAATTCGATGTGGAATTCGCGTTTGT
GCAGATCAGTAGCGATCATGACTGGAAGTTGTTCGATGAGAGTGCCACAGGCGTTACGTATCAGTCCCGGCAAAAGGGAGCGAAGG
TGCCGGAACGCGGAGTCATAGTCCCTCTCGGACCTCGCGCTGCGCTGATCACGTTGGTGGGTCCGCATCAACTGAAAACCGACCTG
CAAGGGTGCCCCTCCCCCATACTGGTGTCTATCCACCCGAGCTCAACTTTCAAGGATTTGAGTTACGTGTCAAAGCAGGTGTTCGA
CTTGACCTTTATGAGTTGGCGAAGCTTTAACCCAAGCACGCAGCCCGTTTCCGTGAGTTATCCCAACATGGTGGTGGATCTGCTCG
GTAACCTGCGGCAAATCCCCAACTTCAATCCCGACATTCTGACGACAAAACTGAGGGAGTCTAGGTGGTTTCTGTAGTAA
94 ATGCCTAAGAAGAAGCGAAAAGTTGAAGACCCCAAAAAAAAGCGCAAGGTCGGGAGCGGATCTATGATGGGAGCCAGCGATGAGTA
TTCCTTTTACGCTGAAAAGGCCTATCCCATAGAAGCGGACAGGCAAAAGTACTTCGAACAGCTGGCGTACAACAAAGCCCCCTACA
TTGGCTATAAACTCTTGTGTCTGCTGAATAACGCGGGGCTGATAAAGTCTGTTTGGACCACAAATTTTGATGGCCTGACGGAAAGG
GCCGCTCACCAAATGAACATCACCCCCATCTGCATTACCCTGGACGACCCCGAGAGGATTTTTAGGAATGAGAACTCTCACGAACT
GCTGTATATCGCCCTTCACGGCGATTACAAATATAGCAAGCTCAAAAATACCACCCACGAGCTGGACACCCAAAACAATATCTTCA
GAGACGCACTGAAGCGATACTTCGTGGATAAGAATCTTATTGTCATAGGATACAGCGGCCGAGATAAAAGCCTGATGAACGCACTT
AAAGAGGCATTTTCCCAATCCGGCTCCGGGCGACTGTACTGGTGTGGCTTCGGGGACGATATATGCAGCGACGTTAAGGAATTGAT
AGACATCGCCAGGAGCAATAATCGGATTGCCTACTTCATCCCGACGGACGGCTTCGATAAGACCATGCTCCAACTTAGTCGCGCCT
GTTTCGAGGACGACATTGTGAAGCAGGAGGAAATCAAAAAGCTGATCAAGTCCACGATCAAGAAGGACGAGACGAAGACCAGCTTC
CGAATCGAGAGCAGCAGGAACGATAAACTTATTAAGTCTAACCTGCATCCCGTGGCGTTCCCCAAGGACGTGTACCAGTTCGAGAT
TAAGACTAACGGCGAGCATCTGTGGAACAACATAGACCAGATCATTGGCGGCAATAAGGACATAGTTGCCGTACCGTTCAAAGGTA
AGGTGTTCGCTGTCTCAAGCATTGCGAAAATCAAGGAGAGGTTCGGGGGCTATATCAAGGGGGAAATATTGAAAGACCCGATTGGC
GTCGATGACATCCGCAAAGTATCTGTGTTCCAGCGGCTTATGATGAAGAGCATCCTGATTGGAATCTCTGAGTTGGCAAATCTGGA
AACTGATGGAAAGTGGCGCCTTTGGAAAAAGAACACCCTGAGGCGAATCGTAAACGGCACGGAGTATTTCATCGCCGACGCTGTAG
AGCTGTCCTTTTTCTTCGGAAAAGATACCAAGTTTGCCTATCTCAGCATCAAACCGACCATTTACATTTATACACATAGCGACGAA
TTCATACCGAAGGATATAAAGCTGCAATTCACAAAGGAGAAGTTCGACCGACTCTATAATGCACAATACGACCAATCCCTGGAGGA
GTGGAATAATCTCATCTTCCACAACAACAGCCTGAGGTTCACCTTTCCCGTACTGACCACCTCCGACATGAGCTTTAGCATCAGCA
ACAATGTGGCCTTCTCAGGAATTAAGGTTTTGAGTGACAAGTATAAGAGCTACCCCGTTTCTATCGAGCAGAAGCGCATAGTTTTC
AAGGGCGTGGAGTTCCTGGAGCCCCAGCTGCTGTTTCAAAATAAGAACAGCAACTTCAAGTCACGCGACTTCCATCCCATGAGGGG
ATTGATTAACCACTACCCCTTCGACTACCAGAACAATGGGATCACCAACACGTTTAATGTCAAACTCGGCGTGTTGTGCTCCTCTA
AGTACTCTACTAGGCTGTACGAGTTTCTCATGAAATTGAATGCCCAACATAAAGCGCCCGAGAAAAACGAGTACATAATTGACTAT
GCTGGATTCAACCAAATCTACAACATCCCTATTGAGATACCGCTGGTAAACGACGAGAAGTGGATGGACGTAAAGTTTAATAGCAG
CGTGAGTATCAAAGACGACGCTCTCAACCTGGCAAGAATCATATGCACCCAGATCGAGGCGCTTCACGAGTCTTACAAAACTGACA
TGACCATCGTGATCTTCATTCCCAACGAGTGGCAACCCTACAGACATATCGAGGAGGACACATGGGTTTTTGACCTCCACGACTAC
ATCAAAGCATATAGCGCTCAGAAAAGAATTTCCACGCAGTTCATAGAGGAAGATACTCTGAACGATTCATTGACGTGCCAGATATA
TTGGTGGCTCAGCCTTAGTTTTTACGTGAAATCCTTGCGGACGCCGTGGGTTCTGAATGCTAACAATAATGAGACCGCTTACGCGG
GCATCGGCTACAGTATAAAGAATAACAACGGTGAGGCGTCAATTGTCCTCGGGTGTAGCCATATTTACGACAGCCACGGCCAGGGC
CTCAAGTACAAATTGAGCAGAGTGCAGGACTGCTACATCGACAACAAGCGGAACCCCTACCTGAGCTACAATGAGGCCTACAACTT
TGGCATAAGTATCAGGGAGCTCTTTCTGCACAGCATGGAGTACCTGCCAAAAAGGGTAGTAGTGCATAAACGCACCGAGTTCAAAC
CCGACGAAGTGAATGGCATTGTCGACTCACTGCAGATAGCGGGTATCGAGAATATAGACCTTATCTCCATCAACTTCGAGCGGGAA
GTTAAATTCATGTCCACTAAATCCAACTACGGGCAGTTGCAAATCGATAACTTTCCCATACGCAGGGGCACCTGTATCGTGGTGAA
CGACTATGAAGCCCTTCTCTGGACCCATGGAATTGTGCCGAGCGTTAAGTCCGATAACAGGACCTTCTATCTGGGCGGACGATCTA
TTCCTAGCCCTCTTATCATTAAGAAGCATTACGGTAAGAGCGATATCAACGTTATCGCTACAGAGATACTGGGTCTTACCAAGATG
AATTGGAACTCTTTTGATCTCTACACGAAGCTGCCGGCCACCATCGATAGCTCTAATCAAATCGCGCGGATCGGGAACCTGCTGAC
TAGGTTCGAGGGCAAGACCTATGATTACCGGTTTTTCATTTAGTAA
95 ATGCCCAAGAAAAAGAGGAAGGTCGAAGATCCTAAAAAGAAAAGGAAAGTCGGGTCCGGTAGCATGCCCACCCAGTTCCAGGAGGT
GGAAGTGATACTCAACCGCTTCTTTGTAAAGAAACTGTCTCGGCCCGACCTTACGTTCCATGAGTACCAATGCCAGTTCACCCAGG
TTCCAGAGCAAGGCAGCGAACAAAAGGCCATCAGCAGCGTGTGCTACAAGCTCGGTGTGACCGCCGTGAGGCTGGGCTCATGCATC
ATCACCAGGGAGCCCATAGACCCTGAAAGGATGCGCACCAAAGATTGGCAGTTGCAGCTGATCGGATGCCGAGAGCTGAGCTGCCA
AAACTACCGAGAGAGGCAAGCTTTGGAGACTTTCGAGCGAAAAATCCTGGAGGAAAAGCTCAAGGAAACATTTAAGAAGACCATCA
TCGAGAAGGACTACGAGTTGGGCCTGATCTGGTGGATATCAGGCGAAGAGGGACTGGAAAAAACCGGTCACGGGTGGGAAGTGCAC
AGGGGCAGGCAAATAGACCTCAAGATCGAGACGGACGAAAAGTTGTACCTGGAGATCGACATACATCACAGGTTCTACACCCCCTT
CAAGCTGGAGTGGTGGCTGAGCGAATACCCCAACATCCAAATCAAGTACGTGCGCAACACGTACAAGGACAAGAAGAAATGGATAC
TGGAGAATTTCGCCGACAAGAGCCCCAACGAGATTCAGATAGAGGCCCTTGGCATCAGCCTTGCGGAATACCACCGGCAAGAAGGT
GCTACCCAGCAGGAAATCGACGAGAGTAGGGTTGTGATCGTCAAAAAGATCTCTGACTACAAGGCGAAACCCGTGTATCACCTGTC
TCAGAGGCTGTCCCCGATACTGACCATGGAGACCCTTGCCCAGATCGCCGAGCAGGGTCGGGAAAAGAAGGAGATACAGGGCGTGT
TCGATTACATTAGGAAGAACATCGGCACGAGGCTGCAGGAGAGCCAGAAGATCGCGCAGGTCATTTTCAAGAATGTTTATAACCTT
AGCAGCCAGCCCGAGATCATGAAGGTGAACGGTTTTGTAATGCCACGCGCGAAGTTGTTGGCAAGGAACAATAAGGAGGTCAACCA
GACCGCTAGGATCAAGAGTTTCGGCTGCGCTAAGATCGGAGAAACGAAGTTCGGATGTCTCAATCTGTTCGACAACAAACCGGAGT
ACCCGGAGGAGGTACACAAGTGCTTGCTGGCGATTGCGCGGAGCAGTGGGGTCCAGATAAAGATAGATAGCTACTTCACGGGGAGC
GACTACCCGAAAGATGACTTGGCCCAGCAAAGGTTCTGGCAACAGTGGGCGGCACAAGGAATAAAGACGGTGCTGGTCGTGATGCC
CTGGTCCCCTCACGAGGAGAAGACAAGACTGCGGATCCAAGCTCTTAAAGCCGGCATCGCAACTCAATTTATGATCCCCACGCCCC
AGGATAACCCATACAAAGCATTGAACGTTGCTTTGGGTCTGCTCTGCAAAGCCAAATGGCAACCCGTTTACCTGAAGCCCCTGGAT
GACCCCCAGGCCGCAGACCTGATCATCGGCTTCGACACTTCTACCAACAGGCGGCTCTACTACGGTACAAGCGCCTTCGCGATTCT
GGCGAACGGCCAGTCACTGGGCTGGGAGTTGCCTGACATCCAGAGGGGCGAGACATTTAGCGGCCAAAGTATATGGCAGGTAGTGA
GCAAACTTGTGCTGAAATTCCAAGACAACTACGACAGCTACCCTAAGAAAATTCTGCTTATGAGGGATGGACTGGTTCAAGACGGC
GAGTTTGAACAGACCATAAGAGAGTTGACCCACCAAGGGATCGACGTGGACATCCTGAGCGTGAGGAAGAGCGGTAGTGGCAGGAT
GGGAAGAGAACTGACAAGCGGCAATACTGCCATCACCTATGACGACGCCGAAGTGGGAACCGTGATATTCTATTCTGCCACCGACT
CATTCATACTGCAGACAACCGAGGTAATTAAGACAAAAACGGGCCCACTCGGTTCCGCGCGACCGCTCAGAGTGGTTAGGCACTAC
GGGAACACCCCGCTTGAACTGCTCGCGCTGCAAACGTACCACCTGACCCAATTGCATCCCGCCAGCGGCTTTCGGAGCTGTAGGCT
CCCCTGGGTTCTGCACTTGGCAGACAGGAGCAGCAAGGAGTTCCAACGGATCGGTCAAATTTCATTGCTCCAGAACGTGGATAGGG
AGAAGCTGATTGCAGTGTAGTAA
96 ATGCCAAAGAAGAAGAGAAAGGTTGAGGATCCCAAGAAAAAGCGGAAGGTCGGCAGTGGCAGCCTGGGAGCCGGTGCCAGCATCAG
TTCCGGCATCCAAAGCGCTAATGACTGCATTTGGGACTGGAAGTACTCTATCTACCAAACTAACTCCGGCAGTCAACGAGTGGCCC
TCGTGGACCCTAAGAAATCCGACGCCTCCAAGTCTATCATCCAGAAGTGGCTGGATAATCAACCGAAATTCTCACAGATCGAAGCC
CATCAGGAGTACAGCTTCTACGCCCAGGCGGCTTACCCCATTGAGGCGGACCGAATCAAATACTTTCAGAATCTCTTCCAGGGGAA
GTCCCCCTATATCGGCTACAAATTGCTCTGCCTGCTGAACAAGTACGGTGTAGTGAAATCTGTGTGGAGTACCAACTTCGACGGCC
TGGTCGAACGGGCAGCACAGCAAGCCAACATCACCCTGATCGCCATCAATCTTGACTGTGTTGACCGCATATATCGAGCAGAAAGC
GTGAATGAACTTCTGTATATCGCGCTCCACGGGGACTACAAGTTTAGTACCATAAAGAATACCGCGAATGAGCTCGACAGCCAGCA
CACCGAGTTCGTATCTGCCATGTGCCGGTACTTCGTCGATAAAAACTTGATCGTCATGGGATACAGCGGACGCGACAAGTCACTTA
TGGACGCCCTGGTCCAAGCGTTTAGCAAGAAGGGTGGGGGGAGACTTTATTGGTGCGGCATGGGCGAGACCATCACGATCGAGGTG
CAAAACCTGATACAGAGAGTGAGGACCGCAGGCCGGTCAGCTTATTATGTAGATACCTCTGGGTTTGACAACACCATGCTGTCACT
GGTAAAGTACTGTTTTTCAGAGGACGTCGCCAAACAGCGAGAAATAAACGAAATTTTGAAAATTGTGGAACCGGAGCAGATTACTC
CGTTTGAGATTCAAAAGAGCCAGAACAAACGGTATCTCAAGAGCAACCTGCTGCCAATCGTGCTTCCCAAGGAACTCTTTCAGTTT
CAGATCTCTTATAACGACACGGCGGACAGGTGGGGATTCTTGCGCGAGAGGATTAAGGAGCGGGAAATCATAGCAGTCCCGTACCA
GGACAAAGTATACGCAATCAGCACGGTCTCCATCATTAACGACGTTTTCAAGGACTGTCTCGTAAGCGAGATTGAGCGCACGTCCA
TCTCTCTGAATGAGATCGAGCGCAATGGCTGCTTCAAAGAGCTGTTCCTCAAGGCTATTCTCTACGGGTTTAGCCAAATCCGGAAT
CTGGGCATCAACTACCGCCACGGCATCATTTGGAAGAAGGAGGCGCTCTACACTGAGCCCGGCAAGACCGTACACGAGGCCATAGA
ATGCGGCTTGTCTTTTATACCGCAAGCGAACTACGCTTTGATTAGCATCACACCAAGTTTGCACATCGAATCCAGCAGCCCGATCG
AAAAAGAGAAGAAACAAGAGTATAACAGGCGGTACCTTGACAAGATGAGGAATAAAGAGTACGAGGAAAAGATCCAGGAGTGGTGC
AACATACTGTTCTCCGGTAACAAGCTCGTTTTTGACATCCCGCTGCAAAGCAACAACGACTTGAAGTTCTTCATTTCCAGTAATAG
GGGTTTCGCCGAGGTATACAATTACGGTAAGGACATCGAGAAGAGCTACACGCCCAATGCTTACAATACGAAACAGACCATTTACT
ACGGCATGCAAATCGAAGAGCCTCAGTTGGAGTTTATCAACTCCATAATCAGTAGGCCGTTCTATGACGTTAACCCAATGAGGGGC
CTCTCAAATCACAAACCATTCGACGCGGACTACTATGACAAGTTCCCCCAGGATGTGTGTTTGGGCATTGTGTGTCCGACCAGCTA
CAGCCTGATGTTCTCAGAATTCCTGAAGCGCCTGAACACTAAGATCCCAGCACCGAAGTCATCCGACTACATCCACAACTATATTG
GCTTTAACAGCATCTACAACTGCAGGCTGGACATACCGGACATCAATGCCGATCGCTGGGTGAGCATCGGCGACAACCCCCAGAAC
GCGGAGGAATTGGCCCGCAACATCTGTATGGAAGCAAAAAAGCTGAGTGAACAATATCCGGGCATCGTGGTTAACATATTCATCCC
TACTATCTGGAGCAACTACAGAAACTTTAAACACAACGGTGAATTCTTCGACCTGCATAACTACATTAAAGCATTTGCGGCACAAA
ATCGCTTCACCACGCAACTCATCGAGGAGAAAACTGTTTGTAACACGATGATGTGCGAGATATCCTGGTGGCTTTCCCTTGCCCTT
TTCGTTAAGACCCTGAGGACTCCGTGGACACTGGCTGACCTTAACCCCAACACCGCCTACGCGGGGATAGGGTATTCAGTTAAAAA
GCAGGCCAAGGGCAGGACAGAGATCGTACTGGGGTGTAGCCACATTTACAATGCGCAGGGACAGGGACTCAAGTACAAACTGAGCA
AGGTCGAGCACCCACAGTTCGACAAAAAACGGAACCCATTCTTGAGCTTCGAGGAAGCCTTCAAATTCGGGATGGATATTCTTAAT
TTGTTCCAGAGTGCAATGGAAAAACTGCCGCAGAGGGTGGTTATTCATAAACGGACGCCTTTTAGGGAAGAGGAAATAGAAGGGAT
TACCAGCGCCCTCAAGCGGGCAGGGATCACGGAGGTGGACCTGATCACTATAACGCAGGAGCGAAACATTAAGTTTATAGCACAGG
TTGTCTCCTTCGGCCAACTCAATACCGACGGCTATCCCGTCAACAGAGGCACTTGCATCAAGCTTAGCTCTCGCAATGCACTCCTT
TGGACCCACGGCGTCGTCCAGAGCATTCGAGACAAAAGACGGTACTACCAGGGGGGCAGGTGCATTCCGAGCCCGCTGAAAATCAC
TAAGTATTACGGCAACGGCGATCTCCAGACTATAGCTAAGGAGATCATCGGTTTCACGAAGATGAATTGGAATAGCTTCAACTTCT
ATACGAAGCTGCCAGCGACCATTGACACTAGCAACACCCTGGCCCAAGTGGGCAACCTTCTCAGGAACTATAATGGCACCACCTAC
GATTATCGCTACTTTATCTAGTAA
97 ATGCCTAAGAAGAAGAGGAAGGTGGAGGACCCAAAAAAGAAACGAAAGGTGGGGTCTGGCTCTATGCCACACACCTCCCTGCTGTT
GAACTTTCTGCCCGTCTCTCTTAGCGGCGACACACGCATCCATGTCGGCTACCGGCCATATAACGAGGATGTGCTGCGGGAACTGA
GGGAGGAGTTCGGCGAAAGCCACGTGTTTAAAAGGGACTACCAGGAGGACACGATAAGCGAGATACCGGTCATCCCCGGAGCCGAG
CCCCTTAGCGACAAATCTACTGGCGTGGATCTTGCCGAAGCGCGATGGCTGTGGAAACCACTTCTGAACGCTGCATTGCTTCGCCT
CTTCAGCGGAAGCAGAGAGATCACCTCTGATTATCCAGTCAGCGTGCTTGGTAACCCCAAGAACAACTTCATCAGCCATGCCAATC
TCCCCGACTGGGTGAGAATCCTGCCCCTTCTGGAATTCGAGAGCCGAACCCTGTTCGGTGGTAAATCCGGTCCGCAGTTTGGGCTT
GTTTGCAACGCCCGAACTAGGCACCAGGTCCTGGCAGGCTGCGACCATCTCATTGAAAGAGGTATAAGTCCCATTGGCCGCTATGT
TCAGATCGACCAGCCACAAAGAGACTCCAGACTTGCGCCACGCGGTCTGACTGTTGGTAAGGTGAGCTCTATCGATGGGGACACGT
TGATCCTGGAGGATCACCGAAAGGGCTACGAGCGCGTGAAGGCAAGCGACGCTCGCCTTACCGGCAATCGGGCGGACTTCGACTGG
TGCGTGAACGCGCTGTTGCCTGGACAAGGTCAAGCAACGCTGAGCAGGGCGTGGGACGCCATGAGCGCCCTGAATCAGGGACCCGG
CCGCTTGCAAATGATCAATCAGACAGCTGAATATCTGAGGACCGTGAACCTTGAGGCGGTTCCTGGGGTAGCATTTGAGATCGGCG
AGTGGCTGAGTTCTACCGATGCTCAGTTTCCTGTGACCGAGACCATCGACCGCCCTACCCTCGTGTTTCATCCCTCCGGCCGACCC
AACGACACTTGGAACGAGAGGGGGATAAAGGACAATGGCCCGCACGACCAGAGGACATTCACCCCCAAACAGTTGAACATCGCCGT
GATTTGCCAGGGCAGATTTGAGGGACAGGTAGACAGATTCGTGGGCAAGCTGCTCGATGGCATCCCGGACTTTCAGTTGAGGAACG
GCAGGAAGCCCTACGACGACGGTTTCCTTAGCCGGTTTAGGCTGGAGAGGGCCAACGTGCAAACCTTTCAGGCTAACAGTGCGTCC
CGCGAGGCTTACGAAGCAGCGTGTGAGGACGCTCTGAAACATGCCGCTGATAACGGCTTTGGCTGGGATCTGGCTATCGTTCAAAT
CGAGGAGGATTTCAAGGCGCTGCCTGGGCCCCAAAATCCCTACTACGCCACCAAGGCAATGCTCCTCCGGAACAACGTAGCCGTGC
AGAACATCAGGATCGAAACAATGAGTGAGCCTGACAAAAGCTTGGTCTACACTATGAACCAGGTTTCTCTTGCTTGCTACGCAAAG
CTGGGTGGTAGACCTTGGCTCCTCGGTGCCCAACAGAGTGTCGCGCATGAGTTGGTGATTGGACTGGGCAGTCACACCGAGCAACA
AAGCAGGTTTGATCAGTCCGTGCGATACGTAGGCATCACCACCGTATTTTCCAGCGATGGAGGCTACCATCTGAGCGAGCGAACCG
GAGTAGTGCCCTTTGAAGATTACGCCAAGGAGCTGACAGACACCCTCACTAGGACCATAGAGAGGGTGCGAAGGGAAGACAATTGG
AAGAACACTGATAGAGTTCGCCTGGTGTTCCATGCTTTTAAGCAGATTAAGGACATCGAGGCCGAGGCCATCAAACAGGCAGTGGA
ATCTCTTGATCTGGAGAACGTTGTGTTCGCATTCGTCCATGTGGCCGAGCACCACCCTTATTTGATCTTCGACCAAAACCAAGAGG
GATTGCCCCACTGGGAAAAGAACAGGAGCAAGCGCAAAGGCGTCTTGGGACCCAGCAGAGGCGTGCATATAAAGTTGGCGGACAGC
GAATCCCTTGTGGTATTTGCTGGTGCTAGCGAGTTGAAGCAGGCGGCACACGGTATGCCTCGGGCCTGTCTGCTGAAGCTGCACAG
AAACAGCACCTTCAGGGATATGACCTATCTGGCGAGACAAGCCTTCGATTTCACCGCCCACAGCTGGAGGGTGATGACCCCTGAAC
CATTTCCGATCACAATAAAGTACAGCGACTTGATAGCAGAGCGATTGGCGGGTCTCAAACAAATAGAGACCTGGGACGACGATGCC
GTGAGGTTTAGAAATATTGGCAAAGCCCCCTGGTTTCTGTAGTAA
98 ATGCCGAAGAAGAAGCGAAAGGTCGAGGACCCGAAAAAGAAAAGGAAAGTGGGGAGCGGCAGCATGCAGCAGGAGATCCAGCTTAA
CATCATCCCCTTCACCGCCCCTGTGGAAGAGGCAGAGTTCGCTTTTTACACCGCCAAGCAAGACGGCTACTGCCCCATCCATAAGG
ATGACCTGAACGGGGCCATCGAAGGCCTCGTGGATGAATCAGACCTGCACTACGGCAACTGGCTGTACACTGACTTCGCTCCCGCC
AAAGAGAACGCCATCATAATTAGCGTCAATCTCAATGACTGTAAGTACTTCGCCCAGCACTACTACAGGCACCTTATCAGGACCCA
CTTCAAGGGAGTGGCCGACATCATGAGGAAGAATTTCACCAACGAAATCGAGGTCTGGTTCCACAATACCAAAGCCAGCTCTACCA
AGTTTAAGGTCTATAACCAGTTTACCCTCAAGGTACAGCACAACAGGGTGACGGACGGACCGGAACTTGTCGTGTCCTTCGACGGG
ACGACGAAGGTGCTGAACAAGTCTATCGCCGAGATACACAACTTCAAAACGGAGCTTTACAACTGGATAAACTGCAACGGCGAGCT
TAATCGCTGGAAATACCTGACCGACGATCAGAAGCTGAATCACGAAAAGAACTACCCGGTAGTGTCAAACACACTTAAACCGCATT
TCGACATTGCCTTTGACGTTCCCGATTTTAAGAACCGGTATCCCAAATACTTCACTCTTCTGAATGACTTCTACAACAACTATCTG
AATACAGACGCCTTTACTGCGATCTTGCCGCTTTCCGCTGACGGATTCTTCAAGCCAAATGGCCTGTCAGTGCAGAGGATCAACGG
CACTAGCAATGAGCTGCAATTCGGCAATGGCGTCGGCGTGGAGCCCAAAAGGGATCTCAAGCGCCTGAAGCCGTATAAACCCGTGC
CCAAACCCAGCAACGTAAAGTTTTTCTTCATCTATCACAAGCCAGATAGGGAGCATGCGGTCAAAAACATCTGGCAGTATTTCAAA
GACGGATACAACGGCCAATACCCCTTCCCCAAGATGGAGGAATACATATCTCAGCCCTTCGAGCTTGAGGAGAATGGATCTATCTC
ATTCGACAATATCGACGACGCGGTAAGCGTTGTCCAAAAAGCCATCAAGAACAAGGATCGGCTGCCCGACACTAAATACTTTGCGG
TATACATCTCCCCCGTACCAAAATGGGAGAAGGACCCTAAACGGAATAGTATCTACCATCGGATGAAAGAGATACTCCTGTACGAG
GGGATCACCAGCCAGGTGATCTGGAAGGAGAACATTAGCAAACCGGCTTTCAACCTCTTCTTGCCTAACATCGAAACCGCCATACT
GGCCAAGCTGGGAGGCGTCCCCTGGAGGCTCAAGAGGGACACCACGAACGAGTTGATCGTTGGCGTGGGTGCTTTCTACTCAATCA
CGCGGAAGTCCAAGTACGTGGGCTCTGCATTTTGCTTCAATAACGAGGGCATCTTTAAGGGGTTCGACTGTTTCGGTGCCAATGAC
ACCGACAGCATCGCGGGCTCTATCAGGGAGGCCGTGGGAAAGTTCATCGCGTCTAATTACAAGGCCACAAGGCTGATCATTCACTT
CTATAAGGACCTGTCAAAGAAGGAGCTCAAACCAATCATCGATACACTTCACGCCCTGGGCTTGCCCATCCCAGTGATAGTCGTGA
CCATCAATAAAACCGAGAGCAAGGAACTCCTGGCATTTGATACCAGCTCACAAAAGCTCATGCCCTACTCTGGCACCATCGTGAAG
GTGGGAGCCAAGGAGTACCTGCTGTTCAACAACACGCGATACGAGGAAGCATCCGCCCCAACGGATCGCGAGCACCACTTCCCGGT
GAAAATCAGCTTTTTCTCAGACAAGGCGGAGCTGTTGGACGATCCCGCACTGATCAACCAACTGATCGACCAGGTGTACCAGTTCA
GCCGCATGTATTGGAAAAGCGTGAGCCAACAGAACTTGCCCGTAACCATTAAGTATCCCGAGATGGTGGCGGAGATTTTCCCATAC
TTTACCCACGATAAATTGCCCGATCATGGAAAGGAGAGCCTGTGGTTCCTGTAGTAA
99 ATGCCCAAGAAAAAGCGGAAGGTTGAGGACCCAAAAAAGAAGAGGAAAGTTGGCAGCGGGAGCATGGAAAATCTGACCCTGAATAT
CATCCCTTTCAGCCACCCCGTGCAGGAGCTTGAGATCGGCTTCTATAAGCAAGAGAAACAGGGATGCTACAGCCTGTGGAAGGGCG
AGTACCCGCAGTCATTCTGGGACGACTTCAACGAGGAAATGCAAAATTGCGACAAACTCTACACCAACTTCATTGACACGGAAAAC
TGTGATTACAAAGCCAGTGTGGACTTTAGCAAAAACAGACGCCTGGCGGTCCATTACTACAGCAGGCTGATCTACAACTACTTTGA
AACAGTGGCAGATGCCGTGAAAATCAACTTCGTGAAAGATATCCAGATATGGTTCAAGGACGAGACCAAGAGCACCGCCGTCTATA
CCAGTTACAAGCGGTTCACGATCAAGGTCCAGTTCCATAAGGTGACCGAGTCCCCAGAGCTGTTGATCAGCTTCGATGGCAATACC
ACGGCCTATAACAAAAGTCTGGCCGAGTTGGACGATTTCCCTCCCGAGCTGATTAACTACGTTAAGTACAATACCCAAGTGGTGAA
GTACGAGTTCGCCGAGGACGCTATTAAGCAGCATATCGAGGAGCTGTACCCGATCCTGAGCAACCCCATCAGGGACTACCTTAAGA
TTGCCAGGCCCGATTTTAAGAGGGGCAACAAGTATAAGCCCTACTACAAGAACATTACAGACTTCTATCACAACCACCTGAACTCC
AAAGAGTTTAAAGCTATCCTGCCTATCTCCGAAGACGGTTTCTACAAAATGCCTAAGCACAAGGTTCACAAAACCAGCTTCAATAG
CAATAAACTGAGATTTTTCAATAACACGGACATCGTGCCCCACAACGGGATGAAAAACATCGGCCCCTATAAGGCGTCCCCCCACC
CCAACGTGAGGTTCTTCTTCATCTACCATAAGCCAGACCGAAACTTCGCCGTCAAGACGCTGTACGAATACTTTACGGAAGGGTAC
AAGAGCCCAGAGGGCTACCTTTACTTCAAGCCTCTCAAAACCTACATTAAACAGCCCTTTCTCATCGACAAGGATACCAGCATCGC
GTTCGAAAGCCCGGAAAGCGCTCTGCGCGAAGTCAAGCAGGGTTTGCTTAACCTGGAAAAGCAGCCCAATACGAAATACGTCGCTA
TCTATGTGACCCCCATACATAAGACCGAGACCGACGAGCAGAGGAAGATGCTTTATTACCAGGTCAAGGAAGAATTGCTCAAGCAC
GACATATCAAGCCAGGTGATATACAAGGACAACATTGGACATAAGGATTTTAGTTTCTATCTGCCCAACATCGCCATCGCCCTGCT
GGCCAAGATCGATGGAATCCCCTGGAGGCTGGACAGAGACACTAAGGAGGAACTTATCGTGGGCGTAGGCGCATTCACAAGCCTGA
ACCACAATATCAAATATGTAGCTAGCGCCTTCTGCTTTAACAACAATGGGGAATTCAAGGGATTCGACTGCTTCAAAGCGAATGAA
ACCGAACTTTTGGCTGGCACCATCGGCAAGCAAATCCTGAAGTATGTGGTGGACAACGGCGAGAGCGCCAAGCGCCTGATAATCCA
CTTTTACAAAAAGATCAGTAACAAGGAACTCGAGCCCATAAAGAAAATGCTGAACAAGCTGAACCTGACCATCCCCGTAGTGATAG
TGACTATCAACAAGACGACCTCAGAAGATAACGTGGCGTTTGACACCAGCAGCCATAACCTGATGCCCGTGAGCGGCACCTACCTC
AAAATAGGATGGGACCAGTACCTCCTTTTCAACAACACGAGATACAACGCCAGCGACACCGAGAAGGATAACCCCTTCCCTGTAAA
GCTGAGCTTCTCTAGCACCGTAGACAATTACTTCGACGACAGGAAGGTGGTCGAGGAATTGATCGACCAGGTGTATCAGTTCTCCC
GCATGTATTGGAAGAGCGTGAAGCAACAGAACCTGCCCGTTACCATCAAGTACCCCGAGATGGCGGCAGAGATCTTCCCATTTTTT
GAAGGCGATAAGCTGCCCGACTTCGGAAAGAATAACCTTTGGTTTCTGTAGTAA
100 ATGCCCAAGAAGAAGAGAAAGGTGGAGGACCCGAAGAAAAAACGAAAGGTTGGCAGCGGCAGCGTGCAGCAGACAGTGGAGCTCAC
CCTCTACACAGAAAAACATCCCGACACCCACCCAGAGCTCGTTTATGCCGACGAGTGTCCCGACCTGTGGCAACAGCACAGCGAGC
TTACGGGGGACAAATCTCTGTTCTACTCTCTTACGAACCCGGCAGAATGCAAGGGAACCCAGTACACAGTGCAAATCAACCTGAAT
AACCAGAAGCAGCGAAGGATCGCCAAGCACATAATTAGCCAGCAACTGTATAATCACTTCCGCCAGACCCAAATCGCTACCTTCGA
CAAGATCGACAATGTGGAGGTGTGGACCAAGAACACCCAACAGCCTACCCAGAATTGCACGGAGTACCTGAGGTTCAGCCTTATAC
CCCAATACGCCGTGTTCTCTGACTCATGGGAGCTGGTCGTGTCCTCAAATGGCATATCCACCGTGTATAACAAGCCTTTGAGCGCA
CTGGACCTTCAGACCGACCGATTCAAGGTCGTCGTTGGAGGGGAAGTGGTCAAGTACAAGAACCTGAGCCCCAATCAAAAGCAACA
AATAGACGAGGCCTTCCCCAAAATCAATAGGGAACTGGCCGCTGAACTGCATATTAACGAGAAACGCTTTCTCAATAAAGACAAGT
ATACGACCACCTACAACCACATTAACAACTTCGTGCGACAGCACCTTCTCACATCCGAGTTCCAGGCACTGTTTTGTCTGAGCGGC
GAGATGTTCAACGTACCCGAGGAGCGGATCGGCCAAGTGGCGAAGGGGGCGAACCTGTTGCAGTTTAAGGACGGCAAGACCGGCAT
TGACCCATTCAGCTGTGTGTTCGGCAGCAAGAGCATGGACGCACTCGGCATCTACCAACCCAGCCTGAAGCCCCAGGTGAAATTCT
TTTTCATCGCCCAGCAAAGCGATATCAACGTGTGCAAAAGCCTGTACGATATTTTCACGAAGGGATACAAGCCCTACGTGGACACA
GCCACTGGCGAGCAGAGGTACGTGTTCCCACCCCTGGCGACGTGCATCAAGCAGCCCTTTTCAACCGACCCCAAGGGGAGCATTTA
CTTCAGCGACCCTCAAAATGCCCTGAGCGAGATCAAGAGCCAGCTTAACAATAAGCCTCTTGACCCCCAAACGCAGTATGTGAGCA
TATACGTGTCACCCATCCCTCGCGACGCCGTCAACAATCCCTACTACGGTCTGTACTTTCAGATTAAGGAGCTGCTGCTCGAAAAG
AGGATAACGTCTCAGGTGATCTATAAGGACCGCCCCAACAACCAGTACTTCAACTTCCATCTGCCCAATATCGCGACTGCCATCCT
GGCAAAAATAGGCGGCATCCCGTGGCAGTTGAACTCCCACACGACGAACAAAGATCTGGTGATAGGCGTGGGCGCCTTCCTTAGCG
AAAAAGTTGGCGAGAGGTATGTGGGCAGCGCGTTCAGCTTTAACCCCAACGGCCTGTTTAAGAACTTCGACTGCTGTAAAGCGAAC
GATCTCGAATCTATCGTAGCCGGGATCAGAAAGGCCATCGGACACTTCGTTGTGGACAGCGAAACAAACCCCCAGAGGCTGATCAT
CCACTACTACAAGACCATGTCAAAGAGGGAGGCCAGGCCCATCACGCAGATGCTGAACACGCTTGGCCTCAACATTCCTGTATTGA
TCGTCACAATAAACAAGACGGAGACCAGCGACATTGTTATGTTTGATGAGAAACAGCAGGGCTACATGCCCCTTTCAGGCACCGTA
CTGAAGATAAGGAACGATGATTTCCTGCTCTACAACAATAGCAGGTACAAAGAGAACGAAAAGTCAGATATGCTTTTTCCAGTGAG
GATCCGCCTGAGTAAGATCGTAAACCAATCCGACAAAGACATCCCAATGACAGACGCCTTCAATTTGCTCAACCAAGTGTACCAGT
TCTCACGCATGTATTGGAAGAGCGTTAAGCAGCAAAACCTGCCGATCACGATAAAGTATCCAGAGATGGTGGCCGAGATAGTGCCA
CACTTTTCAGAAGCCGAATTGCCGCAGTTCGGAAAGAATAATCTGTGGTTTCTGTAGTAA
101 ATGCCAAAGAAAAAACGGAAGGTCGAGGATCCCAAAAAAAAGAGAAAAGTCGGTAGCGGCAGCATGAACTACACAGCCGCCAACAC
GGCCAACAGCCCATTGTTTCTCAGCGAGATTAGCAGCCTTACCTTGAAAAACAGCTGCCTCAACTGCTTCAAACTGAATTACCAGC
TGACTCGCGAAATAGGCAATAGGTTCGGCTGGCAGTTCAGTAGGAAGTTCCCTAACGTTGTGGTGGTGTTCGAGGACAACTGTTTC
TGGGTTCTCGCTAAAGATGAGAAGAGCTTGCCCTCTCCTCAACAGTGGAAGGAGGCTCTGAGCGACATCCAGGAAGTGCTGCGAGA
GGATATCGGAGACCACTACTACAGCATCCACTGGCTTAAAGACTTCCAGATCACCGCCTTGGTGACCGCCCAGCTCGCCGTGCGAA
TTCTGAAAATCTTCGGTAAATTCAGCTACCCCATCGTGTTCCCCAAGGACAGTGAAATTAGTGAGAATCAAGTGCAAGTAAGGCGA
GAAGTCAACTTCTGGGCCGAGATCATTAACGATACCGACCCCGCCATTTGCCTCACCATCGAAAGCAGCATCGTCTATTCCGGCGA
TCTCGAGCAGTTCTACGAAAATCACCCGTACAGGCAAGACGCCGTGAAGCTGCTGGTGGGCCTGAAAGTTAAGACCATTGAGACCA
ACGGCACCGCTAAGATCATCAAAATCGCTGGCACTATAGGGGAAAAGCGCGAATACCTGTTGACTAAGGCCACGGGAAGCATATCC
CGGCGAAAGTTGGAGGAAGCCCACCTCGCACAACCCGTGGTTGCGGTGCAGTTTGGTAAAAACCCTCAGGAGTACATATACCCCCT
GGCTGCCCTCAAACCTTGCATGACCGACAAGGATGAGAGCCTGTTCCAGGTCAATTACGGCGACCTCCTGAAGAAAACCAAGATCT
TCTACGCTGAACGACAGAAATTGCTTAAACTGTACAAGCAGGAGGCGCAGAAGACTTTGAATAACTTCGGTTTTCAGCTTCGGGAA
AGGTCCATCAATAGCAGGGAAAATCCAGACTTCTTCTGGACGCCCCCAATTTCATTGGAGCAGACCCCCATCCTGTTTGGGAAGGG
TGAGCGCGGTGAAAAGAGGGAGACCCTCAAGGGCCTTTCAAAGGGCGGAGTCTACAAAAGGCACAGGGAGTACGTTGATCCTGCCA
GGAAAATTAGGCTGGCCATCCTTAAACCGGACTCTTTTAAAGTGGGCGACTTCAGGGAGCAGCTGGAGAAGCGACTCAAGCTGTAT
AAGTTCGAGACGATTCTCCCCCCTGAGAACCAAATCAATTTTTCTGTGGAGGGTGTTGGGAGCGAAAAAAGGGCCCGACTGGAAGA
AGCCGTAGACCAGTTGATAGGTGGCGAGATCCCCGTGGACATCGCCCTCGTCTTTCTGCCCCAGGAGGACCGGAACGCGGACAACA
CCGAGGAAGGCTCCTTGTATAGCTGGATCAAAAAGAAATTCTTGGATCGGGGGGTGATAACACAGATGATATATGAGAAAACTCTC
AACAATAAGAGCAACTACAATAACATCCTGCACCAGGTGGTTCCCGGCATATTGGCAAAGCTCGGAAACCTGCCGTATGTGCTGGC
CGAGCCTCTTGAAATCGCCGACTACTTCATCGGCCTGGACGTCGGAAGGATGCCTAAGAAGAATCTCCCTGGTTCACTGAACGTGT
GCGCGTCCGTTAGGCTCTACGGAAAGCAAGGTGAATTCGTCCGATGTAGAGTCGAAGATAGCTTGACCGAGGGGGAGGAAATCCCC
CAAAGGATTCTTGAGAATTGTCTGCCGCAGGCAGAACTTAAGAACCAGACCGTCCTGATCTACAGGGACGGGAAATTCCAGGGTAA
GGAGGTGGAAAACCTTTTGGCTCGGGCACGAGCCATCAACGCCAAGTTCATCCTGGTAGAGTGCTACAAGACCGGCAGCCCGAGAC
TTTACAATTTCGAACAAAAGCAGATTAATAGCCCCAGCAAGGGGCTGGCGCTTGCATTGAGCAACCGGGAGGTCATCCTCATCACC
AGCCACGTTAGCGAACAGATCGGCGTGCCTCGGCCTCTCCGCCTGAAGGTGCACGAACTGGGAGAACAGGTGAACCTCAAGCAACT
TGTGGACACGACCCTGAAACTGACTCTGCTGCATTATGGCTCTCTGAAGGAACCTCGGCTTCCAATCCCCTTGTACGGAGCCGACG
CCATCGCGTATAGGAGGTTGCAAGGAATCTATCCAAGCCTGCTGGAGGACGACTGTCAGTTCTGGTTGTAGTAA
102 ATGCCCAAAAAGAAGAGGAAAGTTGAGGATCCCAAGAAAAAACGAAAAGTGGGTAGCGGTAGCGTTCCAGGCGGTAGGGGACCGCT
GCTCGTGCTTAACTTCCTTCCCGCTCGCTTCGACGGCCGAGTTGATGCGGGCACCCTCCCCTTCGAGACCCCTGATAAATTGAGGG
CCATTAGGGAGGAACTGAGAACTTCCCATGTAGTTGTAACGCGAGGAAAAGAGGTCGTATGCGTGCCCTTCGTTAGTGGCGCGAAA
TTGATCGGCAAACGAACCACTATCACCGCAGCGGGACCCGACCTCGTCGTACAAACGAGTCTTCTCGAATCCAGCCTGAGGCGGAC
CTTGACCGAAAAATGGAAGTACGAATTGCGCAGGGAAAACCCGCTCACCTTTGTGTCAAGGACGCCAGGAAGGGACCTGCTGGAGA
AGGCCCTTGGTCGGGAGTTGCCGGGACTCCATGTGTTCCCCGCTTACAGCCTGGACGTGCGCAGATACGGTCCTGGGGGGTTCAGC
GGGGTTGTTGTAGGATTGAAGACCCGCTATGAGATCGACCTGCCTGTCGGAGTGCTGCTCAGGAGGGGCGTTCAAGTAAACGGCCT
TTATGTCCTGGCTGAAAGCCCCCTCGCGCCTACGTGGCCCTTCCAAGATCCCCACACCAGAAGGCGGCTCGTGGGACAAGTTGTCG
CGGTGGATGGCGACAAATTGCGAGTGAGGTGTAGGGACGGGGAGCTGGAACTTGATGCCGCCGAAGCATGGATTGAGCCCAACACT
GCCAACTTCTACGCCGTCCTGCGGAAGGCGTGCGGACGCTCTTACGAACGAGACTTTCACGCCCTGGAAGCCCAAGTCGTGTCCCT
GACTAACGCCCAGCAGCGAATCGCCGATACCAACAGGATCGCCGCCAACCTGATAGGCCTTGGTAAATTCGACATCAGTAACGGCT
TGACTGCCGAGCTGGGGAAACCACTCAGACTGACTTCCACTCAACATCCACACGTTCGGACTCTGGCCGAGCCCACATTTGTGTTT
GACCAGAGCGGAGACAAAACCGCGCCTTTTCCCGAGACCGGGCTGACCAAGTGGGGCCCATTGGACGCTGAGAGCTTTACACCCAA
GGCACCACACATCGCCGTGGTGGTTCCGCGGCAGTTTCAGGGTCGCGTCGAAACGCTGGTTGAGCGGTTCAGGAACGGCGTGAGGG
GCAGCAACGCCTATGCCGAGGGCTTTGTCCGAAAGTTTAGGCTCACCGACTGTACCTTCAGCTTCACCGTTTTTGACGGTGACGCT
ACTGACGCAGCCGCATATAGGCAAGCGTGCCTTACCGCCCTGAGTAATGACGAGCAAATTAACCTCGCCTTCGTCTTCACATCAGC
CGTGCAGGAGCATCAAACGGGGGACGACAGTCCCTATCTTGTCAGCAAATCCACCTTCATGAGCCAGGGTATCCCCGTGCAAGAGT
ATCAAGTGGAGAACATCATCGGGGATTCAAACTTGGCTTATCCCCTGTCCACGATGGCGCTGGCGTGCTACGCCAAACTGGGTGGC
ACCCCTTACGCCATAAGCGATCGAGGACGACCTATGGCACGAGAACTGATCTTCGGCATCGGGTCTGCCCAGGTAAGCGACGGAAG
GATGGGCGAAACAGAGCGATTTGTGGGCATTACCACCGTGTTCAATTACGACGGTAGGTACTTGGTTAGCAACGTTAGCCGCGAGA
CACCCTACGAAAGGTACCCGCAAGCCCTGCTTGACGCATTGCGGACTTGCATTGCCGACGTGAAGGTTAGGCAGGGATGGAGGTCC
GACGACTTTGTGCGGCTTGTCTTCCATATCTTCAAACCTCTGAAGGACAAGGAAGCACGCGCCGTAAAAGAGCTGGTGACGGAGCT
GACGTCTGAATATGCCAGCGTGGAGTTCGCTTTTGTGACAGTGGTGGACGATCACCCGTGGCTGGTGCTCGATGAAAACAGCGATG
GGGTTAAGGTTGGGCGAGGGACTAAGGGCAAGCACGTAGCTCGGAGGGGTTTTGCCCTGCCGATTTCCAAAAGGGAGCTTCTTGTG
ACGGTTAAAGGTCCCCGGGAAATGAAATCCGATAAGCAAGGGGCTCCCAAGCCCCTCTTGCTCAAGCTCCATCGCGAAAGCACCTT
TACAGACATCGACTACCTGGCTTCCCAGGTCTTTCAATTCACCGCCATGAGCTGGCGCAGGCCATACCCTACCAGCAAACCCGTGA
CTATAAGCTACAGTGACCTGATTGCGGGACTTCTCGGAAAGCTGCGACACGTGACGAACTGGAATAGCGACATGATCTACATGAAG
TTGCGCTTCAGCAGATGGTTCCTGTAGTAA
103 ATGCCTAAGAAGAAGCGCAAAGTCGAAGACCCCAAGAAAAAGCGAAAGGTGGGCTCTGGCAGTATGATTAACAAACTGCAATTCGA
CGAGTTTCAGAGGGCCATAGGTATTTCTAAGAACGACACCTTCAGTCTTTTGCTCGGAGCGGGTTGCAGCATCAATAGTGACATCC
CTAGCGCGGAAGACTGTATATGGGAGTGGAAGCGAGATATTTACAAAACAAATAACAGTTCTAGCTTCGGCTGGATTGACAATTAC
AAGAATCCCAAGACTCAGGAGATCATTCAGAACTGGCTCAACAACCAAGGCATCTATCCCGAACGCGGCTGCAAAGAGGAGTACAG
CTTTTACGCCTACAAATGCTATCCCATCGACGAACATAGGCGACAGTATTTTCAGAAAATCTGTAGTGGTAAAAAGCCATCCATCG
GGTACAAACTTATTCCCCTGCTTGCCCGAAAGGGCATGCTTGATAGCGTGTGGACCACGAATTTGGACGACCTCGTGGTGACCGCC
TGTATAGGCAACGGGATCCAGGCGATCGAAATCACGCTCGACTCCGTGCAAAGGTTGAACAACCGGCCTCAGAACCGACATGAGCT
TCCTGTGATCAAACTCCACGGAGATTTTAAGTATGGCGATCTTAAAAACACCGAGGAGGAACTCCTCAATCAGGATAAAACGTTCA
GGGAGAGACTTATTGAATACGTACAAGACAAGCACCTGATCGTGCTCGGCTACAGTGGCCGAGACACCAGCCTGATGGACACACTT
AAAGAGGCCTACTCAAAACAGGGGGGTGGAATTCTGTACTGGTGTGGATATGGTGACAACATAAACTCCGACATCGCCGAACTGAT
TCAAATAGCCACTAAAAATGGCCGACGAGCCTTTTACATCCCCACTGATGGTTTCGATTCTACGCTCCGGAAAATCACACAGATAG
TGGTCGAGGATGATAACAACCTGAAAAAAGAGCTTCTCGAGCTTCACCAGACCAGCAATATCAATGACACTATCACACCTTTTGAT
CTGAAGTGCGAGAGGGTGAATAAGCTGTTGAAGTCAAACATATTCCGGATTAGCTTTCCAGACGAAGTGTTCGTTTTCGATGTGAG
CATCAGCGATAAACCCTGGAAGTTCGTGGACGAAAGGACTCTTGAGCGCAACGATATTAGCGCCGTTCCCTATAACAAGCAAATCT
GGGCATTCGGTAGGCTTGACATCATAAAAGACATCTTCAAAGACGTGATGAACTCAGACATTCAGCGAAAACCCCTGGCAAACATC
AAGATATACAACACGGCGGTTAGTCGGCTGTTGCTTACTACGATTTGCAAGATACTGGCGCTGCAGAGCAACCTTAAGACCGACTA
TAAGGGTAAGATATGGACCGAGAACAACAGTAAGTCCATTTCCGGCCACATAGTATACAATGCCGTGCTGCTGTCCTTTGATCGGA
TAAGCGGTGAGTATTACCTTAGCCTCAACCCCGACTTCGTGCTGGCTAACCCCAACATTGAGAAGAGTAGCATACAGACCATAGGA
CTGTTCTTCTTCCAGAAGCTGTGGAATCAGCAGTTTAACGAGTACATTAACTATTGGAGGGAAATTTTGTTGAAAAAGAATAATGA
GTACGAGTTCCCCATAAATAGCGGAACCGGCTTCAAGTTCAAGATCAAGAACATCCCAGTGTTCACTAACATCTGCGACCTGAATA
ACCCTCGCATCAACAATCACAACGTGTCCAGCCACCACCTGCTGCTTCAGGGGGTGCAATTTAAGGAAATCCCGCTGCTTTTCAGC
ACCAACAATGGCAACCGCACGGCCACCGACACCCACCCTATGAGAGGACTTCTCATAAACAAACCGTATGAAACGGGCGTCAACGA
CTTCCTCGAAAAGTCTATCACCCTGGGAATCATAAGCCCCAGTCAGGACGCCCTCAGGTTCTACCAATTCCTGGAAAACCAGAACT
CTAAAATCAAAAAGCACAACGACAAGGACAACTACATAATAGACTACGAAGGGTTTTTCGCCATCTACGGCGTTAGTCTCAGCTTC
CCAACACCTAACGACAACGAGTGGGAAAGGATCAACGAACCGCTGATTATGGGCATCAAGGAGACCGCCCAACAGATAAAGCAACT
GATATGCGACAGCATCGTGAAGATCTCAAGCACGACCAGGAGAAAAATCATCGTCATCTATATCCCCCAACGCTGGGAGCCCTACA
CCTCTTACCAGCTCGATGGTGAGTCATTTGACCTCCATGACTACGTGAAAGCGTTCTGCGCGGAGAAAGGGATTATGAGCCAACTC
ATTCGAGAGAAGACCATTAACGATACTATCCAAAAATGCCAGATACATTGGTGGTTGTCTCTGTCATTTTTCGTAAAATCCTTCCG
GACCCCATGGATTCTCGCAAATACTAACAACACCACCGCCTTCGCGGGTTTGGGGTACAGTGTAGAAAACAAGAAGGATATTAACG
GACATATTGTGCTGGGGTGTAGCCACATTTACAGCTCAAACGGAGAAGGGCTCAAATACAAGCTGGCCAAAATAAGTAATGATAAG
ATTCAGTGGAGGCATAAGAAGCCGCACCTCTGCTACGACGACGCGTATGAGTTTGGCAAGTCAATTGTGAACCTGTTCTACGAATC
TATGAACGAACTGCCAAAAAGGGTGGTCATCCACAAGAGGACCTTCTATACCGATGAAGAGAAACAAGGGATCATAGACTCCATTA
GCGACAATAAGAAAATAGAGAGCATCGACCTCATCGAGATCAACTTTGAAAACAATATAAAGTACGCCTCTAGCAAAATCCACGAC
GGAAAGGTAGACATTGACGGATTTAGCGTATCTAGGGGAACCTGCATACAACTCAGCTCTAAGGAGGCGCTCCTGTGGGCGCATGG
AGTGATTCCTAGCGTCATTAACCCTAACTGGAACTTCTACCCTGGCGGCAGGTACATACCTAAACCACTTAGGATCATTAAACATT
ACGGTACAGGTAGCTTGGAACAGATCGCGAACGAGATTCTGGGCCTGACTAAAATGAATTGGAATAGCCTGAACATGTACAGCCAA
TTGCCTGCCACAATTTCAAGCTCCAATGATATAGCTAGGATAGGTAAATTGATAGGGGCGAACAGTATGCACGAATACGACTACCG
ATACTTCATCTAGTAA
104 ATGCCTAAGAAGAAAAGAAAGGTGGAGGATCCAAAGAAAAAACGCAAGGTGGGTAGCGGCAGCATGCCATCAGCCGAGAGGTGCAT
CTGGGAGTGGAAGAGGGAAATCTTCATCACTAAAAACCCCTTGCTCAGGGAAACCGTCGGCGAGCTGTCCCTCCAGGGCACGAAGG
ACCGAATCCAAAAATGGCTCGATCAACGCGGCGAATACCCCGCACTGAACTCCCCAGAGGAATACTCATTTTATGCCGAGGAGTGC
TACATCACCGAACAAGACAGGCGGAGCTTTTTTCAGCAGTACGTAGAGGTCGCCAAGCCGCACATAGGTTATAGATTGTTGCCCCT
GCTGGCACAGACCAAGATCATAAAAACTGTATGGACGACTAACTTTGACGGGCTTGTCGCCAGGGCCTGTCATTCCAACGACGTGG
TGTGCATCGAAGTCGGTCTCGACAATACCCAACGCATTACGCGCCAGCATTCTGAGGGGGAGCTGCGGGTTGTAAGTCTCCACGGC
GACTACCGATACGATGAGCTTAAGAATACAGATGAGCAGCTCAGGTACCAGGAGGAGGCGCTTAAAAACAATATAGAGCACGAGCT
GCAGGACTACGACCTGGTAGTGATCGGTTACTCCGGCAGGGACCGGAGCCTCATGAACGTACTCGAAAACATATTCAGCAAGGCCG
TGAAGAGCAGGTTGTTTTGGTGTGGCTACGGCGAAACGATAAGCCAGCCCGTTATGGAGTTGTTGGAGCTGGCCCGCAAGAATAAT
CGAGACGCATTCTATGTCAGCACCGAAGGCTTCGACGACACCGTTGAAAGAATCAGTAGGAAGCTGCTTGACGGCAACATGCTGTC
CAAAGCCTTGGCTGAGATACAGGAGACCACTTGCATCACCAACCAATCTGCCAAATTCACCGCACCTGAAAACGACATCAGCAGCC
TTATTAAGTCAAACGCATACCCCCTCCTGAAGCTCCCGTCTCAGTTCCTTAAAGTGACCCTCAAATACCCGGAGGGGTCCTTTAGT
TACATTGATTGGCTTAACTCCAAGGTTGACTTCAAGGAGGTTGTGTTGTCTAAGATAGACAAGGAGATCATCGCGTTCGCGGATGT
TGATAAGCTGAGGAAGTATCTGGGCGAGTTCTACCTGTCTACGCCCACGGTGGTGAACTTTAGCAAAACGGACGTGCTTAACGATA
CTCGCATTCAGAGTCTGGTGAGGCGCGGACTTATACAGTCCATCGTAAAAAACCTGAACCTGTCCAGCGACCAGAACAAGCGAATA
TGGAATCCAGACGTGAGCTCCATCGAATTCTACAACGGCAAGAAGTACAAAATCATCGACGCGCTCATCCTCAATCTTAGTTTTAT
CAAAGATGACATCTACCTCACGTTCAAACCCGATCTGCTGGTCCTTAACCTCGACGAGAGCCTGCCAGACAACGATATAGTTAAGA
CTATCAAGAACAAAAAGTTCGGCTACCAGCACAACAAAGAGTACAGTCAGATCCTGGAGAAGTGGGCCAACCTTATAACGAAGAAG
GATTTGGTCGTGAGTGGCGGGAGCGTGTTCTTCCTTGGGAAGAAACCGCTGTATGCCGGACTTGTGTCTTACGCCGCGAGGAAACT
CCCAACAGATTATAACAAGCACGCCACCCAGAAAGGACTGATCATTCAAGACGCGAAACTGATTTTTTGCAGCAATTCCATCTCCA
ATGAGATTTCTCACATCAACCCCCTGAAGGGGCTCGTGGAAAATCGCCCGTGGGACTACAAAAACACCAGCTCTGGGCTGTGCCCC
GAGATCTGCATTAACGTGATCTCAACCAGGCAGGACGCGGGTGTGGTGAGCAACCTTCTCCGAGGTATTCACGAGAAGTCCTTCCC
GGAAAAATCCGAGCAAGATTACTTGCACCCCTTCCATGGGTTCACAAACGCTTTCGGGGTGCCCATCACGATCCCTAAGATCGGTG
AGAATACGTGGCGCTTTGTGGACGAAGCACTGAGTGCACAGAAGGCCATCGATAACGCGAAGAACCTCGCGAACCGCATTTGCTAT
GAACTTGACAGCCTGAAGAAGCTTGAACTGCGGACGGGCACCGTCGTGATCATATACATCCCCAAGAGATGGGAAGCATTGACATC
CATCAAGTCTGAGCATGAGTACTTCGACCTGCATGATTACATCAAGGCCTATGCTGCGCAACAGGGCATTAGTACGCAATTCGTGC
GCGAGAAAACGGTTAATTCAAGCCAAAGCTGCCGGGTAAAATGGTGGCTCAGCCTGGCGTTCTACGTGAAGGCTATGCGCACTCCG
TGGCGGTTGGAGAGTATTGATAACCAAACGGCTTTCGTGGGGATAGGGTACAGCATCAATCGCAATATGCATCCCGAGAATTCCAA
GCGGATAATTCTTGGATGCTCCCACATATACTCCGCCCGAGGCGAAGGCATGCAGTTTCAACTTGGGCGAATTGAAAATCCCATTA
TCCACCATCACAATCCCTACATGAGCGAGGAGGACGCTAGACGCACCGGCGAGAAGATACGACAAATGTTTTTTGATGCCAAGATG
CAACTGCCACGCAGGGTCGTCATCCACAAGAGGACCGCTTTCACTGAAGAGGAACAGCGGGGGTTCATACAAGGATTGGAAGGCGT
TGAGGACATCGAGCTGATCGAAATTAACTTCGAGGACTCCCTCCGCTATTTGTCTAGTAAGTTTGTAAACAGCAAGCTGGAAATCG
ACGGGTTCCCCATCGCTCGGGGGACCGTAATCGTGCAAAGCAGCAACACCGCGCTCCTGTGGGTGCATGGTGCAACCCCTAGCGCG
CAAAATCCAACGTTTAAGTATTTCCAAGGCAAACGACGGATCCCCGTGCCCCTTGTCATAAAGCGCTACGTGGGGCAGAGCGACAT
TAGCCAGTTGGCGAACGAAATATTGGGCCTCAGCAAAATGAACTGGAACACCTTTGACTATTACTCCAGGCTTCCTGTAACCCTTG
AGAGCGCCAATGATATTGCCCGGATCGGCGTGTATTTCAACAATTTCTCCCCCATGAGCTACGACTATCGGCTCCTCATATAGTAA
105 ATGCCCAAGAAAAAGCGAAAAGTGGAAGATCCGAAAAAGAAGAGGAAAGTGGGCAGCGGGTCTATGAATAACGTGATGCAGGAGTT
TCCCGTCGCAAGCTTCCCCACATTCTTGTCCGAGATCAGTCTGCTTGACATCACACCGAAGAACTTTATCTGCTTTAGGCTCACCC
CCGAAATCGAGCGCAAGACCGGTAACAGTTTTAGCTGGCGCTTCAGCCAAAAATTCCCTGACGCCGTCGTGATTTGGCATAACAAG
TTTTTCTGGGTACTCGCTAAGCCCAATAGACCAATGCCCAGCCAGGAGCAGTGGAGAGAAAAGTTGCTGGAAATCTGCGAGGAACT
TAAGAAGGACATAGGCGACAGAACCTACGCCATTCAGTGGGTTAGCCAGCCCCAAATAACCCCTGAGATCCTGTCTCAACTCGCCG
TCAGAGTGTTGAAGATCAACTGTAGGTTTAGCTCTCCCAGCGTAATTTCTGTCAATCAAGTTGAAGTGAAGAGGGAGATCGACTTT
TGGGCCGAAACAATTGAGATTCAGACCCAGATCCAACCCGCTTTGACCATCACCGTGCACAGTTCATTCTTCTATCAACGACACCT
GGAAGAGTTCTACAATAATCACCCTTACAGGCAGAACCCCGAGCAACTGCTCATCGGCCTCAAGGTGAGGGACATTGAAAGGAATA
GCTTCGCGACGATTACTGACATTGTGGGCACCATAGCGGACCACCGCCAGAAGCTGCTCGAGGATGCCACTGGAGCTATTAGTAAG
CAAGCCCTTATAGAGGCCCCAGAAGAGCAGCCCGTGGTCGCCGTACAGTTCGGTAAGAACCAACAACCCTTCTACTACGCAATGGC
CGCGTTGCGGCCTTGTATCACCGCCGAGACCGCTAGGAAGTTTGACGTGGACTACGGCAAACTGCTGTCCGCCACCAAGATACCCT
ACTTGGAGCGGAAGGAGCTGTTGGCTCTCTACAAAAAGGAGGCGGGTCAATCTCTGGCGACTTATGGTTTCCAATTGAAAATCAGC
ATCAACAGCAGGAGGCATCCGGAGCTTTTTTTCAGCCCAAGCGTGAAACTGAGCGAGACCAAACTCGTATTCGGGAAAAACCAAAT
AGGGGTGCAGGGGCAAATTCTTAGCGGATTGAGCAAGGGTGGGGTGTACAGAAGGCATGAGGACTTCAGCGACCTCTCAAGACCTA
TACGCATCGCTGCGCTTAAATTGTGCGACTACCCTGCGAATTCATTTCTGCAAGAGACCCGGCAACGCCTCAAACGGTACGGTTTT
GAGACTCTGCTGCCCGTCGAGAATAAGAAAACCCTGCTGGTAGACGATCTGAGCGGGGTCGAAGCACGCGCGAAAGCCGAGGAAGC
CGTTGACGAACTGATGGTGAACCACCCCGACATCGTGCTCACTTTCTTGCCGACCAGTGATAGGCACAGCGACAACACGGAAGGCG
GCTCATTGTATAGTTGGATTTATTCCCGACTGCTGCGGCGAGGGATTGCTTCACAGGTTATCTACGAGGACACGCTTAAGAGTGTG
GAGGCGAAATATCTCCTTAACCAGGTGATCCCCGGAATATTGGCAAAACTCGGCAACCTGCCGTTCGTACTTGCGGAGCCCCTGGG
AATCGCTGACTACTTCATAGGCCTGGACATCTCCAGGTCAGCAAAGAAACGGGGGTCTGGAACCATGAATGCCTGTGCCAGCGTTA
GGCTGTATGGTAGGAAGGGCGAATTTATCAGGTACAGGCTTGAGGACGCACTGATCGAAGGGGAGGAAATACCTCAGCGCATTCTG
GAGAGTTTTCTGCCAGCCGCTCAACTGAAGGGCAAGGTAGTGCTCATTTACAGGGACGGCCGATTCTGTGGTGACGAGGTCCAGCA
CTTGAAAGAGAGAGCAAAGGCTATAGGAAGCGAGTTCATCCTGGTTGAATGCTACAAGAGTGGGATTCCACGACTGTATAACTGGG
AAGAAGAAGTCATAAAGGCACCAACTCTGGGACTGGCCCTTAGGTTGAGTGCGAGAGAAGTGATTCTGGTGACAACCGAGCTGAAC
AGCGCAAAAATCGGTCTTCCTTTGCCTCTGCGACTCAGAATTCACGAAGCCGGTCACCAAGTATCTCTCGAGTCTTTGGTAGAAGC
CACACTGAAGTTGACCCTCCTCCACCACGGCAGCCTGAACGAACCGCGGCTGCCTATACCACTGTTTGGTTCCGATCGAATGGCCT
ACCGGAGACTCCAGGGCATATATCCCGGATTGTTGGAGGGGGATCGGCAGTTCTGGCTTTAGTAA
106 ATGCCTAAGAAAAAGAGAAAGGTAGAAGACCCAAAGAAGAAGCGGAAGGTGGGCTCCGGTTCAATGAACCTGACTCTGTTCAACGA
GATCCTCCCCATCAACATCAGCCAACTGCCCAACCAGTACTTCTACAAGCTGTGCACTGCCGGCGACGTGGACCTGGATTCTCTGG
GCAGGAGCATCAAGTACCGGATCCAGAAATACTTCAGAGGAATCTGGGTGTGGAGTACCAACGACCAACTCCTCATTTCAGACAAG
CTCATCGAGTACCCCGAACTGCAAAAGTTCACCCAGTATCTGTGGACCGACCAGTCTAACCTCACATTCAACCAGCTCGAGGGGAT
AGAAATCGAG+ACATTAGGTGTTGCACCCCCCAAGGCATCGCTGATTTCTGTAGCCAAGGTCTCATCAAAAAGTACGACCAGCAGA
TCAAGAAGATACTCGAACAGTCCAAGACAGCACGGAGAGACTATCATATCAAACTGATCCACAAGTTCGGCTCCTGGGTGGTGAAC
AATCAGCCCTGCATAAGCCTGAGCCTGAAACAGGAGATCGATTTTAACGGAACTCTCCAGGACTACCTGACCAAGTTCCCCAACTC
TAACATCATCGGCCTGCATGTGCTCGACATCACTAAGCCTTTCAACACCGCACAGGAGGTCATCAAGATTCTCGGTATCTTGGGTG
AGGGAAATCGGCGGCAGCGCCTCCTGACTTGGGTCAAGGAGCCAACCATGAAAAAACTCGTGGAAGAGGCCCCAGATAGTGAGCTC
GTAGTTGAGATCGGGAACAAGAAAAAATCCTATCATTACATCATTTCTGCCCTGCGCATCAGAGTCCTCAACCAAGATTACCTGAG
GCTGGGGATTAGCGAGAAGCTGCAAATAGTCAGTGAAGAGAGGTTGAAGTACATCGAGCCACTTTTCCGCATACTGCAATCAGAGG
GCTTCCTGGACAAGGTGTATACTAGCCAGCGCAACCCCGAGCTGTTTAGGTCATGCAGCGAGGAATGGGGTTACAATCCCCTGCTG
AAGTTCAAGAATAACGCCACTGTTGCGGCGGAATCCGTGCAGTCCACGGTCCAGGTGGTGCAGAAACACGGCGAATTCAGGAAAGC
CGACAAAAGCGAAATTAGGATCGCCATACTCAACACACTGAAGAGTGAAAACAGCACCAAATTGATTGAGATTTTCCGAAACAACT
TTAAGCGAAGCTTTAACCAGAATTTGGAGGGAATCGGTAATCAGCTTAAGTATAAACTCAAGTTGGTGGGCCAGCCCATTGCACTG
GATCTCAGTAAGAACTCCCTCAGCCTGCTGGACAGCAAAATAGGAGAATTGTCTAAAAAGAAGCCGGACATTGTGATCTGTGTGAT
CCCTAACTTCCTTAGCAAGGGCGAAGACGGGCGGACACTTTACGACGATTTGAAGCAGACGTTCCTCAAATACAATCTCCAATCAC
AAATGTTGCAGGAGAAGACTCTCACGACGTCATTTGCCACAAAGAACATCGTGTTGGGCGTGCTGGCGAAAATTGGAAGCGTTCCC
TATATTCTGCAAGAACCGCTGACGTACACGGACTTTGTCGTAGGTTTGGACGTGAGCAGGCGACGCAAAAAAAACCTGCAAGGAAC
CAACAGCGTAGCCGCCATGACCCGAATCTACAGCAATCAAGGCGAACTGGTCCACTATAGCATCCGAGACGCAACCATCGACGGCG
AGATCATTCCCAAGAGGATGCTCTACGACCTCTTTCCACTTCACGAATATCAGGGCAAACGCGTGGTGATTCACCGGGACGGAAAC
TTCCCCGAGGAAGAGCGCCAGGCACTCGAGGAAATTGCCGAAAAGATTGACGCGAAGTTCTACTTCGTAAGCATTATCAAATCTGG
CAATCCCAGGATCTACGGTAGGACCAAAAACGAAGAGGGCATCGGCAGTTATCGCAAGGCACCTAAGGGTAGCATTTTCCTCCTCA
GCGAGACGGAGGCCTTGCTTATCAGCAGCGACTTTCCGGACCGCTTCAGGGCCACGCCACAGCCTCTCAGAATTAAGACGTTTGGC
AACTTTCCCCTTCAAAGCGCCGTCCATAGCGTTCTGTCACTCACCTACCTGCACTACGGTTCCGAGCGCCCACCGAGGCTGCCGGT
GTCTACCTACTACGCAGATAGCATTAGCACTATGGTATCCAAGGGCATTAAGCCCAAGGACGTTGACGGCAATATACCCTTTTGGC
TGTAGTAA
107 ATGCCCAAAAAAAAGAGGAAGGTGGAGGACCCGAAGAAGAAGCGCAAAGTGGGTAGCGGGTCCATGAAAGAGTTTAACGTCATTAC
CGAGTTCAAGAACGGCATAAACAGCAAATCTATTGAGATCTACATCTACAAAATGATGGTCCGAGATTTCGAGAAGCGACACAATG
AAAATTACGACGTGGTGAAGGAGCTGATTAACCTTAACAACAACTCCACCATAGTGTTCTACGAGCAGTACATCGCCTCCTTTAAG
GAGATTGAGAAATGGGGGAACGAGCAATACATAAATGTGGAGAAGAGGGCTATCAACCTGGAGTCCAACGAGAAGAAAATTCTGGA
GAGGCTCCTGCTGAAGGAAATCAAAAATAACATAGACAATAACAAGTACAAGGTCGTCAAGGACAGCATATACATCAATAAGCCAG
TGTACAACGAGAAGGGCATCAAAATTGACAGGTATTTCAATCTGGACATAAACGTTGAGTCAAACGGAGACATTATCATCGGGTTT
GACATCTCCCATAACTTCGAGTATATCAACACTCTGGAGTATGAAATAAAGAACAATAATATCAAGATTGGGGACCGGGTAAAGGA
CTACTTCTACAACCTGACCTATGAGTACGTGGGCATCGCCCCCTTTACTATCTCCGAGGAAAACGAGTACATGGGCTGCTCAATCG
TCGACTATTATGAGAACAAGAACCAGAGCTATATTGTGAATAAACTGCCTAAAGACATGAAGGCCATCCTGGTAAAGAATAATAAG
AACTCTATATTTCCCTACATCCCGAGCAGGCTTAAAAAGGTGTGCAGATTCGAAAACCTTCCCCAGAACGTGCTGAGGGACTTTAA
CACGAGGGTGAAGCAGAAGACAAACGAAAAAATGCAGTTCATGGTTGACGAAGTGATCAACATCGTGAAGAATTCCGAGCATATCG
ACGTCAAAAAGAAAAACATGATGTGCGATAACATTGGGTACAAGATCGAGGACCTGCAACAGCCCGACCTGCTCTTCGGTAACGCC
AGGGCCCAGAGGTACCCCCTCTATGGTCTCAAAAACTTCGGGGTGTACGAAAACAAGCGGATAGAGATCAAATACTTCATAGACCC
CATCCTCGCCAAGTCAAAGATGAACTTGGAGAAAATCTCCAAATTTTGTGACGAGCTGGAACAGTTTAGCAGCAAGCTGGGCGTGG
GGCTCAACCGGGTTAAGCTGAACAACATAGTTAATTTCAAAGAAATCCGCATGGACAATGAGGACATTTTCAGCTACGAGATAAGA
AAGATAGTGAGCAACTATAATGAAACTACCATCGTAATCCTGAGCGAGGAGAACCTGAATAAGTACTACAACATCATTAAGAAAAC
ATTCAGCGGCGGAAACGAGGTGCCCACCCAGTGCATCGGTTTCAATACGCTGAGCTACACGGAAAAAAACAAAGATTCTATCTTCC
TGAACATTCTGCTGGGGGTTTACGCCAAGAGTGGCATCCAGCCCTGGATCCTGAATGAGAAGTTGAACAGTGACTGCTTTATCGGC
CTGGACGTGTCTAGGGAGAATAAGGTCAATAAAGCGGGAGTCATCCAGGTGGTCGGGAAAGACGGCAGGGTGCTCAAAACTAAGGT
GATCAGCAGCAGCCAAAGCGGAGAGAAGATCAAGTTGGAGACCCTCAGGGAGATCGTGTTTGAGGCAATCAACAGTTACGAGAATA
CGTACCGGTGCAAACCCAAACACATTACTTTCCACCGCGATGGAATCAACCGCGAGGAACTGGAGAACTTGAAGAACACCATGACC
AACCTCGGTGTTGAGTTCGACTACATCGAAATTACCAAAGGCATTAACAGGAGGATCGCCACTATCAGCGAAGGTGAGGAATGGAA
GACGATTATGGGGAGGTGCTACTATAAGGACAACAGCGCGTACGTGTGTACCACCAAGCCTTACGAGGGAATCGGCATGGCCAAGC
CCATCCGAATCAGGAGGGTGTTCGGCACGCTCGACATAGAAAAGATTGTCGAAGACGCCTACAAACTGACCTTTATGCACGTTGGC
GCAATTAACAAAATCAGGCTTCCCATTACTACGTACTACGCAGACCTGAGCTCCACTTACGGCAATCGGGATCTTATCCCCACAAA
CATCGACACTAACTGTCTGTACTTTATATAGTAA
108 ATGCCTAAGAAAAAAAGGAAAGTGGAGGACCCAAAGAAGAAGCGGAAGGTGGGCAGCGGTAGCATGCAAGGCACTATATCCATAAA
CGAGGTGAGGATCCAGCTTAATACTATTAAGAATCTTTCAGTGTTCAAGTGCAGCCTCAGCGGAATTAGCACCCGCCATAAGAACC
AGATCGAGTTCATCCTTCGCAGCGAGCAAAACCGAGTTAGCATCTTTGAGGGTGAAGTGATCTTTGCGCTTCCCGTCGAACAGCAG
AACCTCGAAAGAGATAAGCAGGCTCTGTTCAGCTTCCTGGTCAAACAACAAAGGGATCTCAATCTGAAACAGCTGAGCCTGGTGCC
CCTGAGGGAGGTGCCCGAGCGCGTTATCGAGCGACTGACTTTCGCAATGGTTAGCTATCAGGCCATGAAGCAGGGCATCTTCTCTA
TCTATGGTCATACATTTTTTCGCCCCACCCTTATGACGGATAGGCTTGCGCACAAGGCGGTGGAAGTCACGACGTGCATCGAGGAT
GGCTTCCTCAAGTTTTATCTGGACCCGACGTACATTGCACTGACATGCATAACGGACACAGCACGCGAAAATAGGGAGAACCTGGA
ACTGGTCGGGCTCTGCTCTTTCCGCAACAAAAACCTTTGTAGCCTTGTCAGGCCGGACGGCTCATGCAACTGCCTCATACCTGGTA
AGTTGGGGTATTACGTCCAGGAGATGGGGATTAAGGACGTTGAGGATGATAGCAAGGACTTTCTGGCCAAACGGTTCAATAGCTGT
CCCCGGTTTAGTGAGCACACGCGCTTTATACAAGTGAAGGCGAGTAAAAGAGGCACGAAGTACTCCCTGTTCCCTTCTTACGTAGT
TTTTAGCAGGTTGTCCCGAATGGACCTGTCCGCTAAGCCAGATGTGCGGTCCAGTTATCGGAAGGCCACATTGATGGACTCTCACG
AAAGGCTTAACTTGACCAACGACTGGATAAGACAAATTTTCATGATCGGGCAGAAGGGCCTTCAAAATTGGGGTGTTATAAAGGTC
AACCAGACCGAGATTCCCGTTGAAATTGTACTCACAATTGCCCACGCCATCGCGCCCAAGACTTCTCAAGGCATCTATAAGGCTAT
ATTCCTCCCGGACCAGCAAATTACGAATGACAGCAATAACCCAACGCCTCAAACGCTGAGCGGGGGTTGGCTCTTCACGAATAGGG
GTGCGTTCGACAGGAGGGATCCTAATAGGCCTTTTAAAGTAATCAGCCCCTACATCATCGTGCCCAACAATGAGCAAAGCATCAGC
TCTTGCCGCCAGCTGATCAACTACTTCAGCAACGGCAGGTACAAGGCCCGGTGCAAGGGTGACAGAGACTTTATTGGTATTTCATT
GCCCGAAAACAAGGGCAAGTACAACACATCATTTGTCAATGCTTTCGAAGAGGAGGACGGCCTGTATTTCGTTGAAGAGACGATAC
AGGGCTACCAGAAGGCGCTGCAAGACATTGTTAGAGACTGGAATATCACGTCCAAGCGGGACATCAATAAACACGCTATAGTGATC
ATACCGGGCGAGAACGATATTGACGACAATCCTTTCTATTATCAACTGAAAAAGGCGTTCGTAGAGGAAGGGATTCCCAGCACCTT
CATCACGTACGAGACTATGAACAAAATCAACGACCCCGACATCGCGTTCGGGCCAATCATGGACAGCCTGTGGTTGAACATTTACA
GCAAAATGGGGGGCAAACCGTGGCGCCTCGCTAATAGCCTCGGCAACGTGCACTGCTTTATCGGTATTGGGTTTGGAATTAACCCC
GAGACCACCGGAAACCACATATTCGCAGGGATCGCCCACATCTTCGACAACTACGGGAGTTGGATAGACGTAGCGAGTGATTCCGC
CAACCTCTCCCAAAACGATCTGAACTCATTCGAGGGCACGGAAAAGTACACACAGGGGAGTGCTAGCTTTAAGATCAGTCAGAGCG
TGTCCCAGTCCATTGTGTATAACGCATTGAAGCTGTACCAACAGAAGCAAACTAAGACCCACGAAAACGCCACAAACATCGTCCTG
CACAAACTGGGCCAGATCTACGAGTGTGAGGTCATCGGGTTCCTCGAAGGAATTCGCCAAGTGCTCGGGAGTCTGGGCGACTGCAA
GCTGGGATTGCTGCAAATTGAGCAGGAGCACCACCTGCGCCTCTATGGCGCAGCAGCCCAAACCGGCAAGGAGAACAACACGATCT
TTCGCGGTTCAGCACTTCAACTCAACCCGGAGAAGCTGGTTATCGCGTCCACTGGCCGCTCTTACCGGCAGACGAGCTCCGGGCTG
TTTATGAATTATCCGGGCATCGGCACCCCCCAGCCGCTCCTGTTGACTTCTATCGTACCGAATCAGCAGATCCTGCAGAAGTACGG
CTGTAACGCAAACCAATTCTACTCAAGCGAGGACCTGGCGAAACATGCAATGGCCCTGACGCAACTTCACTGGGGGTCACTGAAGG
ATAATGTAAGATTGCCGATTACCACGCTTTACGCGCAAAAGGTCGCCGACTTGATTAGCAAGACCAACATGCGGATCAATCCAGGC
TTGGGCTACTTCCGACCCTGGTTTCTTTAGTAA
109 ATGCCGAAGAAAAAGCGAAAGGTGGAAGACCCAAAGAAGAAACGCAAGGTGGGCTCCGGCAGCATGAATAACCTGACACTGGAGGC
CTTTCGGGGCATTGGCACCATCAAGCCACTGTTGTTCTATCGGTACAAGCTGATCGGCAAAGGGAAAATAGAGAATACCTATAAGA
CGATACGCAACGCACAGAATCGGATGTCTTTCAACAATAAGTTTAAGGCCACCTTCAGTAAGGATGAAATCATATACACCCTGGAG
AAGTTCGAGATTATCCCGACGCTGGATGATGTGACGATCATCTTCGACGGGGAAGAAGTGCTTCCTATAAAGGACAACAACAAGAT
TTACAGCGAGGTAATAGAATTTTACATTAACAACAATCTCCGGAACGTTAAGTTCAACTATAAGTACCCGAAGTACAGGGCTGCCA
ATACAAGGGAGATCACGGGCAACGTGATCCTCGACAAAGATATGAACGAAAAGTACAAGAAGAGCAACAAAGGCTTCGAACTCAAA
CGGAAGTTCATAATCAGCCCCAAGGTCGACGATGAGGGTAAGGTCACATTGTTCCTGGACCTGAACGCGTCATTTGACTACGACAA
GAACATCTACCAGATGATAAAGGCCGGAATAGATGTGGTAGGAGAGGAGGTCATCAACATCTGGAGCAATAAGAAGCAGCGCGGTA
AGATCAAGGAAATCAGCGACATTAAGATAAACGAACCCTGCAACTTCGGCCAGAGCCTGATAGATTACTATATAAGCAGCAATCAG
GCGTCACGGGTGAATGGATTTACGGAGGAAGAGAAGAACACAAACGTCATCATCGTGGAAAGCGGCAAAAGCCGCCTGTCATACAT
ACCGCACGCGCTCAAGCCTATCATAACGCGAGAGTACATCGCCAAGAACGACGAAGTCTTTAGCAAGGAGATAGAAGGGCTCATCA
AAATCAATATGAATTACAGGTACGAGATTCTCAAGAGGTTCGTCTCCGACATCGGCACTATTAAAGAACTGAACAACCTGCGCTTC
GAGAAAATCTATATGGACAATATAGAAAGCCTGGGTTACGAGCAGGGTCAACTCAAGGACCCCGTGCTCATCGGCGGCAAGGGTAT
ACTTAAAGACAAAATACATGTCTTCAAGAGCGGCTTCTACAAATCCCCCAATGACGAAATTAAGTTTGGCGTGATATACCCGAGAG
GCTACATAAAAGATACCCAGAGCGTTATCCGAGCCATCTACGACTTTTGCACCGAGGGCAAGTACCAGGGAAAGGATAACATATTC
ATCAATAACAAGCTCATGAACATCAAGTTCTCCAATAAGGAGTGCGTCTTTGAAGAGTACGAGCTCAATGACATAACCGAGTATAA
GCGGGCTGCAAATAAGCTCAAAAAGAATGAGAACATAAAGTTCGTGATCGCAATCATCCCCACTATCAATGAAAGTGACATTGAGA
ACCCCTACAACCCCTTCAAAAGGGTCTGTGCCGAGATCAACCTCCCCAGCCAAATGATCAGTCTCAAAACTGCAAAGCGGTTCAGC
ACCAGCAGGGGCCAATCTGAGTTGTATTTCCTGCATAACATCAGCCTCGGCATTTTGGGCAAAATAGGCGGCGTACCCTGGGTAAT
TAAGGACATGCCAGGCGAGGTCGATTGTTTTGTGGGCCTGGACGTGGGCACAAAAGAGAAAGGAATCCACTACCCCGCATGCAGCG
TGCTGTTCGACAAGTATGGCAAACTCATTAACTACTACAAGCCGACGATCCCGCAGAGTGGAGAGATCATTAAAACAGACGTGCTG
CAGGAGATCTTTGACAAGGTTCTGCTGAGCTACGAGGAGGAGAACGGCCAGTATCCCCGCAACATCGTGATACACAGGGACGGCTT
CAGCCGGGAGGACCTGGAGTGGTATAAGAACTACTTCCTGAAAAAAAACATCGAATTCAGCATAGTAGAGGTCCGCAAGAACTTTG
CCACGCGACTTGTAAACAACTTCAACGATGAAGTGTCCAACCCAAGCAAAGGTTCATTCATTTTGAGGGACAACGAAGCGATTGTC
GTCACGACGGATATTAACGACAACATGGGAGCGCCCAAACCGATCAAAGTTGAGAAAACGTATGGCGATATTGACATGCTCACAAT
TATCAACCAAATTTACGCACTGACACAGATTCACGTGGGGTCCGCGAAATCCCTTAGACTGCCTATAACCACGGGCTACGCCGATA
AGATCTGCAAGGCTATCGATTACATCCCGAGCGGCCAAGTCGATAACAGGCTGTTCTTTCTGTAGTAA
110 ATGCCCAAGAAAAAGAGAAAGGTCGAGGACCCGAAGAAGAAAAGGAAAGTGGGCAGCGGCAGCCTGAAAATCAAAATTCTCAAGGA
GCCGATGCTGGAGTTTGGCAACGGCGCTCACATATGCCCCAGGACCGGTATCGAAACCCTGGGAGTGTACGATAAGAGAGATGAAC
TGAGGAGGAGCGAGCTGCGAATAGGCATTGTGGGTCGGGGCGAGGGCGTGGACCTTCTGGATGAGTGGCTCGACAAGTGCAAGCGC
GGCATCGTGGGTAAAGAGGAGACCAAGTTCCCCAACTTGTTCAGGGGCTTTGGGGGCGTCGATGAGTACCACGGTTTCTACACCAA
GATTCTGAGCAGCCCCCAGTATACCCGGACTTTGCAGAAAAGCGAGATTAACAACATCAGCAAGATCACCGCCCGAGAGGACAGGG
TAGTGAAGTGCGTGGAGCTGTACTACGAGCAGATCCGATTCCTGTCAGAGAACAGGAGCATTGACGTGATCGTGTGCGTCGTTCCC
AATGATATTTTCGACAGCCTTACTAAGGCCACCGGAGACAAAGACACCGAGTCCCTGGAGGCCTACCTCGAGCACAACTTTAGACG
GTTGCTCAAGGCCCGCTGTATGCACCTTGGGATACCCTTGCAGCTTGTGAGGGAGAAGACCATCCTGAGCGTGAAGCCTAGCATAG
ACCAGCAGGACCTTGCCACAAAGGCTTGGAACTTCTGTACGGCCCTCTATTACAAGGGGAATAGGACTGTACCATGGCGCCTGGTG
GAGGATAAATTCAAGCCTAAGACCTGCTACATCGGCATTGGGTTCTATAAGAGTAGAGACGGCGAAACGGTGAGCACATCACTTGC
ACAGGTATTCGACGAGTTCGGCCACGGGGTCATCCTTCGGGGAGCACCAGTTAGCCTGGACAAACGAGACAAGAGGCCCTACATGG
ACGAGTCTCAGGCTTACGAACTGCTGGACAGTGCCCTGGCGGAGTACGAGAAGGCCCTGATGCAAAAGCCCGCTCGAGTGGTGATC
CACAAGAGCAGCAGGTTCCGGCCCACCGAGGTGAGCGGCTTCAGCAGAGTGCTGAACGCGAAAGGAATCAGAACGAAGGACCTCGT
GAGCATCACATCAACCGACATCCGCCTGTTCAGCGACAAAAACTATCCCCCCACCCGCGGTACCTTGTTGTCCCTGTCTGAAACAC
AAGGAGTACTGTATACCAAGGGAATCGTAGATTTTTACAAGACCTATCCGGGCATGTATATCCCTTCACCCCTGAGGGTTGAGGCG
TTCGAGTCCGACAGCTCTCTTGAAGACTTGTGTAAGGAAATCCTGGGCCTGACCAAAATGAATTGGAACAACACACAACTGGACGG
CCGACTGCCCATTACCCTGGAATGCGCCAATAAGGTGGGCGATATCATGAAGTATGTGGACGCATCCGAAAAGCCACAGGTTGGTG
TGGCGCTGTTTATCTTCATGTTGGAGCAACTCGTACCCGGCTGGAAGCTGCCTAAGGTGAGTACATGGGTAGCACGGGTAATTTTC
CTGAATATTGTACAGGTGTCTATCGCTCTGCTTGCCGGGATTACTTGGAATAAATGGATGATGGGCCACAGTTTGTTGCATACCAG
CGATGCCCTGCCCCCCTTGCTCGCAGGATTCGCCGCCTACTTCGTTAACACCTTCGTGACCTACTGGTGGCACAGGGCCAGGCACG
CCAACGACACCCTTTGGCGACTTTTTCACCAACTGCACCATGCGCCCCAGAGGATCGAGGTGTTTACTAGCTTCTACAAACACCCA
ACGGAAATGGTATTCAACTCTCTTCTTGGCAGTTTCGTGGCCTACGTCGTTATGGGGATCTCCATCGAAGCTGGCGCGTATTACAT
CATGTTTGCGGCTCTTGGCGAGATGTTCTACCACAGCAACTTGCGAACACCGCATGTTCTCGGTTATCTCTTTCAACGCCCTGAGA
TGCACCGGATCCACCACCAGAGGGACCGACACGAGTGCAACTACAGCGATTTCCCCATCTGGGACATGCTCTTCGGCACCTACGAA
AATCCCAGGAGAATAGACGAACCACAGGGGTTTGCCGGCGACAAGGAACAGCAATTCGTTGATATGCTTTTGTTTAGGGACGTGCA
TTCCCTCCCCGGGAAGACACAACCAGCTCCCGTACTCGTCAAACCCGACGTGAGGTAGTAA
111 ATGCCGAAAAAGAAGCGGAAAGTAGAGGACCCGAAGAAAAAACGCAAGGTGGGCTCCGGGTCTATGGCCAACCATACCTTTAACAT
CCTGACTTTCAACCACCCCCAGGAGGAACAGACCTTCTACTTCACGGACCAGGAGCAAGACAACCTGACCCGCATCTACAAGAGCC
TGGTGCCCGACGAGGTCATCGAGAAATATGGCGAGCAGGATCACTACTACACCTCTTTCACCGTAGAGAAGGATGGTTTCCTGGCC
GTCAGCAAGCCCACAACGCCCCTGTTCGAGACCAAGACTACGGAGGCGGGCGAGGAGAGGAGCTATACCATCAGGAATTCAACGTT
CAGCAGCAGCGTGTTGAAACGGTACTACAACAGCCTTATCCACAGCCACTTCAAGGAGAAGGGCTTCCTGGTGAAGCCCAACTTCG
TGAGCGACACGGAGGTGTGGCTGCCTAGCGCCAAGCAGGACACGACCGGCAAATACAAAATATTCGACCGCTTTAGCCTGAAGGTG
CAGTTCAAGACCGTCTCTGATTCCCTGGAGTTGCTCGTCACGTTCGAGGGGAAGTCAAAGATATTCAAAGTACCTGTTAGCACCCT
GCTGGAGGATGTGAGCCCCACGGACATCAACTGGGTTGTGTACGAAAAGGGATTGTACAGGTTCGACGAACTCCCGGACAGCGGCA
AGAGGGAGTATGACAAGGTTTACCCCGTGTGGACCTTCGAGATCAGGGACGCGCTTATGCAGGGCACCGAAGCCCCAGACAAGACC
AACAAGTACAAAAAGTTCAGGGAGGGCATCGACAAGTTCTATAACCAGTATCTGAACACAGAGGAGTTCAAAGCCATCATTCCAAT
CACGTCTAATGGCTTCATCCCGGTCAATAAGATCAATGTCGGTAGTGTGAATAATAGTAGCAACAGGCTGCTGTTCGGGGAACAAA
AGAGCGGTATCGTGCCAATGGACGGCATGAAGGAACATGGCCCATTCGACTTTTCCAGCACCAGCAAGATCCATTTCTTCTTTATC
TTTCATAAAGACGACCAGCACATCGCCCAAAAGATGGATGGCTATTTCAAAGGCAGCGAGTTCGGGTTCAAGGGACTCACCAAATT
CATACACACCCCCTATCACACCGAGAAAGGATTCTCAATCAGGTTTGAGGACCGCGACAATCCGTGGCCCGAGATCTACGAAGCCG
TCACTAACAAGCACTTCGAGTCCGACATACAATACATTGCGATCTACATCAGCCCCTTCAGCAAAAACAGCCCCGACAAGAGTCGG
CGCAAAATCTATTACAAGCTCAAAGAACTGCTCTTGAAAGAAGGCGTGAGCAGCCAGGTGATTGACGGCGAGAAGGTGATGACCAA
CGAGAAGTATTACTACAGCCTCCCCAACATAGCAATCGCCATTCTGGCCAAGTTGAATGGCACCCCTTGGAAACTGGACACCAAGC
TGAAGAACGAACTGATCGTGGGAATCGGCGCCTTCCGCAACAGCGAGGTTGACATTCAATATATCGGCAGCGCGTTCTCTTTCGCA
AACAACGGCAAGTTTAATCGCTTTGAGTGCTTCCAGAAGGACCAGACGAAAGAATTGGCGGGAAGCATCATACGGGCGGTGAAGGA
GTACGCCAACGTAAACACCGGCATTAAGAGGCTTGTGATCCACTTTTACAAAAGCATGCGACAGGATGAGCTCCAGCCGATCGAGG
ACGGCCTTAAAGACCTCGGCCTGGACATTCCGGTATTCATCGTATCTATCAATAAAACAGAAAGCAGTGATATCGTGGCGTTCGAT
AACAGCTGGAAGGATCTGATGCCGATGAGCGGCACATTCATTAAAGTGGGGTACAACAAATTTCTCCTGTTCAACAACACCAGGTA
TAATCCAAAGTTTTACAGCTTCCACGACGGGTTCCCCTTCCCCATCAAACTTAAGATTTTTTGCACTGAAAAGGAACTCGTGGAGG
AGTATAAAACGGTTAAAGAGCTGATCGACCAGGTGTACCAATTTAGCCGCATGTACTGGAAGTCTGTCCGCCAGCAGAACCTGCCC
GTGACCATTAAGTATCCGGAAATGGTGGCCGAAATGTTGCCTCACTTTGACGGGAATGAGATACCTGAATTCGGTAAGGACAACTT
GTGGTTCCTGTAGTAA
112 ATGCCCAAGAAAAAGCGAAAAGTAGAGGATCCAAAGAAGAAACGGAAGGTCGGCAGCGGAAGTGTGAACCATTACTATTTTTCCGA
ATGCAAGGCGGACGAGAAAGCCAGCGACATAGCCATCCACCTTTACACCGTGCCCCTGTCCAACCCCCATGAGAAATACAGCTATG
CGCACAGCATCGCCTATGAATTGAGAAAACTCAACTCATACATAACCGTGGCCGCGCACGGTCAGTACATCGCGTCTTTCGAGGAG
ATATGCCACTGGGGCGACCACAGGTACATACAGCACGAACATAGACCAATCCAGTGCAGCCTCCCGATGGAGAGGACCATACTGGA
AAGACTCCTCAAGAAAGAGCTCGAGAATAGGTGCAAAAGCAGCTATAAGATGGACAACGACCTTTTCCGGTTGGCTAACGAGCAAA
GCATGCACGTGGGCGAGATCAGCATACACCCAGCGATCTACATCTCATTCAGCGTGGAGGAAAATGGTGACATATTTGTTGGCTTC
GACTACCAGCACCGGTTCGAGTACCGCAAAACACTCCAAGACGTCATCAACAACGATCCCTCCCTGCTTAAGGAAGGCATGGAAGT
GGTGGACCCCTTCAATAGAAGGGCCTACTATTACACTTTTGTGGGCATGGCCGATTATACCGCCGGACAGAAAAGCCCCTTCCTGC
AGCAGTCTGTGATCGACTATTATCTCGAAAAGAATGAGCTGTGGAAGCTCAAGGGTGTGCACGAAAAAACCCCCGTGGTGCACGTC
AAGAGCCGAGACGGTCACTTGCTCCCGTATCTGCCGCACCTGCTCAAATTGACATGTTCATACGAACAGCTCTTGCCCAGCATGAC
CAAGGAAGTCAATCGCCTGATTAAGCTGAGCCCCAACGAGAAGATGAGTAAGTTGTATACGGAGATGTTTCGATTGCTCCGGCAGC
AACAGGTGCTGACCTTCAAGAAGGAAAACGTGCGAGCCGTCAACCTCGGCTACGATGTGAATGAACTTGACAGCCCGATCATGGAG
TTCGGACAAGGCTACAAGACAAACGAGATCTATCGAGGCCTGAAGCAGAGCGGAGTATACGAGCCCAGCTCAGTGGCCGTGAGCTT
TTTTGTTGACCCCGAGCTTAACTACGACCCCCAGAAGCGGAAAGAAGTAGGTTGCTTCGTCAAAAAACTGGAGAGCATGAGCGAGG
CCCTGGGAGTAAAACTGAACATAAGCGACCAGCCCCGACAACTTTATGGCCAGCTCCCCAAGGACTTTTTCAAGCAGGACAACCTC
TCATATCATTTGAAATCTATCACCGACCAGTTCAGGGGAACGGTGGTGGTTGTTATCGGCACTGAAGAGAACATCGACCGGGCATA
CGTTACAATCAAAAAGGAATTCGGCGGCAAGGAGGATCTGATGACCCAGTTTGTCGGCTTCACCTCCTCCCTCGTCACGGAGAACA
ACATTTTTCACTACTACAACATCCTGCTCGGCATCTATGCGAAAGCTGGTGTTCAGCCCTGGATACTCGCCAGCCCAATGCACTCA
GACTGTTTCATTGGACTCGACGTAAGCCACGAGCACGGTAAGCACGCATCAGGGATAATACAAGTGATTGGACGGGACGGCAAGAT
TATCAAACAAAAGAGCGTTGCGACAGCAGAGGCCGGAGAGACTATTGCCAATAGCACGATGGAAGAAATCGTCAACGAAAGCATTT
ATTCCTACGAGCAGATCTACGGGGCCAAACCGCGCCACATAACATTCCATAGAGACGGGATCTGTCGCGAGGACCTCGATTTTCTG
CAAGCGTATTTGCGGAGTTTCCAAATCCCATTCGACTTCGTAGAAATCATAAAGAAGCCGCGACGCAGAATGGCGATATACTCTAA
TAAGAAGTGGGTCACGAAACAGGGAATATACTACAGTAAGGGCAACACCGCTTATCTGTGTGCCACGGACCCCAGAGAATCCGTGG
GTATGGCGCAACTTGTCAAGATCGTACAGAAGACTAACGGATTGAGCGTTCACGAGATAGTGAGCGACGTGTATAAGCTGTCCTTC
ATGCACATACACAGTATGCTCAAGACCAGGTTGCCTATCACGATACACTATAGCGACCTCAGCTCAACGTTCCACAACCGGGGCTT
GATCCATCCCCGGTCCCAACATGAGAGAGCACTCCCGTTCGTGTAGTAA
113 ATGCCTAAAAAGAAGAGGAAAGTAGAAGATCCAAAGAAAAAGCGAAAGGTGGGAAGCGGCAGCATGACCGGCGAGACTAAAGTGTT
GGTCGGGAGGCAACCCTTCGACGTGGATCGGCTGAATGAACTCAGAGACGAATTCCGGGAGACGCACGTGTTCAGAAGGGATGGCA
TCGACGATGTCATTGTTGATGTTCCGGTCGTGGCCGGACAGAAGCCCATCGGCAACGTCCAGGAGGAAATAGACCTGGCTAGGTAC
CAAAAGGTGTGGCCCTCCCTCCTCAGTGCTGCTCTTGTCCGGGCGTTTAGCGGCGTAAGGGACATCCTGAGCGATAGGCCCGTGAG
CGTGGTGGGGAGCACACTGCGGGGTCTGGTTCAACATCCGGAACTCCCCGAATGGATGCAGAAACGCACACTCCTTAGGTTCGACA
CCCGGACCATCTATGCTGGTGATAAAAGAACCTTTGGCTTGGTGTGCGAGGCCAGATTGAAAAACCTTATCCAAGGTAGTTGCGCG
GAGCTGCTGGCACTTGGAGTTTCCCCACTGGGTCGATATGTCCAAGTCGAGGAGCCACATTACGATCCCAGGCTTATGAAAAAACG
GCGCCTTGTGGGCAGGGTATCAGCGATCTCCGGCGATAATCTGGTGCTGGAGGACCATGCCGAGGGCTTTCCGACCGTGAGTGCAA
AGCTGGCATTTCTGGAGGCGCGAAGGGAGATTTTTGACGACTGTGTGCGGAGGATTTTGAACTCTGATGCGGCCTCCGTGCTGAAC
AAGGCCGAAGCTACTGCTGCCTCATTTCACTCAGGGCCAGGTAGGAAAGAGCAAATAGAGGAGGCTCTCAAGTATCTCAGGGAGAA
GGTGAGCCTCGAAGCTGTACCCGGAGCGAAATTCGTGATCGGGCCGATGCTGAGTAGCGGCAACAAGGGCTTCCCCATCACGGAGA
TGATCCCGAAACCCATTCTCGTGTTCGATCCGAGCGGTACACGGAAGGATGAGTGGAACGAAAGGGGCATTAAGAAGAACGGGCCC
TACGACCAGAGGACGTTTTCACCTAAGCAGTTGAAGGTGGCGGTCATTTGCCAGGCGAAGCACGAGGGGCAGGTGGATGGATTCAT
CGCGAAGTTCTTGGAAGGTATGCCAGACGTTATGACGGGCAAGAACCGAGTTGCTAGATATGGTGACGGTTTTCTGCGGCGATTCG
CCCTTGAGAAACCTTCTGTGACCTTCTTCACAGCGCCCTCAGCCAAGGCGAGCGATTACCTGGTGGCCAGCCGGGCTGCGCTGACC
AAGGCAACGGACGAGGGTTTCAAATGGGACCTCGCGCTTGTGCAAGTGGAGGAGGAGTTTAAGGGATTCGACGACGAGAGCAACCC
CTACTATGCCACTAAATCCGTCTTCCTGAAGCGAGACGTGCCGGTCCAAAGTGTACGACTCGAAACCATGGCTCAGGCCGACAGCC
AGCTGATTTTCTCTATGAACCACATGAGCCTGGCGACATACGCCAAGCTCGGTGGTACCCCCTGGCTTTTGGCGTCACAGCAGACG
GTAGCGCATGAACTGGTTATCGGTCTTGGCAGCCACAGCGTGGCCAACAGCAGGATCGGTAGCCAGCAACGATTCGTCGGGATTAC
GACGGTGTTCTCCTCCGACGGGAGCTATCTGCTCTCAGACCGCACGGCGGTTGTCCCCTATGAGGAGTATGCGACTGCGCTTTACG
ATACGCTCAAACGGAGCATCACTACGGTGAGGAAACAAGACAACTGGAGGTCTACGGATAAAGTCCGCCTGGTGTTCCACATGTTC
AAGCCCCCCAAGGACACCGAGGCCGAGGCTATAAAACGGACAGTGGACGATCTGGAGCTGGAGAACGTGACTTTCGCCTTCGTGCA
CATCGCCCCATCTCATCCCTACCTCATCTTCGACAATACACAAAAGGGAATTGGTTTCCGAGACCCCAAGAAGGGGATACTCGGAC
CCGAGAGAGGTCTGCACTTGAAGCTGGGGGACTACGAGTCCTTGATCGTATTCAGCGGCGCAAGCGAGCTGAAACAGGCAAGTGAC
GGGATGCCCAGGCCATGCCTGCTCAAGTTGCACCGGCTTAGCACGTTCACTGACATGACGTATCTGGCGCGACAGGCATTCGAGTT
TTCAGGTCATTCATGGCGAATGCTCTCCCCAGAACCGTTCCCTATAACTATTAGGTACTCCGACCTGATCGCCGAAAGGCTCGCAG
GTCTCAACGCCGTCCCGGGTTGGGACGCGGAGGCTGTCAGATTCGGCCAAATCGGCCGCACGCTCTGGTTTCTGTAGTAA
114 ATGCCCAAAAAGAAACGGAAGGTGGAGGACCCGAAGAAAAAGCGCAAAGTAGGTAGCGGCAGTATGCGATTGGGGCACATAGGCAA
CGGCTGTTACAGGGAAGGCGTTAAAGCACAATTCCAGACACGAGAGAGGGAGGATGCCGGTTCAAGGGCTGCGGCTGCCCAACCCC
CGATTAAGCAATTCGGATACACCGATAGACTCGGCCTGAACCTCGCCCCCATAAGGTTTTCTAGCGAAGAGTTTGAAGCCGGACGG
ACGGTGTACCGCGACGAGGAACAGTACCGAGCTCTTAGGGAAGCCCATCAAGCCACCCATGCCTTTAGGTATGACGCAAGGGACGC
GGCTATATACGACATCCCTATGGCAGAAGGGGTGGCGCCTCTGGGTACTCCCGTGAGGATCAAAACTAAGGACCACCTCGCTCTGC
TCGGCAAAGCGGCTAACCACGCGCTGCTCGATTGGCTCGCACCACGCAGAACCATTCTGCGGAGGGCGAGACCTCTTCAGTGCTGG
GGCAACAGGAAGGCCTCACTGTTGTCAGCCGCCGTGCGGGATCAAGGACTTGCCGAAACAAAGGGTCTGGATGTTCTGGTAAGGCA
TTCTTTTGATTTGAGGGCTTTGGGCGCACCTCACCAGGGTGCTGAACCGTACCTTGCCCTGATGTTGGACGTGAGTACGAGCAATG
AGCTGGAGATACCTGTGGGCGAGCTTCTGCGCGAGAGATTCGACCCCATCGGTCGATACGTTTGTGCCAGAGCCGACTCTGGCCAA
GATAACGTACTTGCTAGGTTGGAAACACTGGGTAGGGTCGTGGGTGTGGATGGTGGTAAGCTTCAACTGAACGACTTTACCGGAGA
AGAATTCGTGGACGCTGATTCAGTCACGTTGGAGCCTAGATTGGAGAATCTCGATGCGCTCATTCGCCACTTCTATCCCAGGGATG
CGCCAAAAATCCTGGAGGGCCTTCGCAAAAGGAGAGTGCCTTTCTCCACCGCGAACGACAAGCTGGCGAAGATACGAGAAGTGCAC
GGAGGAGTAGCCGGCCACCTTGAAACGATTAGGATCGCTGGCATGGCTATAGAGGTGGGTGCCCTGCTGCAGAGAGGCTCTAACCT
GTTTCCCCCACTCATAAGCACGGACCGGCCTGGATTTCTGTTCGGCGCTCAAGGTAGGGAAACTGGCGCGTTCCCCGACGTGGGGG
TGAAGCAGCATGGGCCCTACAAGTACATGCAACACGAGCGCAATGAACCTGTGATCGCCATCATCTGCGAGAGCAGGTTTCGGGGT
CGGATAGACCAACTCGCCCGAACACTTCGCGATGGTGTCGCGGAAGATGCCTGGCAAGACGCGATGAGGGGCAGAAATAAGGTGCC
GGAAAACCCCTTTAGAGGCGGGCTGATCGGTAAATTGAGATTGTCTCGGGTGCAGTTTGAGTTCGAAGAAGTAACCGAGCCCACTC
CCGAAGCCTATCGCGAGGCCATCCTTCGGCTGCTTGCGAGACTCCCAGAGACACCCGACCTCGCGTTGGTTCAAATACGAGCGGAT
TTTAAGCAGCTCCGCAACGACAGGAACCCATACTTCGCTGCAAAGGCCGCATTCATGACGGTGGGAGTGCCCGTGCAGTCCGTACA
AGCCGAGACTGCGGACATGCAGCCCAGTAATTTGGCCTACATGGCCAACAACCTGGCCCTCGCCGCCTACGCAAAATTGGGCGGTA
GTCCGTTCGTGATCTCCACACGCATGCCGGCGACGCATGAGCTCGTGGTTGGCTTGGGCTACACAGAGGTGTCAGAAGGACGCTTT
GGACCGAAGTCCCGATTTGTAGGCATCACCACCGTGTTCCAAGGCGATGGCAGGTACTTGGTGTGGGGGCAAACTAGAGAAGTAGA
ATTTGAAAACTACGCCGACGCTCTCTTGGCGAGTCTGAAGACTACCATCGACACAGTGCGCAAGGACAATAACTGGCAGCCACGCG
ATCGAGTGAGGTTGGTATTCCACGTGTATAAGCCCCTTAAACATGTCGAGATCGACGCTATCAAACAGTTGGTGCAGGAGTTGCTG
AAGGGCGAACATGAAGTGGAGTTCGCATTTCTGGACATCTCCCGCTTCCACGATTTTGCCCTTTTCGATCCTTCCCAAGAGGGCGT
GAATTACTACGCTGACCGCAGACGACTGCTGAAAGGCGTGGGCGTCCCCCTTAGGGGTATCTGCCTCCAACTGGACGAAAGGAGCG
TGCTCTTGCAGCTGACAGGCGCTAAGGAGGTGAAGACCAGTGAACAAGGTCTGCCCAGGCCCCTGCGACTGACGTTGCATTCCGAG
AGTGATTTTAGGGACCTCACATACTTGGCGCGACAGGTGTACAGCTTTAGCTACCTCTCCTGGCGCAGCTACTTCCCGGCCATAGA
GCCGGTGAGCATTACCTACAGCAGACTTATTGCCAATGCACTTGGCAACCTTAAGAGCATCCCGAACTGGAACAGCACATTCTTGA
CAGCTGGCCCACTGAGGTCAAGGATGTGGTTTCTGTAGTAA
115 ATGCCTAAGAAAAAGAGGAAAGTGGAGGATCCGAAGAAGAAACGAAAGGTCGGCAGCGGCAGCATGTATCTTAACCTCTACGAAAT
CAAGATCCCCTACAGGGTTAAACGATTGTACTACTTCAATAAGGAGAACGACCCCAAAGAGTTCGCCCGGAATCTGAGCCGAGTGA
ACAACATACGGTTCAACGACAGTAAGGACTTGGTGTGGCTCGAAATCCCCGACATCGACTTCAAGATTACACCCCAGCAGGCGGAA
AAGTACAAAATAGAAAAGAATGAGATAATTGGGGAGAAGGAAGACAGCGATCTGTTCGTCAAAACCATTTACAGGTACATCAAAAA
AAAGTTCATCGACAATAACTTCTACTATAAACGGGGAAATAACTACATTTCAATCAATGATAAGTTCCCGCTCGATTCTAATACAA
ACGTTAATGCGCACTTGACATATAAGATTAAACTGTACAAGATAAACGAACGGTATTACATTAGCGTGCTTCCAAAATTCACCTTC
CTCAGTGACAAGCCAGCCCTTGAGAGCCCCATCAAGAGCACCTACCTGTTCAACATTAAAAGCGGCAAGACGTTTCCCTATATTAG
CGGGCTCAACGGAGTCCTGAAAATTGACCTGGGCGAGAACGGCATAAAGGAGGTCCTTTTTCCGGAGAACTACTATTTCAACTTTA
CCTCCAAGGAGGCCGAGAAGTTTGGGTTTTCTAAGGAAATCCATAACATCTACAAGGAAAAAATCTTCAGCGGCTACAAGAAAATC
AAACAGAGCTTGTATTTCCTCGAAGACATCATCAATATAAACAATTACAACCTTACCATGGACAAAAAGATCTATGTGAACATAGA
ATACGAGTTCAAAAAGGGCATCAGCAGAAACATAAAAGACGTGTTCAAATACAGCTTTTACAAAAATGACCAGAAGATCAAAATTG
CGTTCTTTTTTAGCAGCAAGAAGCAAATCTATGAGATTCAACGCAGCTTGAAGATGCTGTTCCAGAACAAGAATAGCATATTCTAC
CAGACCATCTACGAGATGGGGTTCAGCAAGGTGATTTTTCTCCGCGAGCCGAAGACTAACAGCAGCGCATTTATGTATAACCCCGA
GACCTTCGAGATTAGCAACAAAGATTTCTTTGAAAACCTGGAGGGGAACATTATGGCAATCATTATACTCGACAAGTTTCTGGGCA
ATATCGACAGTCTTATCCAAAAATTCCCTGAGAACCTCATCCTTCAACCCATACTCAAAGAGAAACTGGAAAAGATTCAGCCGTAT
ATCATTAAGTCCTACGTCTATAAAATGGGAAACTTTATTCCAGAGTGCCAACCATACGTCATAAGGAACCTGAAGGACAAGAACAA
AACCCTCTACATCGGCATCGACCTGTCCCACGACAACTATCTCAAGAAGTCTAACCTCGCCATCAGCGCCGTAAACAACTTCGGTG
ACATTATCTACCTGAACAAGTATAAGAACCTTGAGTTGAACGAGAAGATGAACCTCGATATAGTCGAGAAAGAGTACATACAGATC
CTCAACGAGTACTACGAGCGCAATAAGAATTACCCCGAAAACATCATTGTTTTGCGAGACGGACGCTATCTCGAGGACATAGAGAT
CATAAAGAACATACTGAACATTGAGAACATCAAGTACAGCCTCATCGAAGTTAACAAGTCCGTGA/TATCAACTCCTGCGAAGACC
TTAAAGAGTGGATTATCAAGCTTAGCGACAACAATTTCATATACTATCCCAAAACGTACTTTAACCAGAAAGGTGTAGAGATAAAG
ATAATAGAGAACAATACCGACTACAATAATGAGAAAATACTGGAGCAGGTGTACTCACTGACGAGAGTGGTGCATCCCACCCCCTA
CGTAAACTACCGCTTGCCCTACCCCCTGCAAGTCGTCAACAAGGTCGCCCTTACCGAGTTGGAATGGAAGCTTTATATCCCTTACA
TGAAATAGTAA
116 ATGCCCAAGAAGAAGCGGAAGGTGGAAGATCCGAAGAAAAAGAGGAAGGTTGGCAGCGGGAGCATGACTGAGGACTTGTACCTCGA
CTACGACGCGTTCCTGCGGAGCTTTAAAAGAAACATAGATGTGCCGCACTCCTTTCTCCTGGGAGCAGGTACATCCATTAGCAGTG
GCATCCAGACCGCCTACGATTGTATCTGGGAGTGGAAAAAGGACATTTACCTCTCCAAGAACATCAACGCCGCTGAGTTCTATAAG
AACCATAAGGACGAGGCGGTAAGAAAGAGCATCCAAAAGTGGCTGGATAACCAAGGTGAATACCCAGTTCTCGACAGCACGGAGGA
GTATTGCTTTTATGCCGAAAAGGCCTATCCCATCCCCGAGGACCGCCGCAAGTATTTTCTGTCTCTTATCGAAAATAAGGAGCCCT
ACATAGGGTATAAGCTCCTCTGTCTGCTGGCCGAGCGCAGCATTGTAAAGGCTGTCTGGACTACTAATTTCGATGGCTTGACCGTC
AGGGCTGCTCATCAGAACAAGTTGACGCCCATTGAGATAACCCTCGATAACTCTGATAGAATATTTCGCAACCAGTCTACCAAGGA
ATTGCTCACAATTGCGCTGCATGGTGACTACAAATTCTCTACGCTGAAAAATACGGAGAAGGAGCTCGACAACCAGAACGACACAT
TCAAACAGCAGCTGGGGACGTATCACGTGGACAAGAATATGATCGTAATAGGCTACTCAGGGCGCGACAAGAGCCTCATGGACGCC
ATCAGCGAGGCCTTCAGTACGCGGGGTGCAGGGAGGCTTTATTGGTGCGGCTATGGCGAGACGATCCCCAACGAGGTTAGCGAGCT
CATACTGAAAATCAGGTCCCAGGGTCGCGATGCATACTACATATCAACGGATGGATTTGACAAAACGCTGATACACCTGTCTAAAA
GTGCGTTCGAAGACAACCCCGAGATTACGAAAAACATCCAACTCGCGCTCGAAAACAGCGCGGACGAAGAGTACTTTAAGACTGAC
TTTTCACTGAACTTTAGCAAGCCGGATAAGTTCATCAAGTCAAACCTCCACCCCATCGTGTTCCCGAAAGAAATCTTTCAATTCGA
GCTTGACTTCAAGGAGGACAAGCCTTGGCAACTCCTCAAAACTATTTCACGCGAGACAAACATTTGCGCCGTGCCGTTCAAGGGTA
AGGTGTTCGCACTGGGCACGCTTACTGACATTGGGAACGTCTTCAAGAACCGCCTGAAGAGTGATATAAAGCGCGAAGCAATTAGC
ACCTCCGACGTGGATAATGTGAGTGCCTTTAAATCTCTGATGCTGCAGGCTGTGCTGAAGTTTTTCATTGGTATCGAAGGCGTGGA
GTCCAACCTCAAAGACAGATTGTGGCTTACCAACGCGGAGCAGCTCGTGGGTGATATTAGTGTGCATAAGGCTATCCACCTCAGCC
TGTACTTCGACAAAAACAAAGGATTCGCTTACCTGTCCTTCACCCCCACCGTACAACTCATCTCTCCTGAGGAAATCAGCAAAATC
CAGAAGCAGAGAATCTCTAAGAGTAAACTCGAGAAGCTGTTCAATGACAAGTATGACGAGATATTGGAGTTCTGGAACCAAAAGCT
CTTTAACAATAGCCAAATCAAGTTCGAGTACCCGATCAGCTCAGGTAGTGGGTTTGAGTTCAAAATCTCCGCCAACACCGCATTTG
GGGAGATAAACGTATTGGACCCCAACTTTCGCTCCTTTTCCCCTAGAAATTATGACCCGAAGCGCACACAGTTTAAGGGCGTGCAG
TTCCTCGAACCGCAGCTGATATTCCGCAACATCAGTACTAATGTGGAATTTAAGGACTACCACCCGATGAGGGGGCTGGTGAACAA
CCGACCGTTCGACGTGAACCTGAACGGTATAATTCATTCTAACGAAATAAACCTCACGGTCATCTGCGGCAAGTCATACGCCAACG
ACCTGTATGAATTCCTGAGCAAGCTCCAAGTGAAGCACGCCACTGAGAATGTCAACCCGGACTATCTTATTGAGTATCCGGGCTTC
CAAAGTGTGTTCAACCTGCCACTCAACATACCCCACTTTGACTCTTCCGAGAAGTGGTACGACATCGACTTCGTAGCTGACAATAA
CGGGGAGAACCACGAGAATGCCATTAAGCTTGCCAGACTCATCACCACCAAGATCGACCAGATTGCCTCTACACAGAACCAGAGCA
CGGTCGTGGTGTTTATTCCAAATGAATGGCAGTTGTTTGAGGGGTACCTGAATCAGGGGGAGAGTTTCGATTTGCACGATTACATC
AAGGCATTCAGCGCTAGTAGGGGCATTTCAACGCAGCTCATCCGCGAGGATACACTGGCGGATACGTTGAAGTGCCAGATCTACTG
GTGGCTGAGCCTCTCATTTTACGTTAAAAGCCTGCGAACTCCTTGGATTCTGAATAATCAAGAAAAGAACACGGCCTACGCCGGGA
TCGGTTATAGCGTGACTAAAATACAGGACCGGACGGAAACGGTGATCGGCTGTTCCCATATTTACGATTCCAACGGCCAGGGGCTC
AAGTATCGGTTGAGTAAAATTGACGACTACTTCCTTGACAATCGCAATAATCCATTTCTTAGCTATAAGGATGCGTTCCAATTCGG
TGTGTCCATACGGGAATTGTTTTACCAGTCCCTGGACAAATTGCCTGAGCGGGTAGTTATACACAAGCGGACCCGATTTACCGATG
ATGAGATCAATGGTATTAAGGCGTCTCTGAACAAGGCGGGGATTAAGAAGATTGACCTGGTGGAGATTAACTACGAGACGGACGCC
CGCTTCGTGGCCATGTCCGTATACCAGAATGCACTGCAGGTAGACCGATTCCCTATCAGTCGGGGTACTTGTATAGTCACAAATAA
GTACACTGCCCTTTTGTGGACGCACGGGATTGTCCCAAGTGTACGGCAGCCAAACTACAAGTTCTACCTTGGCGGTAGAAGCATAC
CGGCTCCGATCAAGATCACAAAGCATTATGGTGATAGTAATATAGACGTTATCGCCACCGAAATCCTTGGGCTGACCAAAATGAAC
TGGAACTCCCTTGACCTTTATAGCAAACTTCCCTCTACGATCGACTCCAGCAATCAGATCGCTCGGATTGGCAAACTGCTCTCCCG
GTACGAAGGCAAGACGTACGACTATCGATTGTTTATCTAGTAA
117 ATGCCGAAGAAGAAAAGGAAAGTGGAGGACCCCAAGAAAAAGCGCAAGGTTGGCAGCGGGTCCCTGGAGAACCTCACCATAAACAT
AATCCCCTTCAAGCACCCCAGCATCCAAAAAGAATTTGGCTTCTATACCGAGAAGAAGGAGGGCTATTTCCCCATTCATAGGACCG
AGTTGCCCAACGAGCTGTGGGACAACCAGAAAGAGGAAGTGGTGAAGCACAAGTTCTACTACACGAACTTTGAAGACACGGAGGAT
TGCGTTCTGAAGACCAAGGTGGACCTGTATAGTAGCACTAAGTTTGCCAAGCATCTGTACACGCGATTGGTGTACCAGTATTTCAT
TGGGATAGCGGATGCAATCCAGTTCAACTACGTGGGTGACATAGAGGTTTGGCTGCTGGATGCGAAAGCCAGCACCACCAAATACA
ATAGCTACAACAAGTATACCCTGAAAATAGAGTTTAGCGGTCTGACCAAGAGCCCCGCTCTCCTCCTCAGCTATGACAACACTAGT
AAGGTAGCGACTACGAGCATAGACGAAATCAACATTCCCACCGAGTACTTCAAGACCGTCGTGTATAACAAAGAAATCCAGAGGTT
CAAGTACCTGACCGAGGACGCGAAACAACACCTCGATCAAGTGTATCCCCTGCTCAACATACCGTTGAAAAACCATCTTGAGATTC
CTCACACCGTTCCCCGCAAGGGCAACAGGTATAAGCCCTACTTTAACCACATTACGACTTTTTACAATAACTATTTGAACACCGAC
GAATTCAGGGCCATCCTGCCCCTTGATGAGAATGGATTCTTCAATATCCCAGAGGACAGCATTTTGAAAACTAGCAAAAATTCTAA
CAACCTCCGGTTCTATAAGAAAGTCGGAGTAGATCCCAAGGCTGGAATGAAGAAGCCCGGTCCCTACAAGGCCTCCCCCCACGACA
ACGTGAACCTGTTCTTTATCTATCACAAACCCGACGCACATGAATACGCCAAAACGTTGCATGACTACTTCATGGAGGGGTACAAA
AAGTTCTTTCCCCCCCTCAAGAACGTTATCCGGCAGCCGCTGTTCCTGGACAAAGGCACCTCACTTGCATTTGAGAGCTTCGACAG
CTGCATCGCCGAGCTGAAAACCCATCTGTTCGACCTCAAAAAAAAGCCCAATACCCGGTACGTGGCCATCTACGTGAGCCCCATCC
ATAAGGAGGACGAAGACAATAAACACCTGTACTACCAGGTCAAAGAAGAGCTGCTTAAACATGACATCACCAGCCAGGTGATTTAC
AAAGAGTCCATCAAAGATAAATACTTCGGCGCTTTCCTCGAGAATATCGCACCAGCTTTGCTTGCAAAGATCGACGGCATTCCCTG
GCGACTGGACAGGGAGTTGAAACAGGAACTGATCGTAGGCGTCGGCGCCTATAAAAGCAGCGTCACCAACACAAGGTTCGTTGGAA
GCGCCTTTTGCTTTAACAACAAAGGAGAGTTCAAGAGCTTTGACTGCTTCAGGGAGAAGGAATTCGATCTGATTGCCGGGAAAATC
GGCAAGCAGGTGCTCACCTTCATTGAGGAGAACGAGAACAAGTTGGAGAGGCTGATCATCCATTATTTCAAGCCTTTCAACAAGGA
TGAGATAGATCTCGTGCAGGAGACCCTCGGCCTGCTGAAGCTGGAAATCCCCATCATCATCGTGACTATCAATAAGACCGAGAGCT
CCGATTACGTCGCTTTTGACACCAACGACGACGCCCTGATGCCCCTGAGCGGCACCATTATCGAGATAGCACATCTGAAGTATCTG
CTGTTCAATAACGCGAAGTACAGCAGCATCGGCTTCGCCAAAGACCACCCCTTCCCCGTTAAGCTCAGTCTGTACTGCACCGACCA
GGATTACTTCGAGGACATCGCCATCGTCAAGGAGCTCATAGATCAGGTTTATCAGTTTTCTAGGATGTACTGGAAGAGCGTCAAGC
AGCAAAACCTGCCCGTGACAATCAAATACCCCGAGATGGTGGCCCAAATCTTCCCACACTTTGAGGGCGATAAACTGCCTGATTTT
GGAAAAAACAATCTCTGGTTTCTGTAGTAA
118 ATGCCGAAAAAGAAGAGGAAGGTTGAAGATCCCAAGAAGAAACGAAAGGTGGGGAGCGGCAGCGTGAGGCTGGTAAACCAGAAAGA
GAAACCGGAAGGCGACTACGTGTATGGCTACACTCTCCCAATAGACCCCAGTAACAGGAACATGAGGCAGCCCTTCTGGATAAGCA
TGGATAAAAAGGAGGGCTATGAAGCTCATTTCGTTGGCCCCTATGAGAACATTGAGTTGACCAAGAGCGTGATCTTCTGGGACCTT
CTGAGGAGGACCAGGGAGCAACTCAGCAGCGATAAGTTCACGGAATCAAGAAAAAAGTTCTTTAAGGAGATCTACTTCCCCCTTAA
CCTCTACAATGAGGGCAGCCAAGGGCTCGCCGTGCAACCCTACTACCTGAAGATTGATCAGCAATTTGGACTGCTGGTGGATTTTC
AATTCAAACTTGACAAAGATTTCACCTTCAGCCGGAAGATTCAACAGCTCAGTCTGACATTGGATGGGAAGAACCGGAGGAACCTC
AACTACTACGTCGACAGGATAACCAAAACCAACCAATTCATCAAGGCCCTCTGGAACATCATTGGCACCTTCTCCCATAATGAAAA
CAAGGAAAACTACACGCTGAGGAACGACTTCTACCCCTGCGCCGCAAGCAGGCTGCGGTCTCGAATGTATCTCTTTTCCAATGGCA
GTGAATCCAGGAGCCAGTTCAATGGCTTGAAGGAATACGGCCCACTCCGACCCCTGACAGCCAATCCGACACTGCTGTTTGTGTTC
CGGGAACAAGACCGCGACGCCGCGAGAAAACTGGCGATGGCACTTAAAGGCAGCAAAAAGCAAGATCAATACAGCTTCCCCGGGTT
CAACTCCCTGTTTAAAGCGGACCTGTTGATCGACGGAAATCCCATGGTCTTGAAAGACTTTTCTATCGAGAGCAGCAGGGAGGTGT
TGGCCAGGGTGACAACATCAACATCCAGCTTGTTGCCCATTTTCATCCTGCCCAACCGCGAGGGCGACGGCTACCTGGAGCACAAA
GCCATCTTCGCCGAGAACGGCATACCTACTCAAGCGTGCACACTCCAAGTCATTCAGGACGACGTGACCCTTAGGTGGAGCGTCCC
CAACATCGCCCTGCAAATATTCTGCAAAGCGGGTGGCTGGCCCTGGAAAGTGCAGAGCCCCGTAACCGACAACGCCCTGATTATAG
GCATAAGTCAGAGCCACAAGTTGAATTATAGTGACGGTAAGACAACTGTGGACAAGCACTTCGCTTTTAGCGTGCTGACTGATTCA
AGCGGCCTCTTTCAGAAAATTCAGGTGCTGAGCGAGCAGAAGACGGAGGAGACCTACTTCGAACAACTGAAGCTGAATCTCAAAAG
CATCCTGAACGCCAATAGCAAGAACTACCAACGCATCGTGATCCACACCTCATTTAAGCTCAAATACAAAGAAATAAGTGCAATCG
AGGAAGTTGTTAGCGAATTTGCAAGGAACAGCAACAGCGCCGACTGCAAGTTCGCCGTTGTGAAGGTTAATCACAAGCATAGGTAC
TTCGGGTTTAATCGGGAAGTGAATAGCTTGGTGCCCTACGAGGGAACCGTGTGTAAGCTGGGCGATAGAGAGTACCTGGTCTGGTT
CGAGGGTATCTATCAGGAGAAGCCGACCGTTACCAAAGCATTTCCGGGTCCCACCCACATCGAATTTCTTAAAATCGGGTCTAATA
ACGTGATTAGCGACGACCTTTTGTTGCAAGACCTGATGAACTTGAGCGGAGCGAACTGGAGAGGCTTTAATGCGAAGAGTGCTCCG
GTATCCATCTTTTACTGCCACCTGGTGGCCGACATCGTGCATGATTTCCAAATCAAAGGCCTCCCTATGCCCGCCATAGATCTTAT
ACGACCCTGGTTCATCTAGTAA
119 ATGCCAAAGAAAAAACGAAAAGTAGAAGACCCTAAAAAGAAGCGGAAAGTAGGGTCAGGCTCTATGCTTCAACTGAACGGCTTTAG
CATCGAAATCGCCGGAGGTTCCCTGACTGTCTTGAAATCTAAAATCGCGCCTACCGACGTTAAAGAAACCCGCAGGAGCCTGGAAG
ACGACTGGTTCACCATGTATCACGAGGGCCACTTGTACTCACTTGCAAAAAACAGCAACGCATCCGGCGGATTGGGTGAGACCGAG
CTCCTGGTCCTGTCTGATCATCTGGGTCTTAGGTTCGTTAAGGCTATGTTGGACCAAGCCATGAGGGGCGTATTCGAGGCCTACGA
CCCCGTTAGAGATAGGCCCTTCACATTTCTGGCGCGAAACGTAGATCTCGTAGCCCTCGCGGCAGAAAACCTCGAGTCCAAGCCCA
GCCTTCTCTCCAAATTCGAGATCAGGCCCAAGTACGAACTGGAGGCCAAGGTAGTGGAATTCAGACCGGGCGAGCTGGAACTTATG
CTGGCGCTCAATCTGACTACACGGTGGATCTGCAACGCCTCCGTAGACGAGCTCATTGAGAAGAACATACCGGTCCGAGGAATGCA
CCTGATCCGACGGAACCGGGAGCCGGGACAGAGAAGCTTGGTTGGCACCTTCGACCGCATGGAAGGCGACAACGCCCTGCTGCAGG
ATGCTTACGACGGACAAGACAAGATAGCAGCCTCACAGGTGAGGATCGAGGGGAGCAAGGAAGTCTTCGCGACCTCTCTGAGGAGG
CTCTTGGGCAATCGCTATACCAGTTTCATGCACTCCGTGGATAACGAGTACGGCAAGTTGTGCGGGGGTTTGGGGTTCGACGGCGA
ACTTAGGAAGATGCAGGGATTTCTCGCGAAAAAGAGTCCTATACAACTGCACGGAGGTGTAGAAGTGTCCGTGGGGCAGAGGGTAC
AACTTACCAATCAGCCTGGGTATAAGACAACAGTTGAGCTTTTGCAGTCAAAGTACTGCTTTGACAGAAGTAGGACGAAGCTCCAC
CCCTACGCCTGGGACGGGCTTGCTCGATTCGGCCCATTCGACAGGGGCAGCTTCCCGACGCGATCCCCCAGGATTCTGCTCGTGAC
ACCCGACTCCGCGAGCGGTAAGGTCTCTCAAGCTCTGAAGAAATTCCGCGACGGGTTCGGCAGCAGCCAGAGCAGCATGTATGACG
GCTTCCTCGACACCTTTCACCTCAGTAATGCTCCTTTCTTCCCCCTTCCCGTGAAGCTGGACGGCGTGCAGCGCAGCGACGTGGGC
AAAGCTTATCGAAAGGCGATCGAAGATAAACTCGCACGAGACGACGACTTCGACGCCGCCTTTAACATTCTCCTGGACGAGCACGC
CAATCTGCCGGACAGCCATAACCCCTATCTGGTCGCCAAGTCCATCCTCCTCTCCCACGGCATCCCAGTGCAAGAAGCACGAGTGA
GCACTCTGACGGCCAACGAATACAGCCTGCAACACACCTTCAGGAATGTCGCCACAGCCCTGTACGCCAAAATGGGTGGTGTCCCA
TGGACCGTTGACCACGGGGAGACCGTGGACGATGAGCTGGTAGTAGGAATCGGAAACGCGGAGCTTAGCGGGAGCAGGTTCGAGAA
AAGACAGAGGCACATCGGAATCACGACAGTGTTTAGGGGGGACGGCAACTACCTGCTTAGCAACCTCAGCAAAGAGTGCCGATACG
AGGATTACCCGGACGTACTCCGGGAGAGTACCATCGCCGTGTTGAGGGAGGTTAAGCAAAGGAACAATTGGTTGCCGGGTCAAACC
GTGCGAATCGTTTTCCACGCCTTCAAGCCTCTGAAAAACGTGGAGATTGCCGACATCATCGCGAGCTCTGTAAAGGAGGTAGGCTC
CGAACAGACCATAGAATTTGCATTCTTGAATGTTTCCCTCGACCACTCCTTCACCCTTCTGGACATGGCTCAAAGGGGAATAACGA
AGAAGAATCAGACCAAGGGGATATACGTTCCCAGGAGGGGCATGACAGTCCAGGTTGGGCGCTACACCAGGCTTGTAACCAGCATC
GGTCCGCACATGGTAAAAAGGGCAAACCTTGCCCTCCCGCGACCCCTGTTGATTCACCTGCACAAGCAGAGCACCTATCGGGACCT
GAGCTATCTGAGCGAACAGGTTCTGAACTTTACCACCCTGTCCTGGAGGAGCACCCTCCCCAGCGAGAAGCCTGTTACCATTCTCT
ACTCATCACTGATAGCCGACTTGTTGGGAAGGCTCAAGTCAGTGGATGATTGGAGCCCCGCAGTGTTGAATACCAAACTGAGGAAT
AGCAAATGGTTCCTGTAGTAA
120 ATGCCGAAGAAAAAGAGGAAGGTTGAAGACCCCAAAAAGAAACGCAAAGTGGGCAGCGGAAGCATGTCCGGCCTTTTCCTGAACTT
TTACCAGGTAGACATCCCCACCAAATCCGTACCGATCCACAGCGTAGAGTATAGCCATTACAGTTCAAAGGAGGCCTTTATCGCGT
TGAAAGAAAACTTCCCCTACTTTAGCTTCTACCGGGATGACGACCGAATACTGATCTGGAAGAAAGACAAGGATGCCGAGCTCCCC
GAGAAGAACTCATTGATTGAAATTGATTTCACCGAGAAAGCGAAGGTCCTCAGCAAAATACTCGAGAGGGCCATCATTGACTTCAT
CGAGCCAAAGGGCTACAAGATATTCAAGAACAAGTACAGCAACAGCTGGGAAATAGTGAGCATGAAGGACATCCTGAATGGTGGGA
TCGAGGGACTCAGCATCAATCGAATCGTGCATTTTTCCCCCTGCTTCTTCTTCAAGGAGAACAAACTCATGCTGGGTTTCAGCCTT
AGCACAAGCCTCAAAAACGTGTTTACCTGGAATAAGGCGGACTTCGAAAGGTACGGCTTTGACATCAAGGGCCTTAAAGGAGACGA
AGAGCGGATTTTTGCCAACAAGCAATCCCTTAAGAGGTTCCTGGAGACCAAGGGCGCAGTTGCAATGTATGACCAAATTATCGCAA
AGGAAAACAAGAACGCGAAAATGTTTAGCATCATCGACGGCTTCTATCGGTGGCTGGAGAGGAACAAGACTGAAATCCAGCTTCCA
TTCGGACTGAAGATAAATTCAGTGTCTAAAAAGTACCTGCCGTTCGAGGATGAGCTGATCAAGAGCGAGATCATCCCTAAGCCCCA
AAGGTATTTCTATAGCAATAGGAAGAACACCCAGAGCCTGCGGTACTATGACGAGATGGTGAAGACTTATCAGCCCTACTCTCTGG
AGCTCTACCAAAACAAACAGATCAACATCGGAATCATCTGCCCCAGCGAGTACCAGGGAGAGACGGAGGGGTTCATAAAGAAGATC
GAACTGAAGCTCAAGGAAGTATTCCATTTCAACAGCCTGATCTTTCACTTCAAGACCATTACGAACAAGGACCTCGCGTCCTATAA
GGAGGTTTTGTACGACGATGAACTGCTGAAGTGCGACCTGATTTACGTCATCGTGAATGAGGCCCAGGAGAAACTCTCACCTAATA
ACTCCCCTTACTACGTGTGCAAGGCCAAGTTTATAGGCAATGGCATACCTACGCAAGACATTCAGATTGAGACCATCCGGCAGAAC
TTGAATGCGTTCACAATGACGAACATCTCACTTAACAGCTACGCCAAACTGGGAGGCACCGCGTGGACCATCGAGAAGGAAGACAA
ACTTAAGGACGAGCTGGTCATTGGCATCGGCTCCACCCTGTCAGAAAACGGCCAGTTCGTGCTCGGTATCGCACAAATCTTCCATA
ATGACGGGCGCTACATGGCGGGTGACTGCAGCCCCCTTTCTACCTTCTCCAACTACGCGGAGAACCTGGAGGATCACCTGTACAAG
ACCCTGAAGCCCCTGGTGGAGGAGATGAGCAAAAGCGGCACCTTCCGGCTGATTTTCCACTTGTTTAAAAGTGCCTCTGAGGAGTA
CGAGATACGCGCGATCAACGGCCTGCAGAAGAGGCTGGCGAACTACAATTTCGAATTTGCACTCGTTCACCTGGCCTATGGACACA
ACTTCCGACTCTACTACAACGACGGCAACGGCGACATTAATCAGGGCACATATATACAACTGTCAAAACACAGCGCCCTGCTCCAC
TTCGTTAGCAAGTCAGACTTGCCCCTGAAAATCGACCTGGACAAGCGGTCTACTTTCACCAGCCTGTTTTACATCGCCAAGCAGGT
GTACTGGTTCAGCCATCTGAGTCATCGCAGCTATATGCCCAGTAAGAGGACCGTGACCATCATGTATCCGTCAATCATGGCGAAGA
TGACCGAGGAGCTTAAGAAGGTGGAAGGATGGGACTACGAGCGCCTGAAAGCAGTAAGCGATAAGCTGTGGTTCATCTAGTAA
121 ATGCCGAAGAAAAAAAGGAAGGTGGAGGACCCAAAGAAGAAACGGAAAGTTGGCAGCGGCTCCATGAGCGTGGCGATCGTGAGCCC
CCAAATGTACAAGAGTCTGAGCGAGGTGTTTCCTCTGACCGCCTCCCAACTGAACTTTATGTGCTTTAGGCTGACTCCCGAAATCG
AAAAGAAGGATGGTAATAGGCTCAGCTACCATTTCAGTCTGAAGCTGCCGGAAACTGTTGTGATCTGGCACCAGCCCTACTTCTGG
GTGTTGGCGAGTAGTAACAGGCAAATCCCCAATAAGGACGAGTTGCAAGAAACTCTGATAAGGATCCAAAACGAGGTGGATGACTT
CAAAGAACGACTCTTCGGTTTCCAGAGCGTTCGCCACCCCCAACTCACCCCCTTTATCATCAGCCTCTTCGCCGTGCAGGTCCTCA
AAAAAACAAAGTTCGACTACCCCATTGCATTCAGCAACAACGGTGTAATCGTCAGGAGGGAGCCCGACTTTTGGACGGAGAGCATA
GAGCTTCAAGACAGCCTGCATCCTGCCCTCACGCTGACCGTAAGTTCATCAATAGTGTTCCGCGACAACCTCGCGGAGTTCTATGA
AAAACATCATCAAAGGGAGAAGCCCGAGCAGTTTCTGATCGGCCTGAAGGTGCAGGAAATAGAGAGGGGCAACAATGCGATCATCG
TGGGACTCGTCGGCACCATCGGCGAGCACCGGGACCAGCTGCTTGAAAAAGCAACCGGGAGCACTAGCAAGCAGGCGCTGCGAGAG
GCACCGGACAACCAGCCGGTGGTTGCGATACAGTTCGGCAAGGATACGAAGCAGTTCTACTACGCAATGGCCGCGTTGCGGCCGTG
CGTAACCTCAGAGACGGCAAACCAGTTCGAGGTAGAGTACGGTAAGCTCCTGAAAGCTACAAAGATAAGCCACCAGGAGCGAACCA
ACCTGCTGGCCTCATACAAGAAGACGGCCCAGGAGTCATTGGCCGCTTATGGCATCCGCCTGGAGCTGAGTGTGAATAGCAGGGAT
TACCCCAGCTTCTTCTGGCAACCCCCCGTGAAGATCGAAGATACCAAACTTCTGTTTGGCAACGGCATAACCGGCAAGCGGACTGA
GGTGCTCAAGGGGCTTTCTATAGGGGGCGTGTACCGACGCCACGGGAAATTCCAGGACAAGTCAAAAGTGATCCAGATCGCGGCTC
TTAAGCTTTGCGACGTGACCGTTAGCTTGTTCCTGAAGCAACTTACTCAAAGGCTGGCAAAATACGGCTTCCGAAGCGAGATAATC
ACCAAGAAGCCTCTGTCAATCAAGAACCTTGCCACCGCCGAAGCCAGGGCTGCTGTTGAGAAAGCGGTCAATGAGCTCGTGGAAAT
ACCCCACGACATCGTGCTTGCCTTCCTGCCTGAGTCCGACAGGCACACCGACGACACGGATGAGGGTTCCTTCTATCACCAGATCT
ACTCCCTTCTCCTCAGAAGACAAATAGCCTCACAAATTATCTACGAGGACACCCTGTCCAACTCTGGGAACTACCAGTACATCCTG
AACCAGGTCATTCCGGGGATCTTGGCGAAACTCGGGAATCTGCCCTTCATTTTGGCGGAAAGCCTCGATATAGCGGACCACTTCAT
CGGACTTGACATCAGCAGAATCTCTAAGAAAACGCAGGTCGGGACACGAAACGCGTGCGCCAGCGTGCGACTTTACGGACGCCAGG
GTGAATTTATCCGCTACCGGCTTGAAGACGACCTGATCGACGGCGAGGCGATTCCACCCAAGCTGCTGGAAAGGTTGCTGCCTGCG
ACCGAGCTTGCGAATAAAACCATACTGATCTACAGGGACGGGAGCTTCGTGGGCAAAGAGGCCGACTATCTTGTGGAGCGAGCCAA
GGCGATAGACGCGAAGTTTATCCTCGTCGAGTGTAAGAAATCCGGCGTGCCGCGCTTGTATAACTTGGAGCAAAAGACCGTGATCG
CGCCGAGTCAGGGACTGGCTCTTCGACTGAGCAGTAGGGAAGCAATACTCGTGACCACCAAGGTGCCCGATAAAGTGGGCCTGGCT
AGACCCATCCGGCTCACAATCCACGAAAAGGGCCATCAAGTAAGCATCGAATCCGTGCTGGACACTACACTCAAGCTTACTCTTCT
TCACCATGGCGCGCTGAAAGAACCGCGACTGCCCATGCCCCTGTATGGGAGCGACAGGATGGCATACCTCCGGCTGCAGGGGATAC
GGCCTAGCGTTATGGAGGGCGACCGCCAATTCTGGCTGTAGTAA
122 ATGCCCAAGAAAAAGAGAAAGGTGGAGGACCCAAAGAAGAAACGGAAAGTTGGCTCTGGGTCAATGAACCTGACCGTAAACCTCGC
CCCCATCAGCGTGCAGGGCGACTGCTCAGTCCTGATTGGCAGACAGCGCTACGACGAGCAGAGGCTGGCTGAACTTAGGTCAGACT
TTCGGGGCACCCACGTGTTTCGGCGAGACGGTCCAGATAGCATGATTGACATCCCCGTGGTCCCCGACGCGGCACCTCTGGGCAAC
CTGAGGGAGACGATCGACCTTAGGCGGTACCAGCGGCTGTGGCCCATGCTTCTGCAGGAGTCCCTCATCCAGCTGCTTGGTAAGCG
CCCCATCCAGTCCAGCAAGCCCTTGAAGTTCCTGGGAGCTAGGTCTCCTCTGATCGAGCACCCGGATCTCCCTGAGTGGTTGAGGC
GGGTGAGCGTTACCGAGATCCACACCCGACACATCACCGTGGACGGCAAGCAAATCTACGGTATCGTGTGCGATGTGAGGGCCAAG
TCTTTTATCCTCGCCACCTGCAGCGAACTTCTGAAATTCGGCGTGACCATCCTTGGTAGATACGTCCAAATAGAACAGCCCGCGAT
AGACGAGAGAACCATGCCTAAAAGGAAGCTCATCGGCAGGGTAAGGTCCATCCAAGGGGATGATCTGCTTCTTGACGACTGTGAGG
CCGGCTTCGAAAAAGTCGCTGCGAATGAGGCATTTCTCGAGCCGCGGAAGGAAAATTTCGAGGACTGCGTGAGGCAGGTGCTGAAG
CGGGACGCCGAGAGGGTGTTGGAGAGGTCAGCTCGCGCCAGCCAAAACCTGGCCGCAGGCCCTGGGAAACTGGAACACATCGACGG
AATCATCAGGTATCTTAGGGAGAAGAAGCCCGCAGCGGTGCCCGGCTGCCATTTCGTGATCGATGCCATGCTCAACACAAACGGCC
ACATTTTTCCACCCGGGGAAACAATGGACAAACCCTTCCTCTTGTTCGACCCTAGCGGTTCACGGAGAGAAGACTGGCCCGAGAAG
GGCCTTAAAGATCACGGCCCCTATGATGAGCAGGTGTTTTCCCCCAAGTCCCTGAAGATCGCTGTTGTGTGCCAAAGCCGGTTGGA
GGGCAGAGTGGACGAGTTTCTGGCGAAGTTTCTCAATGGGATGCCGAAGGTCTTTCAACCCGGCAAGAGCTTCGCCCGCTACGGCG
ACGGATTCGTGAAACGATTCAGACTGAACAAGCCCGAGGTGCACTTCTTTCTTGCAGATGGCAACTCCGACGAGGCATACGCCGTG
GCCAGCCGCGAGGCACTCGATAAAGCGAGGGATAGCGGGTTCGAGTGGGACCTGGCGATTGTGCAAATTGAGGAGGAGTTCAAGTC
ACTGGCCGACGGCTCCAATCCCTACTACACCACTAAGAGCATCTTCTTGCGGAGGGACGTTCCGGTGCAGAGCGTCAGGCTGGAGA
CCATGAGCCTGTCAGATAATGACCTGGTGTTCCCCATGAACCACCTGAGCCTCGCTACCTACGCCAAGCTGGGGGGCACGCCCTGG
CTCCTGGCTAGCTCACAAACCGTGGCGCACGAACTGGTGATCGGACTGGGTAGCAGCACCAGCTCCGAATCAAGGCTGGGCAGCCA
GATGAGACATGTGGGAATCACCACCGTGTTCAGCAGTGACGGCAGCTACCTGCTTTCTGATAGAACCGCCGCAGTGCCCTTCGAGC
AGTACCCACAAGAGTTGAGGAAAACGTTGCGAAAAACAATCGAGGCCGTCAGGGCCGAGGACAATTGGCGGAGTAGCGACAAGGTG
AGGTTGGTATTCCATTCATTCAAGCCGTTCAAGGACAGCGAGGTAGAAGCCATAGAGGCGCTGACCACCGACCTGGGCCTGGGCGA
CGTGAAGGCCGCCTTTCTGCACATTGCGCCCGACCACCCGTTCCTTATCTTCGACCACGACCAAATGGGCATCGCCGCACGAGGGG
GCAAAAAAGGCGTGTTGGGCCCTGCTAGGCAGTTGCACATCCGGCTTAGCGACGCTGAGAGCCTTGTGGTCTTCGCAGGGGCCAGC
GAGCTTAAACAGGTGACGGATGGTATGCCGCGACCCGCGCTGCTCAAGCTGCACCCCAAAAGCACCTTCAAAGATATGACCTACCT
GGCAAGGCAGGCCTTTGCCTTTAGTGCCCATAGCTGGCGGATGCTGTCCCCCGAACCTTTCCCAATTACTATCCGCTACAGCGACC
TGATCGCCGACCGCCTGGCGGGACTCGCGTCTGTTAAGGGCTGGGACCCCGATGCCGTGACGTTCGGCGCTATCGGTCACAAGCCT
TGGTTCTTGTAGTAA
123 ATGCCCAAAAAGAAGCGAAAAGTAGAGGATCCAAAGAAAAAGCGGAAGGTCGGGAGCGGCTCCATGGCGTTTAGGCCCGGTGAACG
AGTCAGACCGCAGCTCGCGCTGAATGCGATCAGGGTCCTTACACCCCCTGGCACCATCCCCGCCAGTGTAGTCCAATTCGACAGAG
CGCTGCTGCACGCATATCTTGACAGACCCGAGAACGACGTATTCGCTACCCGACACGGGGAGACTGATATGGCGGTCGTACCCCTG
ACCAGCGGTGCGAACCTGCCAACGGACAGAATGGGGCTTCCAGCTGCAGAGCACCTCAGGCTGGTATCTGCGCTGACAAGAGAAGC
TGTGTTTCGCCTCCTCGCGGCCAGCCCGGAAGCGGATCTGCTGATCCGGCGACGCCCACCGACCGTCGCGGGGAAGAGAGAAAACG
TACTTGCAGAGGACATTGGGCTCCCGGACTGGTTGAAGAAAAGACTTGTGCTGGAGTTCGACACGCGCATATTGCAACCACCGAGA
GGGGACGCCTACGTGGTGCTGACGTGTAGTAAAAGGCTGCGCACGACAATAGACGCGAGTTGTCGCACCCTTCTGGAACTCGGTGT
ACCACTGACGGGTGCCGCAGTCAGCTCCTGGAGGGAAGATCCTGACCCCAAGGTGAGCCGGCGATTGGCCTACGCTGGGCGCGTTG
TAGAAGTAGGGCAGGACACGCTCACTCTGGACGACCACGGAGCTGGTCCGAGTGTTGTCTCCAGCGAAGACGTGTTCCTCGAGCCG
ACTCGAGCAAACTTCAACAAGGTGGTGGAAGTGATAACCCAGGGTAACTCCGAACGAGCCTTCAAGGCCGTACAAAAAGCAGAAGC
CGAATGGCACGGCGGGAGGCGGACAATCGAAATAGTGCATGGTGTCCTCAACCAACTCGGCAACCGGTCAATGGTTCTTGCCGATG
GCGTGCCTCTGCGGCTCGGGGGCTTGATAGACCAAGCGGTCGATAGCGACGCATTCCCCCCAGCCGAGGCGGTGTGGCGCCCTAAG
CTCTCATTCGACCCCGTGCACAGCCCCGAGACATCAAATTCCTGGAAACAGCAGTCACTGGACAGGACGGGCCCTTTCGATAGGCA
AACCTTTGAAACAAAGAGACCGCGAATCGCGGTTGTCCATCAGGCCGGAAGAAGGGAGGAAGTGGCTGCGGCGATGCGCGATTTCC
TCCACGGAAGGCCTGACATCGCCAGCGATACGGGCCTGGTTCCCCACGGTTCAGGACTCCTCGGACGCTTTAGGCTCCACGAACCC
GAAGTGAGATACTTTGAGGCCGCAGGCAGGGGGGGACCCGCTTATGCCGACGCAGCACGGAGTGCGCTCAGGGACGCGGCGTCAAG
GGACGAACCATGGGACCTCGCAATGGTGCAGGTAGAGCGGGCGTGGCAAGATCGCCCACATGCCGATAGCCCGTACTGGATGAGCA
AGGCAACGTTTCTCAAGAGGGATGTGCCGGTGCAAGCCCTTAGCACAGAAATGTTGGGTCTTGATGCATTTGGGTACGCGAACGCA
CTTGCGAACATGTCACTTGCAACGTATGCGAAACTGGGCGGTGCCCCGTGGCTTTTGTTTGCCAGGTCACCAACCGACCATGAACT
GGTGGTCGGGCTCGGAAGCCACACTGTAAAAGAGGGCCGAAGGGGTGCGGGTGAGAGGTTTGTCGGTATCGCGACCGTATTCAGCA
GCCAGGGCCATTATTTCTTGGATGCCAGGACAGCCGCGGTCCCGTTTGAAGCCTATCCTGCTGCCTTGAGCGACAGCATCGTTGAC
GCGATCAAAAGGATTGGACGAGAGGAAGCCTGGCGACCAGGCGAGGCCGTCAGGTTGGTCTTTCACGCCTTCACCCAGTTGAGCCG
AGAAACCGTTCAGGCAGTGGAGAGAGCAGTAGCAGGCATCGGGGCCACCAACGTAAGCTTCGCGTTTCTGCACGTTGTCGAAGATC
ACCCGTTTACCATGTTTGACCGAGCGTGGCCAGACGGAAAGGCGACATTCGCCCCTGAAAGAGGTCAGGCGCTTCGACTCTCCGAG
CGCGAATGGTTGTTGACACTTACCGGCAGGCGCGAAGTTAAGAGCGCCAGTCACGGGCTGCCTGGGCCGGTTCTGTTGCGACTTCA
TGACAGCAGCACCTATAGAGACATGCCCGTGCTCGTCCGACAAGCATCCGACTTCGCCTTCCACTCTTGGCGCAGTTTTGGACCCA
GCGGACTCCCCATCCCGTTGGTTTACGCGGACGAAATTGCAAAACAGCTCAGCGGCTTGGAAAGAACCCCCGGATGGGACACGGAT
GCGGCTGAGGGTGGCCGGGTTATGAGAAAGCCTTGGTTTCTGTAGTAA
124 ATGCCTAAGAAAAAGCGCAAGGTTGAGGACCCGAAAAAGAAGAGGAAGGTCGGCAGCGGGAGCATGCAGCTGAACTACTTCCCCAT
AAAGTTTGAGTTTGAAGAGTACCAGATAAAAACTGAGCCCTACAGCGAAGAACGACTTAAAGAGTTGAGGGCCAGTTACAACGCCA
CCCACTCCTTTTTTAGAAATGGAGACAATATATGCATTAGCAACAAGGAAGGCGAGGACATTAGTCTGACCGGCGAGGTGATACCG
AAAAGAATTTTCGACGACAGTCAAGTGACCGCCTCATTGATAAAGCACTTGTTTTTCAGGACGTTCAAGGAGAGGTTCCCCAACTA
TATTCCTGTGGACTTTTACCCCTTCCGCTTCTTCTCCGCCCAGGCTAAAGACGACATCATCTATAACGCCCTGCCCGGCAACCTCC
GGAAACGAATCGCTTACAAAAAGCTGATCGAGGTTCAGTTGCGGCTGACGGAAATAAACGGCATCAAGCAGTTTGGCTTCCTGATC
AACATTAAACGAAATTGGGTGTTCAACAAGTCATGCTTCGAGCTCCACTCCGAGGGCTACAACCTGATCGGGGTGGACGTGCTGTA
CGCCGAGGAACTGCCGGGGTTGACCGAGGTGCTGGCCCCAAACGAAGAGCTTTTGGGCGTAATCGCGGAAATCGTGGACGACAATG
CCAGGATAGAAACCAACGAGGGCATTAAGGAGTTCCCTCTGAACCAGTTGTTCATCAAGAAAAGCAAGTACAACATTGGCAATTAC
CTTAGCTTCGCGATCTCTCAGCAAAAGAGCGACGAAATAATGAATCTTATCGAGAGCAAACGCTCCGACATCTACAATACCAAGGG
TCTTTACGACGAGATCTTGAAAATTGCGAACCATCTTTTTTGCGAGAACAGCGCACCCATACTGTTTCATAATAAGGACGGATTCT
GCTTTACTGTCGATTCCCAGCCGCTCAGTGTGACGAACAGCATGGAATTGAAGACTCCAACATTCATATACGATCCAGCGGCCACG
AAGACGAATTCTAGCAATCCCGACTTGGGCCTGTCCAATTACGGGCCCTACGACTCCAGCATTTTTGACATAAAGATACCCAACGT
GTTGTGCATCTGCAATAGGAATAATCGAGGCAACTTTACAAAGTTTCTGTCTAACCTGAAAGACGGGATACCTCAAAGCCGCTATT
TCCAGAAAGGCCTCCAGAAGAAATACGACCTCCAGGATGTGATCCTCAATATCCGAGAAATCCAGGCCTATAGCATCGCCGACTAC
CTTAACGCCATCAGGGACTACGATGAGAACAAGCCTCATCTGGCGATCATCGAGATCCCTGCCAGCTTCAAGAGGCAGGCCGACGT
GGCGAACCCCTACTACCAAATTAAGGCCAAGTTGTTGAGCCTGGAGATTCCCGTGCAATTCGTTACCAGCGAGACCATCGGTAACC
ACAACGAGTATATCCTGAACTCTATCGCGCTGCAGATCTACGCAAAGCTCGGCGGGACCCCGTGGGTCCTGCCCTCTCAACGCAGC
GTTGACAAAGAGATAATCATCGGAATAGGCCATTCCTGGCTTAGGCGCAACCAGTACGCTGGCGCAGAACAGAATAGGGTAGTGGG
GATCACGACCTTTATGAGCTCCGATGGCCAGTACCTTCTGGGTGACAAGGTCAAAGATGTTGCCTTCGAGAACTATTTTGAGGAGC
TTCTGAAAAGCCTGAAGCAAAGCATCCAGAGGCTCAGCACAGAGCAGGGCTGGAGCGATGGCGACACCGTGAGGCTGATATTCCAC
ATATTCAAACCGATAAAGAACACTGAATTCGACGTGATCAGTCAGCTTGTCAGAGACATCACGCAGTACAAGATTAAGTTCGCATT
CGTAACCATCAGCACTGTGCACCCTTCCATGTTGTTCGACATTAATCAGTCCGGTATCGCCAAATACGGTTCCAATATCATGAAGG
GACAATACATACCAAACAGGGGCAGCAACGTTTTCCTGGACGAGAAGACATGCATCGTACAGATGTTCGGCGCGAACGAACTGAAA
ACGGCCAAGCAAGGCATGAGCAAGCCCATCCTTATAAACATTCGCACCCCCCAGGGGAACTACAATTCAAGCGACCTGAACGATCT
CCTGTTTTATGACCTGGGGTACATCACACAACAGATATTTAGCTTTACCTACCTCAGCTGGCGGTCCTTCTTGCCCGGTGAAGAGC
CGGCGACTATGAAGTACAGTAACCTCATTTCCAAACTTCTCGGGAAGATGCGGAACATCCCTAACTGGGACGCCGACAATCTTAAC
TACGGCCTGAAACGGAAAAAGTGGTTCCTGTAGTAA
125 ATGCCCAAAAAGAAGAGGAAAGTGGAGGATCCAAAGAAAAAGAGAAAGGTGGGTAGCGGAAGCATGACCGAGGCCTTCCTCACAAC
CAGGAGGGGCTTCGTGCAAAAGCTGACGCTGACCAGGTACGATTACCTGAACTGGATCATCGAGTCCGAGGCGCAGAAAGCCAAGC
TGAAGAACTGGCTTAAGAACAAGAGCGGGTTTCTGACCCACGAGATCGAGGATACCTGTTTCTTCACCTTCGAGAGGCTTCTGGAG
GAGAGTACTAAGCAGTATAGAGCCTCCGGCGAGAAAACTCTGTCTGCCCCGTTCAAGAACACGCAACTGATCTCAAATCTGATCGG
TACCATATTGAAAAAGGAGTTGAGCAAGAAATACAAGCAATTCTTTAGTCAAAACATCTTCATCGTGAGCACCATCGATCTGTATC
CATTCAATCTCTTGAAGGCGTTCGAGTTCAACATCGAAGTGTTTGACAGCGGCCACTTCCTTATCCACGTCAACCCAGTGTCTAAA
ATTGTAAGCAGCAAGGTTGTGGACAAGGAGTATCTGGACTACCTCAAGAAAAGCAACCTCAACAACAGCAAAACCACCGAGATGGA
GTTCGCGGTGATCAACCATGAAAGGAATTTCAGACTTAAATTCGACCTGCTTGACGAATGCATCTTTGAGAAGATAGAGAAGCTGC
ACAGCGAGAAGAATATGTTTACAGCCACTTTTGATTACCATTTCCTGGCCAACTTCAGCCCCGAGATCTTCGGCAAAATCGTGGAA
CATACTAGCAAGGATCTGAAGCAGGCCATCATGTTCCTGAATGACATACTGAGCAATATCAAGCTGCCGAGCTTTCTCAACCTGCA
CGAGGAACGATACTTTAAGGTCAATATCTCCGAATTGGACCGAAAGAATAATCTTCTGATTGGAAGCAGTTTCGAGGTAATAACCA
TATACTCAAAAAGCCAGACCCAGTATGGACTGAGGATTGAGTTCACTCGCGACAGCATAAGCCGGGACGAGCTTATAACAATCTTT
CTGAAAAACGAAGAGCTGATCGAGAAACTCAACGACATTAAAGTGGTCCCCGCCACCATCAACGCAAAAATCGAACAGAAGACCGG
CTGGAAAAACCCCTACATCACCAATGTTTTCATCGATAACGTGGGTGCCTTCAGCACCAGCAGCCTGCAAAGCGCCTCATACTTCC
ACGGCATCTACAAGGCCGTTAACAACTGGAATATCCTGCCCATCGTGTACGAGGACCTCGACATCAAAGTATTCGAGAACCTGATG
CTGCACGCCTTTAACAAGAACGCCACCGAATTCAAGATCCTGGAACCCATCATAATCAAGTCCACGAACGAAATCGACAAACAGGA
GGTGCAGAGGAGCATCAAAAACCAGGCCGGCAAGACCATGATCGCAGTGTTCTGCAAGTACAAGATACCCCATGACAGCTTCGCCC
CCCTCAAGGGCTTCAAGTATCAGATCTATCAAGGCGACACCACGGACAATAAGCAGAATAGGGCCAAACTGAGTAACTTCACGTGC
AAGTGCCTGGAGAAAATGGGAGGGGTGATTGCGGCAATCGCGGACACAAGCATAGCCGAGGATGGATATTTCATTGGCATCGACCT
TGGCCACACCACAAATGGCAAGGAAAAGTTCTCCAACCTCGGAGTGAGCTTGTTTGATAGCCTGGGCATCCTGTTGGGCGATTACG
TGGAGAAGGAGATTCCAAGAAGGGAAAACCTCATCGACACGAACTGCCTCAATGCTTTTAAGAAACTTGACAAAATGCTGGAAGCT
AAAAAACTGAACAAGCCCAAACACCTGATCATCCATCGGGACGGCAAACTGCACTTCAAGGATATCAACATTCTCGTAAGCTGCGT
GGAAACCGTGTGGGGTAAGATAAACGTCGATATAGTCGAGATCATTAAGAGTGGCTTCCCCGTGATGGCTATAAAGGACGAGACCA
ACAAACCAATCAATCCCATAAGCGGGACCAGCTACCAGGACGACATCCATAAGTACGCCATACTCGCCACAAACGTACAAGCCGAC
GAACAGTCAGCCGTAATAAACCCGATAATCATAAAACACAAATACGGAGAGCTGGAGTTTAGCAAAATAGTTGAACAGGTGTACTG
GTTCACGAAAGTGTATACCAATAACCTGTACAATAGTACCAGGCTCCCAGCGACTACACTCAAGGCCAACAACGTGGTTGGCACGT
CTAAGAAGCTCCACAGAAGTACATACTTGGGCTAGTAA
126 ATGCCCAAAAAGAAACGGAAGGTGGAGGACCCTAAGAAAAAACGAAAGGTCGGAAGTGGCAGCGTTCCAGTGTACCTTAATCGGTT
CCTGCTGGACCACCTCACATCACCCTTGTCCTTGCCGGCGTTTCGGGTCGAACTGGACCCTCCCCCTTCCAAAGATGAAGTGCACC
CGCTCCTGGCTCTCGTCGGTCGGGAAGCGGGAGGGCTCGTGAGGTTCCAGAACAGGCTGATCGGCTGGGAGGCTCCACGGGCCCTC
GAAGGTCAGGTTAGGCGAGGCAAGCAGTCATATAGACTGGTGCCCCTTGGCCGGCAGGCACTCAATCTTAGAAAACCCGAAGAAAG
GCAGGCGCTCGAGAATTTGTATAGGATCCGACTGGAAAACATCTTGAAAGCCCTCGCCAAACGACATAGGGCTAGAGTCGAACGCA
GGGGCAACGGCCTTTTTCTGTGGAGGCCAGAGAATCCCCGAGAGGAGAAGGAGGGGTGGCACCTTTACCGGGGAAGCCTGTACCGC
ATACATCTCTATCCTGACGGCGAAGTGATACTTGAAGTCGACGTGCAGCATCGATTTCAACCCACTCTCCATCTCGAGGAGTGGCT
GCAACGAGGCTATCCACTCCCTAGGCGCGTGACTAACGCCTACGAGGACGAGAAAGAATGGGCACTCCTGGGCATCGAAGAGGGGA
AGGATCCCCGCTCTTTTCTCTTGGATGGGGGCGAGTCATTGCTTGACTACCATCGCAAGAAGGGACGATTGGCAGAGGGGCAGGAC
CCCGGTCGAGTGGTCTGGGTTGCTAGAGGTAAAGAACGCGAGCGGATCCCACATCTGAGCGTCTTGTTGAAGCCAGTCATCACCAT
GGAGCTGCTGGCGGAAGTCGCTGAGGTCACGCAGGAGGCCTTGCCTGCGCTTCAGCTCGAACCCGAGGAACGGCTGAAGGACATTA
GGCGCTTCGCTGAACCTGTACTGCAAGCGTTCGGCAAACGCGAAACTGCAAAACCCCTTGAAGGCAGAGCCCAGCGATTGCCGCGA
CCCAGTTTGTTGGCACGGGGAAAAAAGCGAGTGGGCAAAGTAGCGGACGTACTCGAAAAGGGAGCATTGTCACCGGGCGAGACACG
GTTGGCCCTGCTCGCATGGGAGGGAGACGGGAAGGCCAAAGGCGGTCTCGCGTACTTGGAGGAGAGGCTTCAGGGCGTCGGGTCTG
CATCCGGCATCAAACTTGAACTTAAACGGCGATTTCTGCCCCGAGGCGATAACCTCGAAATGGCACAGGTGTTTGAGGAGCTCTCC
CAGGAAGGAGTAGGTGCCGGTCTGCTTCTGACTCCGCGCCTCACAGAAGGGGAAAGACGCGAACTGAAAAATACTGCGGCGAGCCA
TGGGCTCGCTCTCCAACTCCTTAACCCGTTTGACCCTGGCGACATCTACAGGGTGAATAACGCTCTGCTTGGATTTCTCGCGAAGG
CCGGGTGGCTGTTCCTGAGACTGGAGGGAACTTATCCGGCCGACCTGGTGGTGGCCTATGACGCAGGCGGGGAGAGTCTCCGATTC
GGCGGAGCCTGCTTCGCCCACCTGACTGATGGCACGCATCTGGGGTTCAGTCTGCCAGCCGCTCAGGGTGGTGAACGGATGGCCGA
GGAGGTCGCGTGGGAGTTGCTGCGACCCCTGCTGTTGAGATACCGGAAAGCGAAGGGCCAGACACCAGGGAGGATCTTTCTGCTCC
GCGACGGTAAGATTCAAAAGGAAGAGTTCCGAAAAGTGGAAGAGGAACTGAGAAAGCGCAATATTCCCTACGCGCTGTTTAGCGTC
CGGAAGACGGGGGCTCCCCGACTGTTCAGCAAAAATGGGCCGCTCGGTGACGGTCTTTTTTTGCGACTGCCAGAGGAGGAGGGCGG
GTTTCTGTTGCTTAGCGCCGAGGGTGGGAAGGGCACCCCACGGCCGGTTAAGTATGTGTTGGAGGCGGGAGAAGTGGACCTCAACC
TGGAGGAAGCTGCCAGGCAATTGTATCACCTGAGTCGCATCTACCCGGGCTCCGGTTACCGATTCCCCAGGCTGCCCGCACCGTTG
CATATGGTTGATAGGATGGTGAGGGAGGTTGCACGGCTCGGCGGCAGCCATAACTTGAGACTCAAAGAAGAACAACTGTTTTTCCT
GTAGTAA
127 ATGCCGAAGAAGAAACGAAAGGTGGAGGACCCAAAAAAGAAGCGGAAAGTGGGGAGTGGCAGCATGTTCGTGGAACTGAACGCCTT
CCCCATCGACATCCGCAATATCGGTATCGTGGAGGCCTGCGAGGTGCCGTACGACAAGGAGGTGCTTTATAGCCTGCATGATAACC
CACAAAAAGATTACCATGCTATCAGAAACGGCAACCAGATATTGATATTTTCTAATAGCAAAAACTACCCCATCCAGGGTACAATC
AAGGAGATAAATCTTGCACAGGACTACCGCATCCTGTTTTTCCTTATTAAGGAGTCCATTATCAAGATCCTGACGCAGATCAAACG
GGAGCCTTTCAAGTTCAACCCGATTGAGTTCATCTCACCAAAGGAGAACATCACCGAGAATATCCTGGGAATCAATTACCCATTTC
AAATAAACGCCAAATATTCAATCGATACCAGAATCATTCAGGGGGTGCCCTGCCTCACCATTGATTGCAGCACGAAGAAATACAAC
AAGGAATCCCTGATCTACTTCATTAACGACGGCTTCAACCTGATTAACAGGTACGTGATCTCAAAGCAAAACGAGAAGTATAAGCG
CGTAGGTAAGATACTGAGCATTGACAACAACATCGTGACTGTTCAGAGCTGCGACAAGATAAAGAAGTACTCCGCCGAGGAAATCA
CCTTGGAGGCGAACTCTAAGAACACCAAGGACTATCTGGCATACAAGTTCCCCTATAAGTTCGAGCAGATCCAAGAAAGCATTAAG
AAGGCGATCAGTACCTTCACCCAGGGGACCTCTAAGCAGATAAACATTGGCAAGATCTGGGACTTTTTCAGCCAGAAAGGCATCTT
CCTGTTCAACGGCCACCGAATTAACATAGGGCTGCCTCCCGACATCTCCCAGCAATGCAAGAACCTTGTGTACCCGCGCTTTTTCT
TTAGCAACTCCCGAGAAAACAATTCCAAAGAGAACGGCCTGAAGGATTATGGCCCTTACACCAGGAATTACTTTGACAGGAATAAC
CCCAGCATTTGCGTGATTTGCAACGCTAAGGAACAAGGCAAAGTGGAACAGTTCCTGCACAAATTTCTGAAGGGCATACCCAATAG
CCATAACTTTAAGACGGGCTTCGAGGGCAAGTTTCATATTGGCCTCTCTCAGATAGAATTTTTCACGACCAGCGACGACAGCCTGG
GCAGCTACCAGTTGGCTATCCAGAAGGCAATCCAAACGAGGACTAACCAAAACTCTAGCCAGTGGGACCTGGCCCTGGTGCAAACC
AGGCAGTCCTTCAAGAAATTGTTGGTGGAGCAGAATCCGTACTTTATTAGCAAGAAAATGTTCTTTCAGCATCAGATCCCCGTTCA
AGACTTCACCATCGAGCTGACCAATCAGAACGACAAAAACCTGGAGTATTCTCTGAATAACATGGCTCTGGCGTGCTATGCGAAGA
TGAATGGAAAGCCCTGGCTGCTTAAATCAAGCCCTACTATCAGTCATGAGCTGGTTATTGGCATCGGGAGCAGCAACATCATCATC
GAGGAGGACAGTCTGAACCAGAGGATCATGGGCATCACCACCGTGTTCAGCGGCGACGGGTCTTACATGGTCTCAAACACTAGCAA
GGCGGTGGCGCCCAATGAGTACTGTTGCGCCCTCATAGACACACTTGAGCAAACGATCAAGAAGCTGGAGAAACTTATGAACTGGC
AGAGCAATGACACCATTAGGCTCATCTTTCATGCCGCCGTGAAGACCTTCAACAAAAATGAAATCCTCGCCGTAAAGGAAGTGATC
AAAAAGTATAGTGAGTACAAGATCGAGTACGCTTTTCTCAAAATCAGCAGCGACCACGGTCTGCACCTGTTCGACCACTCAACTAA
GAATGAGAATAAGGGTAAATTGGCTCCCAAGAGGGGTAAGTATTTTGAACTGAGTAGCCATGAAATTTTGCTGTACCTCGTGGGGC
AGAAAGAGCTGAAGCAGGTGAGCGATGGCCACCCCCAGGGCGTGATCGTGTCCCTGCATAAGGACAGCAGCTTTCAGGACCTTAAG
TACCTCTCTAATCAGATTTTCAGTTTTAGCTCCCACAGTTGGAGGAGCTACTTTCCCTCTCCCCTGCCCGTGACAATTCATTATAG
CGATCTCATCGCGGAGAACCTGGGCTGGCTTAACAAGCTGAGCGGCTGGGACGATACAATCCTGCTGGGCAAACTTGGACAGACCC
AGTGGTTTCTGTAGTAA
128 ATGCCCAAGAAAAAGAGAAAGGTCGAGGACCCGAAGAAGAAGCGAAAGGTAGGAAGCGGTAGCATGAAAAGCAACTTCTTCCCCAT
CCAGTTCAACTTCGACGACTTCCATATCCAGAGGCTTCCCTACCAGAAGGAGGTGCTGGACAAGCTTCGGCAACAACACAATGCGA
CCCATAGCTTTTTCCGCAGAGACGATTTTATCTATATTAGCCCAGGGGTAGAGGCCGCAGCGAACCTGGGAGACGTAGTACGCCTC
TCTATTACCAAGCACCCCGAGGTCGTTGCTTCTCTTGTTAGGCACATATTCTTTAGGACAATCAAGGATAAGGTCCCCGGTCTGCT
GCCAAGCTTTCACCCATTCACCTTTCCCGCCAAACAGGACAAATACGATCTGGCCCTGAACATGCTCCCCGAGCGCCTGCAGAATG
TTATCACCTACAAGAGGATAACCGAGGTACAGCTTCGATTCAACGAGACCGAAGAGCAACCCCAGTTCGTCGCCGTAGTTAACCAC
AGGTACCAGTGGACTATCGACCGAACTTGCGAGCAATTGGTAAACGAGGGTCTGGACATCCTTGGCCTGGAGGTGAACTCTAGTAC
GAGCCCTGATTATTCAGACGGAGTTGTGGCACCAGAGCTGACACTGTTGGGCAGGGTGATGGCCGTGAACGGGGATCACGCCACAG
TAGGGACCAACCAGGGTCCGACAGAGTATGCCCTGTTCGAATTGACCTTGTTCAAGTCCAAGGAGAACATAGTGAACTACCTTGGA
TCTTTGGTGGGCGAGGGTAAAGCCGAACAAATAGTCAACCATATCAAACAAGATGAAAGCAGAAGGCTGCAACCGGACGTTGTGAT
GAGGGAGATCGAGGAAATGGGAGTGTGGCTGTCTAGGCTGGCCTACAGAAACTTTGACTCCTTTTGCTTCACCATCGGAACGAACA
ACGCTGTCAGCGGCCAAGCAGGTATCAGACTGGAGGAGCCAAAGCTGATATTTGACGTCTCAGGTACGAACATACACGCTACCCCC
ACAACCGGGCTCAACACCTTCGGCCCCTATAGTAGAAGCACGAGTTTCGACGTTAACTCTCCGAAGATTCTGGTTGTGTTTCACCA
GCGGAACGCAGGCCACTTCGCAGAGTTTCTCGCACAGCTGAAGGGCGGCATCGCTCAGCACGCATACTTTGCTAACGGGATGGTCA
GGAAGTATGGTCTCACGGCAATGGAGTACCGGATTGCCGAGATCACTGACTACACCGTGCCCCAATATCTTACCGCCATCAATAAG
CTGCTTAGGGCGGAGAACGGAAGCTTTGACATCGCCATCGTGGAGACCTGTGAGGATTTCCGGAGGCTGCCTCCCATGGATAATCC
GTATTTTCAGGTTAAGAGTTTGTTGTACAGCCATGGAATCAGCACCCAATTCATCAGAGCGGAAACCGCTCAGAAACCGATTTATT
CAATAGATAGCATCGCGCTCCAAATGTACGCCAAATTGGGCGGAACACCATGGACGGTGCCAATAGGGCCGAGCGTAGATCACGAA
TTGGTGATAGGCATCGGTAGCTCCATATTGCGCAGCAACCAGTATGCAGGTGCAACCCAAGCTCGAATAGTGGGGATTTCTACCTT
CTTCAGCGCCGACGGGAAGTACATAAGCAATAGAAAGACCCAGGACGTGCCTTACGATCAGTACTTCGATGAGCTCTTGCATAACC
TTAAAGTCTCCATCGACGAGATTTCCAATAACTACAGCTGGAGCTCAGGCGACCGCATCAGGATCATATTCCACATCTTCAAGCCC
ATAAAACACATCGAGGCAGACGTCGTCGCAAGCCTGATGGAACAGTACCAGGAGTTCGATATAAAGTTCGCTTTTGTGACCTTTAG
CGAGTTCCACCCGTATGTGCTGTTTAATGAAAATGAAAGGGGGGAATTTGATGCGTATAGGAAGGTTTACAAGGGCACCCATGTAC
CGTGGCGCGGTTACAATGTTCTGCTGGATCCTCGGTCATGCCTGGTCCAGATGCTGGGACCCCATGAGATGAAGACCAGCCGGCAC
GGCGCTTCTAGGCCCGTCCTTGTGAGAATCCACCGCAGTTCTACGTTTGTAGACCTCGCGTACGTCGTGCAACAGGCCTTTAAGTT
TACTAGGCTCTCATTCCGCACGTTCTACCCTGTGCATAGCCCTGTGACGCTGCTCTACAGTAATATGTTGGCCCGACAGCTCAAGG
ACCTGAGGGGCATTCCGGGTTGGAACTACGATGTAGCTAGCAGGCAGTTGAGGCACAAGAAATGGTTCCTGTAGTAA
129 ATGCCGAAGAAGAAGCGAAAGGTCGAGGATCCCAAAAAGAAACGGAAGGTTGGCTCCGGGTCTATGGGCAGGCAACTCCAACTGAA
CTTTACCCCGCTCAGGGTTAGGGGCGACGCCATCAGACTTCAGGCGCTGCCTTTCGAGGACGCTCAACAATTTAGGAATCTGCGCG
ATGAGCATCGAGCACACTACGCTGTGACGAGAAGGAGCGACCACATCGTGGCCCTCCCACTTACACTGAATGCCTCCCCAATCGGC
GAGGAGAAGATCGTGAGCGTTGTGGAGCATGCGAGTTTGATTCGGCCCCTGCTTGAACAGAGGTTGGTGACCCTTCTGTCCAGTAA
CCGGAGGCCGGTGGCCCGGTATAATCCGATCACCACCATTGGAAGAACCTTGCCAACGGGCTTCATAGAAGCCGACCGACACCTCC
ATTTGCAGTCCCGCGTGCTTATTGCTATCCGCTCCCTCAAGCTGCCGGACGCCGAGCCCTTGGGATTGCTCTGGGACATCGAAATC
CAGAAAACATGCGCGACTAGCCTTGCCGTCCTGCACGCACAAGGGGTACGGCTGGACGGTCTCACAGTGGAACGGCTTGTCCCGGT
GGAGGACGTGCGAATGTTGCCTTATAGGCGACTGGTGGGCAGAGTAGGCGCGCTGACCGATGGCCACGCCCGATTGAGCGAGCGGT
TCCAGAACGTCGAAGAATTGCTGCCCCTGGACGAGCTTTACCTGGAGGCCAGTCCGGAGAACCTGAGGCACCTTCTGCAGCATTTC
ATGCGCAACACAAGCGGGCGAGTGCAAGGGAAGATAGACGAGATCGTCTTCGAGAACTCACGGGGACGCGCTCGGATGGAGCACAT
TGCCCGGATCTCCGACTGGCTTAGAGGCCTGGGCGAGATTGAACTGCAGGAGGGTTTGTCTGTAGGCATCGGAAACCTGCTCTCTG
AAAAGGACGCCCAGAACTTTCCCAGGTTCACTGAGGGAACGACCCCAACCTACGTGTTTGACGCTGGGACGTTGAAGAGCGAGTCA
AGGGCCGCAGTGGGCCTCAGTAAATTCGGGCCCTACAGCCGGCATGTATTTACACCGACTCGACCCAACGTTTGCGTCATCTGCGA
CCGCGCAAGAAGAGGACAGTTTGAGCTGTTCCTGCGGAAATTCCGGGATGGCCTGACTGTTGATGGGAAGTCCCTGCCGTTTGGTC
GCGGGTTTCTGGGAATATATGGCCTTCAGGATATCAACCTGACCTTCGTCGAGGCGGATGCATTCACCGCGGACGCGTACCATGCT
GCCGCAAGCAAGGCAGTACGGATGGGAGCCGAGGGCGCACCGTGGCACCTGGCACTCGTGCAAACAGAACGCGACAGTCGGCAACT
GGCTCCCCCCAAGAATCCGTATTTGGTAGCGAAGGCGGCGTTTCTGTCTAATCAAATTCCTACCCAGTTTGTGGCGTTCGAGACAT
TTTCTATGGCGCCTCTGAACCTCGCGTACACACTGAGCAACCTGGCGTTGGCGGTTTATGCCAAGTTGGGCGGCATCCCATGGCTG
ATCAAGAGTGATAAAGGTATAGCCCACGAGGTCGTCATCGGGTTGGGTAGTGCCGCGATCGGGGAGTCCCGATTCAGCCGGAAGGA
GAGGATTGTCGGCATCACAAGTGTTTTTCGGGGTGACGGCGGGTACCTCTTGTCTAACCTGTCCAATGCCGTGCCCATGAGCAAGT
ACGGCGAAGCATTGACCGAATCTCTCCAGGCGACCCTGCAGAGGGTTCGCAATGAGATGAACTGGATCAGGGGGGACAGCGTTCGG
GTCATAGTTCACGCTTTCAAGCCAATGAGGAACACGGAGGTGGAGAGCGTTAAGGCTGCGCTGAAAGAATTCAGCGAGTTCGACCT
GCAATTTGCTTTCCTTCACGTTAAGCAAGACCACCCGTACCTCCTTTTTGACGACGACAGCATCGGTACAAAAGGGCGAGGCGAGA
AAACCCCCGTGCGAGGCTTGTTCGCGGAGGTCGGACACAACGAGACACTGCTGACCCTGACCGGACCACAGCAGCTGAAGAGACCC
ACCGACGGGCTGCCGAAACCGCTTCTGCTCAGCCTCCATAGGGACTCTACTTTCACAGATATAATCTACCTCACGAAGCAGGTGTA
CTGGTTTAGCAATCACTCATGGCGGTCTTTCCTGCCAGCAGCGATGCCGGTGACGATATACTACAGCGACCTGGTGGCTGGTTTGC
TCGGAAGACTGGATAGGCTGGGGTCTCGCTGGTCACCGAGTGTAATGCTGGGCAAGATCGGAACCACAAGATGGTTCCTGTAGTAA
130 ATGCCCAAAAAGAAGAGAAAGGTGGAAGATCCCAAGAAAAAGAGGAAGGTGGGTAGCGGGAGCATGAGGGAAACCAACATCTACGA
GCTCAGCGGCCTCGAAACCGTGAGTACCAGCTACAGACTTTTCGAGTTGCAGGGCGCGCCAGAGTTCTCTCCTGAGTATTATGCTG
GTGTGAGCCGCCTCGTGAGGACGCTTAGCAGGAGACACCAGGCACCCTTCACCAGTATCCAACGGGGCGAGACCATGTTGCTCGCT
GCACCCGAGGCCCTGAGCGGTGATCTCGCAGAACACCATAATCTGGCACGCTGGGTGGCGACCCTGAAGTCACTTGGAGATAGCAT
AGAGATAGACTGCAGCGTGAGCGGAGATGAGCTGGACCCCATAAGGCTGCGATTCCTGAACTTCATGATCCAATCTCCATTGTTCA
ACCACGGCGAGCTCTGGCAGCCCAGGGCCGGTGATGCCTTCTACTACCGGAAGCCTGCCGACACGTTCGACGGAATCGAACTGTTT
GAGGGTATTGCCGTGAGGGCCGTGCCCTACCCAGGAGGCGGGTTCGGCGTTATGCTCGACGCGAGGACTAAGCTGATCTCACAGCG
GGCTGTGGGCGCCTACGCGGACCCGAATTTCATAAGGAGGCTGAAAAACACTAGCTGCCTGTACCGAATGGGAGACATCTGGTACG
AGATAAAGATCAGTGGCGCGAATCAGACCGTTTCTCACCCCATCCTGTTTAAGGACAACCAGCCCGTGTCACTCAAAGCCTACCTG
CACGAACAAGCACGGCAGCCAATCCCCAAGTCTCTGATTGATCTTAAAGGTGACGGCGTGGTGTTGACCTATCGCGGCAGCGATAG
CGCCGAGGTCAAAGCGGCACCCGCGGAACTTTGTTTCCCCATAGTAGACACCCATAGCAAGAGGGGTGCCCGGCACCAGAGAAGGA
GCATCCAAGCCCCACACATCCGACGCAGCAAGGCTTACCGATTCAAGCAAAGGTTCTTGCGGGACATCAAAATAGGAAATGCCGTG
TTGAGCGTGGCCGACCAACCCGCAGCCCTCAAGACCAGGCCCATCGACTTGCCCGAGCTGCAATTCGGCTCCAATAGGATTCTGTA
CGGCACGGACAGGGGCGGAGACCGAATCGACCTTCGCCAGTATGCCAAGAATCGGCGAACGCTGCTGGAGCGCGCAGACGTGGGCT
TCTTTGAGACTTCTCCCCTGGAGCCCCAATGTTTGGTACTTCCTAAGAGCGTGATGAACGCATGGGGCAACGAGTTCGTTCGAGAC
CTGACTGCCGAAGTGAAGCGACTCCACCCCACCGGTAACTACAAGCCAACCGTAATCGCGTTTGATGATGTCAGCGCAACCGTGGA
CGCCAGGAGCCAAGCAGAAGCCATCTTCAAGCTCGCGGAAGACGGGGATCTCCCTCCAGGCGACTGCGCCATTATGATACACCGAA
CCAAAGGAAAGGCAAGAGCGCAGGAGGAGCTGCCCGCACTTCTTATAAACAAGCTGAGAAAGAGCTACGGAGTGAATGCCGCCATA
TTCCACGCGACTGTCCCCGGCAACGCCTACCGAAGGGAAAGCGCCAGCGATGGCGCTCGCTATGTGCGCAAGCGGGATGAGAAGGG
CAGGTTTAGTGGATACCTGACCGGAGCGGCGCTTAACAAGATTCTTCTGCCCAACGCCAAGTGGCCCTTCGTGCTCAAGGACGAGT
TGGTGGCAGATATAGTGGTGGGCATAGATGTGAAACATCACACCGCAGCTCTCGTTTTGATCGCCGAAGGCGGGAGGATTATCAGG
CACACTCTTCGCCTCAGCACCAAGAACGAGAAACTCCCTGCTGGTATCGTGGAAACGAAGCTGGTGGAACTGATTTCAAATGAAGC
ACCACACCTGAGCAGGCTCACCAAAACAATCGCCATCCATAGGGACGGCAGGATTTGGCCCTCCGAGCTTAAGGGATTGCGAGCAG
CCTGTAGGAAGCTTGCCGACGACGGCCACATCGATCCTGCGTTCGATCTGAACGTCTTCGAGGTGAGCAAAAGTGCCCCTGCTAGG
CTTAGGCTGTTTAGCGTCGACCGCAGTGCTGGCAGAAAGCCGAGGATTGAAAACCCGGAACTGGGGGACTGGATGATGCTGACAGA
AACCGACGGCTACGTTTGCACGACCGGTGCTCCGCTGTTGAGAGGTGGTGCGGCTAGACCCCTGCATGTAAAGCAGGTCGCAGGTG
ATATGAGCTTGCAGGACGCCCTTTCCGACGTGTTCCGACTGAGCTGTCTGACCTGGACTAGGCCCGAGTCATGTAGCAGGTTGCCT
ATCAGTTTGAAGCTCTGCGATATGCTGCTGATGGACGAGGGAACTGCCCACGACGAGGACGAAATCCTTCATGCTAACGACGACAC
CCCAGCCGTTAGCGCCTAGTAA
131 ATGCCCAAAAAGAAGAGAAAGGTAGAGGATCCCAAGAAGAAACGAAAAGTAGGCAGCGGCAGTATGGTCGCGCTGAGGCTGAACGG
CGTACCCATCTTGTGCGCCGCTGACGTAACCGTGGCCGTGGCGAAGTTGCCGTACACGAAGGAGAGCCTGGACGAGTTGAGGAAGG
AGCATGCGGGGAGGTATTTGATTAGGAGAGGCGGAGATGACGGGCAGGAAATCATGTCTGTTCCCTTGCTTGCTGATGCTCCGCAG
CTGAGCGATGCCGTTGTGGAAGTTAAGCTGTCAGAAGCCCACTGGTTGCTCGCCTCACTCGCGGTGGAGGCCCTCACCAGGTTGTT
CACAGAACTTGGTAGACCTATCCTGCGGTCCCGGCCATTGCGGCTGCTCTCCCAAAAGCCGGCCAATCTTTTTCCGGAGAACGTCG
GACTGCCAGACTGGCTGCAAAGGAGGGTTGTGCTGGATTTGGAGACTAGGAAGATCTGGCGGCAGGATGGAGACCCGACATTGGTG
CTGCTGTGCGATGTGCGGACTCAAAACTTTATCGACGTGCCAACGGATAAACTGATGGCCACCGGCGTAAGCGTTATGGGTCGCTA
CGTTAGCCGAATGGTGAGCTCTGATGATCCCCGGATCACCTCACATCTGAAGCTCGCCGGCAGGGTCATTAGCATAGAGGGCGACC
GACTGCTCCTCGCCGACTTTGGCGAGGGACCGGATAGTATAAGCATTGCTCATGCCTATCTGGAGAGACGACGGGAAAATGTCGAC
TGGTGTGTTCAACAGCTGAACCCCGCGAAAGCAGGGCAAATCCTGATGAGCGTGCAGGCCGAGGCTGCGAAATTCTTGAACGGACC
TGGCCGATTCGAGCTGATCAAGAGGACATTCGATTACCTGCGCACGCAGAGTATAGAGCTTGTGCCCGACGTGAAGCTGGAGTTGG
GGGACTTGATTGGCATGGGAGCCGCACGCTGGCCCTTCCGCCAGGAAACAATTAAGAAGCCTACCCTGGTGTTTGATCCGTCTGGT
GTCAAGACCGATACCTGGAACGAGCGAGGGCTTGACAAACACGGACCCTACGACCAGAGGACCTTCAGCCCCAAGGAAATGAGGAT
CGCCGTTATCTGCAGGGAAGCAGACGAAGGTCGGGTTGAAGGATTTCTGGCCAAGTTTCTGGACGGGATGCCACACGTTATCGTCG
GGGAGAACCGAAAACCCTATGAAAAGGGATTCATAAGGAGGTTCGCCCTGAGTGCCCCGAAGGTGCACACTTTCACCGCTAAGTCT
TCTAGTGTGCCGGACTACCTGAATGCGTGCCGAGCGGCCCTGAAGTTTGCCCACGACCAAGGCTTTGAATGGAGCTTGGCAATCGC
GCAAATCGACAAGGACTTTCGGGAACTCCTCGGTCCTGACAATCCCTACTTCGCGATCAAGGCCGCGTTTCTCAAGCAGAGGGTGC
CCATCCAGGAGTTGACGCTCGAGACAATGAGCACCCCCGACAGGCAGCTGGTGTACATTTTGAATAACATAAGCCTCGCAAGCTAC
GCCAAGATCGGCGGCATTCCGTGGCTGCTTAAGAGCGGTCCTACCGTGGGCCACGAGCTGGTCATTGGTATTGGTAGCCAGACCGT
TAGCAGTAGTCGATTGGGCGAGAAGCAACGGGTGGTGGGCATTACCACCGTATTCACCCACGATGGCAGATACCTTTTGGACGACA
GGACGCGAGCCGTGCCATACGGCGAGTACGAAGCAGCTTTGTCCGAGACGCTGACCAGGGCCATAGAGAGGGTAAGGACGGAAGAT
AACTGGAGGTCAACCGACGCGGTGCGACTTGTATTCCACGTGTTCCAGCAAATCAAAGACTACGAGGCCGACGCAGTGGGGAAACT
GGTCGAGAATCTCGGCTTCAGCGATGTCAAGTACGCCTTTGTGCATGTCGTTGACAGCCACCCCTACACCCTGTTTGACGAACACA
TGCCAGGCGTTAAGTTTGGCTACGAGATGAAGGGCGCCTACGCACCTGAGAGAGGCCTGTGCATCAGTCTTGGCAGGGACGAACGC
CTCCTCAGCTTTACCGGGTCTAGGGAGGTTAAACAAACCCATCATGGCCTCCCAAGGCCAACCCTTCTTCGACTGCATAGGAACAG
TACCTTCCGGGACATGACCTACATCGCCAGGCAGGCTTTCGACTTCGCAAACCACTCATGGAGGATGCTCACCCCAGCGCCCCTCC
CCATCACCATCCACTACGCCGAACTCATCGCCCGGTTGTTGGCTGGTCTGAAAGACACACCCGGCTGGGACGAGGACACAATGCTC
GGCCCAGTAGGTAGAACCCGATGGTTTCTGTAGTAA
132 ATGCCTAAGAAAAAACGCAAAGTAGAAGATCCTAAAAAGAAGAGAAAGGTCGGCTCCGGGAGCATGGATTACATACTTGAATTCGA
CGAGTTTATTCGAAGCATCAAGCAGAATATTGATACAAAGTATTCATTCCTGTTGGGGGCTGGCGCTTCAGTCGAATCAGGTATTC
CGTGTGCCAGCGAATGCATCTGGGAGTGGAAGAGGGATATCTTCATCAGCCAAAATCCGACCCTGGCTGAGATGCACAACAACATC
AAGAGCCAGAACATTAAGCGCAGCATCCAGAACTGGCTCGATAACCAGGGCACCTACCCAAAGGAGGGCGAGGACATCGAGTATTC
CTACTATATTGAGAAGGCTTTCCGGATTCCCGACGACCGGAGGAAGTATTTCGAACGAAACATCACCGGCAAGACTCCGTCACTGG
GCTACCATATCCTGTGTCTGCTGGCGGAACGCGAGATAATCAAGTCCGTTTGGACAACAAACTTCGACGGCTTGATCATTAAAGCC
GCCCATAAGTACCAGTTGGTGCCCATCGAGGTCACCCTCGAGAGCCAAGATAGAATCTATCGGACGGATGCCAACAAGGAGTTGCT
TTGCATAGCCTTGCATGGGGACTACAAGTACGGTCCGCTGAAGAATAGTAAAGAGGAGCTGGACAGCCAGTCTGACATCTTCGTGA
ATGCCCTTTCCTTCGAGGCGTCTAAGCGCTATTTTGTGGTGATGGGATACAGTGGGCGCGACAAAAGCCTCATGCAGGCTATTGAG
CGAAGCTTTTGCAGAAGCGGCGCTGGCCGCCTTTACTGGTGTGGATACGGCCGGAACATCGCGCCTGAGGTACGCGTGCTGATCGA
GAAGTTGAACTTGTATGGACGCGAAGCGTTCTATATTCCCACGGACGGGTTTGACAAGACGATGTTGAACATAGCCCATATGTGTT
TCGAGGATAAGGAATTGCAGGAAGAAGTGGAGAAACTCAAAGCGGATCTCGGTGCGGGGTATGAGTGTCGCACCACCACGTTCAGC
CCCTACAAGGAAGGGGTGAATAAGATCGTGGACACAAATGTTTACCCGATCAAATTCCCCGACAAGTGCTATCAGTTCGAGGTGAA
GAACAGCAGCGTAATGAACCTCTGGGATTACTGCAAGCAGCTGATAGACTATAACATTGTGGCCGTCCCCTATAACGGAATGATCT
ACGCCTGGGGAAACCGCAACAGCATCAGCAACATGTGCGGACCAAATGTGAACGGGACGATCGAACTCGTTCCTCTCACTAGGAAA
ATCTTTTTCGACAACGGCACTCTCAAGTCAATGCTCCTTAAAACTTTGCTCATCGTGATTGGAAAGCACTCCAATTGCAAGTATAA
CCGAAACAAAATCTGGCGAGAGTCCAAGAAAATCAACTACACTATTAACGGCAAAAACATTGAAGCGTACCAAGGCATTAGGTTTA
GCTTGTTCATGGACTGGAAATACAGCTACCTCACCCTGACCCCCGCTTTCTACTACAAAGACAGGAACAACGTTAGCAAGGAGGAG
AACAAAGAGTTCAGCGACCGGTTTATGGAGCAAATATGTAAGATGCAAGCCAATAAGAATTACGCCGCGTACATAAAACACTGGAT
TAACATTATCTTTCCTGATGGCAAGTCCATCATTTCCATGTACCCGTGTAACAGCGAGAGCGGATTCGAGTTCACCATTGTTAATA
AGTCACTGCTGGTCGGACTGCGGAGTAGGCAAGCACTGCATAATCCTGACGATGACATGAAGAAACGGATTTGCATCGGTGGAGCT
GAGTTGGCGGACACCGAGCTCAAGTTCTACAATCCGGCTCAGAATGCAATGCACACCGACTTCCACCCCATGAGGGGCCTTATCAA
CAATAAGCCCTACGACTTCTACATGAATAACAGGCTGTTTAAATCTAACATCTCCCTGGGCGTGATCTCTCCTGTGGGTTCAGAGA
AAAAGCTGGAGGACTTCCTGGACCGACTCAACAAAAAGCACAAAGTGAACTACAACGTCGACTATGTCATAGATTATCCTGGGTTT
CAGTCCGTCTACGGGGTTGGCCTTTCTGTCCCTCTGATCGCAGAATGGGCGTTGTTGGATGATAAAATGCTGAATAAAGCCAACCT
GTATCAGAGCTGCCTTAACTTCGGGGATCAGATCAAGAAGAAGATTGAGTACCTGAAGAGCCGCGACAGCGTGGACGTGATCATCA
TATACATTCCGAAAGAGTACGAGCTGTTCACCTTCTTCAACGACGGAAATATCCATTATGACCTGCACGACTACGTGAAAGCATTC
AGCGTGCAGAGGCACATTAGCACCCAGTTCATACGGGAGAAAACAATTGACTCTGAGCTTGACTGCCAGATCGCGTGGGCCCTCAG
CCTCGCTATCTACGTTAAAGCAGGCCGCACTCCGTGGATTCTCAGTGGCTTGAGGACTGATACCGCCTTCGCCGGCATCGGCTATA
GTGTGGACCATATAAAGACCGACAACCAGACCCTTATCGGCTGTAGCCATATTTACGGGGCAGATGGCCAAGGTCTCCGGTACAAG
CTCTCCAAGATTAAGGATGTGACCTTCGACAGCAAGAACAATCCCTACCTGTCCGAAAACGAGGCCTACCAACTCGGCCTGAATAT
CAAGGAACTTTTCTTTGATAGCTTCAAGACGTTGCCCCAACGAGTGGTCATACACAAAAGGTTTCCGTTCCAGAAGCAGGAGATCG
ATGGCCTGACTAAGTGTCTTGGGTCCGCGGGAGTGAAAGACATAGACCTCATCGAAATCACCTTGGAGGATCGATTTAGGTGCTTT
GAATACGACAGGCGACTCCAGATTGACGGCTACCCCGTGAGGAGGGGCGTGTGCTTCGCCATCAACGAGAACACCGCCTATCTGTA
CACCCACGGTATTGCACCAAGCGTCAAGAATGCCAATCTCCGCTACATACAGGGCGGTAAGAGCATCCCTGCCCCCCTGAAAATCG
TTAAGCACTACGGGAACGGCGACCTGGCCCAAATTGCGACAGAGATCTTGGGCCTGTCAAAGATGAATTGGAACAGTTTTGGTCTG
TATAGCAAGCTTCCGTGCACTATCCAATCTAGCAACGCTATCGCTCGCGTAGGGTGGCTGCTCTCCCAGTATGAGGGCGTAGTTTA
CGACTATAGGAATTTCATGTAGTAA
133 ATGCCCAAAAAGAAGAGGAAGGTAGAAGATCCAAAGAAAAAGCGGAAGGTCGGGAGCGGGTCCATCACCAGCTACCCTTACGCTAG
GAACAAGGCCGACATGATTCGCAAGGTTAATTGGAATCTGATCGTGTTCGACGAAGCCCACAGGATGAGGAATGTCTATAAGAAGT
CCAATAAGATCGCCCGAACCCTGCGCGAGGCCACTGCCGGCTATCCCAAGATCCTGCTCACTGCAACCCCCCTCCAAAACTCCCTC
ATGGAGCTCTACGGATTGATATCTTTTATTGACCCCCACATCTTCGGGGATGAGACAACTTTCCGCAGACAGTTTAGTCGCGGCAC
CAAGGAAATGAGCGAGATGGACTTTATCGACCTGAAACAACGAATTAAACCCGTGTGTCACCGCACCCTGAGGCGCCAAGTCACAG
AGTACGTTAACTACACTCAGCGCATTCCGATCACCCAGGAGTTCATGCCCACCAACGAAGAATGGGAGCTGTACGAGAAGGTCAGC
GCCTATTTGCAACGAGAACATCTCTTCGCGCTCCCCGCGTCACAACGAGCACTTATGACCTTGGTAGTGCGCAAACTGCTCGCCAG
CTCTTCATTTGCTATTAGCGATACCCTGCTGAGCCTCATCAAGAGGTTGGAACAACTGCTGGAACAGCTGGACTCCGGCAAGACGG
AGATTACCGTAGAACACAGCGATGTCTACGCGGACGTGGACGAGTTTGATGATACAGTGGAGGAGTGGGAGGAGGACGACCAGCCT
TCTTACATAGATAAACTGAGCCCAGACGAGATGAAACGGTTGATTCAGGAGGAAAAGGAAGAACTGGAGCAGTACTACAGCCTTGC
AAAAAGCATTAAAGAGAACTCAAAGGCTGAGGCCCTCCTCATAGCGCTTGAAAAAGGGTTTGAAAAGCTCAGGATGCTGGGGGCTA
ATGAGAAGGCCGTGATCTTCACAGAATCCCGACGCACACAGATGTATCTGAGAGAATTCCTGGAGAGAAACGGCTACGCCGGGAAG
ATAGTGCTGTTCAACGGTGAAAACCAAGACGAACAAGCGAAGCAGATCTATGAGCAGTGGTTGGAGAAGCACCGACACGACGACAA
GATTACGGGCTCTAAGACGGCGGACATGCGAGCCGCGCTCGTGGAGTACTTTAAGGAGCAGGCTAGTATAATGATAGCGACCGAGA
GCGCCAGCGAAGGCATCAATCTGCAATTTTGCAGCTTGGTTGTGAACTATGACTTGCCATGGAATCCGCAAAGGATAGAGCAACGG
ATCGGGAGGTGTCATCGCTATGGTCAAAAGCACGACGTGGTGGTAATAAACTTTCTCAATTGTAAAAACGAAGCGGACAAGAAAGT
AGATGAGATATTGTCCGAGAAGTTTCGGCTGTTTGAGGGCGTATTTGGCAGCAGTGATGAAGTCCTGGGGTCCCTCGAAAGCGGCG
TGGATTTCGAGAAGAGAATCCAACAAATCTACCAGACCTGCCGAACCGCGGAAGAAATTGAGCAAGCGTTCAAGAACCTGCAAGCT
GAGCTCGACGAGCAAATTCAACTGAAGATGAAGGAGACCCGAATGCATCTTTTGGAAAACTTCGATGACGAGGTGAGGGAAAAGTT
GCGAGACCATTATCACCAAACCTCCCTGCATCTGAATAGGATGGAAAGGTATTTGTGGAACCTCAGCAAGTACGAGGGGGCACGCG
AAGCCATCTTTGACGACGAGACGCTGTCCTTCGTGAAGGACTACGAGACCTATCAGATGATCAGCCAGGCGAAGAAACAAAACAGT
CCAAACGTGCATCACTTTCGATTCTCCCACCCGCTTGCGCAGAAGTGGATCGAACAGGCCAAGAGCAGGGAATTGTTGCCAAAGGA
GATAACGTTCAGGTACAGCGACTACAAGGGCAAAGTCTCCATCTTGGAAAGACTCATCGGCAAGGAGGGTTGGTTGAGTCTGGACC
TGCTTCACGTCCAGAGCCTTGAGAGCGAACAACACCTCATCTTTAGCGCCATCGACACCGAGGGCGGTCAACTGGACCAGGAGATG
TGCGAGAAAATGTTCGAGCTGCCCGCTGTGGAGGGCGAGGAAGTAGAGATATCCGACTCCATCCGAAACACATTGAGACGAATCTC
AGAGGGCCAGCAAGAGGCAATACTGAATGAGATTATGGAACGGGCGTCCGCCTACCTCGACTCAGAACTCGAGAAACTGGAAAAAT
GGTCACAGGACCTCAAGAATAAGCTGGAGAAAGACATTGATGAAATGACGGTGGAGATCGAGCATCTTAAACGGGAAGCTAAATTG
ACACGCAACCTGGCAGAAAAACTCGAAAAAAACAAACAGATCAAGGAGCTTGAGAAGAAGCGCAACGAAATGCGCCGGAATCTCTA
TGACCAACAGGACGAAATCGATGAACAAAAGGACCGCCTCTTCGAGGAGGTAGAGAAAAAACTTGAACAACGGACTGCGACGGAGC
ACCTCTTCACTATCAAATGGCGGATCGTGTAGTAA
134 ATGCCTAAGAAGAAGAGGAAGGTCGAAGATCCCAAAAAGAAACGAAAGGTTGGATCAGGGTCTCTTCACCTTAACTACCTCCCATT
GCGCTTTACCGCCGATATATTCAAGGGTGGTGCTTTGACATTTCCCGAAGGCAGCGAGAAAAACTGGACCAGCGACGATCCAATCA
GCAAGGAGCTGAGCAAGTTGCGAGAGAAACACGGAGATAGTCATGTCTTCCACCGGATGGGAAACAAAATTGCATGTATCCCCGTT
GTGGAGAACGCCATTGCTATAGGCACCGAGACGGATTTCAACATCATTAGTGACTTTCAGCTGGCTAATGCTCTTGCTCGCAGCGC
CCTCCACAGGTACTTCAAAGCTGCGGGAAGGGAGACTGTAATTGGGTTCCGACCCGTAACCCTTCTCTTGGAAAAACACAACTTGG
CCAGCAACAGGAAGGACGTGTTCGGCATTTTCCCCGAGTACACTCTGGACGTCAGGCCTCTTGCACCACATGAGGGCGACATAGCG
AGCGGAGTGCTTATCGGCTTTGGAATAAAGTATGTTTTCCTTCAGAACGTAGCCGAGCTGCAGGCACAAGGGGTGAGTGCCGCAGG
GATGTACGCCGTGAGGCTGGTAGACGAGAGCGAACATCAATTTGACCGGGCCTACCTGGGAAGGATTGATCGGTTCACAAAAGATA
ACGTGACGCTCGTTGACAGCGATTACGCGGAATATCCCGCCGACCAGTGTTACTTCGAGGGAAGCAGGACCAACATCGAAGCCGTG
GGCCGAAGTCTCCTGGGGAAAGACTATGATGCCTTCAGCTCAAGCCTTTTGCAGGAGAGCTACAAAGTGACCGGAGCCCCCAACCA
AACCCAACGACTGCACCAGTTGGGCGCGTGGCTCGAGGCCAAGAGTCCGATCCCCTGCGCCGTTGGTCTGGGAGTACGGATTGCAA
AAAAGCCGCATGAGTGCTCACGAGGCAACGACGCCGGGTACAGCCGCTTTTTCGACAGCCCCAAGTGCGTGCTGCGGCCTGGCGGC
TCTCTGACCGTGCCCTGGCCGGTCGACAAGCAGATAGATCTCAATGGCCCTTACGACGCTGAGAGCTTTCCCAACAAGAGGGTACG
AATTGCCGTCATCTGCCCTCAGGAATTCACCGGGGATGCGGAAGAGTTCCTCCGGAAGTTGAAGGAGGGCCTTCCTAACGCACCGG
ACGGCAGTCCGTTTCGCAAGGGCTTTGTTCGAAAGTACCATTTGTCTAGCTGTGACTTCACGTTCCATGAGGTTAAGCGGAGCTCA
AACAGTGACGACATCTACAAGGATGCGTCCCTTGAGGCACTGAAGCAGAAGCCAGATATGGCAATCGCCATAATCCGGTCCCAATA
TCGCGGGCTGCCCGATGCTTCTAATCCCTATTACACGACAAAAGCTAGGCTGATGGCCCAGGGCGTACCAGTTCAACTGCTGAACA
TAGAGACCATCAGGAGGAAGTCTTTGGACTACATTCTGAATAACATCGGTCTTGCGATGTATGCCAAACTTGGAGGAATCCCTTGG
ACCCTCACCCAGAATAGCGACATGGCGCACGAGATCATCGTCGGGATAGGGTCAGCCCGGCTCAATGAGAGCAGGAGGGGTGCTGG
CGAGAGGGTCATCGGGATCACGACCGTGTTCAGTGGTGACGGACAGTACCTCCTCGCCAACAACACCCAGGAAGTTCCCAGCGAAG
AGTACGTAGACGCATTGACTCAGTCTCTTAGCGAGACAGTATCAGAGCTTAGGAGCCGGTTCGGTTGGCGCCCTAAAGATCGAGTG
AGGTTCATATTCCACCAGAAGTTTAAGAAGTACAAAGACGCAGAGGCGGAGGCGGTTGATAGGTTTGCACGCTCACTGAAAGATTT
TGACGTGCAATACGCCTTCGTGCATGTGTCTGATTCTCATAACTGGATGCTGCTGGACCCAGCTAGTCGGGGGGTGAAATTCGGCG
ATACGATGAAGGGCGTCGCCGTCCCTCAGCGGGGACAATGTGTGCCCCTGGGGCCAAACGCTGCGCTGCTTACTTTGAGCGGTCCG
TTCCAGGTAAAGACCCCACTGCAAGGCTGTCCGCACCCCGTGCTGGTGTCAATTCATGAGAAGAGCACTTTTAAGTCTGTTGATTA
CATAGCCCGCCAAATCTTCAATCTCAGCTTCATCAGTTGGAGGGGCTTTAACCCTAGCACCCTCCCAGTGTCCATTTCCTACTCCG
ACATGATCGTAGACCTCTTGGGACATCTTAGACGCGTTAAGAATTGGAATCCGGAAACCCTGTCTACCGCTCTTAAGGAACGAAGG
TGGTTTCTGTAGTAA
135 ATGCCCAAGAAGAAGAGAAAAGTGGAAGATCCCAAAAAGAAGCGAAAGGTGGGTAGTGGGAGCATGAATTTCCAGCTGTGCGACCA
ACGCAAAGCCATTATCGCCGAACCAGGCCATCTGTTGGTCCTCGGTGGGCCAGGAAGCGGGAAAACTACCGTCGCCCTCTTCAAGG
CCAAGCAGAGATTTAGCACTCTGAAACCTAGCCAAGAAATCCTGTTCCTGTCATTCAGTAGAGCTGCCATCAGGCAGGTCCTGCTG
CGGTGCAAGGAGATTCTGAAGCCCGCAGAGAGACGCGCTGTCGCCGTTCAAACCTATCATAGCTTCTGCATGGACATGCTGAGGGC
GCACGGTAGACTGCTCCTGGGCCACCCCGTGCGATTCATGTATCCCGGCGACGAGAGGCTTCAAAAGGCCGCATTCGAGGGGGACT
GGGAGGCGGAAAGACAAAGGCAAGCCAAAGAGATGGGCATCTTTTGCTTCGACCTTTTCGCGCAAGGCGCAGCTGAGTTGCTCGAG
AGGTGTGCCGCACTTAGGAAGCTTATAGGGGACAGCTTCCCCATGATAATAGTGGACGAGTTCCAAGACACCGACGACAACCAATG
GCGGATCGTGGCGCAACTTGCCAAGGTAGCGGACATCTTCTGCCTTGCCGACCCCGACCAGAGGATCTTTGACTACCGAGACGACA
TCGACCCCCTTCGGATCGAGGGTTTGCGGACCACTCTTGCCCCCAGGGAGTTCGATCTTGGCGGTGAGAATCACCGCTCCCCGAAC
GCAGGGATATTGAACTTCGCCAACGCTGTGCTGCATAACCAGAGCCCCCTGCCCGATACCAGCGACATCATGCAACTGCGGTACTG
GCCTAGAGCGTTCGCGAGCACCGTGCATGCCTGCGTAGTGTTTACCTTCAGCGAACTCAGGAAACTGGGCGTGGAGAACCCCAGCG
TGGCAGTGCTGAGCCGATCCAACGGGCTTATCAGCGATGTGAGCGCCATACTGGCTGAGAAGCACGCGTACAACGGGAGGGAACTG
CCAATCGTGGAACACGACGTGGTTTGGGACGCGGAGCTGTCTGCGGCAGCAGCCGTCGTCGTTGCGTCCACCCTGGAGTGGCCAAC
AGCCGCTGCAGAGGTTGCTGTTGCCAGGACACTTGCGCTCATAGCAGCCTATTACAAGCTGAAGAACGCCGAGGAACCCACCAAGA
GCGCGGCTGAGGCTGCCCAAAAGTACGAGGCGGCTGCAAGCAAGGTGGCCAGTGAGGAGACCCCAAGGATCAAAGCCGCGAAAGAA
TTGCTGGCCGCTCACCAAAGTGGCATCCAGATGGTGGGCGACCCGGTGGCCGATTGGAAGTCTGCGAGGAGGGTATTGCAAGAGAT
AAGCGCCCTGGGTGAGTTGTACAGGGAGGTCCGGCTCGTGAGGTTGTTCCGGGCAACCGACGCCTTGGCTTCCGGCCTGAGCAATA
GGTGGTTGGCTACTGGAAGCTACGAGGGCGTGTCCGACCTGGTGAAGGGCATCCTTGAGCAGGAGAAACTGATTGCCGTGGAAAGG
GACCCAAGAGGCTGTATACTGATGAACATCCATAAAAGCAAAGGTAAGGAATTCGACGGCGTGGTACTCATTGAGGGGGCATTTAA
GTCCCATTTCTTCGATGAGCGGAAGGAAGTCAGCCCCTATGAGAGGTCCAGACGGCTCCTGAGAGTCGGTCTGACCCGCGCTAGGC
ATAGGGTGACAATCCTTAGACCTCAGGGAGCGAGGCCCCTTGTGGATCCCATCTAGTAA
136 ATGCCCAAAAAGAAACGAAAGGTAGAAGATCCCAAGAAAAAAAGGAAAGTGGGAAGCGGAAGCATGGAGAACCTGGCTCTTAGTGC
GCTGCAACTGGACTCTAAGCTCGACCGCTACATCGTGTGCAGGTACAGAATCGTGTACCAGAAGCGAGACGAGACCATTCCCGGCG
AACAGTTGGCCCGGAAGGCGGCCTACGAGATCCAGAAAGCGAATGACTTCGCCCTTTTGACCAACCTCGGCAATCAACACATCGTT
TCCCTCAAGCCCATCTCACAGAGGGGCATTGAAAGCACCCACCTTCAGGCGAATCTCATCGAAGACGGGGACCTGGAGCTCGATTG
CTCCATCGAACAACATCAGCAGGCACTCCAGCGGCTCGTGAACCAGGACATCAATAAAGCTGCGTGGAAGCTTAAGAAGAGCTCAC
AGGGCAAACTCGATTACAAAAAGGCAGCTAGCGGGAACACCGAGATCTTTGAGCCAATTCATAGCACTCGAATCAACGCCCGAGCC
ACGTATCTTGACGCTTTTTGCTCACTGCAGCTTAGCCCCGAGGTGCTTGCTAATGGAACCGTACTGATAGGGCTGCATCTCAAGCA
CAATCTGGTAGCAAAGTCTGACATCTCTTTGCAGTGGATCATTGATAAAAGGCCCGATTGGCTGCAGAGCATCAAGAAGGTGCGGC
ACAGGTACTTCGATCCCGGCAAAGCGCCCCTGGTCGCCGAATTCCTGAGGGTGGAGGACTCCCTGAATGGCAACAGCGTCTTGCCC
CACATGGGCCAGAGTCTTGTTTCATACCACCAAGCGAAGGGACTCTTGTCAGAAAGACAGCTCGCAGAGGCCACGAAGAGCGTGCT
GATAAAGGTAAAATACGGCAAAAACGAGGCGGACCACATCGCATCTCTGGTTGAACCAATGTTTGATTTCGACACGCTCAGCAAGA
TCGATAGTATCTTCCTTAACAAGTTGGCAAAGGACCTGAAGTGGAGCCTGAACGACAGGATACGCACTTCCGCGAAAATGGTGAAA
GGCTTGTATCTCCCAAACTTCAACTGCAAGCTGGAACAGGTTGACTATCAGATCCTTCACAGGCAGCGACTTAATCACCAACAGAT
GCTTCAATTCGCCAACGGGGCGAAATCTTCAAGAGAGCAGGACGTGCTGCGACATAAGGCGTTCGGCAACATGACGCGCACACAAG
TTATCCCGCTTATTGCGGGCGAGAAGAACAATACAGAACAAAATAAGCAGCTCCTGTGCAACGCATACCAAGCATTGCAACAACTG
ACCACCACGGAATTGCCTCCGTTCACCAAGTTCCCCAACCCCGTAGAGAACGCAGCCGAGCTGGACGCAAGACTGAATGAACGGTG
TCCCCCAAATGCGATACTGCTCATCGGCCTTATCGACAAAAGCGACAAAGTGGCGATCCGCGACACCGCGTTTAGCTACGGTCTTG
CAACCCAGTTCATGCGCCTGGATCACAGACCGAACGTCTACAGCCCCTCATATTTCAACAACGTGGCGGCTGGTTTGTTTTCCAAA
GGTGGCGGGCAGCTCTGCGCCATTGATGACATGCCGGGTGAAACCGACTTGTTTATCGGTCTCGACATGGGAGGGATCTCTGTAAG
GGCACCAGGCTTCGCGTTTCTGTTTCTGCGATCTGGTGCGCAGTTGGGGTGGCAACTCGCGGACAAACAACAGGGAGAAAGGATGC
AGGATGAGGCCCTGATGTCACTGTTGGACAAGTCTCTCACCACCTACCTGAGAAGCTGCTCTGGTGAGCTTCCTAAGCGCATAACC
CTCCATAGGGATGGCAAGTTCTACGAAAGCATAGAAGTGATCGAGCAGTTTGAGCAGAAGCACGGCGTGAAAGTAGATGTGCTGGA
GGTTCTGAAAAGCGGTGCTCCGGTTTTGTATAGACGAAGCCGCATGGCCGACGGAACCAAGGAGTTTAGCAACCCCAATGTGGGCG
ACGCGATCTATCTCAGTGATCATGAGATGATCCTGAGCACGTATAGCGGCGAAGAACTCGGAAAGATATGGGGTGACAAGGTCAGC
GTCAGGCCTCTTAGGCTGCGCAAGAGATACGGTGATGTGAGCCTGGAGACCCTGGCACATCAAGTGCTCGTGCTGTCTAGGATACA
CGGCGCTAGCCTGTATCGCCATCCTCGACTGCCCGTGACCACGCACCACGCCGACCGATTCGCAACACTGAGGCAGGAAACATGCA
TAGACGCCCTCTCTAAGATGGACCGGCTCTGTCCGGTCTACCTGTAGTAA
137 ATGCCCAAGAAGAAGAGAAAGGTCGAGGACCCGAAAAAGAAGCGAAAGGTAGGTAGTGGTTCCATGGTCGGCGGCTATAAAGTCAG
CAATTTGACAGTGGAAGCGTTCGAAGGTATCGGGAGTGTCAACCCGATGCTGTTTTACCAATACAAAGTCACCGGAAAGGGAAAGT
ACGATAATGTGTATAAGATTATCAAAAGCGCACGGTACAAGATGCATTCTAAGAACCGATTCAAGCCCGTGTTCATCAAGGACGAC
AAACTGTACACCCTCGAGAAGCTCCCGGATATAGAAGACCTGGATTTCGCAAACATTAACTTCGTGAAAAGCGAGGTTCTCAGCAT
AGAGGATAATATGTCAATTTATGGCGAGGTGGTGGAATACTATATCAATCTCAAGCTGAAAAAAGTGAAGGTGTTGGGAAAATACC
CCAAGTACAGGATCAATTACAGCAAAGAGATTCTCAGTAATACGCTGCTGACACGAGAGCTCAAAGACGAGTTTAAGAAATCAAAT
AAGGGTTTTAACCTGAAACGGAAGTTTAGAATTTCCCCCGTGGTGAATAAGATGGGCAAAGTGATACTCTATTTGTCCTGCAGTGC
TGATTTCAGCACCAACAAGAACATTTACGAAATGTTGAAAGAGGGCTTGGAGGTTGAGGGGCTGGCCGTTAAGAGCGAGTGGAGCA
ATATCAGTGGCAACCTGGTGATCGAGAGCGTACTGGAAACCAAGATATCCGAGCCCACTAGCCTGGGCCAATCCCTGATAGACTAC
TATAAGAATAACAACCAGGGCTATAGGGTGAAGGATTTCACCGATGAGGATCTGAATGCCAACATTGTCAACGTGAGAGGAAATAA
GAAGATCTATATGTATATTCCGCACGCGTTGAAGCCGATAATCACCCGGGAGTACCTGGCCAAGAACGATCCAGAGTTTTCTAAGG
AGATCGAGCAGCTTATCAAGATGAATATGAACTACCGATATGAAACCCTCAAGTCATTTGTGAATGACATCGGGGTCATTGAAGAG
CTGAACAACCTGAGCTTCAAAAACAAATACTACGAAGATGTGAAACTGCTGGGTTACTCCAGCGGCAAAATAGACGAACCCGTCCT
GATGGGGGCAAAAGGGATCATAAAGAACAAAATGCAGATTTTTTCCAATGGATTCTACAAACTCCCCGAAGGCAAGGTACGATTTG
GCGTTCTGTACCCAAAAGAATTTGATGGCGTGTCAAGGAAAGCTATCCGCGCCATTTATGACTTCAGTAAGGAGGGCAAATACCAC
GGCGAAAGCAACAAGTATATCGCGGAACACCTGATAAACGTGGAGTTCAATCCAAAGGAGTGCATATTTGAGGGATACGAACTGGG
CGATATCACCGAATACAAGAAGGCGGCTCTGAAACTTAATAACTACAACAATGTCGACTTCGTAATCGCAATAGTCCCGAACATGT
CCGACGAAGAGATAGAGAACAGCTACAATCCGTTCAAGAAAATATGGGCCGAACTGAATCTGCCCAGCCAGATGATTAGCGTCAAG
ACGGCCGAAATCTTTGCCAATAGCAGGGATAACACGGCGCTTTACTACCTGCATAACATCGTCCTCGGTATCCTGGGTAAGATAGG
AGGGATTCCCTGGGTGGTTAAAGACATGAAGGGCGACGTGGATTGCTTCGTTGGACTCGATGTCGGCACCAGGGAGAAGGGCATAC
ATTACCCCGCCTGCAGCGTTGTGTTTGACAAGTACGGCAAGCTTATTAACTATTACAAGCCTAACATCCCGCAGAACGGAGAGAAG
ATTAACACAGAAATACTTCAGGAAATTTTCGACAAGGTGCTCATAAGCTATGAGGAGGAGAATGGAGCCTACCCGAAGAATATCGT
GATCCACAGGGACGGCTTTAGCCGAGAGGACCTTGACTGGTATGAGAACTACTTCGGTAAGAAAAACATAAAGTTTAACATCATCG
AAGTCAAAAAGTCAACTCCGTTGAAAATCGCCAGTATAAACGAGGGAAATATCACGAATCCTGAAAAGGGTTCCTACATCCTGCGC
GGCAACAAAGCCTACATGGTGACCACAGATATTAAGGAAAACCTGGGAAGCCCAAAGCCCCTGAAGATAGAAAAGAGCTACGGCGA
CATAGACATGCTCACAGCTCTCAGCCAAATATACGCACTCACGCAAATCCATGTGGGGGCGACCAAAAGCCTGCGCCTCCCAATCA
CCACCGGCTACGCCGACAAGATTTGCAAGGCGATCGAGTTCATCCCCCAAGGGCGCGTGGACAACCGCCTTTTCTTTCTGTAGTAA
138 ATGCCAAAGAAGAAACGAAAAGTGGAAGACCCCAAAAAAAAGCGGAAGGTGGGCAGCGGCAGCATGAACAATCTGATGCTGGAGGC
GTTTAAGGGCATTGGCACCATCAAGCCCCTGGTGTTCTATAGGTACAAGCTCATCGGCAAGGGGAAGATTGAGAATACCTACAAGA
CGATCAGCAACGCCAAGAATAAGATGAGTTTCAATAACAAGTTCAAAGCGACGTTCAGTAAGGGAGAGACCATCTACACCCTTGAG
AAATTCGAGGTCATGCCCAATCTTAACGATGTGACCATTGAGTTCGACGGAGAAGAGGTTCTCCCGATAAAAGACAATAATGAAAT
TTACTCCGAAGTCGTGCAATTTTACATCAACAATAACCTTCGAAAGATCAAACTGGATAACAAATATCAGAAGTATCGAGCAACGA
ATACCAGAGAGATAACTGGCAACGTCATACTCGACAAAGACTTCAAGGAGAAGTACAAGAAGTCTAAGTCAGGGTTCCAGCTCAAG
CGCAAATTCATAATTTCCCCCAAGGTGAACGACGAGGGTAAGGTAACCCTGTTCCTTGACCTGAACAGCAGCTTCGACTATGACAA
AAACATTTACCAGATGATCAAGGCCGGGATGGACGTGGTGGGGCAGGAAGTGATTAATACGTGGAATAATAAGAAGCAGAAGGGCA
AGATTAAGAAGATTTCTGAGCTGACGATCTCAGAGCCTTGTAACTTCGGCCAGTCCCTTATCGATTACTACGTTTCCCTCAACCAA
GCTGTGAGGGTGAAGAACTTTACGGAAGAGGAAAAGAACACAAACGTTATCGTCGTCCAGGTGGGAAAGGGCGAGGTTGAGTATAT
TCCGCACGCGCTCAAACCCATCATTACTAGGGAGTACATAAAGAAATACGATGAGGCCTTCAGCAAAGAGGTAGAAAACCTGATCA
AAATCAACATGTCATACAGGTACGAAATACTGAAAAAGTTCATCGACGACATCGGCTCTATAACCGAACTGAACAACCTTAAGTTT
GAGAACACGTACATAGATAACATCGAGTCACTGGGCTACCAACAGGGAAAGCTGAACGATCCCGTGCTGATAGGCGGCAAAGGCAT
CCTGAAGGATAAGATACATGTGTTCAAATCCGGCTTTTACAAAAGCCCCATTGACGAAGTCAAGTTCGGCGTGATTTACCCGAAAG
GCCACACCAATGATAGCAAGTCCACCATCCGGGCGATTTATGATTTTTGTACCGACGGGAAATACCAAGGCAAGGACAACATCTTC
ATTAACAACAAACTGATGAATATCAAATTTAGCAACCAGGACTGCGTGTTTGAGGAGTACGAGCTCAATGACATAACGGAGTATAA
GCGAGCCGCGAATAAGTTGAAAAACAACGAGAACATCAAGTTTGTAATCGCCATCATCCCCGCGATTGATGAGAGTGATATAGAAA
ATCCCTACAACCCTTTTAAGCGGGTCTGCGCCGAGTTGAATCTGCCCAGCCAGATGGTAAGCCTGAAGACCGCGAAAAGATTCGGC
ACCAGCAAGGGTAATAACGAGTTGTATTTTCTGCATAACATTAGCCTGGGTATCTTGGGTAAGATAGGGGGGGTCCCTTGGGTCAT
TAAGGACATGCCTGGGGAAGTTGACTGCTTCGTGGGCCTGGATGTGGGCACCAAAGAGAAAGGGATCCACTACCCCGCATGCAGCG
TCCTTTTCGACAAGTACGGCAAGCTGATTAACTATTACAAGCCCACAATCCCGCAGAGCGGCGAGATCATCAAGACAGACGTGCTG
CAGGAGATCTTCGATAAAGTGCTGCTGAGCTACGAGGAGGAGAACGGGCAGTATCCTCGAAACATCGTGATTCACAGGGACGGGTT
CAGCAGGGAGGACCTGGAGTGGTATAAGAACTACTTCATCAAAAAGAATATAAACTTCACGATTGTAGAAATCAAGAAAAACTTCG
CCACCCGCGTCGCGAACAACATAAACAATGAAGTGTCCAACCCATTTAAAGGGAGCTTCATACTGCGCGAGAACGAGGCCATCGTT
GTAACCACCGACATCAAAGATAATATCGGCGCTCCGAAACCAATCAAAGTCGAGAAGACATACGGCGATATTGACATGATGACCAT
AATCAACCAGATCTACGCCCTCACGCAAATCCACGTCGGAAGCGCGAAATCTATGAGGCTGCCGATCACGACCGGCTATGCCGACA
AAATATGTAAATCCATCGAATACATCCCGAGCGGTAGGGTGGACAACCGGCTCTTCTTCCTGTAGTAA
139 ATGCCGAAAAAGAAACGGAAGGTGGAGGATCCAAAGAAAAAACGCAAAGTTGGCAGCGGCAGCATGATAGCCGTGGAAGAGTGGCA
ACCTGCGGACGGACTGACCCTTGAGCCTAATGCAAAGAGGGCTGCGAAGGCTAGAAAGAGGTGCCTGGCCCTGACAGCGGGTCCCG
GTGCCGGAAAGACAGAGATGCTCGCACAACGCGCCGACTTCTTGTTGAGGACCGGAACCTGTCGGTACCCCAAGAGGATACTGGCC
ATCTCATTCAAAGTGGATGCAAGTAGAAACCTGAAGGACAGAGTGGAGAGGAGGTGCGGCTATGATTTGGCGTCAAGGTTTGACAG
TTATACTTTCCACGCGTTCGCCAAAAGGATCATCGACCGCTTTAGGCCGGTGCTGACAGGCAAGGACGCCCTCGACGCAGGCTACA
CCATCGTGGATAAGAAGAATGGCCCCTCTAGGACCCAGATCGAGTTCGGCGACCTTGTCCCCCTTGCCATACAAATCCTGCAATCA
AGCAAAATTGCACGAAACGCGATCCGCCAAACTTACAGCGACATCTTCCTGGATGAGTTTCAGGACTGTACAAACCTGCAGTACGA
CTTGGTAAAACTTGCGTTCCAGGGTACGTCAATACGGCTGACGGCTGTTGGCGATACCAAGCAGAAGATAATGGCCTGGGCTGGAG
CCCTGGACGGCATTTTCCAGACGTTTGCCAACGATTTCAACGCCGTGTCCCTGAACATGTATAGGAATTTCAGAAGCAAGCCACAA
CTGCTCAGGGTTCAAAATGAAATTATCAGGAAGTTGGACCCCGATTCCGTGATGCCTGACGAACAACTTGACGGTGATGAAGGCGA
GGTCTATGCGTGGAGGTTCGAGGATAGCTGCAAGGAAGCCGTGTATCTTGCGGACCTTATCAATGGCTGGATCAACACCGAACAGC
TGCCCCCAGCGGAGATCGCCGTACTGGTCAGCAAACAGCTCGACCTCTATGTCGACCACTTGATGACTGAGCTCGAGGCTCGGGGA
ATCCCCTACAGGAACGAGCAGCAGCTTCAAGACATCACCATAGAGCCGGCAGCTAGACTCATTGTGGACTACTTGAGTTGCCTCTA
CGGCAAGAGAGAGCCGAAAGCATGGATCCGGCTCATGAACCAGCTGATCCCATTCGCGGACGAGGAGATCCAATCTAGTGCTCGAA
AGGACCTCGACCAGTTGATAAAGAAGCAGAGAAAAAGGGTGAGCGACGCGAAGCACACCGATTCACCTTTCAGCGATTGGGCACAA
CTCGCAATTGAATTCCTGAAGTACATAGGCAGTAAGATGCTGGTGGCACTGAGTCCAGATTACGAGACGCGCGAGAGGCTGAATGA
CGTGATCAGGGAAACTTTCGCGAGGATCAAGGAACTGTTGAAGAGCGAGCCCGACCTGCCCAAGGCGCTGGGCCGGTTTGCCGATG
ACCAGGCGGTGCGAATACTGACCATCCACAAGAGCAAGGGCCTGGAATTCGACAGTGTGATCATCATGGCCGTCGAGAACGAGATA
TTCTTCGGGAACCAGGACGAGAATAGGTGCGCTTTCTTCGTAGGTGTGAGCCGAGCAAAAAGGAGGTTGATACTTACCCACGCCGA
CCAGAGGGAAAGGCCAGCGTCTGCCAAGCGATGGAATGTTAGTAGAACCGCTCAGACTGAGTACATTAGTTACGTCACCCCTTTCG
TGAGGCCACAGTAGTAA
140 ATGCCGAAGAAAAAACGGAAGGTGGAGGACCCCAAAAAGAAACGCAAAGTGGGTAGCGGCTCAATGCTCGACTTTAGCCTTACCCA
GAAAGGTTGGGTGCTGCCCATCGTACTGAACGCCTTTCCGCTCAAGGTACCGGACATGGAGCTCAAATTCGTGCAGATCCCCTACG
ACAAGACGACCCTGGACTCACTGAGGTCAAGCCACAAGATGACCCACGTCTTCAGGAGGCAAGGCGACAGTATCCAGATCTTTTCT
AGCGACGGCACCTTTCCAAAGAGCGGCACCCCCCAGACCCTCCAACTGAAGGATAATCTGGGAATCTTTTTCTCTCTTGTAAAGGA
CGGCCTCCTCAAGCACTTCGCCGGTTTGGGCCGAACCCCGTGCGGATTCAACCCCATTGAGGTCGTGTCAGCTCAGGCCAAAGACA
ATCTTCTGGCTAGCATCCTCGGAGAAGCCTACCCGCTGAAAATTTGCGCCAAGTACTCCATCGACACCAGGACAGTGCAAGGTCAA
CCGTGTCTCATCATCGACTGCAGCACTAGGAGAGTGGTTAAAGAGAACTGCCTCTTCTTCCTTAAGACCGGCTTTAACGTGATTGG
CCGCTATGTAGTGACCGAGCAGGACGACGGGTTTCGGAAGCTGCTGGGTTTTGTGGAAAACTGCCACGAAGGCAGGACACTGAGCG
TTATAAGGCCAGATGGCCAAGCCGTGCATGCCGAGGCCAAGGACGTGTATCTCGAGGCATCTAGGGCCAACTTCGACGACTACATC
CTTTATACGCACGGAACTAAAAAGGATAGCATCGTGGAGCGAATCAGACAAAGCGTGAGTATCTTCAACGGCGGTAAGAACAAGAA
AGATAGAATCGACGCGCTCAAAAAGTACATCCAGGCCACCAATATAAGCCTTTTGGATGGGACCAGGATCGAAATCGAGGAGCCCA
GCGACATTCAGAAGGACTGCGCCCAGATGCAGAAGCCCGTGTTTGTGTTCAATGACAATGGCGAGGCCGACTGGACCGAGAAGGGG
CTGACTCAGAACGGCCCCTACACCAAGCGCACCTTCGACCGAAACGACCCCAGCATCTGCGTGATCTGCGCACAACACGACAGGGG
GCGAGTGGAGCAGTTCGTTAGGAAACTGCTGAAAGGCATGGCTAACAGCAAATACTTCAGAAACGGCCTTGAGGGCAAGTTCGCGC
TGGGAACGTCCCGGGTAGAGGTGTTTGAGACCAGCACAAATAGCGTGGACGCCTATAAGAGCGCGATCGAAGCCGCCATCCGCAAG
AAGGCCGATGACGGCGGCAGGTGGGACCTGGCATTGGTTCAAGTTAGGCAGAGCTTCAAGCAGCTGAAGGTGACTGACAACCCCTA
CTACTTGGGAAAAAGCCTGTTCTACATGCACCAGGTGCCAGTGCAGGATTTCACTATCGAGCTCCTGAGCCAGTCCGACTATTCAC
TGGGCTACAGCCTTAACAACATGAGCCTCGCTTGCTACGCCAAAATGGGAGGAGTGCCCTGGCTGCTCAAGTCCTCTCCCACCCTT
AGCCACGAGCTGGTGATCGGCATCGGCAGCGCCAACATTGTCCAGGAGAGGGGGGCACACAACCAGAGGATCATGGGGATAACCAC
CGTATTTAGTGGCGATGGCAGCTACATCGTCAGCAGCACGTCCAAAGCTGTGGTTCCCGAAGCATACTGCGAGGCGCTGACTAGCG
TGCTGGGCGAGAATATCGAAAAAATCCAAAGGAGAATGAATTGGCAAAAGGGTGACTCAATCCGACTGATCTTCCACGCCCAAGTG
AAGAAGTTCAACAAGGAGGAGATTCAGGCAGTGCGAGCCGTGATAGACAAGTATAGGGACTACCAGATCGAGTACGCTTTTGTGAA
AATCAGCGAGAACCACGGCCTGCACATGTTTGACAGCTCAACCGCCACCATGCCCAAGGGCAGGTTGGCCACACACAGGGGTAAGA
CCTTTAAGCTGTCCAAAAACGAGATGTTGGTCTACCTGATCGGACAGAGGGAGCTGAGACAGGAAACCGACGGCCACCCCAGGGGT
GTCATCGTGAACGTACACAAGGACAGCACTTTCAAAGATATCAAGTACCTGAGCGCCCAACTGTACTCTTTTGCGAGTCATTCTTG
GAGGTCATACTTCCCCAACCCTATGCCCGTGACCATCACCTACAGCGACCTTATCGCCCACAACCTCGGCTGGCTGAACCAGCTGC
CCGGGTGGTCTGACAGCGTAATGATAGGTAAAATCGGTCATAGCCAGTGGTTTCTGTAGTAA
141 ATGCCTAAGAAAAAGAGGAAAGTTGAGGATCCAAAAAAGAAACGAAAGGTAGGCAGCGGCAGCGTAAAGCTTAATCACTTCCCCCT
GAATCCCGCTCTTGCAGTGTTCAAGACTACCTACAGGCACAGAAACCCCAGGGGCTTCCTGGGATTCGTTAGGTCACAAGGGTTGA
CCGCGGAGAGAGTTGGCGAGGAAGTGTGTGTCTATCACGGTCTTCCCCACCCGGCTTTTAGAGGAGCCACCGCCCAAGGACACACC
AGACTGGCGCCTGGTGACACCGATTACGACAGGGGCGTACTTAGTCTGATCGGAGCCGCCCTGCTGAAAGCGGGTTACGTGCTTAC
TGAGCGCGAAAGGGCCGCAGTGCACCCCACGCAGCAGAGAGTGCCCCTGCACACCCCTAGGAAACTCCCTGCCGAAATTGCGGTGA
ATGCCCATCTTCGATGGGAATGGGAACTGGAACGGCACAGCGGGAAGTCTTGGCTTGTGCTTAGGCCCGGACGCATGTTTTTGAGT
GCGCTGAGCTGGCACGATTTGGACCTGAGGGCATGGGCACAGGAGTTGCCCCAGAGCGTACAGCAACTGCACGCGCTGTGTCTTCG
CTCCGGACGACGAGAACGACTGAGGCGCATGGGTAACACGTGGGCGTTCCAACGAGAGGATAGGGAGCAAGAGGGCAGGTGGCACC
TGAGCTTTAGCACTAAGGCGCTTTCCGACCTGAACCTGTCCGGCGATGCTCACCATGCTGCTAGCCTGAGCATGCCCGATGTGCAG
AGGCTCGTAAATCTGCCGGGTCTGTGGCAGCCCTTTGTGACAAGCCTTGAAGTCCTTGAGGTGCCTGGTAAGGTGATCGAGGGCAA
AAGGCTGAGGTTCGGACGAGGAACAGGGCGCGACGTCACGGATGTACACAAAAGGGGCATCCTTCACCCTCCGCCGCAGCCAGTGC
GCCTTGCGGTCGTGCCCCCCATTCAGGCGGACGAAGAGGCGGATGAGCAGTTGAGACGCGAGCTCCTTGCCCACCTCCTGCCACGG
GAAAAGGTGTTGGCCCACCCCGAGGCTTCCCAGGGCCTCAAGAAGCACTTGAATCGAAGGGAAACCGACGACACCTTCTACACCCT
GTGGAGCGCTGGAGACTACTGCAAACTGGGGCTGGAACCCTTTGATCTGGTGCGCGACCTCCATAGGTACGACCCCGGCACGGGTC
GCCTGCTGGCTCCAGAGAAGTTGCATGGAGCAGCAGCCGCCGCGAGAGAGGCTGGCAGGCAATTGATTGGCCTCGTGATCCTGCCC
GACACCATAGGGCGAGATGAGAGGGACGCACTGTCCGACGAACTGGCCAAGCTGGGTGTGAAGAAACTTCAGCACATCCGCAGGGA
CATGCTGAACCGGCCCAGGACGCAGTATATGGCCTGGGTGAACGTGGCCGTGAAGCTCGCCCAGAGGGCCGGAGCAGTCAGCTGGG
ACCTGGAAAAGTTGCCTGGAGTGTGCGAACAGACCTTCTTCGTTGGCGTGGATCTGGGCCATGACCATCGGGAGAAGCAAAGCGTC
CCGGCCTTCAGCCTGCACGAGTTCCGAGGCAGGCCGGTCGACTGCCTCACCCTTCCAAGGCGAGCCGGAAATGAAAGGTTGAGCCT
GGCGGAGCTGAATCAAGGCCTGAGGAAGCTGCTTAAGGGTAAGAGGCCAGCCCAAGTGATAGTGCATAGGGACGGCAAGTACCTGG
AGGGGGAGGTTGATGACTTCATAATCGCTTTGAACGACCTCGGCGTGCCGCGCGTCAGTCTTCTCGCCGTCAAAAAGTCCAACCTC
TCCATGGTTGCCGGCGCTAAGGAGGGAGCGTTTTTGCCACTGGACGAGCGGCGGTGTCTGCTGGTTACCAATACCCAAGCCGCGGT
AGCTAGGCCGACAGAGCTGGAGGTGATGCACTCAGATCATCTGACTTTCGCCGAGCTGACCGAGCAAGTGTTCTGGCTGACCCGAG
TATTCATGAACAACGCACAGCATGCGGGTAGCGACCCTGCTACCGTAGAGTGGGCGAACGGGATCGCTAGGACCGGAAAGAGAATT
GCCCTGTCTGGGTGGTCCGCCTAGTAA
142 ATGCCCAAGAAAAAGCGAAAAGTAGAGGATCCAAAGAAGAAACGGAAGGTCGGCAGCGGAAGTGTGAACCATTACTATTTTTCCGA
ATGCAAGGCGGACGAGAAAGCCAGCGACATAGCCATCCACCTTTACACCGTGCCCCTGTCCAACCCCCATGAGAAATACAGCTATG
CGCACAGCATCGCCTATGAATTGAGAAAACTCAACTCATACATAACCGTGGCCGCGCACGGTCAGTACATCGCGTCTTTCGAGGAG
ATATGCCACTGGGGCGACCACAGGTACATACAGCACGAACATAGACCAATCCAGTGCAGCCTCCCGATGGAGAGGACCATACTGGA
AAGACTCCTCAAGAAAGAGCTCGAGAATAGGTGCAAAAGCAGCTATAAGATGGACAACGACCTTTTCCGGTTGGCTAACGAGCAAA
GCATGCACGTGGGCGAGATCAGCATACACCCAGCGATCTACATCTCATTCAGCGTGGAGGAAAATGGTGACATATTTGTTGGCTTC
GACTACCAGCACCGGTTCGAGTACCGCAAAACACTCCAAGACGTCATCAACAACGATCCCTCCCTGCTTAAGGAAGGCATGGAAGT
GGTGGACCCCTTCAATAGAAGGGCCTACTATTACACTTTTGTGGGCATGGCCGATTATACCGCCGGACAGAAAAGCCCCTTCCTGC
AGCAGTCTGTGATCGACTATTATCTCGAAAAGAATGAGCTGTGGAAGCTCAAGGGTGTGCACGAAAAAACCCCCGTGGTGCACGTC
AAGAGCCGAGACGGTCACTTGCTCCCGTATCTGCCGCACCTGCTCAAATTGACATGTTCATACGAACAGCTCTTGCCCAGCATGAC
CAAGGAAGTCAATCGCCTGATTAAGCTGAGCCCCAACGAGAAGATGAGTAAGTTGTATACGGAGATGTTTCGATTGCTCCGGCAGC
AACAGGTGCTGACCTTCAAGAAGGAAAACGTGCGAGCCGTCAACCTCGGCTACGATGTGAATGAACTTGACAGCCCGATCATGGAG
TTCGGACAAGGCTACAAGACAAACGAGATCTATCGAGGCCTGAAGCAGAGCGGAGTATACGAGCCCAGCTCAGTGGCCGTGAGCTT
TTTTGTTGACCCCGAGCTTAACTACGACCCCCAGAAGCGGAAAGAAGTAGGTTGCTTCGTCAAAAAACTGGAGAGCATGAGCGAGG
CCCTGGGAGTAAAACTGAACATAAGCGACCAGCCCCGACAACTTTATGGCCAGCTCCCCAAGGACTTTTTCAAGCAGGACAACCTC
TCATATCATTTGAAATCTATCACCGACCAGTTCAGGGGAACGGTGGTGGTTGTTATCGGCACTGAAGAGAACATCGACCGGGCATA
CGTTACAATCAAAAAGGAATTCGGCGGCAAGGAGGATCTGATGACCCAGTTTGTCGGCTTCACCTCCTCCCTCGTCACGGAGAACA
ACATTTTTCACTACTACAACATCCTGCTCGGCATCTATGCGAAAGCTGGTGTTCAGCCCTGGATACTCGCCAGCCCAATGCACTCA
GACTGTTTCATTGGACTCGACGTAAGCCACGAGCACGGTAAGCACGCATCAGGGATAATACAAGTGATTGGACGGGACGGCAAGAT
TATCAAACAAAAGAGCGTTGCGACAGCAGAGGCCGGAGAGACTATTGCCAATAGCACGATGGAAGAAATCGTCAACGAAAGCATTT
ATTCCTACGAGCAGATCTACGGGGCCAAACCGCGCCACATAACATTCCATAGAGACGGGATCTGTCGCGAGGACCTCGATTTTCTG
CAAGCGTATTTGCGGAGTTTCCAAATCCCATTCGACTTCGTAGAAATCATAAAGAAGCCGCGACGCAGAATGGCGATATACTCTAA
TAAGAAGTGGGTCACGAAACAGGGAATATACTACAGTAAGGGCAACACCGCTTATCTGTGTGCCACGGACCCCAGAGAATCCGTGG
GTATGGCGCAACTTGTCAAGATCGTACAGAAGACTAACGGATTGAGCGTTCACGAGATAGTGAGCGACGTGTATAAGCTGTCCTTC
ATGCACATACACAGTATGCTCAAGACCAGGTTGCCTATCACGATACACTATAGCGACCTCAGCTCAACGTTCCACAACCGGGGCTT
GATCCATCCCCGGTCCCAACATGAGAGAGCACTCCCGTTCGTGTAGTAA
143 ATGCCTAAGAAAAAGCGGAAAGTTGAAGACCCCAAAAAGAAACGAAAAGTCGGAAGCGGCTCACTGGGGCTGAATAATGAGTCCAA
AGAGTTCTTTAAGGGCATTAGCCGCATTTGGAGAAATTACAAGGACTACACCTACCTTGACGGGATTAAGCTGAGCCAGGCGCAGA
TCGATATCATCGAGAAGGAGGAAGACCAATTGCTTATAGAGGGCTACGCCGGCACCGGTAAGTCCCTGACCCTTATATACAAGTTC
ATTAACGTGCTGGTTCGGGAAGATGGGAAGAGGGTGCTGTATGTGACTTTTAACGATACGCTGATCGAGGATACGAAAAAACGCCT
TAGTTATTGCAACGAGTACAACGAGAATAAAGAGAGGCACCACGTAGAGATTTGCACATTCCATGAGATCGCCAGTAATATCCTGA
AAAAAAAGAAGATCATAGACAGGGGTATTGAGAAACTGACGGCTAAAAAGATAGAAGATTACAAAGGTGCCGCTCTCCGCAGAATT
GCGGGAATCCTGGCTAGGTACATCGAGGGGGGAAAGTATTATAGCGAGTTGCCTAAAGAGGAACGCCTCTACAAGACACATGACGA
GAACTTTATCAGGGAGGAGGTGGCCTGGATCAAGGCCATGGGCTTTATAGAAAAGGAGAAGTATTTCGAGAAAGATCGCATTGGGA
GGTCCAAGAGTATCAGGCTGACGCGCTCACAACGCAAAACTATATTCAAGATATTTGAAAAGTACTGCGAAGAGCAAGAAAACAAA
TTCTTCAAAAGCCTCGACTTGGAGGATTACGCCCTGAAGCTCATCCAGAACATAGATAATTTCGATGACCTTAAGTTCGACTACAT
TTTTGTGGACGAGGTACAGGATCTCGATCCCATGCAAATTAAGGCGCTGTGTCTGCTGACCAATACGAGCATCGTGCTGTCAGGCG
ACGCGAATCAGCGGATTTACAAGAAATCTCCCGTGAAGTACGAGGAGCTCGGCCTCAGAATCAAAGAGAAGGGGAAACGGAAAATT
CTGAACAAGAACTATCGGTCCACGGGTGAGATTGTCAAGCTCGCGAACTCAATCAAGTTCTTCGACGAGTCCATCAATAAGTATAA
TGAAAAGCAGTTCGTAAAATCCGGTGATCGCCCGATCATCCGGAAGGTGAACGACAAAAAGGGTGCGGTGAAGTTCCTGATCGGCG
AGATCAAAAAAATCCACGAAGAGGACCCCTACAAAACAATCGCCATCATCCACCGAGAGAAAAACGAGCTTATCGGCTTCCAAAAG
TCCGAGTTCCGAAAGTACCTGGAAGGCCAGCTGTACATGGAAAAATTCAGTGACATCAAGTCCTTTGAGTCAAAGTTTGATTTGAG
GGAAAAGAACCAGGTGTTCTACACCAACGGCTACGATGTAAAGGGGCTGGAATTTGATGTGGTGTTCATCATAAACTTCAACACGG
CCAACTACCCACTGAGTAAAGAGCTGAAGAAAATCAAGGACGAAAACGACGGCAAGGAAATGACGCTCATTAAAGACGATGTGCTC
GAGTTTATCAATCGCGAGAAGAGGCTGCTGTACGTAGCTATGACCAGGGCCAAAGAAAAGCTGTATCTCGTGGCCGACTGCAAAAA
CAGCAACATCAGCAGCTTCATCTACGACTTTAACACCAAGTACTATGAGGCACAAAATTTCAAGAAGAAAGAGATAGAGGAGAACT
ACAACCGGTACAAGATTAACATGGAGCGCGAATACGGCATCATCATTGAGGACGACGACTCCAACAACGTTAAGAACAATGACACG
AAACAAGAGAACAAGTTTAATACCGAATCTAAGGAAAAGGGCAAAGATGACATCGACAAGATAAAGGTGTTTTTCATCAACAAGGG
AATCGAGGTGGTGGACAACCGAGATAAGAGCGGGTGCTTGTGGATCGTCGCCGGGAAGGAAGCGATCCCTCTTATGAAGAAGTTCG
GTGTCCTGGGCTATAACTTCATATTCATCGCAAACGGCGGTCGGGCATCTAAGAACCGGCCAGCCTGGTACCTCAAGAATAGCTAG
TAA
144 ATGCCAAAAAAGAAGAGAAAGGTAGAGGATCCCAAGAAGAAACGCAAGGTGGGGTCCGGCAGTATGGACCGCGAGATCATTGAAAA
CTTCAACCCCAGCGACCCCAGGACCGAGGGCGAGAAGTATCTGATGGATAACTTTTCAACCTCCCCCAGGTTTAATGGCTGGACAA
TATTTGAGCAGCCCCACATCAACTCAATGAAGCCCGACTTCATCTTGCTGCACCCCCACAAGGGCATCATAATCATAGAAGTGAAG
GACTGGAACCTCAGCAGCGAGACATATGAGAACGGCGGTTACATCTGGGGGGAAAACGGCGAGAGGATTAAGAAAAACCCCATCAA
TCAAGTAGAAAACTACAAAAACTCTATACTCAAGATGGAACTTACAAACAGCATCGAATTTAGTGAAGTGTTCGGCGACAAATACT
TCGCGTGCATAGAAACGGTGGTATACTTTCACAAAGCCAACAAAATTCAAGCCGAGAACTTCTGCAGGAGGAACAATAACTACACC
AAGATCTGGACCAAGGACGAGTTCGACTACATATGCAATATCAATAACAAACTGAAGGGCAGTTGTCACACCTATGCCCTGAGCTA
CGAAAAAAGCACCCTTGAAGACAACAGAGGTATGCTGAGTAAACTGGTGGAGGAGCTCAAGTGCAATCTCCAGTACAGTGACTACA
ACTATGAACGACGCCAACCGATTAAGTTGACCTATGAGCAAGAGAAGTTGGCGAGGCTGCAAAAGAATTCAATCAGGAGGTGGAGC
GGCGTGGCAGGCGCTGGCAAGTCCCTGAGTCTGGCGCAAAAAGCCGTGAACGCCCTGAAGGAGGACCATAGCGTTCTGATCCTGAC
CTACAACATAACCCTGAGGCACTACCTGCGCGATCTGTGCTCTCAACAGTTCGGACCCGGCTCCTACAAAGGCGAGCGCAAGAAGC
TGAGGAGCGACCTGACCATCTGTCACTTTCATGACTTTTTGAGAATCATCATGGCCGAGTACGAGATCGAGGTCGAACATGACGAA
GACGACAACTTCACCCAGCACTGGATAAACAAGATCGACAGTTGCATAAAGGTGAACGGCATCAAGAGCCACCTCAAGTACGACTA
TATCCTGATCGACGAGGGCCAAGACTTTGAAGGCGAATGGATTAGGTTCCTGAAGCAGTTCTTCACCGAGGTGGGTGAGATCTTTA
TCGTGTACGACAAGGCCCAGGATCTCTACGAGCATGGCGTGTGGATCGAAGACAGCAACCAAATCAAAAACATCGGCTTTAAGGGC
AAGCCCGGGAACCTGAAAATCAGTATGAGGATGCCTGAGAAGATGGTGTACCTGGTGCAGGACATCAGAAATGAGTTCAAGATAGA
TGAGGAGGAGATCACCCCAAACGTGAACAGCCAGCAGAGCTTCATCGAGATAACCAAGTGGATTAACTGTATGCCCCTGACGCTCA
CTGAAAAGCTCGACCAGATTGAAATACAGGTGGACTTTCTGCGCCGAAACAACAACAGCCTGGAGGATATCACGATCATTACGACC
AACGAGGAGACCGGAGTGGAGATAGTGAATAGGTTCAAAAGCAGGGGTATCAAGACCAGCCACGTCTACGATATGGAGAAGCGGGG
GAACCAGGCCAGGCGAAGGATGGAAAAATGGAAATTCCAGGGCGGCACCGGCAGACTGAAGATTTGTAGCTATCACAGCTATAAGG
GCTGGGAGACTCCGAACATCATCCTTGTGCTGGACGAGCCGAGCACAAAGTATGAAGACGGCATAATTAGTAAGGGGGAGTATAAC
GAGAAGAACATTTTCGACGCTATCTTCATTAGCATGTCCAGGGTGAAAAGGAAAGCCCAAACCGGTGAGTTTAGCTTTACGTGCCT
GAATTATCTTAGCGAATACAATAAGATTGAGGGCCTCTTCCACTAGTAA
145 ATGCCCAAGAAAAAGAGGAAGGTTGAGGACCCCAAAAAGAAGCGCAAAGTAGGTAGCGGCTCCATGCTGACCAATAATCAGATTGT
GCTGGAGCAGGAACTTCTGGGAAGCATATTCAAAAACAATAACCTGATGCTGAAAGCCCGAGAGAAGATAAAACCGGAGATGTTCC
TGTATAGCAAACACATGAACATTTACCTGGGCATCCTCGACATGGTGGCCAACAAGCTGGAGGTGGACCTGATCACCTTTCTCGAG
CACCATAAGAAAAGGGTGGGGGATATGGATGGCGTAACTTACGTGACCGAGATCTACACCTGCAGCGCGTCCGACATTGGCTTCAA
TACAAAACTTGACATGCTGGTGAACAACTACAAACGGCATCTGTATGTGGAGATGAAGGACAAAATCAACAGTGATATGAGTCTTG
AGGAGATCGAGAGCGAGGTTGAAGGGGTGAAGGTAAAGGTGCACAAATGCAACATCAAGAAAGAACTGGATATAGACAAGCAATAT
GACGATTACATCAACTGGCTTTACGACGAAAACAGAGACAAGGGGATGAAAAGCGGCCTGACCTATCTGGACAAGTATCTCGGCAA
CTTCCAGAAGGGCAGGCTCGTCACCGTGTTCGCCAGGAGCGGCGTCGGCAAGACCACGTTCAGCTTGCAGCTGGCCGCCAATATGG
CTCTGAAGGGCCACAAGATATTCTACGGGAGCGCAGAGATGACCCGCAACCAGGTCTTTAACAGGATCGTGGCCTCAGGTTTGAGC
CTTAGCGCGAAGGCGATTGATGAGGACACCATCCTGAAGGAGGACAAGGAGAGCATCGCCAAGTTTATGACCAAGGTTATCAACAA
CAAGTTCTACGTGTCAACCGAGACCGACTTCGAAAAGTTCATCGACGAGATAAAGGTTTATAAGCTGCAGAACAGTCTGGACGTGG
TGTTCGTGGACTACATTAACAAGTACATCGACTTCACCGACAGGGACATGTTGACCAACAAACTGGGGAAGATCAGCGGCATGCTC
AAGAGCCTGGCCATGGAAGAGGATATCTGCGTGGTGCTGATGGCCCAGGCCAATAGAGTGATTGACAAGAAGGTGGGTGACAATGC
CGTCGAAAAAATCGACAGCAGCGACATCCAGGACAGCGCCAGAATCGAGCAAGACAGCGACCAAGTGATCGGCCTGTACCGGAACG
TGAAGCTCGATGATAAAATGTATAGGGAGAACCTGTTCAATCAGGGCAAGCTCAAGTATAATTCCAAGAACGCCGACGACAATCCG
GAATGCATGAACGCTGTGATCATTAAGAACAGGCATGGCGACCGAGGCACGTGTGCACTGAGGTGGCACGGCAGGTACAGCAGGGT
CAGCGACTTCTAGTAA
146 ATGCCCAAGAAAAAGCGGAAAGTCGAGGATCCAAAGAAGAAGCGCAAGGTGGGTTCCGGGAGCAAAGGGCGGCACCAGGCGAAACA
CTACGCGGACGGCCTGGAAAAAATGCACGGGCAAAGGCCTGTGATTTTCTACACCAACGGCCACGATATATGGATATGGGATGACC
ATCCGGCTCAGCACTACCCGCCCAGACGGTTGTACGGATTCTACGCGAAGTCCAGCCTGCAGTATTTGATAAGGCAGCGCAGTGAA
CGCAAGGCGCTGAATACGGTGAGCTCTAAAACCGATATACTCGGAGAAAGACTCTACCAGCACGAGGCACTGAAGCGGATCTGCGA
ACGCTTCGAGACCAAGCAGAGGAAGGCACTCGCAGTCCAAGCGACCGGCACGGGGAAAACCCGCTTGTCCATCGCACTTACTGACT
CTTGCATGAAGGCCGGGTGGGTGAAAAGGGTGCTTTTCCTGTGCGACCGAAGGGAACTTAGAAAACAAGCTAAGAACGCCTTTAGC
GAATTCCTCAGCGCGCCTATTAGCGTACTGACAACGAAAAGTGCGCAGGATACCCACAATAGAATCTTCGTGGCAACCTACCCCGC
GATGATGAAGGTGTACGAGCAACTGGATACGGGATTCTTCGACCTGATCATAGCCGACGAGAGTCACCGAAGTATTTACAACATCT
ACGGCGACCTCTTTCGCTATTTTGACGCCCTTCAAGTGGGCCTGACCGCAACCCCCGTGGAGATGGTATCTCGGAGCACCTGCCAG
CTCTTCGGGTGTGACTTTAAGCAACCAACTTCTAATTACACACTCGAAACGGCTGTGGAGGAGGGTTATTTGGTGCCCTACCAAGT
CGTGAAACATACCACAAAGTTTCTGCGCGATGGGATCAAGGGCCACGCGCTTAGCGCGGAGGAACTGGCGGAGCTGGAGGACAAGG
GCATCGATCCTAACACTCTTGATTTCGACGCCGAGCAGATCGACCGAGCGATCTACAATAAAGACACCAATCGGAAAATCCTGCAG
AACCTCATGGAGAACGGTATCCGGCAGGCCGATGGCCAGACCCTCGGTAAGACGCTGGTATTTGCTAGGAACCACAAGCACGCCAA
ACTCCTCGAACAGTTGTTCGACGAGCTGTACCCCCAGTACGGCGGTAAGTTCTGTCAGGTTATAGACAACTACGACCCCAGGGCGG
AAGAGTTGATAGACGATTTTAAGGGCGAGGGCAGCAACGAACAGCTCACTATAGCAATCTCAGTCGACATGCTCGACACCGGGATT
GACGTCCCGGAGATCGTAAACCTCGTATTCGCACGGCCGGTTAAAAGCCCCGTGAAATTTTGGCAAATGGTTGGTCGGGGAACGCG
ACTCTGTAAGAATTTGTTTGGACCCGGCAAGCACAAGACGCACTTCCTTATTTTCGACCACTGGGGAGTCGTGGAGTATCACGGCA
TGAAACAACGCGAGGTAACTGTGTCCCAGAGCAAGTCCCTGATGCAGCAATTGTTTGAAAATAGATTGGAGCTCGCCAAGACCGCG
TTGCACCACGCCGAAGCCGACTTTTTTGAGACGATGGCGGGGTGGCTGCACAAAACGATAAATAGCCTGGACGATCGAACGATTGC
CGTTTGTGATAAGTGGAAAACTAAGCAGCAAATGTCCGACCTGGAGACGCTTAGACAGTTCGGTGCAAACACCGTCACGCTGCTTG
AGTCAGAAATCGCCCCGTTGATGCAATGGCTGGATGTCAGAGGGCATAGTGACGCATATCAGTGGGACCTCCTGGTCTCACAGATC
CAACAACAAAAATTGAAGCAGGCGGCAGCCTTCGATGATCTCGCTGGGAGGGCAATCAATCAACTGTGGCAGTTGCAGATGAATTT
GAATCAAGTTAAGGCAAAGTCCGAGTGGATTAAGCAGTGCCGAGAGACGGAGTGGTGGCAGAAGGCGTCCCTGGATGAACTGGAAC
AAATGCGACAAGAACTGCGGGGCATTATGCAGTACAGGAACAAGGGTGACATTCCGAAGACAGAGGCGCCCATCATAGACATAACG
GACTCAGAGGAGGTGCGCGAGAAACAATCCTCCTACCTGAACTCAGTTGACATGGTCGCGTATCGGGTCAAGGTTGAACAGGCGCT
CCAGGAGCTCTTTGAGAGAAACCCCATCCTTCAGAAGATCCGGAACGGGGAGGCCGTGTCTGAGCGCGAGCTTGAGAACTTGAACG
CTCTCGTGCATACACAACACCCGGATATCGATCTCAACACACTTAAAAAGTTCTATGGGACCGCGGCTCCGATGGATCAAATCCTT
CGGACAATAGTAGGCATGGACGGGAACACGGTTAATCAGCGCTTTGCGGCGTTCATACAACAGTACCCCTCACTGAGTGCGCGCCA
AGTTCAATTCCTGTCCCTGCTGAAACGACAAATTGCTCAGAGTGGGGCCATAGAGATTGACAACTTGTACGAAATGCCATTCGCAG
CTATCGGCGAACCCGACAGCGTATTTAGTAACGCGGAACAGATTGATGACCTTCTGGCGATTGTGGAGAGCTTCGGGAAGCAGCCC
CAGCAGCAGTCTACGAGACAGGCCAATGAGACATAGTAA
147 ATGCCGAAAAAGAAACGGAAGGTAGAGGACCCCAAGAAAAAGCGGAAAGTTGGGAGTGGAAGCATGCCGTTCAATAGCAACCTGAT
CTTCGTGAAGCTCGACGACCTCAAGAGAGCCTTTCTCGAGGGCGTCCACAGTGGTCACGCCGTGGTGTATGAGGTGAGCGAGGGAC
TGAGCACCGAGGATCTGAAGAAAAGGCTTATCAAGGCCAGCGTGATGTACCACTATAGGTATGGAAGGAACGTGTTTGTCTTCGGC
GTCAAGGAGGGCACTAAGGTTGACGATCTTGTACCAGGCCGACGACTCGGCGAGCACGAGGTGAAGGAGGTTCTCAAGGGCATCCC
GTCTAACAACCTGGTGTCCATGATGAGCGCCATGCTCAATTACCAGCTCTCTGTGCTTCTCACCAGCAAGGGCTTCCAGTATAGCT
ACGAAGAGATGCGGAGGGGCAAGTATCTGTGTGTCAGCAACTATTACGGCAAGCTGATACGGAACCCCGTGAAGGTTTGCCTCAAG
GTAAATGTCATAAGGAGCCTCATTGACGAGCAGGATCAGTACCTGCCCATCGCGCTTAACTACAGGGTGAAGAAGAGCAGGCGGCT
TAGCCCCGAAGTAATGAATGAGATCCACGCGGAGTTCATGGAGGCCTTCCCCAGCTACCTCAACGACCTGAAAATCATAACTCGCG
TCTTGAACGACGATATGGTGAGGAACAGGGAACTGAAATTCCTGGAGATCGAGTACAAACCCCCTGCTATCATTACGTTCCGGTTT
CGAGGCAACAGCACCGGCGAAAACGTGACCGACATTCTGAAGCTGGGCCCCTACTTCCTGCCTGGGGAGGAGGAGAAGATCGATGT
GGTCTTTGTGTACGAAAATGCTCTCGCTAGCCAGGCGAAGAAACTCACCAAGGTTTTGGAGGATACCATCAAGGACGGGCTGGGCA
TAAAGCTGAACATAGACGACGAACATAAGTTCAGCCACGACAAGCCGCTGGGCGACGTTATTAAGCTGGTGCGCGACCGATTCATC
AACAGCGGGAGTTGTCTGCTGGTCCTTAGCAAGGAGAACCGCCTCGGTCCTATCTTCATGAGCATTAAACCGCTCACGCTCAAGAA
GAACTTCTACTTCAAGTCTCAATTTATCACCAACGAAACGATTAGCAAACTGGACTCTTATGCGGTCAAAGCCAATATCGTGAATA
GCATCCTGTTCAGGGTTGAAGGTACCCCGTACATGCCCGTTCTGCGGGGCAATATAGACGTACTGGCAAACAATTTGTTCGTGGGC
ATCGCCCTGAGTAAGCCTCTGAGGAAGGGCTACACCAAAGGAGGCATAGCCCTCATAGACCCCTACAGCGCCCGAATTATCACAAG
GGCCATCGTGTTGAAGCGCAAGATGAGGAGCGGCAAATTCGAAGCCTCAGACATGCACGAGATCGTGTCCAACATCAAAGGCGTGC
TGAAGGACTACAAGGAGCTGTACAACGTCAACGAACTTGTTATACATATCTCCAAGTTTCTGAGCGATGACGAATACGGCCTTTTT
TACGAGTACTTGCAGGACCTTAATGTCAACGTGCGACTCCTGAGCATCAGGAAGAGGGACGACATTACACTGGTTAGGGACGGGAG
GATGGACAGCCTGACCATGATCAAGCGCGGCAAGAGTCATGTCGAGGTCATGTATTGGCCTCACGAAAGGGCCTACCACCCCCTTA
CTATCAGGATCTACGGCGACAATGTGGACAGGGACGTGATGATGCGACACCTGAGGTTTATCGAGCTGCTCCGGCACATGTACTAC
CCGGCCAGCAGCCGCTTCATAGTTGAGCCCGCGACCATTAGCTACAGCAGGAGGGTCGCCAGATTTGCCCCCTGGCTTTCAGACAA
TACCTAGTAA
148 ATGCCCAAGAAAAAACGCAAGGTGGAGGACCCAAAGAAGAAGAGGAAGGTCGGAAGCGGCAGCATGGAGAAACAGACCTTCTACCA
GGGCAACATGTACAGGCTGAAGGATGAATTGATACAAGATATCCTCTCTGACATTATCGTGGCGAGAGTAACTAACATGCCAAGCA
ATCCCGAAGAAGCCTACAGTGAAATACAGAAGATTGGCGGCATTATACTCAATTACGATGAGATGACCAACAGCGCCTGGGTGGTG
GGCAAGGAGTCTCTGCTGCAAAATCACTATCCCGACGACATGAAGGAGGTGCGAGCCTTCTCCTTTTCTGAGCTGTCCAAGGAAAA
CAAGACGAAACTGGTCCTTAATATCCTTAACGCCGAGGGCTACCTGCGCGACATTAGGGGGCACCGAGAAGTGGTGAAGTCAATCA
ACTCAGAGCGATCAATCATTAGAAAATTCTTGGTGACGGTCGAGTACGATGGTCAACACTTCTATCTCGTAACCCTCCCAAAGTAT
AAGATCATAGAGAATCACACAATAATGGAACTCCTCATTGAGGGCAAGATCACCGTCAAAGAGCTCGTCCACAACCTCCTCAAGGA
CCCTAAGTGGAAAATCCAGACCAGTCGCAAAGATGTGCCCCTGCCTCCTGGGCACAGGGTCGTGGAGATCATTCTGAAGACTAAAG
ATCCCGATCGATACCAGCAGGAACTCGAACGCATCAACGAGTATTTTACTAAGAAGACGGAACTGGGGCCCATTGACGATAGCAAG
TATCCAGATGATTATAACATCATTTTCAGAAGCCAGACGCGAGGCAAATACTTGAGCTATCACAGTGCGCGGACCAAGCTCATCAG
ACCGATTAACAAAGAAATCCTCCGAGAAATCTACAGGAGTAACGAATTTATCAAAGCACTGAACATCGCCAAAAAGCTGGTGGCCG
ACATCATATACGACAGCACCAAATACCCGGGCAGGGCCATATTCCCCGCCTTTAAGATAGACGAACGGACGATCTCATACAAGGCC
GTGTTCCTGAAGAATAAGACGATAACTGAGAAAACCATCCAACCCTACTACAATATCAAGGGTACCTTTAATTGGCTTTTCACCAA
CACGCCGTTCGACGATATTAGCGAGCTGATAATACCAATCCAGTCCCCCGAGTTCTTGAGGGATAAGACCATTGGAGTGTACATCC
TGTACCCTGCGAAGTACAGAGAGAACTCCGAAAGCCTGAAAGTGATCCAGAATCTTATCAAGAGCGTAGATAGCACGATCAAACGG
CTGAGCGAGTACTTTACATTCCTTCGAAAAGTCAACGAAGGCCTGTCTCTCCCCTCTGCTATAGATATCATCTCTCGGATCCCGGT
TAACTATGAAAACTTGATAGAGAGTGCGTTTACCCGGATCCACAGCAAGAAGGGCGTTGAATATGACTACCACCTCGCGATAACAC
TGATACCTGACATGCGGCAGGAGCAGTTCGATAAAATCAAAGGGTTCTTTTTCAATAACGGGATTCTGCACAAGGCAATAAACATC
AATAATCTGAGGGACCCCAGCAAAGACCAAAAGAAGCTGATTGAGAGCATGATCCTCCAGGCACTGTACGCCTTTGGCATCTACTT
CTACAGCCTTGACAACCTGAACTACGACTTTATCATAGGTCTCGACGTGACCAGGGAAATGGACAAGTCTGGTAGGTACTACGGTA
TATCCGGAGCCGCGGTGGTCCAAAATAAGAACGGCCAGGTATTGAAGATTATACCGATCACCAGCCCCCAGAGCAGCAGCGAAACC
GCAAACATTAACTACCTCATCGGCAATATCCAACAGGAAGCCGCTGCAATCCTGAATCGGAAGGGATACGCGGACATATTGTTCCT
CAGGGACGGCAAAGTGCCCGGTGGCGAACTGGAACAGTTTAAAGAGATCAGCCGCAAGTACAACTACAGGTTTACTATAATAGAGA
TCCTCAAACGACCCCTTGTCCGCTTTTTCTGGGAGAATTACAAGGAGCACACCGTGAAGAGCCCTAGGCATAACTACTACTTCAAG
ATAGGCGACACGTATTACTTGACCGCGCATTACTTCACGAATTACCTGAAGGTCCCACTCAAATTGGGTAATACCTATTTCGTGGC
CCGAGGAAAGATAAGTAAAAACGTGATTAGCCGCGAGGACATAATGACAATCACAAAGCTCACTAAGCTCAACTATAGCCAGCCCG
AGAACCCGGACAAAATGAAGCTGCCTGCCCCCGTGCACCTGAGCCACCGACTGATCAATTATGAGAGGAGAGAGCTTAAGTTCAAC
AGGTATGAGTTTCTTAAGGAAGGAGCGCTTTATTTCCTGTAGTAA
149 ATGCCTAAGAAGAAACGGAAGGTGGAAGATCCAAAAAAGAAGCGAAAGGTTGGTAGCGGCTCAATGGCCTATAGCCTTAACGCTTT
CGAACTGGAAATTCCCGACATTGACGCCGACCTCTACAAAGTTGACCCTCAACCCTCTGATGACCCATATCGAATCCTGGGGGGTT
TGGAACGGTCCTTCGAGCAACAACTGGACGGCAAGGCCCAGAAATGGAAACAGGCGGAGGACGGAGATTGGTATATCGCCGTGATA
GGCGCGTCAGAAAGGAAAACTATCGAGTCCCCCTCCAGCGGTACGAGGGCAGGCTACACCACCACGCATACGCTGGATCCGAGTAG
CTTTTGGGACAGGATGGTGTTGCAAAGGGCAATTAGCGACTCTGTACGATGGTACATGACCAACTATCAGGACTTTTGGTATCATG
AGGATGCGGATGCACTCTTTTATCCTTCTCCTAGAGGCAAAGTGGACGAGTACGACGTCTACACCGGATTTAGTCATAGGGTCGAG
TTTTATGACAGCCCACAACTTGTCGTGCGCAGCGTCACTAAGTTCATCTCCAGTGAAAGCCTGGCGGACCGGATCAACCATCAGGG
CACAGAAGAAGCAACGGAAAAATACGGTGGTGAG+ACTTTAGGCTGGACAGGCCGGAACCAACCAAATGTACTTTGCACGGCATCT
CAACCGAGCGAACGGTAAGTGACAAGACGATAGATTTTGGTGACGAGATGCTGTCCGTGTTGGAGTTTGCACAAAGAAAATATGGC
AGCGAGTGGGCGGACAAAATCGATCCCGACGAACCATTGGTGCAGATACGCTTCGGGAACAGCGACCCCTACGACACCGCTCCGAG
CCTGCTGAATGCGAGCCCTGAGGAGCTGAATCGCAGGCTGACCAGCGAGGCAGCCCTCAGCGCACAAGAAAGGCAGAAGGCCATAC
AGAACTTCATCGGCAGGATACACTACATCCAGGTTGAAGACGAGAAGGTGAGCGTCAGCGATGACGGCGTACGGCCCACCGAGCAG
GGCGACTTCGACTACCCCGATCTTGCGTTTGGCAATGACGAGGTGCTCAGCACCGGCGTCCCGAACGCGGTAGATCCTAGCCAGGA
GGTGCACCCGGGCAACTGGCGATGGATAATCAGGGACTACCTGGAGGAATACGGCTTCTGGGAGTCACAACGAAAGCTGTCTGAGA
TCGTGCTGGTGTACCCGAGAGGCGAAGAAAGACGGGCAGAGAACCTGTACCAGGACGTTAGGGAGAAGCTTTCAGAGATAGGAGGC
GTTCAGATCAGGAGCGATCCACATCGCGTGTGTTACACCGATCAGGTGGAGTTCGACGAATGGGTGGCTGAATTCGGTGACTCAAT
CGACGGTGTTCTTGGATTGATTGAGGGAGATGGAGACGAATACTACGAAATCATAGATGCATTTGGCGGAGCACCGACCCAGTACG
TCAACACTAGCACCTACTCAGAGCACAGAGGGGCGAGCGACGACGTGATCTTTAACACTGCTTGCGGACTGGCCGTGAAGTTGGGC
GCATATCCTTTTGGCCTGGCCAACGACCTGAACAGTGACGTGTACCTCGGCCTTAGCGTGGCAGGGGATAGAAGCACAACGGCCAC
CGCCGTTGCCATAGACGGAAGAGATGGGAGGATTCTCTATCAAACAGAGGAACCCCTGGGCCAGGGTAGCAGCACAGTAAGCGAGG
GCTATCCCGCTAAGCGAATCATCCAGAGGAGCCTGAAGACCGCCTCAAGCGCCTTTGATCGACCAATCGAGAGCTTCGACATTCAC
AGGAACGGAGACTTTGGCGACGCTGAGCTGGAAACCCTTAGCAGTGAATTGCCTGCACTCCAGGACCAGGAATATGTGCATACCGA
TGTTTCATGGAGCGCCGTCGAGGTAATTGAAAACCACCCTTACAGGCTCTTTAGTGAACGGGGCAGCAGAGCTCCCGATACCGGAG
CCTATGCTAAGCTGGACGACGAGCATGTACTGGTTACTACCTTTGGAGAGCCCCAGATCCACCAAGGTACGCCAAAACCGGTCCTG
TGCAAGAGGAGAGCAACGAGCCAAGATCAAGACATCACCGCCATCGGAGAGGACGTGTTCAAACTCAGCTTCCTTAACTGGGGTAG
CCCAATGATGAAGATGAAGCCACCTGTTACCACTAAGATTCCGAAGGAACTCAACGAGATTTTCGAGAAGTGCTCTAGGGTGAGAT
ACCCCCCCTTCTAGTAA
150 ATGCCTAAGAAAAAAAGAAAGGTAGAGGACCCGAAGAAGAAGCGCAAGGTCGGCTCCGGAAGCATGAGTCAAGACTCTAGGAGCAC
CGAGGTGGAGAGGCAGGCCGAAATACAACCTGGTACCTACCTGTTGAACGGCCGGGGGGAAATTCAGTTGGATGAGGTTGACGCAT
TCCAGTACGACCTCAAGGTGAGTGGAGGCGTGGAGCAGTATTGGGATCGGGAACAATTCACCAGCTCTGCAGCCTACTACCTGGAC
CAGGAACACGGGAGCCCTGTCGCTGAGATAGGCAAAATGAACGTGCTCAGCAAGACGGATTTGTCTAGATCAGTTAGAGTGTGGCA
GAGAAACGTGACTCCCATCAATAGGCAGAGCGTTACACTGACCGCAGCCCAACCCGAGGACCGAGAAAAGATCAAATCATTCGTGC
AAAGCTGCTTCAAGAGGGCAGTGCCGACCGAAAAATACAGCTTTCGCTTTCTCAACAAGATTGTCAGGGATGAGCCCGAGTTCACC
ACCGGCAGCGAAGGCTTTTCTGCACATCCGAAGCACGACGTTAAGATACAGGTCACCGCTGATGGCAATGTGCTTGTGCACGTGGA
TAGCGGGTTCAGCATCAGGAGCAACAGCACCCTGGACGAAATCTACTCTGAACAGGATAACCCTTACGGTAAGCGCGTTGCCCACG
ACCCCGAGAGGTATGGTACCCAGGGCCAAGGCACCCTTCGCGGTTGGAGCGACTATCGGTACACAGACCATATTAGCGATGCGGGT
AGCTCTGTGAACGAAATGCACAAAGGGGTGGCGGACGAAGAATGGCGGCAACGACTCGCAGAGGAGAATCCCCGACTTCTGAAAGT
GGAGTATGGCAACAAAACTAGGAGGCAAGCCCCCCATTTCCTGAGGCTCTCACCGCGGATCGAGCAGGTGCAGGATCAGGATCGCG
AGTTCTATAGCAGGTTTAACAGCCGGAGCGCGATGATGCCCGACGAAAGATTTGAACTGTCTAAAGAGTTCCTGCAGAACGTGAGC
CGCTTGCCGGTATTGGACATGGAACTCGAGCCGGGTCCGGTGAACAGCAGTTACGAGTTGCTGGAAATGCGAGAGGAAAACAGGCT
GGTTTTTGGAGGGAAGCAGAGGGCTAGAGACCCGGGCAGCGGGCTTAGAGAGAATGGGGTGTATCAAAGTCCCAGTCAGTACCGGC
TGGGGGTGTTGACCCCCGAACGATGGGGAGAGAAGGCGAGCGAGCTGATCCCCCTGATTGTGTCCGGCCTGAACGATCTGAGCGCA
TCAGCAGGAGTTCGAGCATATGGATACGAATTGGGGGACGTCAGCAATTACACACCCGTGGTTCAGGACCTCCACGAGGAGACGGA
CGCTGTGCTCGCCGTGGTCCCCAATAAGGGTGTGGCCGAGGATTTTGGGATAGACGATCCATACAAGGAGCTGAAAAGAACCCTCC
TGCGGAAAGGGATACCCACCCAAATGATGCAAAAGTCCACGGTCGATGAAATCGTGGGTCAAAAGGCGGGAATCGGCAATGACAAG
TTTCTGAACGCACTTAGTGCAGTCGTGGCCAAAGTGGGCGGTACCCCATGGCAGATCGATAGCCTCCCCGGGAAAACCGACGCCTT
CATGGGCTTGGACGTAACTTACGACGAGAGTAGCGAGCAGCACGCAGGCGCCAGTGCAAGCGTAGTACTCGCGGATGGGACGACTT
TCGCAGCCGAGAGCACCACCCAGCAAGGTGGCGAGAAGTTCAGTGCACGGCATGTAGAACAGTTCGTGAGGGACCTCGTCTTCGAC
TTTGCGGGGGAACAGGGCCGAGACATCGACAGACTGTGCATAATGAGAGATGGGAAGATCAGCGAGGATATTGACGCCGTAAGAGA
GGGACTCAGTGGTATTGAGGCGGAGATCGACATAGTTGGCATACGAAAATCCGGGCAACCTCGCATAGCTGAGTTTGACGGTACTC
GGTTTCGGATCGCCGAAAAGGGCGTGGGCTTTGTGGACGCCGACAGAAGCCAGTCTATCATCCATGCATTCGGCAAACCCGAAATC
CACGACGACAATCCTGTGGGCACCCCACGAACCTTTCGACTGACCAAGGACTCTGGTCCCACAGATGTGGAGACCCTGACCCGACA
GGCATACTGGTTGTCCGAGATCCATTTTGGAAGCCCCGTTAGGTCCCCTAGGCTCCCCGTGCCAATAGAGTACGCAGACATGGCTG
CTGAGTATGTTCGGGAGGAGTACGTCTCACCAGGGACTGTAATAGAAGGGCCAGCATACATCTAGTAA
151 ATGCCTAAGAAAAAAAGGAAGGTTGAAGACCCGAAGAAGAAACGCAAGGTCGGCAGCGGAAGTATGAAGACGCAGGATGATATCGC
GCACAAGCAACCCATTACCATCGAGGTCCAGATCCTGAAGGAGCTCGACAAGCCAAGCCCAAAAATGGCCACCCGGTTCCTCGTGG
CCGATAGGGACGGCAACAGGTTTAGCCTGGCTATCTGGAAGAACAACGCACTCAGCGACTATGACTGGACGATTGGCCAGTGGTAC
AGGCTGGAAAACGCCAGAGGAAATGTCTTTAACGGCAAACAGTCCCTCAACGGTAGCAGCAAAATGCGCGCCACTCCACTTGAGGC
CAGCGAGGAGGACGAAACCAGCACGGATGATGTGGGACGGGTCGACACAATCCTGGGTAATATGAGCCCGGACCAGGCTTACCTGA
GCCTGTTTCCCATCAGTAGGTCTTTTGATACCCTGTCTGTGTACGAGTACAGCATTGAGGCAGCCGAGGCATTCGAGGATGCGCCG
GACACCGTGACCTACAGGTGCGCTGGCAGGCTTCGGAGAATCACGGGTGCGGGGGTCGCTTATGCTGGCTCAATGAGGATCGTGTC
AACCCGCAAACTCCCGGACAAGCTCGCGGACCCCTTTAGCTTGAGTGAACCCACGGAGAGGGAACTGAACGCTACGGACGCCAGGG
ACAGGCATAGGATAGAGCGGCTTCTGAAGAGCCTCGTGAAGGCCGCCATCGACGATAGCACCTACGACCCATACCAGATCAACCGA
ATCAGGGCCAGGACCCCGAGCATTACCGCTGGCGACGGGCTGTTCGAGGCGTGCTATGAATTTGCAGCAAGGGTCGATGTGATGCC
CTCCGGCGACGCCTTCGTGGGAATTGAGGTAAGGTACCACACGCGGAGCCAGGTCACTGCAGACGTTTACGAAGACAAAACCGCGG
AACTGGTGGGCACCATCGTGGAGCATGACCCAGAGAGGTACAACATTAGCGGTACGGGCCGAGTAGTGGGTTTCACTGACCACCAC
TTCACCGACGCCCTCGACGAATTGGGCGGTCTTAGTTTGGCGGACTGGTACGCGCAGAAGGATCGCGTCCCAGAGGGGGTATTGGA
GGCGCTGCGAGAGAAAAATCCTAGGTTGGTTGATATTCAGTACCAGGAAGACGAACCAGCCAGAATCCACGTCCCGGATTTGCTCA
GGGTAGCACCCCGCAAGGAAGTTGTCAAGGAGTTGGATCCCGCCTTCCACAGAAGGTGGGATCGAGAGGCCAAGATGTTGCCCGAC
AAAAGGTTCAGGCACGCCATAGAGTTTGTGGATCATCTCGGGTCCCTGCCGGATATAGACGCCACGGTGGCACCCGAGCCTTTGGG
GCCGTCACTGTCTTACATGAGCACAGCAGTCGACAGGGAGAAGAACCTGCGCTTCAAAGATGGAAGGACCGCCACCACCCCGTCAA
GCGGCATCCGGAGCGGCGTATACCAACAACCGACGAGCTTCGACATCGCCTATGTGTACCCCACCGAGTCTGAACAGGAGAGCAAG
CAATTCATTTCTAACTTCGAGAACAAACTGTCCCAGTGCCAGTGCGAACCAACTGCCGCTAGGCACGTTCCTTATGAACTCGGCGG
CGAGCTGAGTTACTTGGCTGTCATCAATGAACTTGAGAGCGTGGATGCGGTGCTCGCTGTGGTGCCTCCCCGAGACGATGACCGGA
TAACGGCCGGAGACATAACTGACCCCTATCCCGAATTCAAGAAGGGCCTCGGGAAGCAGAAAATACCCAGTCAAATGATCGTGACC
GAGAACTTGGGCACAAGATGGGTGATGAACAATACAGCCATGGGCCTGATCGCAGGGGCAGGAGGCGTTCCGTGGAGGGTGGATGA
GATGCCGGGTGAGGCCGATTGCTTCATAGGACTGGATGTGACTCGCGACCCGGAAACCGGCCAACACCTTGGCGCTAGTGCCAATG
TCGTTTATGCCGACGGAACCGTTTTCGCCTCTAAAACGCAGACCCTGCAGAGTGGGGAAACGTTCGATGAGCAGAGCATAATCGAC
GTGATCAAGGATGTATTCCAGGAGTTCGTTAGGCGCGAGGGGCGATCCCCTGAACACATTGTTATCCATAGGGATGGCCGGCTGTT
TGAGGACGCCGACGAAATCCAGGCCCCGTTCGCGGATAGCGGAGTGAGCATAGACATTCTGGACATCAGGAAATCTGGCGCTCCGA
GGATTGCCCAATACGAGGACAACAGCTTCAAGATTGACGAGAAAGGCCGACTTTTCATCAGTCAAGATGACACGCATGGATTCATC
GCCACAACGGGAAAGCCGGAATTTGATGATAGCGACAACCTGGGCACTCCCAAGACTTTGAGGGTAGTGAGGCGGGCTGGTGACAC
ACCGATGCTGACTCTGCTGAAGCAGGTGTACTGGCTTAGCGAGGCACATGTTGGCAGTGTGAGCCGAAGCGTTCGCCTGCCTATCA
CAACTTACTATGCAGATCGCTGCGCCGAACATGCGCGGGAGGGGTACCTGCTCCATGGCGAGTTGATCGAGGGTGTGCCATATCTG
TAGTAA
152 ATGCCCAAAAAGAAGCGCAAGGTAGAAGACCCAAAGAAGAAACGGAAAGTGGGAAGCGGCTCAATGGAAGTGTCCCCCTTCTTCAA
CGAACTGTTCAAGTACTACATATTTCTGTTTTTTGGTTTCAAGGTGAACATCGTGAAATCACATTACCAGAGCATTAAGAAGCACA
AGATAATATTCTATTCCGGTGGGATCATGGACGAGTATTACACTAACGCCTTCCCCATCAACAAATACTTTATCAACCGCATCATC
TCTGAAAACTGCATCCGCTGCCTGTGCAAAATAACCAAGCTCGAGAAAAAAGAGAAGATCGAGGAGTTGCTTTACTCTATCAGCGC
CACCCTGGGGGGCATTTACATCGACGATTACAACCCAATGAAGAATAAGTTCAGCTTCTACATTTGGAAGGGAATCCTGAATAAGA
AGATTAAATCCTACGGGTCTGAATGGCTCATTAACAAGATGAAAAACATGGGCTTTAAGGATCCGGAAAACAAGACGCTGTTGAAC
TATGTGAAAAAAAAGTACGAGAAAGACATAAAGTTCGACATCATAAAGAAAGAGAAGATAGAATGGAGTAACCTCGACTGGGAGAT
AAAGGAAAAGATAGTGCTGGGCGCCATAAAAACTCACCCTACCATTCGCAAACTGATTGAATACAAGAATGAGAAATTCATTGACA
AAATTGGAAAGAAAATTCTGACTTACTTTAGCATCACAATCACCAGCGACGAGAACGAGAATTACTTTCTGATCGTCAAGCCCAAG
CATAAGATCATCAGCTCAGAGACAATTTACAACATGCTGAAGAACAACAAAATCGACTTTAAAACTCTTGAGAGGAAGCTGCTGAA
CGGCAGCGCCCTGATAACCACCAGTAGGGCAGTCGGCAGACGGAAATACGTCAAAATCAAAAAAATCATATCCCCCAAGGAGAAGG
AGTATTGGCAACATACCCAGGACATCAATGAGCACTACGAAAAGGAGGGCGTCCCGATCAGCGTCGGCGGTGACGACATCCACTGC
TATATCTTCATCGGGGAAGACGATTACGCCTACCACACGAAGAACTCCTTGCTCTACGAGGGTGTGACGGAGGACGTGCAGAAAAT
ACTCTTGGATATGGGTAAGTTCCTGGAGGAGCTGGAGACGGCAAAATCTATCCTCAAGCAGGGCAACCTCATAGACTTCAGTCGCG
AATTCCTCAACATTAGCACGAAGGACGACTACACCCTTACTCTCCTGAGCACACTGTCCGATATCAAAGTGAAGCTTAAGACCGAG
TCTGGTATCATCACAGGCGACTACCAGAAACTTAGGGAGATCTTTGACTGGATCTTCGACAAGAGCTTTAACCCCTTGAAGCCTAA
GAATTGCTACCTTCCGCTGAGTATTCCCCCCATACTGAATGACAAGAAAAAGATCGGCGTGTACATCTTCTATAGCAATATTAGCG
ACCCCGAGCTTAGGTTTATCGAAGGGATCTTTAAGAAACTGGGCCTGATATGCGCCATCAATAAGAGTGTGCCAAAAATTGAGGTT
AAACTCAAGAAGGAAGTGGACTTTGAGGACTACGCCAACAGCAGGATCATAATCACCCAGACCGTACTGAGCAATCTCGAGGATGG
CGAGCAGCCGTTCCTCATATGTATAAGTCCCTTGCTGCCGAATAACGAGTTCGATGAACTCAAAATGCATCTGTTCTCTCACCCGC
AGCTGATATTTCACCAATTCATGTATCCGTTCAACCTTCGAAAGTGCCTTGAGAAAGAATCATTCAAGAAACCCTTCATCAACTCA
ATCCTGTCTCAGTTCTTTCACAAAATGGGCATGTACCTCTTTAGTCTGTCTGACGAGCTGGGGAACTACGACTTCATTATTGGTTA
CGACATAAGTAGGGAAAAGGATGACATCGGGAAGATAAAAGGTATCGGCGGCTCCGCGATCATCTACAACAATTACGGCCATGTCA
AGTCAATCATAACGTTCGACGACGTAGGGTCTAGCGAGATAGGCAGGTACGACCTCCTGTTCGCGCAGGTGCACAGCGAACTGATA
CCCCACCTGAATCTGAACAATAAGCGGAAAATTAAGATTCTGCTTCTCAAAGACGGGCGGATTTTCAAAAAGGAACTCGAAAAGCT
CAGCCAAATCAGCAAGAAGTATAACTTCGAGATCACCTACATTGACGTTCGCAAGAGCACGCTGCTCCGGTTCTGGGGTGTGCGGA
GGGGCAAAGTGGTGCCCGAGTATAAGAATAGCTACGGGAAGTTCGGACGCGCATACTATATTAGTAGCCATTACTACAACCGCTTT
TTCAAGCAACCAATCGCAATCGTGGAGAAGTACCACATAGACGAGGGCAATTACAAACGCGTGGAAATAGAGGAGAATGATATTAA
GCAGCTGGTTCTGTTGACCAAGATTAACTACAGCCAACTGATGCCAGATAAGATGCGGCTGCCCGCACCCGTTCACTACGCACACA
AGCACGTGAACGCCGTGCGACGGGGCTGGAAGATCAAGGACGTCTCTATACTGAGGAGCGGGTGTCTTCCTACGATCTAGTAA
153 ATGCCTAAGAAGAAAAGAAAGGTGGAAGATCCAAAGAAAAAACGCAAGGTGGGTAGCGGCTCCATGACTAACAAAACCAAACAAAA
AAGCAGGAAGCAGAGGTCCCTCATAGAATTTCTTAAGGTGAAGAAGATCAACAAGGAAGATGGTAAGAACCATAACCTGATCAAGT
ATAGCACCGAACGGATCGATACAGGAGTGACCCAGAGCCTCATTGACATCAATATATCCAGTAACATCCTTAAGCTGCGGGGCAGC
ATTGCTCAAGAGGTGTTCAAACGGAAAATTGGCGTTTACTACGGGCTTGGGAAGTATTACGTTGCCGAAAACAAGCTGAAGAACAC
CGATCGAATGGATTTCTTGAAGAGGGTCTACGAGACCTTCCCCTATAACTACCTCGATAAACAGGACCCGCACAGCAAGATCAGCT
TTTACGAGTACTACACATTCCAGAAGTCCATCGACAAAGACGTGATAAACCTGCTTGAGCTGCAGAAGATAAACGAGTATAGTTGG
GACATACTGGACCCACACATCGCCACGCGCCTTCTCACAAGCTATGTGAAGCTTTACTTGGGCGACTACTTGAAGCCAATCCTGTC
CTCTTTCGAGTACGTCCGGGCTCGAATCAAGACAAAGCAAAAGACCGTTCCAATCAAAATCCCCGTGACCAAGAAGTTCGAGATCC
GAACTTTGGGGTACGACCCGACGCAGAGCGAAATTACTCTCGCCATAAAACGACACGCCAGCATGAACGCTGTGCTGTTGAGCAGC
TTTCCCCCCGACATCCTCGCGGTTGTGATAACTAAGCTCAAACGCCTCGTGAACGAGGCCGTGAAGCAAGACTACCGAAAGGTCAG
AATATACTCCGAGACCCAGCCGGGGAGCGGTACTGCCGCAGTTGTTGAAATCATCAGCGGCAGCCAAAACGTGATGAAGTTTCTCG
AAGAGCATCCGAAGGGGGCCATCCACGTTGAAAAGCGACTTAAAGAGCTGGGTAAATCACTGCAGGAGGTCCGGTACCTTCTTATC
GGCGTCTATGACAACAACGTCAGCCTGGAGCGGGCAAAAAAAGACGAAAGATACCACTACTACTTCACCGAGCATAACGCTTACCT
TGTACTTACGCCCGAGGTGCAAAAGGCGCTCTTTGGCAAGTTGATCGACGACTGGAAGACAAGCATTCTGAATGAGTACCAAAATA
AGCTCCACGAGATCACGAGTCTTGGGATGTTTAAGCATTTGGAGACCATACGGGGCATCCCGGTTTCCTTGAAAGAGAGGCTTGTG
GTCCGCACCAGCGAGGGCTTGCAAACCGTAGATGACATTAGGGACATTTTGACCAACCCCAAGATTCTTAGTAATATGTTGCCTAT
ATCCGAGGACGCGCTCAAGGAGACGCGAAAGCATAAACTGCGAATCACCCTGTTCTGTCCGGAGAAGTTTAGTGAGAGGATTCACC
GGACTATTTTCTACGACAAATTGAACCAGTTTCGAGACGGTCTGCTTAGCAACAGCTTCGCAAGCGTGGACGAAATCGAATTGTTC
CAGGTCAAAGGCGAAAACTCTAGCGATTATGAGGAGATCATGAAGGACGCTGGCCTTGATAAAATCCACGATTATACCCTGGCGGT
CATCATATTTCCCGAACATTATAGTAAGCGCAACCTTGAGTTGCGCATCTTTTACAACTGGCTGAAAATGCGGTTCTACTCAGAGA
ACAAGCCACTGGTTTTCCAGGGCGCTCGGATTGACAGCGTCTTCGGCCGGTATGCGAAGTACGCATCATACAACCTCATCTTGCAG
ATCCCACCTAAATTGGGCATCTACCCGTACTCACTGGAGGAGCACGAGGACTATGACTACATCATCGGCATTGATTACACCTATTG
GTACGAGAGAGATACGCCTAGTCTGGGCGGTGGCGCCGTGTTGACCAGCCCGTCAGGGCTGATTGAGAGCATATACCCCATCGCAC
TCCCGAGCCGCACTGAATCCCTCAACATGTCCAAGATACTGAGCGAATGGTTCACGCGAACAGTCAAAACGAACCGGCATATCATA
GATAAGGGCCACGTGACCGTGCTTATCTCCAGGGACGGCATGATTCCTAAGTACGAACGCCAGACAATCCAGGAGTTCCTGAGTGA
ATATAGCGGCGACATGGGCATGACCATAGAGGCAGTAGAAGTTAGGAAACGCATCGCCGTGAGGACCTGGGCTACACAAGAGCCCG
TGGCCTACTACAGCCCGATAAAGGTTGGCGACTGTACCTACTATCTGGTCGACGCGCACACCGGATACCCGCTGGGGGAGAAAGGG
AACCGAACCTTCTACAGCTCACCCTATCTCATAGGAAGTTTTTACAGGTTCGAAAAGGGCAAATCCTCCCCCGTGCCAGGTAGCGC
AAAGAAGCACGTGATCGAAAGCCTGATAAGACTTCAAAAAATCAATTACGCCACCACCCGCATGGATAACATCAAGTTGCCCCTGC
CCGTCGACATCACCCACAAACTCATTAACTTTATCCGGGACACCAAGATGGAAATCAAGGGGGTCGGTATCCCAAACAGTCTCTTT
ATGATATAGTAA
154 ATGCCAAAGAAGAAGCGGAAAGTCGAGGACCCTAAAAAGAAACGAAAGGTTGGCAGCGGTAGCATGAAGAACCTGAGATACAAAAT
CAACGCCTACAGAATCAAAAAAGACTATATTCCCAAGGAAGTTTATAGATACAGGATCCGCTCCTTCATAGAGAACATTAACATAT
ATAGGTTCGTCGGTTTTTACGGAGGCGTGGCCCTCAATCAATCTGAGTTTATCCTTCCGTACCCGGTCGAAAATCTCGTCCTGGAA
TACGACGGAAAAGATGTAAAGCTTGAGCATATCGACACACTGAACCTGGAGGACATCGAGAATAAGGACAAGGAGAAAGCCGAGAA
GCTGGTGAGGGGATACCTGACCAGCATATACAAGTTGAAACCCATACTCTACAAGATCCTGCGGGACGTTCGAGAGAGCAAGATCA
TTAACGATATCAGAGTGGATCCTATACCCGACTTTACAGTAAAAAGGCACAATAACGAATACTACCTTGTCATCGATTTTAACCAC
ACCGCGACCGTGTTGAAAAATCTTTGGGACTTCGTGGGAAGGGACAAGCTGAAACTCGAGGATTATATCGGTAAGAAAATCATATT
CAAGCCCAACCCGAAGAAGAGGTATACTATAAAGAGCATTGAAAAGCAGAACAAGAAGGACATTGATGACATTGTCGAGCACATCA
TCGAGTACTACAAGTGGACGGAGGAGGAAATTAAGAGCACCTTCGGCGAAATCGACTATACTCAGCCCATCATCCATTGCGAGGGC
ATCCCCTACCCGTTCGCACCGCAATTTTGCAATATCGTATTTACCATGGAAGACTTGGATGAGAATACCCTCAAGGACCTGCAGAG
CTACTGGAGGTTGCCCAACGAGATCAAAGGCAACATTATCAATCAGATCGCTAAAAAACTGCGATTTGTGGAGAACGAGCCAATCG
AATTGGAATTCATTAAGTTCAATAACACCCCCCTTATCGTGAAGGACGAAAATGGCAAACCAACAAAGATATACACCACCAATCGC
CTCTTCCGATGGAATTACGATAGTAAATCCAAACTGTACTTGCCCTACGACATCCCTGACATAATCAAGAACAAAACACTGACAAC
GTTTGTGCTGATCGACGAGAATCTCAAAAACGTGAGTGGTAAGATCAAGAGAAAGGTCTACCAAATGTTCAAGAATTACAATAAGA
TCGCCAGCAAGACTGAGCTCCCGAAATTTGACTTCGCCAATAAATGGAAATACTTCTCTAACAACAACATCAGGGACGTGATCCGA
AAGATTAAGGATGAGTTCAACGAGGAGCTTGGCTTCGCGCTCATTATCGGCAACCGATACTATGAAAACGATTATTACGAGACCCT
GAAGATGCAATTGTTCAACCTGAATATCATCTCCCAAAACATTCTCTGGGAGAATTGGTCAAAAGACGATAATAACTTCATGACAA
ACAACCTGCTCATACAAATTATGGGCAAACTCGGAATTAAGTACTTCGCACTGGACGCAAAAGTGAACTATGACTACATCATGGGG
TTGGACAGCGGCCTGGGCGCATTCAAAAGCAACAGAGTGTCCGGGTGTACCGTGATCTATGACAGCGAAGGGAAGATCCGACGGAT
TCAACCAATTGACGTGCCCAGCCCTGGGGAAAGGATCCCCATTCACCTGGTAGTGGAGTTCCTGGAGACCAAGACCGACATCAATA
TGGAAAACAAAAACATCCTGTTCCTTCGAGACGGCTTTGTGCAGAATAGTGAGAGGGAGGAGTTGAAGAAACTGAGCAAAGAGCTG
AATAGTAACATCGAAGTGATCTCAATCCGCAAGAATAACAAGTATAAAGTCTTTACCAGCGACTACGGTATCGGCTCCATTTTTGG
CAATGATGGCATATTCCTGCCACATAAAACTACATTCGGAAGCAACCCGGTGAAGCTCAGCACCTGGCTGCGCTTTAACTCCGGGA
ATGAGGAAAAATTGAAGATAAATGAGTCTATAATGCAACTTTTGTACGACCTTACCAAAATGAACTACAGCGCTCTGTACGGGGAG
GGTAGGAACCTTCGCATCCCGGCACCGATTCACTACGCCGACAAGTTTGTGAAGGCCCTTGGAAAGAACTGGAAAATAGACGAAGA
GTTGCTGAAGCATGGCTTCCTCTACTTCATCTAGTAA
155 ATGCCCAAAAAGAAAAGGAAAGTGGAGGATCCGAAGAAAAAGAGGAAGGTAGGCTCCGGGAGCATGAAGCCAGTGAACTTGGATGA
AAACAGCCTCAACGACGTCCCGGTAGGCGACACCTATGCTGTCCGCTTCACTCTTGATGCAGTCTTCGAGAACGAAGGGCAGTATC
CCCGGAGGAATCTGAAATTCACAGACGGAGGGGGGGATGACCGAACCATCACTATTTGGAAAAACTCTGCACCCGAGGAAATTTAC
GAGGCGGACTATGAGCGCGGTGCGACGTATCTTATTACCGCCGTCGAGTATGACATCGACGAAGGTAATGACGGCGAGCGATACCA
GAATCTCACAGTCCAATCAGATGCTACCTTGCTGGAGATGAGCGGTCCCCCTAGTACCGAAGAGGCCTTGGAAGACGGCCTCGCCG
AAACCCCAGATACTAGCGCCGATTCAGGTGACCACGGGTTGACAACCTTTAGGACTACAGACGACCTGCCGGATTATGACGTCTAT
GAGTACGAGCTGGTGCCGAAGCAAGGATTCCGGCCGTCCGGAGAAAATGCCCTCCGAGCCACATACAGGGCACGACGCAAGGTCCG
CCAGCAGTTGGACGTAACACCCGTCGTGGTCGGCGATGCGTTTAAGCTTGTGTCTCTGGTCAAGCTGGCCCACGAGCGGGTCGAGC
TTCCGCGATTCAAGATCAACGAGGTTGACGAGAGGCCCATCGTCTACGCCGATGAGGATGACAGGGATGTGTTGGGGGAAATGCTC
GGTGAGATCCTCAAGGACGCGAAACGGGACCAGTACGACATCCATGGCATCGACAAAATACTGGAGCCAGAGCCCGTCATAGAGAA
AGAGGGCTTCAGGCTCCACGAACGGTACAACCTGACCGTGGAAGTTCTCCCTAGCAGGGCCGCTTACCTGCACGTGGACTATCGAC
ATCGGATATTGAGCGACAGGACCCTGGATCAACTCGATGAAGACGAAATCCACCCTGGCCTGCGCGTGACCCCCTCATATAGGGAC
ATGGGTCTGTACGTTATAGGCGTTGGGCCGGAGACGGTGACCGATAAGCTGCATATCGAGGGCAACAAGAGCCTGGTCCAATACCA
TCGGGAAGAGCCGTGGGTGGACCCGGCGAAGGTGCAAGAAATCAAAGACGCAGATAGGGAAGTGATCTGGACCGTGAGGCAACGGG
GCGATGGCACCGAGATGGCATTCCCGCCGGAGCTGCTCGCGCTTCAAGGGCACCCCGAAAATTTGGCCCAGTTCGCCAGCGACTTT
GCTGAACAACAAAGGCTCAACACGCGCCTTTCCGCTGAGCAATGCATCACCAAGGCTAAAAGGTTTGTGGAGCGACTCGGGCCCTT
GCAATTCGACGGACACACTGTGGAATTCGAGACCAACCCGCTGTTGGGCGATCGGAACATAGCCATAGATGGTCTGTTTCACCCGG
AAGCAAACGTGCTGCAGTTTAGCGGAGGCCAGACCGGCACCCACCCCTCAGATGTGACACAGCTGGGCGTGTACGAAGCCCCGGAC
CCCTTCAGGGTGTGCCACATCAGGATGGAGAAGCGGGACAAAAGAATACAGAGGGGTTGGAGTACCTTGGAGACGAAGCTGGAGCA
GATTGGAGCGCCTCCCGACAGTGTCGAGGAGGTCACGTTCGACGCCACAATGAGCCCTGACCAGTTGGGTATGGAGATAGCGGCCG
AGATACCGGACGACCATGATTACGACGCGGCCTTCTGCACATTGCCACCTAAAGACACCGGCTACTTTGACACCGCAGACCCCGAG
CGAGTTTACGATGAACTTAAGAAAGTGTTGGCCACCAAAGACCTTAACTCCCAATTCGCGTATGAAGCAACGCTGGACGAGCGCTT
TACAATAATCAATATAGCACTGGGTCTTGTCGCCGCAGCGGGAGGTATTCCGTTCACAATCGAGAGGGCGTTGCCAGGCGATAGCG
AACTCCACCTGGGAATCGATGTAACCCACCAATACGACGAGTCCGCGAATGGCAACCACATTCACCTCGCTGCTGCGACGACGGCT
ATCCACGCTGATGGAGCTGTACTGGGCTACACCTCCAGCCGCCCTCAGTCTGGGGAAAAGATTCCCCCCAAGGAGCTGAAAGAGAT
CATCAAGCAAGCGGTGATGGGCTTTCGCACACGCTACGATCGCTACCCAAATCATATAACCATCCACAGGGACGGGTTCGCAAACG
AGGACCTGTCCGAGGTAGAAAAGTTTCTGACGGACCTCGACGTTGAATATGATGTTGTCGAGATCAGGAAGCAGGCCCCAGCGCGC
GTCTTGAAATACAGTGGTGCCCACTTCGACACGCCTCAAAAGGCGACCGCCGCAATCTACGAAGACATCCCGAAAGCGATTGTAGC
GACGTTTGGTGAACCCGAGACTCTCGCTAGCCGGGAGTCAACCGGGCTTCCCCAACCAATCACGGTGGAAAGGGTGCACGGAGAGA
CCCCCATCGAGACACTTGCTGCGCAAACCTACCTGCTGAGCCAAGCCCACATAGGCGCCAGTAACGCTACAGCACGCTTGCCCATA
ACCACCATGTATGCCGACTTGGCTAGTGCAGCGGCAGCCAGGCAACACCTTCCCCCGACCAACAAGCTGAGGGATAAGATCGGATT
CATCTAGTAA
156 ATGCCCAAAAAGAAGAGGAAGGTAGAGGACCCTAAAAAAAAAAGAAAGGTAGGTTCCGGATCCATGGAAGAAAATCTGTATCTTGA
ATACGACGCTTTCTTGAGGAGTGTGAAGCGCAACGTGGACGTCCCTCATAGTTTCTTGCTTGGAGCCGGAGCTTCCATCTCCTCCG
GAATTCAGTCTGCATACGACTGTATATGGGAGTGGAAGAGAGATATCTACATCACGAAGAATATAAACGCCGCCGAGTACTATAAA
AATCATAAAAACGAAACGGTTCGCAAATCAATACAGAAGTGGCTGGACAACCATGGCAACTACCCCATCCTGGATGCAGCAGAAGA
GTACACATTTTACGCCGAGAAAGCTCATCCAATCGCTGACGATAGGAGAAAGTACTTCTTTAGTCTGATTGAGAATAAAGAACCAT
ATATCGGTTACAAATTGCTGTGCTTTCTCGCTTCACAGGGGATTGTAAAGAGTGTATGGACGACCAATTTTGACGGGCTGATTGTA
CGAGCTGCTCACCAGAATAATTTGACGCCTATAGAAATCACCTTGGATAACGCGGAGCGCATATTCCGAAATCAGAGTACTAAGGA
GCTTCTCTGCATAGCTCTGCACGGTGACTACAAATATAGCACCTTGAAGAATACTGATACCGAACTGGATAACCAACACGAAATTT
TTCAGGAGCACCTCGGAAATTATCACGTAGATAAAAATTTTATAGTAGCTGGTTATAGTGGACGCGACAAGTCTCTGATGGATGCA
CTCAAGGCCGCTTATTCCAAGAAAGGATCTGGTAGGTTGTATTGGTGTGGCTATGGTGAGAAGATAAATTCTGAAGTGAAAGATCT
TCTTAAGTATATTAGAGCGAGTGGGAGGGAAGCATACTATATAGCTACGGATGGGTTTGACAAAATGCTCATACACTTGTCAAAGG
CAATATTTGAGGATAGCCAAGAGCTGAGTGAAAAAATCCAGAAAATACTCGAAAGCACGAATCAAACCGAGACCTTCAACACAGAA
TTCAAGTTGGAGTTTAAAAAAACCGACAAATATATCAAATCAAATCTGCACCCTATTGTTTTTCCTAAGGAAGTATTTCAGTTGCA
GATCGAGTATGGCAATGAAAAACCGTGGTCCTTCCTGAAAACACTGACAACTCAAACGAACATTAGCGCCGTACCGTTCAAAGGCA
ATGTCTACGCACTTGGTACGCTTAGCGAGATCAATTCCATCTTCAAGCCGTATCTTAAAAGCGAGGTCAAGAGGGAAGCGATCAGC
CGATTCGACATCGAAAACGTCACCGCATTCAAAAACCTCATGTTGACAGCCATATCCAAATATTTTTGCTACACGAAAGAAGTGAA
CTCTAACTACAAAGATAAGATTTGGTTGAAAAACATCCTGTCCAAGGTGGGGGATATCACTGTTCACAAAGCAATTTTCATATCCC
TGTACTTTGACAAGAATTCCCATTTTGGTTATATGGCGTTCGCTCCTACCGTTTATTTGGATTCCGACTGCGAAATTGAGAAGAGT
CAAAAGCAATCCATCAGTAAGAATTTGCTTGAGAAGTTGTATAATAACAAATATAACGAAGAGCTCGA/CTGTGGAATGGTATCTT
GTTTAATCATAAGAAAGTGAAATTTGAATATCCTCCCTTGTCTGGTACGGGGTTCGAATTTCAGATATCAAGCAACACTGCCTTCG
GGGAGATAGACGTGATTGATAACAAGTACCGCTCTTACGTCCCCCAGAATTATGATAATAAGCAGACTCAGTTCCGGGGAATCCAG
TTTTTGGAGCCGCAGCTGATATTTAAGAACATCGCAACGAACTCTGACTTCAAGGATTATCATCCCATGCGAGGACTGATTAACAA
CCGACCATATGATGTAAATCTCAACGGGATTATCCACTCCAATGAAATTAACCTCTCAATCATCTGTAGCCAAAAGTATGGAGAAA
GGTTGTTCGCATTCTTGACACAGCTCAATAGTAAGCACAGTACAGAAAATATCAACACTGACTACCTGATAGATTACCCCGGCTTC
CTGTCCGCCTTTAATCTGCCCATCAACATCCCAGCCACCAACGATGACGCTAGCTGGATGGACATCAACTTCGTAGCAGATAACTC
TAAAGAAACACACGAGAACGCTATACGACTCGCGAGGGCAATTACCAATAAGATCGAGAAGATTTCTGCTATACAAAGCGCCAGCA
CTATAGTAATCTTTATACCTTTCGAGTGGCAGCCCTTCGAAACATATATTAACGAAATAGAGACGTTTGATTTGCACGACTACATT
AAAGCGTTTAGCGCCAGCAAGGGGATATCAACGCAACTTATTCGGGAGGACACCCTTGACGATAAGCTCAAGTGCCAAATATACTG
GTGGTTGTCTCTTTCTTTTTACGTGAAGAGCCTCAGGACCCCATGGATATTGAACAACCAGGAGCGGAAAACAGCTTATGCCGGAA
TTGGGTACTCCATAAGCAAGGTAAAGAACAAGTCAGAGATCGTGATCGGATGTTCACATATATATGATTCAAATGGCCAAGGCCTT
AAGTATCGCCTCTCAAAAATTGATAACTACTTTCTCGATAAGCAAAATAATCCGTACCTGTCTTATAAGGACGCTTTTCAATTTGG
GGTTAGTATCAGAGAGCTCTTCTATCAGTCACTCGATTCTCTGCCAGAAAGGGTCGTCATCCATAAAAGGACAAAATTCACCGAGG
ATGAGATCAATGGGATAAAGGCTTCACTCAACCAGGCTGGTATTAAGAAGATTGATCTTATAGAGATCAACTACGATATAGATGCA
AAATTCGTTGCCATGAACGTGTTCGATAACAAATTGCAGGTCGATAAATTCCCGATATCCAGAGGAACATGCATTGTGACAAATAA
ACGGACGGCGTTGTTGTGGACGCATGGTATAGTACCTTCAGTTAAGCAGCCCAATTATAAGTTCTACCTGGGCGGGCGCTCTATCC
CTGCGCCCATAAAGATTACCAAGCATCACGGAGAAAGCAACATTGATGTGATAGCTAGTGAGATCCTCGGACTCACAAAAATGAAT
TGGAATAGCCTGGATCTCTACAGTAAACTTCCCTCTACGATAGATTCTTCTAACCAGATTGCTAAGATAGGAAAACTTCTGTCTCG
CTTTGAGGGCCGCTCATATGACTACAGGCTGTTTATTTAGTAA
157 ATGCCCAAAAAGAAACGAAAGGTCGAAGACCCTAAGAAAAAGCGCAAGGTAGGTTCAGGCTCTATGTCTGTGGACGCTATGATCAG
GAGTATCGGGGTCGCACGGGACCGCCCGCTTCTCGTTTTCCTCGGGGCAGGTGCCTCAATGAGCAGTGGTATGCCGTCCGCCACTC
AATGTATCTGGGAGTGGAAACGAGAAATCTTCTTGACAAACAACCCCGACGTTGAGAAGACCCAGTTCTCCGAGCTGAGCCTTCCC
AGCGTCAGATTGCGCATCCAAGCATGGCTGGATCGGCAACGACGCTATCCCGCTCTTGATCATCCCGACGAGTATTCTACCTACAT
AGGTGAGTGCTTTGCACGCTCTGACGACCGCAGAATCTACTTCGAGAAGTGGGTCAAACGCTGTAGTCCGCACCTTGGATACCAAC
TGCTTGCCGAATTGGCACGGCAGGGGCTTGTGGCCAGCGTTTGGACTACTAATTTCGATGCCTTGGCGGCTCGCGCAGCTACGTCC
ATCAATCTCACTGCAATCGAGATTGGAATTGATTCACAGCAAAGACTGTACCGGGCGCCGGGCGAGGCGGAACTGGCGTGTGTGAG
TCTGCATGGAGATTATCGGTATGATCCTTTGAAAAACACCGCTCCAGAACTCATAAAACAAGAGAAGGAGCTCAGAGAGTCACTTG
TCCAAGCGATGAGAACTCACACAGTCCTGGTTTGCGGCTATAGTGGTCGGGATGAGAGTGTCATGGCAGCGTTTTCCGATGCCTAT
GACGCAGCTCATTTTAAGGGTCATCACCCCCTCTTCTGGACACAGTACGGCGATTATCCCGCCAGTGAGCCCGTAGCTGGACTTCT
TGCTTCACCGCTGGATCAGGAACCTGCGAAGTTCCACGTGCCTGGGGCATCATTCGATGATCTTATGCGCAGGATAGCACTCCACG
TGAGTGACGGTGAAGCGCGCGAGCGGGTGCGGAAGATTCTTGAGAACTTCAAGACGGCACCAGTTAACCAGAAGCTCCCCTTTGCC
TTGCCTAGTCTTCCTGTGACGGGTCTCGTCAAGTCAAACGCCATTCCGTTGATACCGCCTGGAGAGCTTATAGAATTTGATCTTGT
CCGGTGGCCGCCGTCCGGTGAAGTTTGGAGCACGCTCCGGGAAATAGGGGATAGACACGGATTCGTAGCTGCCCCTTTTCGCGGGA
AGGTGTATGCTCTGGCTACGATAGAGCAACTGACACAAGCCTTCGCGGACAATGTAAAGGATGGCGCGTTCAACAGGGTGCCGCTG
AATAATGATGACCTCCGCTACGAGGACGGAACCGCCAATCAGCTGATGCGACGCGCTACTGTTCTGGCTTTGGCTGGGAAAGCTGG
ATGCGCGAACGATGGGGATGCCATTGTGTGGGACACGTCTCGCTCAAAAACCGAAAGATTGGATAGGCAACTTTGGACTGTATACG
ATGCAGTACTTCTGCAGATTCGGCCGCTGGGAACTAAGCTCGCGCTCGTACTTAAGCCTACGCTGCGGGTTACGGATTCAACTGGC
GAGGTAGCCCCGAAAGAAATTGAACGGGCAGTCAAGGTGCGCGTATTGGGATACCAGCATAACAAAGAGTTCAACCAGGCGACCGA
CTTTTGGAGGAAAAGGCTCCTGCCCTCAAGAGATCTCCTTGTCAGATTTCCTGATCTGGATGGTGGAATGACTTTCACGATTTCAG
GTCGGCCAATATTCGCCCGGCTCACCGACGAAAGGACTGAAACTGTCACACTGAACGATGCCCAAGAGCGATCAGCATCTCAAGTG
GGGTTGCAGCTTGCAGAGCCTAAACTGGTGTTTGCACGCACTGTAGGTACGGGTCCCGCAACGGACACCCTCCCGGTTAGAGGATT
GCTGCAAAATAGACCTTTCGATGCTAATCTGACAGACTTGGGCATCGCGACGAACCTGAGGATCGCGGTTATTGCGCCCGCTCGGG
ACGCCAGAAGGGTACATGACTATCTTGGGCAGCTGCATCAGCCTATAGATCCTACAAAGTGGGATGCGGACTATCTGATGAGGTTT
CCCGGCTTCAGCTCCGCTTTTAAATGCCCTTTGGACATTCCGCAGCCGGGCCAGGCAGCTTTTGTAACACTTGACGAGCCACACGA
TGAGAGTCCTCAATCAGCGCGGACCCTTGCAGGCCGAATCACAGCGGCACTGTCTGCATTGAGGGCGACGGAGAATCCCTCTGTTA
CAATAATATATATTCCGGCGCGCTGGCACGCGCTGCGAGCATTCGATCTCGAATCAGAGCAATTCAATCTTCATGACTTTGTTAAG
GCCGCCGCAATTCCAGCGGGCTGTTCCACACAGTTTCTGGAGGAGTCAACTCTTGCAAATGGCCAACAGTGCAGAGTGCGATGGTG
GCTTAGCCTCGCTGTTTACGTAAAGGCAATGCGCACCCCGTGGGCTTTGACGGGACTCGATAGGGACTCTGCCTTTGTAGGGCTGG
GCTTCTCTGTAAGACGAAAGATCGATGGCGAAGGTCACGTCGCGTTGGGTTGTTCTCATCTTTATAGCCCAAATGGTCATGGTTTG
CAGTTCCGCTTGAGTAAGATTGATAATCCGATAATGCTGCGAAAAAATCCTTTTATGTCCTTTGACGACGCTAGAAAGTTGGGCGA
AGCCATCAGGGAATTGTTTTTTGACGCCCACCTCCGGCTGCCGAATCGCGTAGTTGTTCATAAACAGACCCCGTTTCTTAAAGAGG
AGCGGGAAGGGCTCCAAGCACGTCTCGAGGGAGTCGCGTGTGTGGAACTCTTGCAAATTTTTGTAGACGATACGTTGCGATATGTG
GCTAGTCGACCAATGCCGAATGGAGATTTCGAAATCCATGGCTATCCTATCCGAAGGGGCACCACAGTAGTGGTCGACGACCAGAC
CCCATTGTTGTGGGTACACGGCACATCAACCGCGCTCAACCCCCGGCAGAGCTATTTTCAGGGCAAACGCCGCATACCGGCCCCCC
TTGTGATGAGGCGGCACGCGGGGACGTCTGATCTGATGATGTTGGCGGACGAAATATTGGGACTGTCCAAAATGAATTTTAACAGT
TTTGACCTGTATGGCCAACTCCCGGCAACCATCGAAACGAGCCAAAGAGTCGCGAGGATAGGCGCTCTGCTGGACCGCTATACGGA
ACGGTCATACGATTATCGACTCTTTATGTAGTAA
158 ATGCCTAAAAAAAAAAGGAAAGTCGAAGATCCGAAAAAGAAACGCAAAGTAGGGAGTGGTAGCATGATCAAACACCTCAAGTTCGA
CGAGTTCCTTCGCAGCGTGTCAATTAGTAAGGATAACACGTACTCCATGCTTATCGGTGCCGGGTGCTCAATCACTAGTGATATCC
AATCTGCCTATGACTGCATATGGGAATGGAAGAAAATAATTTACAAGTCCAATAACTTGAATACTCAGGACTGGATAGAGAATTAC
AAATCCCCCAAAACACAAGACGTGATACAAAAATGGCTTGACAACCAGGGAAACAACCCTGAGAAAGATAATATCGAAGAGTACTC
ATTCTACGCAAAGAAATGCTTTCCGATAGATGAAAATAGACGCCAGTACTTCCAAAAAATCTGCGCTAATAAGAAGCCCAGCGTCG
GATATCGAGCCATTCCTCTCCTGGTGAAGCAAGGCATGCTCGACTCAATTTGGACAACCAATTTTGATGATCTTGTTAATGTGGCG
TGTATAGGTGGTGGCGTTCAGGGGATTGACATATCCCTTCAGACGGTAAACCGCATAAATCAACGCAATCAAAGCAAAAATGAACT
GCCTATTATAAAGCTCCACGGGGATTTCAAGTATGGCGACCTTAAGAACACGAGTGAGGAACTTCAGAATCAAGACGAAACGCTTA
GATCAAAACTTTTGGACTACTTGAGCGATAAGAATCTCATAGTCATTGGCTATAGTGGTCGGGACAACTCACTCATGGAGAGCTTG
AAAGAGACTTATTCAAAACCTGGTGCGGGAATATTGTTTTGGTGTGGGTATGGGAACAGTCCATCAAACCAAGTGAAGGAACTCCT
TAAATTTATCAAGGATAAGGGGCGCAGCGCATTCTATGTTTCCACTGAGGGATTCGATAACACCATGCTGAACCTGACCAAGCATG
TTATTGAGGACGATGATAACCTCAAAGAGGAATTCAGAGAACTCAAGAAGAGTATCATTAATAAAAATACAACGACCCCGTTTACG
TTGAACCCGGAACGAATCAATAAGGTACTGAAAAGTAACCTCTTTCCTATTACATTCCCCAAAGAGATCTTCGTATTCAATGCGAC
CTTCGATAAGAAACCTTGGGAGCTTGTTAAGGAAAAAACTCTGAGTGACTATGAAATTTCAGCGATTCCATTTGAAAAAGACATAT
GGGCATTTGGGACTGCTAATAACGTCTACGAAAAGTTTGCAGATATCATTAAGGGCGAGATCCAACGGAAGCCCCTGACCGATATC
CGGCTTTATAATCACAACATAAAGTTCCTGCTCCTGTCAAGCCTCTGCAAGCTGTTCTCAAAAACCTACAATCTGAAAACGGACTT
TCGGTCTAAGATTTGGGATGAGAGCTCATACAAAACGGTTCACAACCAAAAGGTCTATAACGCTATAAAGATCGATCTCGTCAAAA
TACAAGAACAGTCATATTTGTCACTCAATCCAGACTTTCAATTCGCAGATGATAACGTTCCCAATGATATCAACCAGCAGGTTGGA
CTGGAATTTTTTCATAAGATCTATAACGACAAATTTAACGACTATATAAACATCTGCACAAAGAAGATCCTCGAAACTACGTCATA
CGAATTGCCACTGAACTCCGGCACCGGGTTCGTATTTAAAATCTCTAAGAATCCAATTTTCACAAATATAGATGACCTTAATTCCA
ACTATACGAACGAGCACAATATACCCATAAACATGATTAAACTTAAGGGGGTTCAATTCAAAGAGACGAACCTCCTCTTTAGTTCA
CAAAATGCAGATAAAGTGGTTAAGGAGACCCACCCAATGAGAGGCCTCGTCAATCATAGCCCGTTCGATAAGCGATTCAGTAGTCT
TAAAAACACTACGATCAACCTGGGGATCGTATGCCCCCAACAGGATAGCGAAAATTTTTATACTTTTTTGAATAAACAAAACCAAG
AGATTAAGAACGTTAATATTAAGGATCAATATGTAATCGATTACAAAGGATTTCACAACACATACGGTTTGAGTCTGAACATACCT
ACTACGAGCAGTCCTAATTGGGAAATGACTAACGAGCCTGTCTCAAGGGACTCAAAGAAAATAATTCATGAAATCAAGAATAATAT
TTGCGACAAGATAAATAAGCTTTGTAGTATAGGCGGACAGAAGACAATAGTAATATTTATCCCTAAACGCTGGGACAACTTCGTAC
ACTATAATGATGCCGTGGAAAGCTTTGATCTTCACGATTATATCAAAGCGTTCTGTACCGAAAAAAAGGTTACGTCTCAGTTGATA
CGGGAAAAGACGATACTCGATAATAACCTCGAGTGCCAGATCAACTGGTGGTTGTCACTCAGTTATTTTGTAAAGTCCTTCCGAAC
ACCGTGGGTAATCGACAACACCGACAATAAAACAGCTTTTGCGGGCATTGGTTATTCAGTAGAGTCCAAAAAAGAGGATAAGGGGC
ACATTATACTTGGCTGTTCCCATATTTACAGTAGTAACGGGGAGGGTCTCAAGTATAAGCTTTCCAAGGTTAATGATAAAATAGAA
TGGATCAAGAAAAAGCCGCATCTGTCCTACGACGATGCTTACGAATTTGGTAAAAATGTGATCAACCTGTTTTACGAAAGCATGAA
TGAGGTGCCAAAACGAGTGGTAATTCACAAACGCACCTTTTACACTGAAGATGAGAAGCAAGGCATACTTGACTCTTTGCACGATA
ACAAGAAAATAGAAAACATAGACTTGATAGAAATAAATTTCGAAGACAACATAAGGTACGTCTCCTCTAAGATATATAATCGGGAG
GCAAAAATCGACGGTTACTCAGTATCACGCGGTACCTGTATCCTTCTTAACGAAAAAGAGGCACTTTTGTACGCCCATGGCGTAAT
CCCGAGCGTGAAGAATCCGAGTTATAATTTTTATCCGGGAGGAAGGTACATACCGAAGCCATTGAGGATAATAAAGCATTATGGAG
TTGGTTCCCTGGAACAAATAGCAAATGAAATACTGGGTCTCACTAAGATGAACTGGAACTCTCTGAACATGTATAGCCAAATGCCT
GCCACGATCGACTCAAGTAATAAGATAGCCAAAATAGGGAAACTCATAGAGAATAGGGATAAAGTAGAGTACGATTATCGGTATTT
TATCTAGTAA
159 ATGAAAATTATAGATAAGGAAACCTTCATCAGAAGTTTTAAAGTTTTGAGCAATCAATCCTTTGACCTGTTCCTGGGCGCTGGCGC
CTCCATATCTAGCGGTATCCCTTCCGGAGGCGACCTCGTCTGGCATTTTAAGCGCGAAATACTGAATTCCAACGGGAAGATAAATA
TTAAAAAATTTCAAGATCTTAAGATAGAAGATAATAAGAAGGTTATACAAAGTTTCTTTGAGGAGACTGAGGAGAACAACATTATT
AATCCTTATTCCTATTATTTTAACAAATGTTATCCAGACCCCTTGATAAGAAAAGAATTCTTCACCAATCTTGTGAGGGACAAGAA
GCCTTCCATAGGATTTATGTGCCTGTCTGCTCTCGTGGAGCAGCAAAAAATCAACACAGTATGGACAACTAACTTCGATGACTTGA
TTGAGAAGGCGATTAACGGATTGAATTACAAGTCCTGTCAAATTGTCTCACCCGAGAATGCGGGCAGCGTGAATAACTTTCGAACT
GATATCCCCACTGTTGTTAAGCTTCACGGAGATTTTAGGTATGACCCACTCCAGAATACTGACGAAGAGTTGCAGAAACTCGAAGA
GTCCTTGCATAAGTATTTCGTAGAGCCAAGCACAAAGAGGGGACTTCTCCTAATCGGCTATTCTGGGTCAGATGAGTCTGTGCTGC
AAAGCCTTGAGAAGGCGCTGGAAGACAACAACGCGTTCCCTAAGGGACTCATTTGGTGCATCCCCAAAAGTGTCACCCCAAACCAA
CGACTGGTCCGAATTATATCTAAGGCTAATGAGCAGAACCAGCGGTCCCGATTTATCATTATCGACAGTTTCCATTATTTCTTGCA
TGAACTCTACAAAATATGCGACCTTACGAATGACTATATCGACTCTATTACCAAGGACAGATTTGAAAAAAGCCAGTCATTTAGGC
TTAACCAAACTCCGTCCTCTACTCTGCCAATCTTGCTGAACGCAATAAAAGCAAAGCACTTCCCGAAAAGTACCTTTCTGACTAAA
ACGAATATCTCAGGCATAGGTAAGTGGAAACGCTTGCGAGACGCTATAGGAAATAGCTCTATAGTCGGATCTTTCGGTAAGAACGA
TTCTCTCAGACTTTTTGGAAGTGAACAAGACATTAATAATGTACTTAAGAACTACTTGATTGATGATTTGAAGATCAGTGATATCC
CAGAGCACCTTTTTTTCCATTCTGATTCATTCTACATTGGCATGCTTTATGAACTGATTGAAAAGTGTTTGATTAAAGATTATGGG
CTGTCAGTATATGCAAAGGGGAGAACTATCAGAAAGTTCTATTCAATCAATAACCCGCTGCCGGAATCTGAAATCGCAGATATTAA
GAAGAGAAACAATAATTTTAACATCGACAAAAATATAAATGTATTTGAGGCGTTCGAGTTCTCCATAGAATTCATTAATAAGGAGC
TGTTCCTGTTGCTGTGTCCCACCATACATATTCAGACTAAACTCGGAGGTGAGGTCAATCGCAATATCTCTCAGTACCTGTCAAAC
ACAATCATCAGCAATAGGTATAATAACAAATATGGGAAAAAGCTGAATTGGTGGATTAACGAGCTCAAGAAGTATAACAAGGACTT
GGTTTTTAAATTGGGGGACTTTGAGATACGATTGACAGATTATTACTCCACGAGCGCTAAGCGCGTTAAAGATGACATCTACTGTT
TTGACGGATTTACTAAGTTGAGTGAGCCCAGTATATATTTCCACTATCAAGACGAAGCAAAGCAGAGTATCCATCCCATAAGTGGA
CTGAAGATACTCGGTCCATTGGAAGAATCATTCGAGGCAAACGGTACATCTTCCACAGTCAACCTTGCCATCATTACTCCGGACTT
TGGCTTCTCCAAACTCAAGGCGCACCTCGAAAGTTTGCTTAATACAATTTCCCCTATATGGGAGAAGGAATACTTGAAGGAGTTCC
CTGGTTTCGATAACGTTTTTAAGAAGCACCTGATAATACCCAATTCTATTCAAAGCGAGTATGTAATCAGCATACCTAATAATGAT
GTAAAACAGTTCTCAGCAATTCAATTCTACGACTACCTGAAGAGTAAGATCGACCGACTCGCTCTGAAGTCCAATGACATTGATTG
TCTTGTAATATACATACCCGACCAGTGGAAGAACTTCCGAGAGCTGAAAAATGAAAACACATATTATGACCTTCACGACAGTCTTA
AACTCTACTGCGTAAAAAAGGGGTTGCGAATCCAGTTCATCGAAGATAAAAGCATTAATTATAAAGACCAAGCCAAGATCCGGTGG
TGGCTGTCTCTGGGGCTCTACGTGAAGTCTAACGGCACTCCCTGGAAGATCAAAACAGATAATACAGAGACTGCCTTTGTGGGCCT
CGGTTACGCTATACGACAAAATGTTAAGAATAAGGTTGTTCTCGGGTCTTCACAGATTTTCGACGGTTATGGGAATGGTCTCAAGT
TTCTTTTGCAGCCCATAGAGAAGCCAATTTTTTACAATAAAAACCCCTTCATGAGCAAAGAGGACTCTTTTCGGCTTATCAGTAAT
ATACGAAACACATATCATAAGATCGATCCAGTTATCGGACTTAAGAAACTCGTGTTGCATAAGACAACTCATTTTACTTCAGAGGA
GATGGAGGGGATCTCTAATGCTTTGGAAGGCATAGACAATATTGAACTCTTGCAGATTCAGCAATTCTCATCATGGAGGGCAATTA
AGCTTATGAAAAATGCCACAAAGCACGATTTTAATGGTTATCCGATCGATCGCGGAACTATAATTCAACTCGACGACTTCTCTTTC
CTTCTGTGGACACACGGGCTTATAGAGAACCAAGAGCTGAACGGTAAGTACTACCAGGGAAAAAGAGGAATACCGGCTCCGCTTCT
TATTAAGAGATTTAGAGGCACGGATCCAATAGAGACGGTGGCAAACGATATTCTTAAGCTGACCAAGATGAATTGGAATGGTGCAG
AGCTCTATAAAACCTTTCCTGTAACGATTGATTTCAGTAAAAAACTTTCAGTCATGGGGAAGTAGTAA
160 ATGCCGAAAAAGAAAAGGAAGGTTGAGGATCCTAAAAAAAAAAGAAAGGTCGGCAGCGGGTCTATGTTCGACATTGGATCAATGGT
GAGAGTTAGGGGTCGAGACTGGGTCGTGTTGCCTGGCAGTTCCGCAGACTTTCTCCTGCTTAAGCCACTCGGCGGATCAGATGCAG
AAACGACAGGGGTTTATGCCGGTCCCGGCGGCGAAGTTGTGAGATCAGCGACTTTTGCGCCACCCGATCCGCAAGCGTTTGGAACA
GCCTCTGGCGCTCGGCTTCTCCTGAATGCAGCTAGATTGGCCGTTAGGTCCGGCGCTGGACCGTTCCGCTCCCTTGGCAGGCTGGG
GGTAGAACCACGCCCATATCAACTTGTCCCCCTCCTTATGGCCCTGAGACAAAGTACCGCCCGGCTCCTTATTGCCGACGATGTAG
GTATAGGAAAGACAGTTGAAGCGGCACTCATCGCCAGGGAGCTGCTTGACCGCGGAGAGATAGAGCGATTCGCTGTGCTTTGTCCG
CCCCATCTGGCTGGTCAGTGGGTAGGTGAGCTGAGGAGCAAGTTTGGGATAGATGCCGTCGCGGTCCTCCCCGGAACCGCGCGAAG
ACTGGAGCGCGGCTGTAACCCAGGCCAATCTGTGTTCGCCAGATACCCTTTCGCAGTTGTCTCTCTCGACTTGGTCAAATCAGACC
GATGGCGCCAGGATTTTTTGCAGAACGCCCCCGAGTTTGTTATCGTCGACGAAGCGCACGCCAGTGCTGAGGGCGAGGGGTTGGGC
GCGCGAAGACATCAGAGATATCGCCTTTTGGAGGACCTTGCGCGAGACCCAGAGCGACACTTGATACTCGTGACAGCTACGCCACA
CAGCGGAAAGGAGGACGCATTCAGATCCCTTTTGAGATTGCTCAACCCTGAATTCGCCGCTCTGCCACTGGATCTCTCCGGCGCTC
AAAACGAAAGAGCTCGGGCAGCTATCGCTCGACACTTGGTGCAGCGGAGGAGGGGTGACATCACTGCATACCTTCACGAGGACACC
CCATTTCCAGTCCGAAGGGACGCCGAGGTTAAGTATACTCTGCACCCCGATTATGCGGCATTGTTCGAGGACGTTCTGGCCTATGC
AAGGGAGTCCGTGCACGTTCCAGGCGAGGCGCATAGTCGGACGCGGATACGCTGGTGGGCCGCCCTGGGACTGCTTCGGGCTTTGG
CTTCTTCACCCCAAGCAGCCGCAGCCACTCTCCGGGAAAGAGCAAGCACCGAAGGCGAGACTGATGAAGCAGTTATTGAAAGACTT
GGCAGGGAACTGGTGCTTGACCCCGAAGACGGTGAACATGGGCTGCTGGACGTCACCCCTGGAGCGCAGGTCGACGGTGAAGAAAG
CGGGACCACGCGACGCCTTCTCGCACTCGCAGAGAGGGCCGACGCTCTGGCTGGGGCCAAAGACCGGAAGCTCGCACTCCTGACCG
CACAGGTCAGGGATCTTCTGCAGGAAGGTTTCGCGCCGATAGTTTTTTGTAGGTTCATTGCGACCGCGGAGGCAGTAGCGGAGCAC
TTGAGGGGAGTTCTGAAAGGAGCTGAAGTCGTGGCTGTCACAGGAAGGCTGACGCCAGATGAGCGCGTCGCCCGCATCGAAGAGCT
TGCACCCCACGAGCGACGGGTTCTTGTGGCAACGGACTGCCTTAGTGAGGGCATTAATCTCCAAGCTGCCTTCAGCGCAGTAGTAC
ACTATGATCTCCCCTGGAACCCTACCAGGCTCGATCAAAGGGAGGGCCGAATTGACCGATATGGTCAACGATCACCAGAGGTCCGA
GTGCTTACATTGTATGGGGAGGATAACAGGATAGATACTCTGATACTGGATGTTTTGATCCGAAAGCATCGGCTGATCCGGGCTAC
CTTGGGAATGGGTGTCCCCGCTCCCGACGAGGCAGAAGGATTGCTTGACGTGCTGTTGGCGCGAGTACTGGAACCCGAACGAAGAG
GTTCTATTCAGCCATTGCTTCTGGATGAAGTGCAGGCTTTTGATTTGAAATGGCGCGATGCGGCTGAAAACGAAAAAAGGTCAAGG
TCACGATTCGCCCAGAACTCTATAAGGCCCGAAGAAGTAGCAGGGGAACTCGCAGCGGTACGGGAAGCGCTCGGAGACGCTCGAGC
CGCTCAGGACTTCGTTCTTGATGCACTGCGAGGGGCCGGTGTTCAGGTGACGCCGCGCCCCGACGGAAGCTTCGAAGCGGACCCCA
CCCAAGCCGATGTAGCACCGGAGGTCCGCGACTTTCTGCGGGGAGCAAGGCGCTTCAGATTTGACGCACGGGTAGAACGAGGTGTG
ACGCCCTTGGCGCGGAACCACCCATTGGTCGAGCAACTTGCAAGCACTGTACTGGGTCAGGCTCTGGAGTCTCCGCAGGAGGCCGC
AGCCAAGCGCGTAGGCGTCATTCGGACCTCTGGCGTAAGTACTCAGACCACTCTTTTGCTCCTTCGATGGAGATTTCATCTTTCCG
GACGAAAGGGAAACCGATCTTGGCAAACTCTTGCTGAAGAACTTGATCTTCTGGCTTACGCAGGAAGGGCAGAGGATCCGCAGTGG
TTGGACGCTGAGGCCACCAGAGCTTTGCTCGATCTGACCCCTCAGGGTAACTTGGATCCGGTGCAGAAAGAGGAACGCCTTACTCG
GACGCTTGAGGGACTTAGCGCTTTGGAGGGGGTTTTGGACCAGCGAGGAAGGGATAGAGCCGCAGCTCTGCTTGACGCTCACGAGA
GAGTACGGGGAGCAGCGCGAGGGCAAGGGGTGACCTATTCTGCGGAGCCTCCTGGCCCCCCGGATCTGCTTGGTGTCTATCTCTTT
CTCCCCGCACCAAGACTCGGAGGCCTCGCCTAGTAA
In some cases, a polypeptide construct as described herein can comprise one or more domains. Domains of a polypeptide construct can be arranged in any order. In some cases, a domain organization of a polypeptide construct is in the configuration: (ArgoN);(ArgoL1);PAZ;ArgoL2;ArgoMid;Piwi. In some cases, a domain organization of a polypeptide construct is in the configuration: SIR2;(ArgoN);(ArgoL1);ArgoL2;ArgoMid;Piwi. In some cases, a domain organization of a polypeptide construct is in the configuration: (ArgoN); (ArgoL1);(ArgoL2);ArgoMid;Piwi. In some cases, a polypeptide construct contains a DEDX domain. In some cases, a polypeptide construct is absent a DEDX domain. In some cases, a polypeptide construct is adjacent to a helicase in a natural setting. In some cases, a polypeptide construct comprises the sequence of SEQ ID NO: 190, a modified version thereof, a portion thereof, or a functional fragment thereof. In some cases, a polypeptide construct comprises a genetically similar, phylogenetically similar, or functionally similar Argonaute or helicase sequence as those in Table 18 (SEQ ID NO: 161-SEQ ID NO: 252). In some cases, a polypeptide construct comprises a sequence of that is from about 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to 100% identical to SEQ ID NO: 190, SEQ ID NO: 211, SEQ ID NO: 215, or SEQ ID NO: 249.
TABLE 18
Argonaute and helicase DNA sequences
SEQ
ID NO Argonaute # Sequence
161 36 ATGCCATCAGCCGAGAGGTGCATCTGGGAGTGGAAGAGGGAAATCTTCATCACTAAAAACCCCTTGCTCAGG
GAAACCGTCGGCGAGCTGTCCCTCCAGGGCACGAAGGACCGAATCCAAAAATGGCTCGATCAACGCGGCGAA
TACCCCGCACTGAACTCCCCAGAGGAATACTCATTTTATGCCGAGGAGTGCTACATCACCGAACAAGACAGG
CGGAGCTTTTTTCAGCAGTACGTAGAGGTCGCCAAGCCGCACATAGGTTATAGATTGTTGCCCCTGCTGGCA
CAGACCAAGATCATAAAAACTGTATGGACGACTAACTTTGACGGGCTTGTCGCCAGGGCCTGTCATTCCAAC
GACGTGGTGTGCATCGAAGTCGGTCTCGACAATACCCAACGCATTACGCGCCAGCATTCTGAGGGGGAGCTG
CGGGTTGTAAGTCTCCACGGCGACTACCGATACGATGAGCTTAAGAATACAGATGAGCAGCTCAGGTACCAG
GAGGAGGCGCTTAAAAACAATATAGAGCACGAGCTGCAGGACTACGACCTGGTAGTGATCGGTTACTCCGGC
AGGGACCGGAGCCTCATGAACGTACTCGAAAACATATTCAGCAAGGCCGTGAAGAGCAGGTTGTTTTGGTGT
GGCTACGGCGAAACGATAAGCCAGCCCGTTATGGAGTTGTTGGAGCTGGCCCGCAAGAATAATCGAGACGCA
TTCTATGTCAGCACCGAAGGCTTCGACGACACCGTTGAAAGAATCAGTAGGAAGCTGCTTGACGGCAACATG
CTGTCCAAAGCCTTGGCTGAGATACAGGAGACCACTTGCATCACCAACCAATCTGCCAAATTCACCGCACCT
GAAAACGACATCAGCAGCCTTATTAAGTCAAACGCATACCCCCTCCTGAAGCTCCCGTCTCAGTTCCTTAAA
GTGACCCTCAAATACCCGGAGGGGTCCTTTAGTTACATTGATTGGCTTAACTCCAAGGTTGACTTCAAGGAG
GTTGTGTTGTCTAAGATAGACAAGGAGATCATCGCGTTCGCGGATGTTGATAAGCTGAGGAAGTATCTGGGC
GAGTTCTACCTGTCTACGCCCACGGTGGTGAACTTTAGCAAAACGGACGTGCTTAACGATACTCGCATTCAG
AGTCTGGTGAGGCGCGGACTTATACAGTCCATCGTAAAAAACCTGAACCTGTCCAGCGACCAGAACAAGCGA
ATATGGAATCCAGACGTGAGCTCCATCGAATTCTACAACGGCAAGAAGTACAAAATCATCGACGCGCTCATC
CTCAATCTTAGTTTTATCAAAGATGACATCTACCTCACGTTCAAACCCGATCTGCTGGTCCTTAACCTCGAC
GAGAGCCTGCCAGACAACGATATAGTTAAGACTATCAAGAACAAAAAGTTCGGCTACCAGCACAACAAAGAG
TACAGTCAGATCCTGGAGAAGTGGGCCAACCTTATAACGAAGAAGGATTTGGTCGTGAGTGGCGGGAGCGTG
TTCTTCCTTGGGAAGAAACCGCTGTATGCCGGACTTGTGTCTTACGCCGCGAGGAAACTCCCAACAGATTAT
AACAAGCACGCCACCCAGAAAGGACTGATCATTCAAGACGCGAAACTGATTTTTTGCAGCAATTCCATCTCC
AATGAGATTTCTCACATCAACCCCCTGAAGGGGCTCGTGGAAAATCGCCCGTGGGACTACAAAAACACCAGC
TCTGGGCTGTGCCCCGAGATCTGCATTAACGTGATCTCAACCAGGCAGGACGCGGGTGTGGTGAGCAACCTT
CTCCGAGGTATTCACGAGAAGTCCTTCCCGGAAAAATCCGAGCAAGATTACTTGCACCCCTTCCATGGGTTC
ACAAACGCTTTCGGGGTGCCCATCACGATCCCTAAGATCGGTGAGAATACGTGGCGCTTTGTGGACGAAGCA
CTGAGTGCACAGAAGGCCATCGATAACGCGAAGAACCTCGCGAACCGCATTTGCTATGAACTTGACAGCCTG
AAGAAGCTTGAACTGCGGACGGGCACCGTCGTGATCATATACATCCCCAAGAGATGGGAAGCATTGACATCC
ATCAAGTCTGAGCATGAGTACTTCGACCTGCATGATTACATCAAGGCCTATGCTGCGCAACAGGGCATTAGT
ACGCAATTCGTGCGCGAGAAAACGGTTAATTCAAGCCAAAGCTGCCGGGTAAAATGGTGGCTCAGCCTGGCG
TTCTACGTGAAGGCTATGCGCACTCCGTGGCGGTTGGAGAGTATTGATAACCAAACGGCTTTCGTGGGGATA
GGGTACAGCATCAATCGCAATATGCATCCCGAGAATTCCAAGCGGATAATTCTTGGATGCTCCCACATATAC
TCCGCCCGAGGCGAAGGCATGCAGTTTCAACTTGGGCGAATTGAAAATCCCATTATCCACCATCACAATCCC
TACATGAGCGAGGAGGACGCTAGACGCACCGGCGAGAAGATACGACAAATGTTTTTTGATGCCAAGATGCAA
CTGCCACGCAGGGTCGTCATCCACAAGAGGACCGCTTTCACTGAAGAGGAACAGCGGGGGTTCATACAAGGA
TTGGAAGGCGTTGAGGACATCGAGCTGATCGAAATTAACTTCGAGGACTCCCTCCGCTATTTGTCTAGTAAG
TTTGTAAACAGCAAGCTGGAAATCGACGGGTTCCCCATCGCTCGGGGGACCGTAATCGTGCAAAGCAGCAAC
ACCGCGCTCCTGTGGGTGCATGGTGCAACCCCTAGCGCGCAAAATCCAACGTTTAAGTATTTCCAAGGCAAA
CGACGGATCCCCGTGCCCCTTGTCATAAAGCGCTACGTGGGGCAGAGCGACATTAGCCAGTTGGCGAACGAA
ATATTGGGCCTCAGCAAAATGAACTGGAACACCTTTGACTATTACTCCAGGCTTCCTGTAACCCTTGAGAGC
GCCAATGATATTGCCCGGATCGGCGTGTATTTCAACAATTTCTCCCCCATGAGCTACGACTATCGGCTCCTC
ATA
162 90 ATGATCAAACACCTCAAGTTCGACGAGTTCCTTCGCAGCGTGTCAATTAGTAAGGATAACACGTACTCCATG
CTTATCGGTGCCGGGTGCTCAATCACTAGTGATATCCAATCTGCCTATGACTGCATATGGGAATGGAAGAAA
ATAATTTACAAGTCCAATAACTTGAATACTCAGGACTGGATAGAGAATTACAAATCCCCCAAAACACAAGAC
GTGATACAAAAATGGCTTGACAACCAGGGAAACAACCCTGAGAAAGATAATATCGAAGAGTACTCATTCTAC
GCAAAGAAATGCTTTCCGATAGATGAAAATAGACGCCAGTACTTCCAAAAAATCTGCGCTAATAAGAAGCCC
AGCGTCGGATATCGAGCCATTCCTCTCCTGGTGAAGCAAGGCATGCTCGACTCAATTTGGACAACCAATTTT
GATGATCTTGTTAATGTGGCGTGTATAGGTGGTGGCGTTCAGGGGATTGACATATCCCTTCAGACGGTAAAC
CGCATAAATCAACGCAATCAAAGCAAAAATGAACTGCCTATTATAAAGCTCCACGGGGATTTCAAGTATGGC
GACCTTAAGAACACGAGTGAGGAACTTCAGAATCAAGACGAAACGCTTAGATCAAAACTTTTGGACTACTTG
AGCGATAAGAATCTCATAGTCATTGGCTATAGTGGTCGGGACAACTCACTCATGGAGAGCTTGAAAGAGACT
TATTCAAAACCTGGTGCGGGAATATTGTTTTGGTGTGGGTATGGGAACAGTCCATCAAACCAAGTGAAGGAA
CTCCTTAAATTTATCAAGGATAAGGGGCGCAGCGCATTCTATGTTTCCACTGAGGGATTCGATAACACCATG
CTGAACCTGACCAAGCATGTTATTGAGGACGATGATAACCTCAAAGAGGAATTCAGAGAACTCAAGAAGAGT
ATCATTAATAAAAATACAACGACCCCGTTTACGTTGAACCCGGAACGAATCAATAAGGTACTGAAAAGTAAC
CTCTTTCCTATTACATTCCCCAAAGAGATCTTCGTATTCAATGCGACCTTCGATAAGAAACCTTGGGAGCTT
GTTAAGGAAAAAACTCTGAGTGACTATGAAATTTCAGCGATTCCATTTGAAAAAGACATATGGGCATTTGGG
ACTGCTAATAACGTCTACGAAAAGTTTGCAGATATCATTAAGGGCGAGATCCAACGGAAGCCCCTGACCGAT
ATCCGGCTTTATAATCACAACATAAAGTTCCTGCTCCTGTCAAGCCTCTGCAAGCTGTTCTCAAAAACCTAC
AATCTGAAAACGGACTTTCGGTCTAAGATTTGGGATGAGAGCTCATACAAAACGGTTCACAACCAAAAGGTC
TATAACGCTATAAAGATCGATCTCGTCAAAATACAAGAACAGTCATATTTGTCACTCAATCCAGACTTTCAA
TTGGCAGATGATAACGTTCCCAATGATATCAACCAGCAGGTTGGACTGGAATTTTTTCATAAGATCTATAAC
GACAAATTTAACGACTATATAAACATCTGGAGAAAGAAGATCCTCGAAACTACGTCATACGAATTGCCACTG
AACTCCGGCACCGGGTTCGTATTTAAAATCTCTAAGAATCCAATTTTCACAAATATAGATGACCTTAATTCC
AACTATACGAACGAGCACAATATACCCATAAACATGATTAAACTTAAGGGGGTTCAATTCAAAGAGACGAAC
CTCCTCTTTAGTTCACAAAATGGAGATAAAGTGGTTAAGGAGACCCACCCAATGAGAGGCCTCGTCAATCAT
AGCCCGTTCGATAAGGGATTGAGTAGTCTTAAAAACACTACGATCAACCTGGGGATCGTATGCCCCCAACAG
GATAGCGAAAATTTTTATACTTTTTTGAATAAACAAAACCAAGAGATTAAGAACGTTAATATTAAGGATCAA
TATGTAATCGATTACAAAGGATTTCACAACACATACGGTTTGAGTCTGAACATACCTACTACGAGCAGTCCT
AATTGGGAAATGACTAACGAGCCTGTCTCAAGGGACTCAAAGAAAATAATTCATGAAATCAAGAATAATATT
TGCGACAAGATAAATAAGCTTTGTAGTATAGGCGGACAGAAGACAATAGTAATATTTATCCCTAAACGCTGG
GACAACTTCGTACACTATAATGATGCCGTGGAAAGCTTTGATCTTCACGATTATATCAAAGCGTTCTGTACC
GAAAAAAAGGTTACGTCTCAGTTGATACGGGAAAAGACGATACTCGATAATAACCTCGAGTGCCAGATCAAC
TGGTGGTTGTCACTCAGTTATTTTGTAAAGTCCTTCCGAACACCGTGGGTAATCGACAACACCGACAATAAA
ACAGCTTTTGCGGGCATTGGTTATTCAGTAGAGTCCAAAAAAGAGGATAAGGGGCACATTATACTTGGCTGT
TCCCATATTTACAGTAGTAACGGGGAGGGTCTCAAGTATAAGCTTTCCAAGGTTAATGATAAAATAGAATGG
ATCAAGAAAAAGCCGCATCTGTCCTACGACGATGCTTACGAATTTGGTAAAAATGTGATCAACCTGTTTTAC
GAAAGCATGAATGAGGTGCCAAAACGAGTGGTAATTCACAAACGCACCTTTTACACTGAAGATGAGAAGCAA
GGCATACTTGACTCTTTGCACGATAACAAGAAAATAGAAAACATAGACTTGATAGAAATAAATTTCGAAGAC
AACATAAGGTACGTCTCCTCTAAGATATATAATCGGGAGGCAAAAATCGACGGTTACTCAGTATCACGCGGT
ACCTGTATCCTTCTTAACGAAAAAGAGGCACTTTTGTACGCCCATGGCGTAATCCCGAGCGTGAAGAATCCG
AGTTATAATTTTTATCCGGGAGGAAGGTACATACCGAAGCCATTGAGGATAATAAAGCATTATGGAGTTGGT
TCCCTGGAACAAATAGCAAATGAAATACTGGGTCTCACTAAGATGAACTGGAACTCTCTGAACATGTATAGC
CAAATGCCTGCCACGATCGACTCAAGTAATAAGATAGCCAAAATAGGGAAACTCATAGAGAATAGGGATAAA
GTAGAGTACGATTATCGGTATTTTATC
163 18 ATGAGCGAGCTGGAGACCAACATCTTCCCAATCACCAACTTGCATGAGCTTGAAAGCAGGTTCAGGTTGTAT
AGGGTGAGGGGCCTGAGCATCAACCAAGAGGAGTACGACCCCAACACCCAGACATTGGTGAGGAAGCTGAGC
TACAGCATGAGGTCTCCCGTAGCTGTGATACTTAGGAACAGCGACCCGTTCCTGGCTCTTCCAATCGACGCA
CCCGAGCCCATCTCTCCGTACCCGCTCGTGAGAGCCACTGCTGTGTTCGAGAAGACGGACGAGGTATTTACT
CTCGATTACGAAAGCCCAACTCCCGAGACAGATGCGCTGCGAATAAGGTTCCTGCAATTTATCATCCAAGGC
GCGCTGTTTAGGAATCCCAGCCTGTGGCAGCCCTCAGCTGGCACCCCCTTCTTCGAGAGGAGCCCCGTGTTG
GAGAAGGCCGGCATTTGCGCGTACCGAGGCTTCTCAGTGCGAGTCGTGCCCATAGAAGGTGGTAAACTGGGA
ATCTGTGTGGACGTTTAGCACAGGTACGTCAGCAAAAACCCCATCGAAGCAAACATCAAGCGCGAGGAATTC
AGGAAATACAAGAACGGCAGGTGCATATACCACTACGGCCACAACTGGTACGAGATCAAGTTGCAAGACCAC
ACTGGGCTGTCCGTGTCAGAGCAGATGATCAGCAACGGGACGGCCAAACCCATAAGCTTGTATCAGTTCATT
ATGAATAACGCGCCCAAGCCCCTGCCCAGGGAGGTCATAGACATGCCTCCCGACTCACCCGCAGTCAAATAC
ATGACCAGCAGGGATGAGGTGCGCTACGTGCCCTCCATCCTTTGTTATCCGGTCTTTGACACCTCTGACCCC
AGGGTGAAGCCGACGCATAGGGGCACAATCCTCCTCCCTAACGTGAGGCGACAGTATATCCACAATTTCGTG
AACTCACACCTGACCGATGTGCGATCCAAAGACATGGCAATCCGAATCAGCAGCAAGCCAGTTATCGCCCCT
ACCAAGATTTTCCTGCCGCCTGACCTGGCATTCGGCAACAACACCGTGTTCAGCGTAAGAGGCACACCCGGG
ACCACGTATGTTAGCCTGGAGCAGCTGGGCCAGACGCGGATAAGCGCCCTCTTCAATCAGAAAATAGGCCCT
TATGACAGCAGGCCGCTGGATAGGCAGTACATGATTCTGCCGAAAAGCGTGTGGGACTCCCACGGGCCAGTA
TTTCTGAATGACTTTAAGAAAATCATGAACGAGCTGTACCTGCACGAACTGCCCTACAATCCCATCGTCGTG
ACCTACAACGACTTGAGCGCCAAGACCTACGCGCTTCAGGGAAGGGCTATTCTGGACGCCGTGGACAGCGAA
CTGAGAGAGCCGGGATACGGCGTGGTTATGATACACGAGACGGTGGACCGCCGGAATAGACAGCACGACCAG
CTTGCCGCGATGGTGATGAGGGAGCTGCGGAACAGGAGGCTGTATGTGAGCGTGATCCATACCACGGTGACG
AAGGACTGTTACCAATTGCCCCAGAACGCCCCCATTGGCAAGGCCTACTGCCCGGTAGCAGGCAAGCAGGGC
AAACTCAATGGCTACTTGAGGAACGTGGCCATTACCAAGGTGCTTCTGACCAACGAGAGGTGGCCCTTCGTT
ATATCTACCCCGCTGCATGCGGACTTTACCGTTGCCTTCGACGTGCAGCTTAACACCGCTTGCTTCACATTC
ATCGGCAAGAGCGGCTCCGACATCCGGACCGTTTTGAAGACCAGTAACCAAAAGGAGAGGTTGAGCAAGGCA
CAAGTAAGGCAGACGCTCCTGGAAGTGCTCCGCCAGGAGGTTGGCTTCGGTCGACGGACCATGCAGACCATA
GTGGTTCAGAGGGATGGCAAATTGTTTGCCAGTGAGATCGCGGGAGCAAAAGACGCTATAGAGATAGTGAAG
AAAGAAGGCATCTTGCCCAGCGATGTGTCACTGAATTTCATCGAAATCCCCAAGAGCAGCGTCGCCCCATTT
AGGCTGTTCGATAGCAGCCCCAGGCCAGGGCAGCCTGAAATGGCGAACAACCCAAGAATCGGCTCCTACTTC
ATCGCGACGAATTACGACGGTTACATTTGCACCACCGGCAAGGAGTTTTACCATCCCGGTACGGCAAATCCT
CTCCACGTGAAGTACATCGAGGGAAATATGCCATTTGAGAAGATCCTGGAGGACGTGTACGCCTTGACTTGC
TTGGCGTTGACCAGGCCCGAAGACTGCACAAGGGAACCCTTCACCATGAAACTGGCCGATATCCGACTGAGG
GAACATGCCGGAGGCTACGACGAAGATGCATTGGCGTATGATGATGAAAATGAGAACGACGAGGATAACGAG
AATGAA
164 57 ATGACCGAGGCCTTCCTCACAACCAGGAGGGGCTTCGTGCAAAAGCTGACGCTGACCAGGTACGATTACCTG
AACTGGATCATCGAGTCCGAGGCGCAGAAAGCCAAGCTGAAGAACTGGCTTAAGAACAAGAGCGGGTTTCTG
ACCCACGAGATCGAGGATACCTGTTTCTTCACCTTCGAGAGGCTTCTGGAGGAGAGTACTAAGCAGTATAGA
GCCTCCGGCGAGAAAACTCTGTCTGCCCCGTTCAAGAACACGCAACTGATCTCAAATCTGATCGGTACCATA
TTGAAAAAGGAGTTGAGCAAGAAATACAAGCAATTCTTTAGTCAAAACATCTTCATCGTGAGCACCATCGAT
CTGTATCCATTCAATCTCTTGAAGGCGTTCGAGTTCAACATCGAAGTGTTTGACAGCGGCCACTTCCTTATC
CACGTCAACCCAGTGTCTAAAATTGTAAGCAGCAAGGTTGTGGACAAGGAGTATCTGGACTACCTCAAGAAA
AGCAACCTCAACAACAGCAAAACCACCGAGATGGAGTTCGCGGTGATCAACCATGAAAGGAATTTCAGACTT
AAATTCGACCTGCTTGACGAATGCATCTTTGAGAAGATAGAGAAGCTGCACAGCGAGAAGAATATGTTTACA
GCCACTTTTGATTACCATTTCCTGGCCAACTTCAGCCCCGAGATCTTCGGCAAAATCGTGGAACATACTAGC
AAGGATCTGAAGCAGGCCATCATGTTCCTGAATGACATACTGAGCAATATCAAGCTGCCGAGCTTTCTCAAC
CTGCACGAGGAACGATACTTTAAGGTCAATATCTCCGAATTGGACCGAAAGAATAATCTTCTGATTGGAAGC
AGTTTCGAGGTAATAACCATATACTCAAAAAGCCAGACCCAGTATGGACTGAGGATTGAGTTCACTCGCGAC
AGCATAAGCCGGGACGAGCTTATAACAATCTTTCTGAAAAACGAAGAGCTGATCGAGAAACTCAACGACATT
AAAGTGGTCCCCGCCACCATCAACGCAAAAATCGAACAGAAGACCGGCTGGAAAAACCCCTACATCACCAAT
GTTTTCATCGATAACGTGGGTGCCTTCAGCACCAGCAGCCTGCAAAGCGCCTCATACTTCCACGGCATCTAC
AAGGCCGTTAACAACTGGAATATCCTGCCCATCGTGTACGAGGACCTCGACATCAAAGTATTCGAGAACCTG
ATGCTGCACGCCTTTAACAAGAACGCCACCGAATTCAAGATCCTGGAACCCATCATAATCAAGTCCACGAAC
GAAATCGACAAACAGGAGGTGCAGAGGAGCATCAAAAACCAGGCCGGCAAGACCATGATCGCAGTGTTCTGC
AAGTACAAGATACCCCATGACAGCTTCGCCCCCCTCAAGGGCTTCAAGTATCAGATCTATCAAGGCGACACC
ACGGACAATAAGCAGAATAGGGCCAAACTGAGTAACTTCACGTGCAAGTGCCTGGAGAAAATGGGAGGGGTG
ATTGCGGCAATCGCGGACACAAGCATAGCCGAGGATGGATATTTCATTGGCATCGACCTTGGCCACACCACA
AATGGCAAGGAAAAGTTCTCCAACCTCGGAGTGAGCTTGTTTGATAGCCTGGGCATCCTGTTGGGCGATTAC
GTGGAGAAGGAGATTCCAAGAAGGGAAAACCTCATCGACACGAACTGCCTCAATGCTTTTAAGAAACTTGAC
AAAATGCTGGAAGCTAAAAAACTGAACAAGCCCAAACACCTGATCATCCATCGGGACGGCAAACTGCACTTC
AAGGATATCAACATTCTCGTAAGCTGCGTGGAAACCGTGTGGGGTAAGATAAACGTCGATATAGTCGAGATC
ATTAAGAGTGGCTTCCCCGTGATGGCTATAAAGGACGAGACCAACAAACCAATCAATCCCATAAGCGGGACC
AGCTACCAGGACGACATCCATAAGTACGCCATACTCGCCACAAACGTACAAGCCGACGAACAGTCAGCCGTA
ATAAACCCGATAATCATAAAACACAAATACGGAGAGCTGGAGTTTAGCAAAATAGTTGAACAGGTGTACTGG
TTCACGAAAGTGTATACCAATAACCTGTACAATAGTACCAGGCTCCCAGCGACTACACTCAAGGCCAACAAC
GTGGTTGGCACGTCTAAGAAGCTCCACAGAAGTACATACTTGGGC
165 59 ATGTTCGTGGAACTGAACGCCTTCCCCATCGACATCCGCAATATCGGTATCGTGGAGGCCTGCGAGGTGCCG
TACGACAAGGAGGTGCTTTATAGCCTGCATGATAACCCACAAAAAGATTACCATGCTATCAGAAACGGCAAC
CAGATATTGATATTTTCTAATAGCAAAAACTACCCCATCCAGGGTACAATCAAGGAGATAAATCTTGCACAG
GACTACCGCATCCTGTTTTTCCTTATTAAGGAGTCCATTATCAAGATCCTGACGCAGATCAAACGGGAGCCT
TTCAAGTTCAACCCGATTGAGTTCATCTCACCAAAGGAGAACATCACCGAGAATATCCTGGGAATCAATTAC
CCATTTCAAATAAACGCCAAATATTCAATCGATACCAGAATCATTCAGGGGGTGCCCTGCCTCACCATTGAT
TGCAGCACGAAGAAATACAACAAGGAATCCCTGATCTACTTCATTAACGACGGCTTCAACCTGATTAACAGG
TACGTGATCTCAAAGCAAAACGAGAAGTATAAGCGCGTAGGTAAGATACTGAGCATTGACAACAACATCGTG
ACTGTTCAGAGCTGCGACAAGATAAAGAAGTACTCCGCCGAGGAAATCACCTTGGAGGCGAACTCTAAGAAC
ACCAAGGACTATCTGGCATACAAGTTCCCCTATAAGTTCGAGCAGATCCAAGAAAGCATTAAGAAGGCGATC
AGTACCTTCACCCAGGGGACCTCTAAGCAGATAAACATTGGCAAGATCTGGGACTTTTTCAGCCAGAAAGGC
ATCTTCCTGTTCAACGGCCACCGAATTAACATAGGGCTGCCTCCCGACATCTCCCAGCAATGCAAGAACCTT
GTGTACCCGCGCTTTTTCTTTAGCAACTCCCGAGAAAACAATTCCAAAGAGAACGGCCTGAAGGATTATGGC
CCTTACACCAGGAATTACTTTGACAGGAATAACCCCAGCATTTGCGTGATTTGCAACGCTAAGGAACAAGGC
AAAGTGGAACAGTTCCTGCACAAATTTCTGAAGGGCATACCCAATAGCCATAACTTTAAGACGGGCTTCGAG
GGCAAGTTTCATATTGGCCTCTCTCAGATAGAATTTTTCACGACCAGCGACGACAGCCTGGGCAGCTACCAG
TTGGCTATCCAGAAGGCAATCCAAACGAGGACTAACCAAAACTCTAGCCAGTGGGACCTGGCCCTGGTGCAA
ACCAGGCAGTCCTTCAAGAAATTGTTGGTGGAGCAGAATCCGTACTTTATTAGCAAGAAAATGTTCTTTCAG
CATCAGATCCCCGTTCAAGACTTCACCATCGAGCTGACCAATCAGAACGACAAAAACCTGGAGTATTCTCTG
AATAACATGGCTCTGGCGTGCTATGCGAAGATGAATGGAAAGCCCTGGCTGCTTAAATCAAGCCCTACTATC
AGTCATGAGCTGGTTATTGGCATCGGGAGCAGCAACATCATCATCGAGGAGGACAGTCTGAACCAGAGGATC
ATGGGCATCACCACCGTGTTCAGCGGCGACGGGTCTTACATGGTCTCAAACACTAGCAAGGCGGTGGCGCCC
AATGAGTACTGTTGCGCCCTCATAGACACACTTGAGCAAACGATCAAGAAGCTGGAGAAACTTATGAACTGG
CAGAGCAATGACACCATTAGGCTCATCTTTCATGCCGCCGTGAAGACCTTCAACAAAAATGAAATCCTCGCC
GTAAAGGAAGTGATCAAAAAGTATAGTGAGTACAAGATCGAGTACGCTTTTCTCAAAATCAGCAGCGACCAC
GGTCTGCACCTGTTCGACCACTCAACTAAGAATGAGAATAAGGGTAAATTGGCTCCCAAGAGGGGTAAGTAT
TTTGAACTGAGTAGCCATGAAATTTTGCTGTACCTCGTGGGGCAGAAAGAGCTGAAGCAGGTGAGCGATGGC
CACCCCCAGGGCGTGATCGTGTCCCTGCATAAGGACAGCAGCTTTCAGGACCTTAAGTACCTCTCTAATCAG
ATTTTCAGTTTTAGCTCCCACAGTTGGAGGAGCTACTTTCCCTCTCCCCTGCCCGTGACAATTCATTATAGC
GATCTCATCGCGGAGAACCTGGGCTGGCTTAACAAGCTGAGCGGCTGGGACGATACAATCCTGCTGGGCAAA
CTTGGACAGACCCAGTGGTTTCTG
166 73 GTAAAGCTTAATCACTTCCCCCTGAATCCCGCTCTTGCAGTGTTCAAGACTACCTACAGGCACAGAAACCCC
AGGGGCTTCCTGGGATTCGTTAGGTCACAAGGGTTGACCGCGGAGAGAGTTGGCGAGGAAGTGTGTGTCTAT
CACGGTCTTCCCCACCCGGCTTTTAGAGGAGCCACCGCCCAAGGACACACCAGACTGGCGCCTGGTGACACC
GATTACGACAGGGGCGTACTTAGTCTGATCGGAGCCGCCCTGCTGAAAGCGGGTTACGTGCTTACTGAGCGC
GAAAGGGCCGCAGTGCACCCCACGCAGCAGAGAGTGCCCCTGCACACCCCTAGGAAACTCCCTGCCGAAATT
GCGGTGAATGCCCATCTTCGATGGGAATGGGAACTGGAACGGCACAGCGGGAAGTCTTGGCTTGTGCTTAGG
CCCGGACGCATGTTTTTGAGTGCGCTGAGCTGGCACGATTTGGACCTGAGGGCATGGGCACAGGAGTTGCCC
CAGAGCGTACAGCAACTGCACGCGCTGTGTCTTCGCTCCGGACGACGAGAACGACTGAGGCGCATGGGTAAC
ACGTGGGCGTTCCAACGAGAGGATAGGGAGCAAGAGGGCAGGTGGCACCTGAGCTTTAGCACTAAGGCGCTT
TCCGACCTGAACCTGTCCGGCGATGCTCACCATGCTGCTAGCCTGAGCATGCCCGATGTGCAGAGGCTCGTA
AATCTGCCGGGTCTGTGGCAGCCCTTTGTGACAAGCCTTGAAGTCCTTGAGGTGCCTGGTAAGGTGATCGAG
GGCAAAAGGCTGAGGTTCGGACGAGGAACAGGGCGCGACGTCACGGATGTACACAAAAGGGGCATCCTTCAC
CCTCCGCCGCAGCCAGTGCGCCTTGCGGTCGTGCCCCCCATTCAGGCGGACGAAGAGGCGGATGAGCAGTTG
AGACGCGAGCTCCTTGCCCACCTCCTGCCACGGGAAAAGGTGTTGGCCCACCCCGAGGCTTCCCAGGGCCTC
AAGAAGCACTTGAATCGAAGGGAAACCGACGACACCTTCTACACCCTGTGGAGCGCTGGAGACTACTGCAAA
CTGGGGCTGGAACCCTTTGATCTGGTGCGCGACCTCCATAGGTACGACCCCGGCACGGGTCGCCTGCTGGCT
CCAGAGAAGTTGCATGGAGCAGCAGCCGCCGCGAGAGAGGCTGGCAGGCAATTGATTGGCCTCGTGATCCTG
CCCGACACCATAGGGCGAGATGAGAGGGACGCACTGTCCGACGAACTGGCCAAGCTGGGTGTGAAGAAACTT
CAGCACATCCGCAGGGACATGCTGAACCGGCCCAGGACGCAGTATATGGCCTGGGTGAACGTGGCCGTGAAG
CTCGCCCAGAGGGCCGGAGCAGTCAGCTGGGACCTGGAAAAGTTGCCTGGAGTGTGCGAACAGACCTTCTTC
GTTGGCGTGGATCTGGGCCATGACCATCGGGAGAAGCAAAGCGTCCCGGCCTTCAGCCTGCACGAGTTCCGA
GGCAGGCCGGTCGACTGCCTCACCCTTCCAAGGCGAGCCGGAAATGAAAGGTTGAGCCTGGCGGAGCTGAAT
CAAGGCCTGAGGAAGCTGCTTAAGGGTAAGAGGCCAGCCCAAGTGATAGTGCATAGGGACGGCAAGTACCTG
GAGGGGGAGGTTGATGACTTCATAATCGCTTTGAACGACCTCGGCGTGCCGCGCGTCAGTCTTCTCGCCGTC
AAAAAGTCCAACCTCTCCATGGTTGCCGGCGCTAAGGAGGGAGCGTTTTTGCCACTGGACGAGCGGCGGTGT
CTGCTGGTTACCAATACCCAAGCCGCGGTAGCTAGGCCGACAGAGCTGGAGGTGATGCACTCAGATCATCTG
ACTTTCGCCGAGCTGACCGAGCAAGTGTTCTGGCTGACCCGAGTATTCATGAACAACGCACAGCATGCGGGT
AGCGACCCTGCTACCGTAGAGTGGGCGAACGGGATCGCTAGGACCGGAAAGAGAATTGCCCTGTCTGGGTGG
TCCGCC
167 72 ATGCTCGACTTTAGCCTTACCCAGAAAGGTTGGGTGCTGCCCATCGTACTGAACGCCTTTCCGCTCAAGGTA
(Helicase) CCGGACATGGAGCTCAAATTCGTGCAGATCCCCTACGACAAGACGACCCTGGACTCACTGAGGTCAAGCCAC
AAGATGACCCACGTCTTCAGGAGGCAAGGCGACAGTATCCAGATCTTTTCTAGCGACGGCACCTTTCCAAAG
AGCGGCACCCCCCAGACCCTCCAACTGAAGGATAATCTGGGAATCTTTTTCTCTCTTGTAAAGGACGGCCTC
CTCAAGCACTTCGCCGGTTTGGGCCGAACCCCGTGCGGATTCAACCCCATTGAGGTCGTGTCAGCTCAGGCC
AAAGACAATCTTCTGGCTAGCATCCTCGGAGAAGCCTACCCGCTGAAAATTTGCGCCAAGTACTCCATCGAC
ACCAGGACAGTGCAAGGTCAACCGTGTCTCATCATCGACTGCAGCACTAGGAGAGTGGTTAAAGAGAACTGC
CTCTTCTTCCTTAAGACCGGCTTTAACGTGATTGGCCGCTATGTAGTGACCGAGCAGGACGACGGGTTTCGG
AAGCTGCTGGGTTTTGTGGAAAACTGCCACGAAGGCAGGACACTGAGCGTTATAAGGCCAGATGGCCAAGCC
GTGCATGCCGAGGCCAAGGACGTGTATCTCGAGGCATCTAGGGCCAACTTCGACGACTACATCCTTTATACG
CACGGAACTAAAAAGGATAGCATCGTGGAGCGAATCAGACAAAGCGTGAGTATCTTCAACGGCGGTAAGAAC
AAGAAAGATAGAATCGACGCGCTCAAAAAGTACATCCAGGCCACCAATATAAGCCTTTTGGATGGGACCAGG
ATCGAAATCGAGGAGCCCAGCGACATTCAGAAGGACTGCGCCCAGATGCAGAAGCCCGTGTTTGTGTTCAAT
GACAATGGCGAGGCCGACTGGACCGAGAAGGGGCTGACTCAGAACGGCCCCTACACCAAGCGCACCTTCGAC
CGAAACGACCCCAGCATCTGCGTGATCTGCGCACAACACGACAGGGGGCGAGTGGAGCAGTTCGTTAGGAAA
CTGCTGAAAGGCATGGCTAACAGCAAATACTTCAGAAACGGCCTTGAGGGCAAGTTCGCGCTGGGAACGTCC
CGGGTAGAGGTGTTTGAGACCAGCACAAATAGCGTGGACGCCTATAAGAGCGCGATCGAAGCCGCCATCCGC
AAGAAGGCCGATGACGGCGGCAGGTGGGACCTGGCATTGGTTCAAGTTAGGCAGAGCTTCAAGCAGCTGAAG
GTGACTGACAACCCCTACTACTTGGGAAAAAGCCTGTTCTACATGCACCAGGTGCCAGTGCAGGATTTCACT
ATCGAGCTCCTGAGCCAGTCCGACTATTCACTGGGCTACAGCCTTAACAACATGAGCCTCGCTTGCTACGCC
AAAATGGGAGGAGTGCCCTGGCTGCTCAAGTCCTCTCCCACCCTTAGCCACGAGCTGGTGATCGGCATCGGC
AGCGCCAACATTGTCCAGGAGAGGGGGGCACACAACCAGAGGATCATGGGGATAACCACCGTATTTAGTGGC
GATGGCAGCTACATCGTCAGCAGCACGTCCAAAGCTGTGGTTCCCGAAGCATACTGCGAGGCGCTGACTAGC
GTGCTGGGCGAGAATATCGAAAAAATCCAAAGGAGAATGAATTGGCAAAAGGGTGACTCAATCCGACTGATC
TTCCACGCCCAAGTGAAGAAGTTCAACAAGGAGGAGATTCAGGCAGTGCGAGCCGTGATAGACAAGTATAGG
GACTACCAGATCGAGTACGCTTTTGTGAAAATCAGCGAGAACCACGGCCTGCACATGTTTGACAGCTCAACC
GCCACCATGCCCAAGGGCAGGTTGGCCACACACAGGGGTAAGACCTTTAAGCTGTCCAAAAACGAGATGTTG
GTCTACCTGATCGGACAGAGGGAGCTGAGACAGGAAACCGACGGCCACCCCAGGGGTGTCATCGTGAACGTA
CACAAGGACAGCACTTTCAAAGATATCAAGTACCTGAGCGCCCAACTGTACTCTTTTGCGAGTCATTCTTGG
AGGTCATACTTCCCCAACCCTATGCCCGTGACCATCACCTACAGCGACCTTATCGCCCACAACCTCGGCTGG
CTGAACCAGCTGCCCGGGTGGTCTGACAGCGTAATGATAGGTAAAATCGGTCATAGCCAGTGGTTTCTG
168 92 ATGTTCGACATTGGATCAATGGTGAGAGTTAGGGGTCGAGACTGGGTCGTGTTGCCTGGCAGTTCCGCAGAC
(Helicase) TTTCTCCTGCTTAAGCCACTCGGCGGATCAGATGCAGAAACGACAGGGGTTTATGCCGGTCCCGGCGGCGAA
GTTGTGAGATCAGCGACTTTTGCGCCACCCGATCCGCAAGCGTTTGGAACAGCCTCTGGCGCTCGGCTTCTC
CTGAATGCAGCTAGATTGGCCGTTAGGTCCGGCGCTGGACCGTTCCGCTCCCTTGGCAGGCTGGGGGTAGAA
CCACGCCCATATCAACTTGTCCCCCTCCTTATGGCCCTGAGACAAAGTACCGCCCGGCTCCTTATTGCCGAC
GATGTAGGTATAGGAAAGACAGTTGAAGCGGCACTCATCGCCAGGGAGCTGCTTGACCGCGGAGAGATAGAG
CGATTCGCTGTGCTTTGTCCGCCCCATCTGGCTGGTCAGTGGGTAGGTGAGCTGAGGAGCAAGTTTGGGATA
GATGCCGTCGCGGTCCTCCCCGGAACCGCGCGAAGACTGGAGCGCGGCTGTAACCCAGGCCAATCTGTGTTC
GCCAGATACCCTTTCGCAGTTGTCTCTCTCGACTTGGTCAAATCAGACCGATGGCGCCAGGATTTTTTGCAG
AACGCCCCCGAGTTTGTTATCGTCGACGAAGCGCACGCCAGTGCTGAGGGCGAGGGGTTGGGCGCGCGAAGA
CATCAGAGATATCGCCTTTTGGAGGACCTTGCGCGAGACCCAGAGCGACACTTGATACTCGTGACAGCTACG
CCACACAGCGGAAAGGAGGACGCATTCAGATCCCTTTTGAGATTGCTCAACCCTGAATTCGCCGCTCTGCCA
CTGGATCTCTCCGGCGCTCAAAACGAAAGAGCTCGGGCAGCTATCGCTCGACACTTGGTGCAGCGGAGGAGG
GGTGACATCACTGCATACCTTCACGAGGACACCCCATTTCCAGTCCGAAGGGACGCCGAGGTTAAGTATACT
CTGCACCCCGATTATGCGGCATTGTTCGAGGACGTTCTGGCCTATGCAAGGGAGTCCGTGCACGTTCCAGGC
GAGGCGCATAGTCGGACGCGGATACGCTGGTGGGCCGCCCTGGGACTGCTTCGGGCTTTGGCTTCTTCACCC
CAAGCAGCCGCAGCCACTCTCCGGGAAAGAGCAAGCACCGAAGGCGAGACTGATGAAGCAGTTATTGAAAGA
CTTGGCAGGGAACTGGTGCTTGACCCCGAAGACGGTGAACATGGGCTGCTGGACGTCACCCCTGGAGCGCAG
GTCGACGGTGAAGAAAGCGGGACCACGCGACGCCTTCTCGCACTCGCAGAGAGGGCCGACGCTCTGGCTGGG
GCCAAAGACCGGAAGCTCGCACTCCTGACCGCACAGGTCAGGGATCTTCTGCAGGAAGGTTTCGCGCCGATA
GTTTTTTGTAGGTTCATTGCGACCGCGGAGGCAGTAGCGGAGCACTTGAGGGGAGTTCTGAAAGGAGCTGAA
GTCGTGGCTGTCACAGGAAGGCTGACGCCAGATGAGCGCGTCGCCCGCATCGAAGAGCTTGCACCCCACGAG
CGACGGGTTCTTGTGGCAACGGACTGCCTTAGTGAGGGCATTAATCTCCAAGCTGCCTTCAGCGCAGTAGTA
CACTATGATCTCCCCTGGAACCCTACCAGGCTCGATCAAAGGGAGGGCCGAATTGACCGATATGGTCAACGA
TCACCAGAGGTCCGAGTGCTTACATTGTATGGGGAGGATAACAGGATAGATACTCTGATACTGGATGTTTTG
ATCCGAAAGCATCGGCTGATCCGGGCTACCTTGGGAATGGGTGTCCCCGCTCCCGACGAGGCAGAAGGATTG
CTTGACGTGCTGTTGGCGCGAGTACTGGAACCCGAACGAAGAGGTTCTATTCAGCCATTGCTTCTGGATGAA
GTGCAGGCTTTTGATTTGAAATGGCGCGATGCGGCTGAAAACGAAAAAAGGTCAAGGTCACGATTCGCCCAG
AACTCTATAAGGCCCGAAGAAGTAGCAGGGGAACTCGCAGCGGTACGGGAAGCGCTCGGAGACGCTCGAGCC
GCTCAGGACTTCGTTCTTGATGCACTGCGAGGGGCCGGTGTTCAGGTGACGCCGCGCCCCGACGGAAGCTTC
GAAGCGGACCCCACCCAAGCCGATGTAGCACCGGAGGTCCGCGACTTTCTGCGGGGAGCAAGGCGCTTCAGA
TTTGACGCACGGGTAGAACGAGGTGTGACGCCCTTGGCGCGGAACCACCCATTGGTCGAGCAACTTGCAAGC
ACTGTACTGGGTCAGGCTCTGGAGTCTCCGCAGGAGGCCGCAGCCAAGCGCGTAGGCGTCATTCGGACCTCT
GGCGTAAGTACTCAGACCACTCTTTTGCTCCTTCGATGGAGATTTCATCTTTCCGGACGAAAGGGAAACCGA
TCTTGGCAAACTCTTGCTGAAGAACTTGATCTTCTGGCTTACGCAGGAAGGGCAGAGGATCCGCAGTGGTTG
GACGCTGAGGCCACCAGAGCTTTGCTCGATCTGACCCCTCAGGGTAACTTGGATCCGGTGCAGAAAGAGGAA
CGCCTTACTCGGACGCTTGAGGGACTTAGCGCTTTGGAGGGGGTTTTGGACCAGCGAGGAAGGGATAGAGCC
GCAGCTCTGCTTGACGCTCACGAGAGAGTACGGGGAGCAGCGCGAGGGCAAGGGGTGACCTATTCTGCGGAG
CCTCCTGGCCCCCCGGATCTGCTTGGTGTCTATCTCTTTCTCCCCGCACCAAGACTCGGAGGCCTCGCC
169 71 ATGATAGCCGTGGAAGAGTGGCAACCTGCGGACGGACTGACCCTTGAGCCTAATGCAAAGAGGGCTGCGAAG
GCTAGAAAGAGGTGCCTGGCCCTGACAGCGGGTCCCGGTGCCGGAAAGACAGAGATGCTCGCACAACGCGCC
GACTTCTTGTTGAGGACCGGAACCTGTCGGTACCCCAAGAGGATACTGGCCATCTCATTCAAAGTGGATGCA
AGTAGAAACCTGAAGGACAGAGTGGAGAGGAGGTGCGGCTATGATTTGGCGTCAAGGTTTGACAGTTATACT
TTCCACGCGTTCGCCAAAAGGATCATCGACCGCTTTAGGCCGGTGCTGACAGGCAAGGACGCCCTCGACGCA
GGCTACACCATCGTGGATAAGAAGAATGGCCCCTCTAGGACCCAGATCGAGTTCGGCGACCTTGTCCCCCTT
GCCATACAAATCCTGCAATCAAGCAAAATTGCACGAAACGCGATCCGCCAAACTTACAGCGACATCTTCCTG
GATGAGTTTCAGGACTGTACAAACCTGCAGTACGACTTGGTAAAACTTGCGTTCCAGGGTACGTCAATACGG
CTGACGGCTGTTGGCGATACCAAGCAGAAGATAATGGCCTGGGCTGGAGCCCTGGACGGCATTTTCCAGACG
TTTGCCAACGATTTCAACGCCGTGTCCCTGAACATGTATAGGAATTTCAGAAGCAAGCCACAACTGCTCAGG
GTTCAAAATGAAATTATCAGGAAGTTGGACCCCGATTCCGTGATGCCTGACGAACAACTTGACGGTGATGAA
GGCGAGGTCTATGCGTGGAGGTTCGAGGATAGCTGCAAGGAAGCCGTGTATCTTGCGGACCTTATCAATGGC
TGGATCAACACCGAACAGCTGCCCCCAGCGGAGATCGCCGTACTGGTCAGCAAACAGCTCGACCTCTATGTC
GACCACTTGATGACTGAGCTCGAGGCTCGGGGAATCCCCTACAGGAACGAGCAGCAGCTTCAAGACATCACC
ATAGAGCCGGCAGCTAGACTCATTGTGGACTACTTGAGTTGCCTCTACGGCAAGAGAGAGCCGAAAGCATGG
ATCCGGCTCATGAACCAGCTGATCCCATTCGCGGACGAGGAGATCCAATCTAGTGCTCGAAAGGACCTCGAC
CAGTTGATAAAGAAGCAGAGAAAAAGGGTGAGCGACGCGAAGCACACCGATTCACCTTTCAGCGATTGGGCA
CAACTCGCAATTGAATTCCTGAAGTACATAGGCAGTAAGATGCTGGTGGCACTGAGTCCAGATTACGAGACG
CGCGAGAGGCTGAATGACGTGATCAGGGAAACTTTCGCGAGGATCAAGGAACTGTTGAAGAGCGAGCCCGAC
CTGCCCAAGGCGCTGGGCCGGTTTGCCGATGACCAGGCGGTGCGAATACTGACCATCCACAAGAGCAAGGGC
CTGGAATTCGACAGTGTGATCATCATGGCCGTCGAGAACGAGATATTCTTCGGGAACCAGGACGAGAATAGG
TGCGCTTTCTTCGTAGGTGTGAGCCGAGCAAAAAGGAGGTTGATACTTACCCACGCCGACCAGAGGGAAAGG
CCAGCGTCTGCCAAGCGATGGAATGTTAGTAGAACCGCTCAGACTGAGTACATTAGTTACGTCACCCCTTTC
GTGAGGCCACAG
170 21 GTGGCCGCTTTGAAGCGCTACTTTAATGACAAGAACCTGATCGTGATAGGCTACTCTGGCAGGGACAAGAGC
CTGATGAGTGCGCTTACCGAGGCTTTCTCTGAGAAGGGCTCTGGCCGCATCTACTGGTGCGGCTACGGCAGC
CACATTTCCCCCGAGGTGGAAAGCTTGTTGAGGACCGCGCGAGAGGCAAACCGCGACGCCTACTATATCGAC
ACCGATGGGTTCGACAAAACCATGTTCAGCCTGGTAATAAACTGCTTCCAGGCGGATATCGAAAAGAAGAAA
GAGATAATGAGCATCCTGGAGTCTGCTCCCGAGGACAACGATACCAGCCCGTTCTCAATTCACATCACCAGG
ACGGATAAATACCTTAAGTCCAACCTCTACCCGATCATCTTTCCTAAGGAGCTGTTTCAGTTTGAGATAGAA
TATCATGAGGGCGAACGACCATGGACCCTGCTGAGAGAGATCACCAAAGACCAGAACATCATCGCCGTGCCC
TACAAGCAAAAAGTCTACGCCTTGTCAACGGGATCAGCTATCAACAACGTGTTTGGTAGCCGGTTGAAATCA
GATATAGAGAGGATTCCCGTGTCTATGGATGACATTGAGCGCAAGTCTAGTTACAGGGAGCTCTTCCTGAGG
GCCACCCTTCAGTCTATAGCCATTATAAGGGGCCTGAACGTGGACATACGACACAATACCCTTTGGCGGAGC
GACATCTTTAGGAACGACAATGGCACCCTCATCCACGAAGCGATCGAGTGTTCCCTGGTGTTTGTGCCCCAA
CAGAAGTATGCCCTGTTGAGCTTGAGGCCCACCATCTACATAGAGAACTCTCATACGGTTAGCAAGGAGAAA
AAGCAGGAGTACGCCAGGATCTACCTGGATAAGATGTGGAATAAAGCGTACAGCACGAAGTTGGCCCAGTGG
GAATCTATAATCTTTGGAGACACGAGGCTCGCCTTCGAGGTGCCGCAAAATTCAGGATCCGGGTTTAAGTTT
CTGATAAGCCACAACTGCGGCTTCAGCGAAATCCAGTATCAAGACAACACCGAAAGGGGATACAGTAGCAAG
AGCTACGACAACAAGAGGACGATCTATAGGGGCTTGCAGCTGAAGGAACCCGAGCTGGAATTTGTCAATACG
TTTGCAGACCGGCCCTTCCTGGACAGCAACCCCATGCGAGGCCTGAGCAATCACAGGCCGTACGACAGCTGG
CAGAAAGACGTTCTCTTGCAGAACGTGCGGTTGGGCGTGATTTGCCCGAACACGCACACCGACCGATTCCAC
TCTTTTCTGCAGCAGCTTAACACCACAATTCAAGCCAATGACGATAGCGACTACATTCAGTCCTACACCGGT
TTCCATAGCATTTACAAGACTCTGCTGGAAATCCCCGATAACGGGACCGACAAATGGATAAACATCGAGGAT
ACCCCCAAGGACACCATCAGTCTGGTTCAGAGTATATGTCACCAAGCGAACCGACTGGCCGACAAGTACCCG
GGCATCGTGGTGGTGATTTTCATCCCCGCATTTTGGTCTATCCATCGACAGTTCAAACACAACGGGGAGAGC
TTCGATTTGCACAACTACATCAAGGCCTACGCCGCACAACATAGCTTCACTACCCAAATCATTGAGGAAAAG
ACGCTGCGCGACCACATGGTCTGCGAAATTTGTTGGTGGCTGTCACTCGCACTGTTCGTTAAGGCTATGCGA
ATCCCGTGGGCACTGGCCAATTTGGACTCTGACACCGCTTACGCGGGTATAGGGTACTCAGTGAAGACCAAC
AGCAAAGGCAACGTCGACATAGTGCTTGGATGTTCACATATATACAACGCAAAGGGCCAGGGTCTCAGATAC
AAACTCTCTAAGGTCGAGCAGCCCCAATTCGATGGCAAGAAAAATCCTTACCTTACGTATGAAGAGGCCTTC
AAGTTTGGAATTACCATACGCGAGTTGTTCGTCAAAAGTATGGACCGGCTTCCCAGGAGGGTTGTGATTCAC
AAGCGGACGCCGTTCAAAAAGGAGGAAATAGAGGGAATCACTCACGCGTTGACTCAGGCTGGCATTAAGGAC
ATCGATCTCATTACGATCAATTACGAGTACGACGCCAAGTTCATAGCGCAGAAGGTATACTATGACAACATC
AGCGACGATTCATATCCCGTAAGTAGGGGCACCTGCATCAAATTGTCCAGCCGAAATGCGCTGCTGTGGACA
CACGGCGTGGTTCCCTCAATCCGGGAGAGACGACGCTACTACCCCGGTGGGCGCTGTATTCCCGCACCCCTG
AAGATAACAAAATACTACGGTAAAGGCGATCTTCCGACAATCGCCAGCGAGATTATTGGATTTACTAAGATG
AATTGGAACAGTTTTAATCTGTACACGAAACTGCCCGCCACCATAGATACGAGCAATACATTGGCGCAGGTC
GGCAATCTGTTGCATCAGTATAACGGCGCAACTTACGACTACCGATATTTCATC
171 63 ATGGTCGCGCTGAGGCTGAACGGCGTACCCATCTTGTGCGCCGCTGACGTAACCGTGGCCGTGGCGAAGTTG
CCGTACACGAAGGAGAGCCTGGACGAGTTGAGGAAGGAGCATGCGGGGAGGTATTTGATTAGGAGAGGCGGA
GATGACGGGCAGGAAATCATGTCTGTTCCCTTGCTTGCTGATGCTCCGCAGCTGAGCGATGCCGTTGTGGAA
GTTAAGCTGTCAGAAGCCCACTGGTTGCTCGCCTCACTCGCGGTGGAGGCCCTCACCAGGTTGTTCACAGAA
CTTGGTAGACCTATCCTGCGGTCCCGGCCATTGCGGCTGCTCTCCCAAAAGCCGGCCAATCTTTTTCCGGAG
AACGTCGGACTGCCAGACTGGCTGCAAAGGAGGGTTGTGCTGGATTTGGAGACTAGGAAGATCTGGCGGCAG
GATGGAGACCCGACATTGGTGCTGCTGTGCGATGTGCGGACTCAAAACTTTATCGACGTGCCAACGGATAAA
CTGATGGCCACCGGCGTAAGCGTTATGGGTCGCTACGTTAGCCGAATGGTGAGCTCTGATGATCCCCGGATC
ACCTCACATCTGAAGCTCGCCGGCAGGGTCATTAGCATAGAGGGCGACCGACTGCTCCTCGCCGACTTTGGC
GAGGGACCGGATAGTATAAGCATTGCTCATGCCTATCTGGAGAGACGACGGGAAAATGTCGACTGGTGTGTT
CAACAGCTGAACCCCGCGAAAGCAGGGCAAATCCTGATGAGCGTGCAGGCCGAGGCTGCGAAATTCTTGAAC
GGACCTGGCCGATTCGAGCTGATCAAGAGGACATTCGATTACCTGCGCACGCAGAGTATAGAGCTTGTGCCC
GACGTGAAGCTGGAGTTGGGGGACTTGATTGGCATGGGAGCCGCACGCTGGCCCTTCCGCCAGGAAACAATT
AAGAAGCCTACCCTGGTGTTTGATCCGTCTGGTGTCAAGACCGATACCTGGAACGAGCGAGGGCTTGACAAA
CACGGACCCTACGACCAGAGGACCTTCAGCCCCAAGGAAATGAGGATCGCCGTTATCTGCAGGGAAGCAGAC
GAAGGTCGGGTTGAAGGATTTCTGGCCAAGTTTCTGGACGGGATGCCACACGTTATCGTCGGGGAGAACCGA
AAACCCTATGAAAAGGGATTCATAAGGAGGTTCGCCCTGAGTGCCCCGAAGGTGCACACTTTCACCGCTAAG
TCTTCTAGTGTGCCGGACTACCTGAATGCGTGCCGAGCGGCCCTGAAGTTTGCCCACGACCAAGGCTTTGAA
TGGAGCTTGGCAATCGCGCAAATCGACAAGGACTTTCGGGAACTCCTCGGTCCTGACAATCCCTACTTCGCG
ATCAAGGCCGCGTTTCTCAAGCAGAGGGTGCCCATCCAGGAGTTGACGCTCGAGACAATGAGCACCCCCGAC
AGGCAGCTGGTGTACATTTTGAATAACATAAGCCTCGCAAGCTACGCCAAGATCGGCGGCATTCCGTGGCTG
CTTAAGAGCGGTCCTACCGTGGGCCACGAGCTGGTCATTGGTATTGGTAGCCAGACCGTTAGCAGTAGTCGA
TTGGGCGAGAAGCAACGGGTGGTGGGCATTACCACCGTATTCACCCACGATGGCAGATACCTTTTGGACGAC
AGGACGCGAGCCGTGCCATACGGCGAGTACGAAGCAGCTTTGTCCGAGACGCTGACCAGGGCCATAGAGAGG
GTAAGGACGGAAGATAACTGGAGGTCAACCGACGCGGTGCGACTTGTATTCCACGTGTTCCAGCAAATCAAA
GACTACGAGGCCGACGCAGTGGGGAAACTGGTCGAGAATCTCGGCTTCAGCGATGTCAAGTACGCCTTTGTG
CATGTCGTTGACAGCCACCCCTACACCCTGTTTGACGAACACATGCCAGGCGTTAAGTTTGGCTACGAGATG
AAGGGCGCCTACGCACCTGAGAGAGGCCTGTGCATCAGTCTTGGCAGGGACGAACGCCTCCTCAGCTTTACC
GGGTCTAGGGAGGTTAAACAAACCCATCATGGCCTCCCAAGGCCAACCCTTCTTCGACTGCATAGGAACAGT
ACCTTCCGGGACATGACCTACATCGCCAGGCAGGCTTTCGACTTCGCAAACCACTCATGGAGGATGCTCACC
CCAGCGCCCCTCCCCATCACCATCCACTACGCCGAACTCATCGCCCGGTTGTTGGCTGGTCTGAAAGACACA
CCCGGCTGGGACGAGGACACAATGCTCGGCCCAGTAGGTAGAACCCGATGGTTTCTG
172 33 ATGAACTACACAGCCGCCAACACGGCCAACAGCCCATTGTTTCTCAGCGAGATTAGCAGCCTTACCTTGAAA
AACAGCTGCCTCAACTGCTTCAAACTGAATTACCAGCTGACTCGCGAAATAGGCAATAGGTTCGGCTGGCAG
TTCAGTAGGAAGTTCCCTAACGTTGTGGTGGTGTTCGAGGACAACTGTTTCTGGGTTCTCGCTAAAGATGAG
AAGAGCTTGCCCTCTCCTCAACAGTGGAAGGAGGCTCTGAGCGACATCCAGGAAGTGCTGCGAGAGGATATC
GGAGACCACTACTACAGCATCCACTGGCTTAAAGACTTCCAGATCACCGCCTTGGTGACCGCCCAGCTCGCC
GTGCGAATTCTGAAAATCTTCGGTAAATTCAGCTACCCCATCGTGTTCCCCAAGGACAGTGAAATTAGTGAG
AATCAAGTGCAAGTAAGGCGAGAAGTCAACTTCTGGGCCGAGATCATTAACGATACCGACCCCGCCATTTGC
CTCACCATCGAAAGCAGCATCGTCTATTCCGGCGATCTCGAGCAGTTCTACGAAAATCACCCGTACAGGCAA
GACGCCGTGAAGCTGCTGGTGGGCCTGAAAGTTAAGACCATTGAGACCAACGGCACCGCTAAGATCATCAAA
ATCGCTGGCACTATAGGGGAAAAGCGCGAATACCTGTTGACTAAGGCCACGGGAAGCATATCCCGGCGAAAG
TTGGAGGAAGCCCACCTCGCACAACCCGTGGTTGCGGTGCAGTTTGGTAAAAACCCTCAGGAGTACATATAC
CCCCTGGCTGCCCTCAAACCTTGCATGACCGACAAGGATGAGAGCCTGTTCCAGGTCAATTACGGCGACCTC
CTGAAGAAAACCAAGATCTTCTACGCTGAACGACAGAAATTGCTTAAACTGTACAAGCAGGAGGCGCAGAAG
ACTTTGAATAACTTCGGTTTTCAGCTTCGGGAAAGGTCCATCAATAGCAGGGAAAATCCAGACTTCTTCTGG
ACGCCCCCAATTTCATTGGAGCAGACCCCCATCCTGTTTGGGAAGGGTGAGCGCGGTGAAAAGAGGGAGACC
CTCAAGGGCCTTTCAAAGGGCGGAGTCTACAAAAGGCACAGGGAGTACGTTGATCCTGCCAGGAAAATTAGG
CTGGCCATCCTTAAACCGGACTCTTTTAAAGTGGGCGACTTCAGGGAGCAGCTGGAGAAGCGACTCAAGCTG
TATAAGTTCGAGACGATTCTCCCCCCTGAGAACCAAATCAATTTTTCTGTGGAGGGTGTTGGGAGCGAAAAA
AGGGCCCGACTGGAAGAAGCCGTAGACCAGTTGATAGGTGGCGAGATCCCCGTGGACATCGCCCTCGTCTTT
CTGCCCCAGGAGGACCGGAACGCGGACAACACCGAGGAAGGCTCCTTGTATAGCTGGATCAAAAAGAAATTC
TTGGATCGGGGGGTGATAACACAGATGATATATGAGAAAACTCTCAACAATAAGAGCAACTACAATAACATC
CTGCACCAGGTGGTTCCCGGCATATTGGCAAAGCTCGGAAACCTGCCGTATGTGCTGGCCGAGCCTCTTGAA
ATCGCCGACTACTTCATCGGCCTGGACGTCGGAAGGATGCCTAAGAAGAATCTCCCTGGTTCACTGAACGTG
TGCGCGTCCGTTAGGCTCTACGGAAAGCAAGGTGAATTCGTCCGATGTAGAGTCGAAGATAGCTTGACCGAG
GGGGAGGAAATCCCCCAAAGGATTCTTGAGAATTGTCTGCCGCAGGCAGAACTTAAGAACCAGACCGTCCTG
ATCTACAGGGACGGGAAATTCCAGGGTAAGGAGGTGGAAAACCTTTTGGCTCGGGCACGAGCCATCAACGCC
AAGTTCATCCTGGTAGAGTGCTACAAGACCGGCAGCCCGAGACTTTACAATTTCGAACAAAAGCAGATTAAT
AGCCCCAGCAAGGGGCTGGCGCTTGCATTGAGCAACCGGGAGGTCATCCTCATCACCAGCCACGTTAGCGAA
CAGATCGGCGTGCCTCGGCCTCTCCGCCTGAAGGTGCACGAACTGGGAGAACAGGTGAACCTCAAGCAACTT
GTGGACACGACCCTGAAACTGACTCTGCTGCATTATGGCTCTCTGAAGGAACCTCGGCTTCCAATCCCCTTG
TACGGAGCCGACGCCATCGCGTATAGGAGGTTGCAAGGAATCTATCCAAGCCTGCTGGAGGACGACTGTCAG
TTCTGGTTG
173 19 ATGAACTACACAGAGGCCAAGACCGCCAATAGCCCCTTGTTCCTTAGCGAGATTAGTAGTTTGACACTTAAG
AATAGCTGCCTGAATTGTTTTAAGCTGAACCATCAGGTCACCCGGAAAATAGGCAACAGGTTCTCTTGGCAG
TTCAGCCACAAGTTCCCTGACGTCGTGGTAGTGTTCGAGGACAATTGCTTTTGGGTGCTGGCTAAAGATGAA
AAGAGTTTGCCTAGTCCACAGCAGTGGAAGGAAGCACTGTCAGACATACAGGAAGTGCTGAGGGAAGACATT
GGGGACCACTACTACAGCATTCACTGGTTGAAAGACTTCCAGATAACCGCCCTGGTCACCGCGCAGCTGGCT
GTGCGGATTTTGAAGATATTTGGGAAGTTTAGCTACCCGATCGTGTTCCCCAAGGACAGTCAGATCTCTGAA
AACCAGGTGCAGGTGCGAAGGGAAGTGGATTTCTGGGCTGAGATAATCAACGACACGGACCCAGCAATATGC
CTGACGGTGGAAAGCAGCATCGTTTACTCTGGCGACTTGGAACAGTTTTACGAAAATCATCCGTACCGACAG
GACGCCGTGAAACTTCTCGTAGGGCTGAAAGTGAAAACTATCGAAACCAACGGCATCGCGAAGATTATCAAA
ATTGCCGGGACCATCGGAGAAAAGCGGGAGGAACTGCTGACCAAGGCAACCGGGTCCATAAGCAGGCGCAAA
TTGGAGGAGGCACACCTGGGCCAACCTGTGGTGGCCGTGCAGTTCGGCAAGAATCCGAGAGAATACATCTAT
CCCCTTGCCGCGCTCAAACCGTGTATGACCGACAAAGACGAGAGCCTGTTTCAAGTGAACTATGGCGAGCTT
CTGAAGAAGACTAAGATTTTCTACGCCGAACGGCAGGAGTTGCTGAAATTGTATAAACAGGAGGCGCAGAAG
ACGCTGAACAACTTCGGCTTCCAGCTCCGGGAGCGGTCAATCAATAGCAGGGAGAACCCCGACTTTTTCTGG
ACCCCCTCAATTTCCCTTGAACAAACGCCCATCTTGTTTGGCAAAGGTGAGCGAGGTGAGAAACGAGAGACC
TTGAAAGGCTTGAGCAAAGGCGGCGTGTACAAGAGACATAGGGAGTACGTCGACCCCGCGAGAAAGATTAGG
CTGGCCATCCTGAAGCCGGCCAATCTCAAGGTTGGGGATTTTAGGGAGCAGCTCGAGAAGCGACTGAAGCTC
TATAAGTTCGAGACCATCCTTCCCCCCGAGAATCAAATCAATTTTAGCGTAGAGGGCGTGGGCTATGAAAAA
CGAGCCCGCTTGGAAGAGGCCGTGGACCAACTGATTAGGGGGGAGATACCCGTGGATATCGCTCTTGTCTTT
CTTCCGCAGGAGGACCGAAACGCCGACAACACCGAGGAGGGGAGCCTTTACTCATGGATCAAGAAGAAGTTC
CTTGACAGGGTTGTGATAACGCAAATGATCTATGAGAAAACGCTTAACTATAAGAACAATTACAAGAACATC
CTCGATCAGGTGGTGCCTGGAATCCTTGCGAAACTTGGTAATCTGCCTTACGTGCTCGCAGAGCCACTGGAA
ATCGCCGACTACTTCATTGGCCTGGATGTGGGTCGCATGCCTAAGAAAAACCTCCCCGGGTCACTTAACGTG
TGCGCGTCCGTAAGGTTGTACGGGAAGCAGGGCGAGTTTGTGCGGTGCCGAGTCGAAGATAGTCTCACCGAA
GGTGAAGAGATCCCCCAGAGAATCCTGGAGAATTGTCTGCCCCAAGCCGAGTTGAAGAACCAGACCGTGCTG
ATATACAGGGACGGTAAGTTCCAGGGCAAGGAGGTGGATAACTTGCTGGCCCGAGCCAGGGCCATTAAGAGC
AAATTCATACTTGTCGAATGCTATAAAACGGGCATCCCCAGACTGTATAACTTCAAGCAAAAACAGATCGAC
GCGCCCAGTAAGGGCCTGGCGTTCGCTCTGAGTAACAGGGAGGTGATCCTGATCACGTCCCAGGTTAGCGAA
AAGATCGGCGTGCCGCGACCTCTGAGGCTTAAGGTACATGAGCTGGGAGAGCAGGTAAATCTGAAGCAACTG
GTGGACACCACACTCAAGCTGACCCTGCTCCACTATGGGTCTCTTAAGGACCCGAGGCTGCCCATCCCCCTT
TACGGCGCTGACATCATCGCGTATAGGAGGTTGCAGGGAATATATCCCTCTTTGCTGGAGGACGATTGTCAG
TTCTGGCTG
174 85 ATGACTAACAAAACCAAACAAAAAAGCAGGAAGCAGAGGTCCCTCATAGAATTTCTTAAGGTGAAGAAGATC
AACAAGGAAGATGGTAAGAACCATAACCTGATCAAGTATAGCACCGAACGGATCGATACAGGAGTGACCCAG
AGCCTCATTGACATCAATATATCCAGTAACATCCTTAAGCTGCGGGGCAGCATTGCTCAAGAGGTGTTCAAA
CGGAAAATTGGCGTTTACTACGGGCTTGGGAAGTATTACGTTGCCGAAAACAAGCTGAAGAACACCGATCGA
ATGGATTTCTTGAAGAGGGTCTACGAGACCTTCCCCTATAACTACCTCGATAAACAGGACCCGCACAGCAAG
ATCAGCTTTTACGAGTACTACACATTCCAGAAGTCCATCGACAAAGACGTGATAAACCTGCTTGAGCTGCAG
AAGATAAACGAGTATAGTTGGGACATACTGGACCCACACATCGCCACGCGCCTTCTCACAAGCTATGTGAAG
CTTTACTTGGGCGACTACTTGAAGCCAATCCTGTCCTCTTTCGAGTACGTCCGGGCTCGAATCAAGACAAAG
CAAAAGACCGTTCCAATCAAAATCCCCGTGACCAAGAAGTTCGAGATCCGAACTTTGGGGTACGACCCGACG
CAGAGCGAAATTACTCTCGCCATAAAACGACACGCCAGCATGAACGCTGTGCTGTTGAGCAGCTTTCCCCCC
GACATCCTCGCGGTTGTGATAACTAAGCTCAAACGCCTCGTGAACGAGGCCGTGAAGCAAGACTACCGAAAG
GTCAGAATATACTCCGAGACCCAGCCGGGGAGCGGTACTGCCGCAGTTGTTGAAATCATCAGCGGCAGCCAA
AACGTGATGAAGTTTCTCGAAGAGCATCCGAAGGGGGCCATCCACGTTGAAAAGCGACTTAAAGAGCTGGGT
AAATCACTGCAGGAGGTCCGGTACCTTCTTATCGGCGTCTATGACAACAACGTCAGCCTGGAGCGGGCAAAA
AAAGACGAAAGATACCACTACTACTTCACCGAGCATAACGCTTACCTTGTACTTACGCCCGAGGTGCAAAAG
GCGCTCTTTGGCAAGTTGATCGACGACTGGAAGACAAGCATTCTGAATGAGTACCAAAATAAGCTCCACGAG
ATCACGAGTCTTGGGATGTTTAAGCATTTGGAGACCATACGGGGCATCCCGGTTTCCTTGAAAGAGAGGCTT
GTGGTCCGCACCAGCGAGGGCTTGCAAACCGTAGATGACATTAGGGACATTTTGACCAACCCCAAGATTCTT
AGTAATATGTTGCCTATATCCGAGGACGCGCTCAAGGAGACGCGAAAGCATAAACTGCGAATCACCCTGTTC
TGTCCGGAGAAGTTTAGTGAGAGGATTCACCGGACTATTTTCTACGACAAATTGAACCAGTTTCGAGACGGT
CTGCTTAGCAACAGCTTCGCAAGCGTGGACGAAATCGAATTGTTCCAGGTCAAAGGCGAAAACTCTAGCGAT
TATGAGGAGATCATGAAGGACGCTGGCCTTGATAAAATCCACGATTATACCCTGGCGGTCATCATATTTCCC
GAACATTATAGTAAGCGCAACCTTGAGTTGCGCATCTTTTACAACTGGCTGAAAATGCGGTTCTACTCAGAG
AACAAGCCACTGGTTTTCCAGGGCGCTCGGATTGACAGCGTCTTCGGCCGGTATGCGAAGTACGCATCATAC
AACCTCATCTTGCAGATCCCACCTAAATTGGGCATCTACCCGTACTCACTGGAGGAGCACGAGGACTATGAC
TACATCATCGGCATTGATTACACCTATTGGTACGAGAGAGATACGCCTAGTCTGGGCGGTGGCGCCGTGTTG
ACCAGCCCGTCAGGGCTGATTGAGAGCATATACCCCATCGCACTCCCGAGCCGCACTGAATCCCTCAACATG
TCCAAGATACTGAGCGAATGGTTCACGCGAACAGTCAAAACGAACCGGCATATCATAGATAAGGGCCACGTG
ACCGTGCTTATCTCCAGGGACGGCATGATTCCTAAGTACGAACGCCAGACAATCCAGGAGTTCCTGAGTGAA
TATAGCGGCGACATGGGCATGACCATAGAGGCAGTAGAAGTTAGGAAACGCATCGCCGTGAGGACCTGGGCT
ACACAAGAGCCCGTGGCCTACTACAGCCCGATAAAGGTTGGCGACTGTACCTACTATCTGGTCGACGCGCAC
ACCGGATACCCGCTGGGGGAGAAAGGGAACCGAACCTTCTACAGCTCACCCTATCTCATAGGAAGTTTTTAC
AGGTTCGAAAAGGGCAAATCCTCCCCCGTGCCAGGTAGCGCAAAGAAGCACGTGATCGAAAGCCTGATAAGA
CTTCAAAAAATCAATTACGCCACCACCCGCATGGATAACATCAAGTTGCCCCTGCCCGTCGACATCACCCAC
AAACTCATTAACTTTATCCGGGACACCAAGATGGAAATCAAGGGGGTCGGTATCCCAAACAGTCTCTTTATG
ATA
175 79 ATGCCGTTCAATAGCAACCTGATCTTCGTGAAGCTCGACGACCTCAAGAGAGCCTTTCTCGAGGGCGTCCAC
AGTGGTCACGCCGTGGTGTATGAGGTGAGCGAGGGACTGAGCACCGAGGATCTGAAGAAAAGGCTTATCAAG
GCCAGCGTGATGTACCACTATAGGTATGGAAGGAACGTGTTTGTCTTCGGCGTCAAGGAGGGCACTAAGGTT
GACGATCTTGTACCAGGCCGACGACTCGGCGAGCACGAGGTGAAGGAGGTTCTCAAGGGCATCCCGTCTAAC
AACCTGGTGTCCATGATGAGCGCCATGCTCAATTACCAGCTCTCTGTGCTTCTCACCAGCAAGGGCTTCCAG
TATAGCTACGAAGAGATGCGGAGGGGCAAGTATCTGTGTGTCAGCAACTATTACGGCAAGCTGATACGGAAC
CCCGTGAAGGTTTGCCTCAAGGTAAATGTCATAAGGAGCCTCATTGACGAGCAGGATCAGTACCTGCCCATC
GCGCTTAACTACAGGGTGAAGAAGAGCAGGCGGCTTAGCCCCGAAGTAATGAATGAGATCCACGCGGAGTTC
ATGGAGGCCTTCCCCAGCTACCTCAACGACCTGAAAATCATAACTCGCGTCTTGAACGACGATATGGTGAGG
AACAGGGAACTGAAATTCCTGGAGATCGAGTACAAACCCCCTGCTATCATTACGTTCCGGTTTCGAGGCAAC
AGCACCGGCGAAAACGTGACCGACATTCTGAAGCTGGGCCCCTACTTCCTGCCTGGGGAGGAGGAGAAGATC
GATGTGGTCTTTGTGTACGAAAATGCTCTCGCTAGCCAGGCGAAGAAACTCACCAAGGTTTTGGAGGATACC
ATCAAGGACGGGCTGGGCATAAAGCTGAACATAGACGACGAACATAAGTTCAGCCACGACAAGCCGCTGGGC
GACGTTATTAAGCTGGTGCGCGACCGATTCATCAACAGCGGGAGTTGTCTGCTGGTCCTTAGCAAGGAGAAC
CGCCTCGGTCCTATCTTCATGAGCATTAAACCGCTCACGCTCAAGAAGAACTTCTACTTCAAGTCTCAATTT
ATCACCAACGAAACGATTAGCAAACTGGACTCTTATGCGGTCAAAGCCAATATCGTGAATAGCATCCTGTTC
AGGGTTGAAGGTACCCCGTACATGCCCGTTCTGCGGGGCAATATAGACGTACTGGCAAACAATTTGTTCGTG
GGCATCGCCCTGAGTAAGCCTCTGAGGAAGGGCTACACCAAAGGAGGCATAGCCCTCATAGACCCCTACAGC
GCCCGAATTATCACAAGGGCCATCGTGTTGAAGCGCAAGATGAGGAGCGGCAAATTCGAAGCCTCAGACATG
CACGAGATCGTGTCCAACATCAAAGGCGTGCTGAAGGACTACAAGGAGCTGTACAACGTCAACGAACTTGTT
ATACATATCTCCAAGTTTCTGAGCGATGACGAATACGGCCTTTTTTACGAGTACTTGCAGGACCTTAATGTC
AACGTGCGACTCCTGAGCATCAGGAAGAGGGACGACATTACACTGGTTAGGGACGGGAGGATGGACAGCCTG
ACCATGATCAAGCGCGGCAAGAGTCATGTCGAGGTCATGTATTGGCCTCACGAAAGGGCCTACCACCCCCTT
ACTATCAGGATCTACGGCGACAATGTGGACAGGGACGTGATGATGCGACACCTGAGGTTTATCGAGCTGCTC
CGGCACATGTACTACCCGGCCAGCAGCCGCTTCATAGTTGAGCCCGCGACCATTAGCTACAGCAGGAGGGTC
GCCAGATTTGCCCCCTGGCTTTCAGACAATACC
176 84 ATGGAAGTGTCCCCCTTCTTCAACGAACTGTTCAAGTACTACATATTTCTGTTTTTTGGTTTCAAGGTGAAC
ATCGTGAAATCACATTACCAGAGCATTAAGAAGCACAAGATAATATTCTATTCCGGTGGGATCATGGACGAG
TATTACACTAACGCCTTCCCCATCAACAAATACTTTATCAACCGCATCATCTCTGAAAACTGCATCCGCTGC
CTGTGCAAAATAACCAAGCTCGAGAAAAAAGAGAAGATCGAGGAGTTGCTTTACTCTATCAGCGCCACCCTG
GGGGGCATTTACATCGACGATTACAACCCAATGAAGAATAAGTTCAGCTTCTACATTTGGAAGGGAATCCTG
AATAAGAAGATTAAATCCTACGGGTCTGAATGGCTCATTTACAAGATGAAAAACATGGGCTTTAAGGATCCG
GAAAACAAGACGCTGTTGAACTATGTGAAAAAAAAGTACGAGAAAGACATAAAGTTCGACATCATAAAGAAA
GAGAAGATAGAATGGAGTAACCTCGACTGGGAGATAAAGGAAAAGATAGTGCTGGGCGCCATAAAAACTCAC
CCTACCATTCGCAAACTGATTGAATACAAGAATGAGAAATTCATTGACAAAATTGGAAAGAAAATTCTGACT
TACTTTAGCATCACAATCACCAGCGACGAGAACGAGAATTACTTTCTGATCGTCAAGCCCAAGCATAAGATC
ATCAGCTCAGAGACAATTTACAACATGCTGAAGAACAACAAAATCGACTTTAAAACTCTTGAGAGGAAGCTG
CTGAACGGCAGCGCCCTGATAACCACCAGTAGGGCAGTCGGCAGACGGAAATACGTCAAAATCAAAAAAATC
ATATCCCCCAAGGAGAAGGAGTATTGGCAACATACCCAGGACATCAATGAGCACTACGAAAAGGAGGGCGTC
CCGATCAGCGTCGGCGGTGACGACATCCACTGCTATATCTTCATCGGGGAAGACGATTACGCCTACCACACG
AAGAACTCCTTGCTCTACGAGGGTGTGACGGAGGACGTGCAGAAAATACTCTTGGATATGGGTAAGTTCCTG
GAGGAGCTGGAGACGGCAAAATCTATCCTCAAGCAGGGCAACCTCATAGACTTCAGTCGCGAATTCCTCAAC
ATTAGCACGAAGGACGACTACACCCTTACTCTCCTGAGCACACTGTCCGATATCAAAGTGAAGCTTAAGACC
GAGTCTGGTATCATCACAGGCGACTACCAGAAACTTAGGGAGATCTTTGACTGGATCTTCGACAAGAGCTTT
AACCCCTTGAAGCCTAAGAATTGCTACCTTCCGCTGAGTATTCCCCCCATACTGAATGACAAGAAAAAGATC
GGCGTGTACATCTTCTATAGCAATATTAGCGACCCCGAGCTTAGGTTTATCGAAGGGATCTTTAAGAAACTG
GGCCTGATATGCGCCATCAATAAGAGTGTGCCAAAAATTGAGGTTAAACTCAAGAAGGAAGTGGACTTTGAG
GACTACGCCAACAGCAGGATCATAATCACCCAGACCGTACTGAGCAATCTCGAGGATGGCGAGCAGCCGTTC
CTCATATGTATAAGTCCCTTGCTGCCGAATAACGAGTTCGATGAACTCAAAATGCATCTGTTCTCTCACCCG
CAGCTGATATTTCACCAATTCATGTATCCGTTCAACCTTCGAAAGTGCCTTGAGAAAGAATCATTCAAGAAA
CCCTTCATCAACTCAATCCTGTCTCAGTTCTTTCACAAAATGGGCATGTACCTCTTTAGTCTGTCTGACGAG
CTGGGGAACTACGACTTCATTATTGGTTACGACATAAGTAGGGAAAAGGATGACATCGGGAAGATAAAAGGT
ATCGGCGGCTCCGCGATCATCTACAACAATTACGGCCATGTCAAGTCAATCATAACGTTCGACGACGTAGGG
TCTAGCGAGATAGGCAGGTACGACCTCCTGTTCGCGCAGGTGCACAGCGAACTGATACCCCACCTGAATCTG
AACAATAAGCGGAAAATTAAGATTCTGCTTCTCAAAGACGGGCGGATTTTCAAAAAGGAACTCGAAAAGCTC
AGCCAAATCAGCAAGAAGTATAACTTCGAGATCACCTACATTGACGTTCGCAAGAGCACGCTGCTCCGGTTC
TGGGGTGTGCGGAGGGGCAAAGTGGTGCCCGAGTATAAGAATAGCTACGGGAAGTTCGGACGCGCATACTAT
ATTAGTAGCCATTACTACAACCGCTTTTTCAAGCAACCAATCGCAATCGTGGAGAAGTACCACATAGACGAG
GGCAATTACAAACGCGTGGAAATAGAGGAGAATGATATTAAGCAGCTGGTTCTGTTGACCAAGATTAACTAC
AGCCAACTGATGCCAGATAAGATGCGGCTGCCCGCACCCGTTCACTACGCACACAAGCACGTGAACGCCGTG
CGACGGGGCTGGAAGATCAAGGACGTCTCTATACTGAGGAGCGGGTGTCTTCCTACGATC
177 81 ATGGCCTATAGCCTTAACGCTTTCGAACTGGAAATTCCCGACATTGACGCCGACCTCTACAAAGTTGACCCT
CAACCCTCTGATGACCCATATCGAATCCTGGGGGGTTTGGAACGGTCCTTCGAGCAACAACTGGACGGCAAG
GCCCAGAAATGGAAACAGGCGGAGGACGGAGATTGGTATATCGCCGTGATAGGCGCGTCAGAAAGGAAAACT
ATCGAGTCCCCCTCCAGCGGTACGAGGGCAGGCTACACCACCACGCATACGCTGGATCCGAGTAGCTTTTGG
GACAGGATGGTGTTGCAAAGGGCAATTAGCGACTCTGTACGATGGTACATGACCAACTATCAGGACTTTTGG
TATCATGAGGATGCGGATGCACTCTTTTATCCTTCTCCTAGAGGCAAAGTGGACGAGTACGACGTCTACACC
GGATTTAGTCATAGGGTCGAGTTTTATGACAGCCCACAACTTGTCGTGCGCAGCGTCACTAAGTTCATCTCC
AGTGAAAGCCTGGCGGACCGGATCAACCATCAGGGCACAGAAGAAGCAACGGAAAAATACGGTGGTGAGAAC
TTTAGGCTGGACAGGCCGGAACCAACCAAATGTACTTTGCACGGCATCTCAACCGAGCGAACGGTAAGTGAC
AAGACGATAGATTTTGGTGACGAGATGCTGTCCGTGTTGGAGTTTGCACAAAGAAAATATGGCAGCGAGTGG
GCGGACAAAATCGATCCCGACGAACCATTGGTGCAGATACGCTTCGGGAACAGCGACCCCTACGACACCGCT
CCGAGCCTGCTGAATGCGAGCCCTGAGGAGCTGAATCGCAGGCTGACCAGCGAGGCAGCCCTCAGCGCACAA
GAAAGGCAGAAGGCCATACAGAACTTCATCGGCAGGATACACTACATCCAGGTTGAAGACGAGAAGGTGAGC
GTCAGCGATGACGGCGTACGGCCCACCGAGCAGGGCGACTTCGACTACCCCGATCTTGCGTTTGGCAATGAC
GAGGTGCTCAGCACCGGCGTCCCGAACGCGGTAGATCCTAGCCAGGAGGTGCACCCGGGCAACTGGCGATGG
ATAATCAGGGACTACCTGGAGGAATACGGCTTCTGGGAGTCACAACGAAAGCTGTCTGAGATCGTGCTGGTG
TACCCGAGAGGCGAAGAAAGACGGGCAGAGAACCTGTACCAGGACGTTAGGGAGAAGCTTTCAGAGATAGGA
GGCGTTCAGATCAGGAGCGATCCACATCGCGTGTGTTACACCGATCAGGTGGAGTTCGACGAATGGGTGGCT
GAATTCGGTGACTCAATCGACGGTGTTCTTGGATTGATTGAGGGAGATGGAGACGAATACTACGAAATCATA
GATGCATTTGGCGGAGCACCGACCCAGTACGTCAACACTAGCACCTACTCAGAGCACAGAGGGGCGAGCGAC
GACGTGATCTTTAACACTGCTTGCGGACTGGCCGTGAAGTTGGGCGCATATCCTTTTGGCCTGGCCAACGAC
CTGAACAGTGACGTGTACCTCGGCCTTAGCGTGGCAGGGGATAGAAGCACAACGGCCACCGCCGTTGCCATA
GACGGAAGAGATGGGAGGATTCTCTATCAAACAGAGGAACCCCTGGGCCAGGGTAGCAGCACAGTAAGCGAG
GGCTATCCCGCTAAGCGAATCATCCAGAGGAGCCTGAAGACCGCCTCAAGCGCCTTTGATCGACCAATCGAG
AGCTTCGACATTCACAGGAACGGAGACTTTGGCGACGCTGAGCTGGAAACCCTTAGCAGTGAATTGCCTGCA
CTCCAGGACCAGGAATATGTGCATACCGATGTTTCATGGAGCGCCGTCGAGGTAATTGAAAACCACCCTTAC
AGGCTCTTTAGTGAACGGGGCAGCAGAGCTCCCGATACCGGAGCCTATGCTAAGCTGGACGACGAGCATGTA
CTGGTTACTACCTTTGGAGAGCCCCAGATCCACCAAGGTACGCCAAAACCGGTCCTGTGCAAGAGGAGAGCA
ACGAGCCAAGATCAAGACATCACCGCCATCGGAGAGGACGTGTTCAAACTCAGCTTCCTTAACTGGGGTAGC
CCAATGATGAAGATGAAGCCACCTGTTACCACTAAGATTCCGAAGGAACTCAACGAGATTTTCGAGAAGTGC
TCTAGGGTGAGATACCCCCCCTTC
178 83 ATGAAGACGCAGGATGATATCGCGCACAAGCAACCCATTACCATCGAGGTCCAGATCCTGAAGGAGCTCGAC
AAGCCAAGCCCAAAAATGGCCACCCGGTTCCTCGTGGCCGATAGGGACGGCAACAGGTTTAGCCTGGCTATC
TGGAAGAACAACGCACTCAGCGACTATGACTGGACGATTGGCCAGTGGTACAGGCTGGAAAACGCCAGAGGA
AATGTCTTTAACGGCAAACAGTCCCTCAACGGTAGCAGCAAAATGCGCGCCACTCCACTTGAGGCCAGCGAG
GAGGACGAAACCAGCACGGATGATGTGGGACGGGTCGACACAATCCTGGGTAATATGAGCCCGGACCAGGCT
TACCTGAGCCTGTTTCCCATCAGTAGGTCTTTTGATACCCTGTCTGTGTACGAGTACAGCATTGAGGCAGCC
GAGGCATTCGAGGATGCGCCGGACACCGTGACCTACAGGTGCGCTGGCAGGCTTCGGAGAATCACGGGTGCG
GGGGTCGCTTATGCTGGCTCAATGAGGATCGTGTCAACCCGCAAACTCCCGGACAAGCTCGCGGACCCCTTT
AGCTTGAGTGAACCCACGGAGAGGGAACTGAACGCTACGGACGCCAGGGACAGGCATAGGATAGAGCGGCTT
CTGAAGAGCCTCGTGAAGGCCGCCATCGACGATAGCACCTACGACCCATACCAGATCAACCGAATCAGGGCC
AGGACCCCGAGCATTACCGCTGGCGACGGGCTGTTCGAGGCGTGCTATGAATTTGCAGCAAGGGTCGATGTG
ATGCCCTCCGGCGACGCCTTCGTGGGAATTGAGGTAAGGTACCACACGCGGAGCCAGGTCACTGCAGACGTT
TACGAAGACAAAACCGCGGAACTGGTGGGCACCATCGTGGAGCATGACCCAGAGAGGTACAACATTAGCGGT
ACGGGCCGAGTAGTGGGTTTCACTGACCACCACTTCACCGACGCCCTCGACGAATTGGGCGGTCTTAGTTTG
GCGGACTGGTACGCGCAGAAGGATCGCGTCCCAGAGGGGGTATTGGAGGCGCTGCGAGAGAAAAATCCTAGG
TTGGTTGATATTCAGTACCAGGAAGACGAACCAGCCAGAATCCACGTCCCGGATTTGCTCAGGGTAGCACCC
CGCAAGGAAGTTGTCAAGGAGTTGGATCCCGCCTTCCACAGAAGGTGGGATCGAGAGGCCAAGATGTTGCCC
GACAAAAGGTTCAGGCACGCCATAGAGTTTGTGGATCATCTCGGGTCCCTGCCGGATATAGACGCCACGGTG
GCACCCGAGCCTTTGGGGCCGTCACTGTCTTACATGAGCACAGCAGTCGACAGGGAGAAGAACCTGCGCTTC
AAAGATGGAAGGACCGCCACCACCCCGTCAAGCGGCATCCGGAGCGGCGTATACCAACAACCGACGAGCTTC
GACATCGCCTATGTGTACCCCACCGAGTCTGAACAGGAGAGCAAGCAATTCATTTCTAACTTCGAGAACAAA
CTGTCCCAGTGCCAGTGCGAACCAACTGCCGCTAGGCACGTTCCTTATGAACTCGGCGGCGAGCTGAGTTAC
TTGGCTGTCATCAATGAACTTGAGAGCGTGGATGCGGTGCTCGCTGTGGTGCCTCCCCGAGACGATGACCGG
ATAACGGCCGGAGACATAACTGACCCCTATCCCGAATTCAAGAAGGGCCTCGGGAAGCAGAAAATACCCAGT
CAAATGATCGTGACCGAGAACTTGGGCACAAGATGGGTGATGAACAATACAGCCATGGGCCTGATCGCAGGG
GCAGGAGGCGTTCCGTGGAGGGTGGATGAGATGCCGGGTGAGGCCGATTGCTTCATAGGACTGGATGTGACT
CGCGACCCGGAAACCGGCCAACACCTTGGCGCTAGTGCCAATGTCGTTTATGCCGACGGAACCGTTTTCGCC
TCTAAAACGCAGACCCTGCAGAGTGGGGAAACGTTCGATGAGCAGAGCATAATCGACGTGATCAAGGATGTA
TTCCAGGAGTTCGTTAGGCGCGAGGGGCGATCCCCTGAACACATTGTTATCCATAGGGATGGCCGGCTGTTT
GAGGACGCCGACGAAATCCAGGCCCCGTTCGCGGATAGCGGAGTGAGCATAGACATTCTGGACATCAGGAAA
TCTGGCGCTCCGAGGATTGCCCAATACGAGGACAACAGCTTCAAGATTGACGAGAAAGGCCGACTTTTCATC
AGTCAAGATGACACGCATGGATTCATCGCCACAACGGGAAAGCCGGAATTTGATGATAGCGACAACCTGGGC
ACTCCCAAGACTTTGAGGGTAGTGAGGCGGGCTGGTGACACACCGATGCTGACTCTGCTGAAGCAGGTGTAC
TGGCTTAGCGAGGCACATGTTGGCAGTGTGAGCCGAAGCGTTCGCCTGCCTATCACAACTTACTATGCAGAT
CGCTGCGCCGAACATGCGCGGGAGGGGTACCTGCTCCATGGCGAGTTGATCGAGGGTGTGCCATATCTG
179 87 ATGAAGCCAGTGAACTTGGATGAAAACAGCCTCAACGACGTCCCGGTAGGCGACACCTATGCTGTCCGCTTC
ACTCTTGATGCAGTCTTCGAGAACGAAGGGCAGTATCCCCGGAGGAATCTGAAATTCACAGACGGAGGGGGG
GATGACCGAACCATCACTATTTGGAAAAACTCTGCACCCGAGGAAATTTACGAGGCGGACTATGAGCGCGGT
GCGACGTATCTTATTACCGCCGTCGAGTATGACATCGACGAAGGTAATGACGGCGAGCGATACCAGAATCTC
ACAGTCCAATCAGATGCTACCTTGCTGGAGATGAGCGGTCCCCCTAGTACCGAAGAGGCCTTGGAAGACGGC
CTCGCCGAAACCCCAGATACTAGCGCCGATTCAGGTGACCACGGGTTGACAACCTTTAGGACTACAGACGAC
CTGCCGGATTATGACGTCTATGAGTACGAGCTGGTGCCGAAGCAAGGATTCCGGCCGTCCGGAGAAAATGCC
CTCCGAGCCACATACAGGGCACGACGCAAGGTCCGCCAGCAGTTGGACGTAACACCCGTCGTGGTCGGCGAT
GCGTTTAAGCTTGTGTCTCTGGTCAAGCTGGCCCACGAGCGGGTCGAGCTTCCGCGATTCAAGATCAACGAG
GTTGACGAGAGGCCCATCGTCTACGCCGATGAGGATGACAGGGATGTGTTGGGGGAAATGCTCGGTGAGATC
CTCAAGGACGCGAAACGGGACCAGTACGACATCCATGGCATCGACAAAATACTGGAGCCAGAGCCCGTCATA
GAGAAAGAGGGCTTCAGGCTCCACGAACGGTACAACCTGACCGTGGAAGTTCTCCCTAGCAGGGCCGCTTAC
CTGCACGTGGACTATCGACATCGGATATTGAGCGACAGGACCCTGGATCAACTCGATGAAGACGAAATCCAC
CCTGGCCTGCGCGTGACCCCCTCATATAGGGACATGGGTCTGTACGTTATAGGCGTTGGGCCGGAGACGGTG
ACCGATAAGCTGCATATCGAGGGCAACAAGAGCCTGGTCCAATACCATCGGGAAGAGCCGTGGGTGGACCCG
GCGAAGGTGCAAGAAATCAAAGACGCAGATAGGGAAGTGATCTGGACCGTGAGGCAACGGGGCGATGGCACC
GAGATGGCATTCCCGCCGGAGCTGCTCGCGCTTCAAGGGCACCCCGAAAATTTGGCCCAGTTCGCCAGCGAC
TTTGCTGAACAACAAAGGCTCAACACGCGCCTTTCCGCTGAGCAATGCATCACCAAGGCTAAAAGGTTTGTG
GAGCGACTCGGGCCCTTGCAATTCGACGGACACACTGTGGAATTCGAGACCAACCCGCTGTTGGGCGATCGG
AACATAGCCATAGATGGTCTGTTTCACCCGGAAGCAAACGTGCTGCAGTTTAGCGGAGGCCAGACCGGCACC
CACCCCTCAGATGTGACACAGCTGGGCGTGTACGAAGCCCCGGACCCCTTCAGGGTGTGCCACATCAGGATG
GAGAAGCGGGACAAAAGAATACAGAGGGGTTGGAGTACCTTGGAGACGAAGCTGGAGCAGATTGGAGCGCCT
CCCGACAGTGTCGAGGAGGTCACGTTCGACGCCACAATGAGCCCTGACCAGTTGGGTATGGAGATAGCGGCC
GAGATACCGGACGACCATGATTACGACGCGGCCTTCTGCACATTGCCACCTAAAGACACCGGCTACTTTGAC
ACCGCAGACCCCGAGCGAGTTTACGATGAACTTAAGAAAGTGTTGGCCACCAAAGACCTTAACTCCCAATTC
GCGTATGAAGCAACGCTGGACGAGCGCTTTACAATAATCAATATAGCACTGGGTCTTGTCGCCGCAGCGGGA
GGTATTCCGTTCACAATCGAGAGGGCGTTGCCAGGCGATAGCGAACTCCACCTGGGAATCGATGTAACCCAC
CAATACGACGAGTCCGCGAATGGCAACCACATTCACCTCGCTGCTGCGACGACGGCTATCCACGCTGATGGA
GCTGTACTGGGCTACACCTCCAGCCGCCCTCAGTCTGGGGAAAAGATTCCCCCCAAGGAGCTGAAAGAGATC
ATCAAGCAAGCGGTGATGGGCTTTCGCACACGCTACGATCGCTACCCAAATCATATAACCATCCACAGGGAC
GGGTTCGCAAACGAGGACCTGTCCGAGGTAGAAAAGTTTCTGACGGACCTCGACGTTGAATATGATGTTGTC
GAGATCAGGAAGCAGGCCCCAGCGCGCGTCTTGAAATACAGTGGTGCCCACTTCGACACGCCTCAAAAGGCG
ACCGCCGCAATCTACGAAGACATCCCGAAAGCGATTGTAGCGACGTTTGGTGAACCCGAGACTCTCGCTAGC
CGGGAGTCAACCGGGCTTCCCCAACCAATCACGGTGGAAAGGGTGCACGGAGAGACCCCCATCGAGACACTT
GCTGCGCAAACCTACCTGCTGAGCCAAGCCCACATAGGCGCCAGTAACGCTACAGCACGCTTGCCCATAACC
ACCATGTATGCCGACTTGGCTAGTGCAGCGGCAGCCAGGCAACACCTTCCCCCGACCAACAAGCTGAGGGAT
AAGATCGGATTCATC
180 86 ATGAAGAACCTGAGATACAAAATCAACGCCTACAGAATCAAAAAAGACTATATTCCCAAGGAAGTTTATAGA
TACAGGATCCGCTCCTTCATAGAGAACATTAACATATATAGGTTCGTCGGTTTTTACGGAGGCGTGGCCCTC
AATCAATCTGAGTTTATCCTTCCGTACCCGGTCGAAAATCTCGTCCTGGAATACGACGGAAAAGATGTAAAG
CTTGAGCATATCGACACACTGAACCTGGAGGACATCGAGAATAAGGACAAGGAGAAAGCCGAGAAGCTGGTG
AGGGGATACCTGACCAGCATATACAAGTTGAAACCCATACTCTACAAGATCCTGCGGGACGTTCGAGAGAGC
AAGATCATTAACGATATCAGAGTGGATCCTATACCCGACTTTACAGTAAAAAGGCACAATAACGAATACTAC
CTTGTCATCGATTTTAACCACACCGCGACCGTGTTGAAAAATCTTTGGGACTTCGTGGGAAGGGACAAGCTG
AAACTCGAGGATTATATCGGTAAGAAAATCATATTCAAGCCCAACCCGAAGAAGAGGTATACTATAAAGAGC
ATTGAAAAGCAGAACAAGAAGGACATTGATGACATTGTCGAGCACATCATCGAGTACTACAAGTGGACGGAG
GAGGAAATTAAGAGCACCTTCGGCGAAATCGACTATACTCAGCCCATCATCCATTGCGAGGGCATCCCCTAC
CCGTTCGCACCGCAATTTTGCAATATCGTATTTACCATGGAAGACTTGGATGAGAATACCCTCAAGGACCTG
CAGAGCTACTGGAGGTTGCCCAACGAGATCAAAGGCAACATTATCAATCAGATCGCTAAAAAACTGCGATTT
GTGGAGAACGAGCCAATCGAATTGGAATTCATTAAGTTCAATAACACCCCCCTTATCGTGAAGGACGAAAAT
GGCAAACCAACAAAGATATACACCACCAATCGCCTCTTCCGATGGAATTACGATAGTAAATCCAAACTGTAC
TTGCCCTACGACATCCCTGACATAATCAAGAACAAAACACTGACAACGTTTGTGCTGATCGACGAGAATCTC
AAAAACGTGAGTGGTAAGATCAAGAGAAAGGTCTACCAAATGTTCAAGAATTACAATAAGATCGCCAGCAAG
ACTGAGCTCCCGAAATTTGACTTCGCCAATAAATGGAAATACTTCTCTAACAACAACATCAGGGACGTGATC
CGAAAGATTAAGGATGAGTTCAACGAGGAGCTTGGCTTCGCGCTCATTATCGGCAACCGATACTATGAAAAC
GATTATTACGAGACCCTGAAGATGCAATTGTTCAACCTGAATATCATCTCCCAAAACATTCTCTGGGAGAAT
TGGTCAAAAGACGATAATAACTTCATGACAAACAACCTGCTCATACAAATTATGGGCAAACTCGGAATTAAG
TACTTCGCACTGGACGCAAAAGTGAACTATGACTACATCATGGGGTTGGACAGCGGCCTGGGCGCATTCAAA
AGCAACAGAGTGTCCGGGTGTACCGTGATCTATGACAGCGAAGGGAAGATCCGACGGATTCAACCAATTGAC
GTGCCCAGCCCTGGGGAAAGGATCCCCATTCACCTGGTAGTGGAGTTCCTGGAGACCAAGACCGACATCAAT
ATGGAAAACAAAAACATCCTGTTCCTTCGAGACGGCTTTGTGCAGAATAGTGAGAGGGAGGAGTTGAAGAAA
CTGAGCAAAGAGCTGAATAGTAACATCGAAGTGATCTCAATCCGCAAGAATAACAAGTATAAAGTCTTTACC
AGCGACTACGGTATCGGCTCCATTTTTGGCAATGATGGCATATTCCTGCCACATAAAACTACATTCGGAAGC
AACCCGGTGAAGCTCAGCACCTGGCTGCGCTTTAACTCCGGGAATGAGGAAAAATTGAAGATAAATGAGTCT
ATAATGCAACTTTTGTACGACCTTACCAAAATGAACTACAGCGCTCTGTACGGGGAGGGTAGGAACCTTCGC
ATCCCGGCACCGATTCACTACGCCGACAAGTTTGTGAAGGCCCTTGGAAAGAACTGGAAAATAGACGAAGAG
TTGCTGAAGCATGGCTTCCTCTACTTCATC
181 82 ATGAGTCAAGACTCTAGGAGCACCGAGGTGGAGAGGCAGGCCGAAATACAACCTGGTACCTACCTGTTGAAC
GGCCGGGGGGAAATTCAGTTGGATGAGGTTGACGCATTCCAGTACGACCTCAAGGTGAGTGGAGGCGTGGAG
CAGTATTGGGATCGGGAACAATTCACCAGCTCTGCAGCCTACTACCTGGACCAGGAACACGGGAGCCCTGTC
GCTGAGATAGGCAAAATGAACGTGCTCAGCAAGACGGATTTGTCTAGATCAGTTAGAGTGTGGCAGAGAAAC
GTGACTCCCATCAATAGGCAGAGCGTTACACTGACCGCAGCCCAACCCGAGGACCGAGAAAAGATCAAATCA
TTCGTGCAAAGCTGCTTCAAGAGGGCAGTGCCGACCGAAAAATACAGCTTTCGCTTTCTCAACAAGATTGTC
AGGGATGAGCCCGAGTTCACCACCGGCAGCGAAGGCTTTTCTGCACATCCGAAGCACGACGTTAAGATACAG
GTCACCGCTGATGGCAATGTGCTTGTGCACGTGGATAGCGGGTTCAGCATCAGGAGCAACAGCACCCTGGAC
GAAATCTACTCTGAACAGGATAACCCTTACGGTAAGCGCGTTGCCCACGACCCCGAGAGGTATGGTACCCAG
GGCCAAGGCACCCTTCGCGGTTGGAGCGACTATCGGTACACAGACCATATTAGCGATGCGGGTAGCTCTGTG
AACGAAATGCACAAAGGGGTGGCGGACGAAGAATGGCGGCAACGACTCGCAGAGGAGAATCCCCGACTTCTG
AAAGTGGAGTATGGCAACAAAACTAGGAGGCAAGCCCCCCATTTCCTGAGGCTCTCACCGCGGATCGAGCAG
GTGCAGGATCAGGATCGCGAGTTCTATAGCAGGTTTAACAGCCGGAGCGCGATGATGCCCGACGAAAGATTT
GAACTGTCTAAAGAGTTCCTGCAGAACGTGAGCCGCTTGCCGGTATTGGACATGGAACTCGAGCCGGGTCCG
GTGAACAGCAGTTACGAGTTGCTGGAAATGCGAGAGGAAAACAGGCTGGTTTTTGGAGGGAAGCAGAGGGCT
AGAGACCCGGGCAGCGGGCTTAGAGAGAATGGGGTGTATCAAAGTCCCAGTCAGTACCGGCTGGGGGTGTTG
ACCCCCGAACGATGGGGAGAGAAGGCGAGCGAGCTGATCCCCCTGATTGTGTCCGGCCTGAACGATCTGAGC
GCATCAGCAGGAGTTCGAGCATATGGATACGAATTGGGGGACGTCAGCAATTACACACCCGTGGTTCAGGAC
CTCCACGAGGAGACGGACGCTGTGCTCGCCGTGGTCCCCAATAAGGGTGTGGCCGAGGATTTTGGGATAGAC
GATCCATACAAGGAGCTGAAAAGAACCCTCCTGCGGAAAGGGATACCCACCCAAATGATGCAAAAGTCCACG
GTCGATGAAATCGTGGGTCAAAAGGCGGGAATCGGCAATGACAAGTTTCTGAACGCACTTAGTGCAGTCGTG
GCCAAAGTGGGCGGTACCCCATGGCAGATCGATAGCCTCCCCGGGAAAACCGACGCCTTCATGGGCTTGGAC
GTAACTTACGACGAGAGTAGCGAGCAGCACGCAGGCGCCAGTGCAAGCGTAGTACTCGCGGATGGGACGACT
TTCGCAGCCGAGAGCACCACCCAGCAAGGTGGCGAGAAGTTCAGTGCACGGCATGTAGAACAGTTCGTGAGG
GACCTCGTCTTCGACTTTGCGGGGGAACAGGGCCGAGACATCGACAGACTGTGCATAATGAGAGATGGGAAG
ATCAGCGAGGATATTGACGCCGTAAGAGAGGGACTCAGTGGTATTGAGGCGGAGATCGACATAGTTGGCATA
CGAAAATCCGGGCAACCTCGCATAGCTGAGTTTGACGGTACTCGGTTTCGGATCGCCGAAAAGGGCGTGGGC
TTTGTGGACGCCGACAGAAGCCAGTCTATCATCCATGCATTCGGCAAACCCGAAATCCACGACGACAATCCT
GTGGGCACCCCACGAACCTTTCGACTGACCAAGGACTCTGGTCCCACAGATGTGGAGACCCTGACCCGACAG
GCATACTGGTTGTCCGAGATCCATTTTGGAAGCCCCGTTAGGTCCCCTAGGCTCCCCGTGCCAATAGAGTAC
GCAGACATGGCTGCTGAGTATGTTCGGGAGGAGTACGTCTCACCAGGGACTGTAATAGAAGGGCCAGCATAC
ATC
182 8 CTCCCCATCGTCCTGAACGCCTTCCCACTTAAAGTACCCGAACTGGAGCTGGAAGTTAGGCAAATACCGTAC
GATAAAGAGACGCTTGACGGCCTCAGGGCTGCGCACAAGGCCACCCACGCTTTCCGCAGGCAGGGCGACAAC
ATACTGATTTTTTCCGGTGATGGCACATTTCCCGCGTCTGGGACGCCTCAAACTATTGCACTGAAGGACAAT
TTCGGCGTGTTCTACAGCCTCGTGAAGGATGGTCTTATCCGCCACCTTGCGGGGCTCGGGAGGAATCCCAGC
GGGTTCAACCCCATAGAGTTGGTGTCCGCAAAACCCGAAGACAACCTGCTGGTCCCCATACTCGGCGATGCG
TATCCTTTTAAGGTGTGCGCGAAATACAGCATTGACACCAGAACCGTGCTGGGGCACCCATGTCTGGTGATC
GATTGCACGACCAGGAGGGTGTTGAAGGAAAATGGCTTGTTCTTTTTGAACGCTGGGTTCGACCTCGCGGGC
AGGTACGTGGTGACGGAGCAAGATGACGGGTACAGGAAATTGCTCGGCAGCGTGAGCGGCTGTAAGGGTGAA
ACGCTGTACGTGACTAGGCCCGATGGCCAAGTGGTGCAGGCCGAGGCTAAAAACGTGTACCTGGAGGCATCC
CGCACAAATTTCGACGACTATATTCTGCACACCCACAGGGCTCAGAAGGACGCGATCGTTGAACGAATCAGA
CAGTCCGTTTCCGTGTTTAATGGGGGCGAAAATAAGAAAGCCCGAATCGACACGCTGAAGAAGTATATCCAG
TCCAAAACCATTCCCTTGATCGACGGCACCAGGATTGAGATCCAAGATTCCCCTAACATACAGAAAGACTGC
GGCCAGATGCAAAAACCGGTATTCGTCTTTAACGACAACGGCGAGGCGGACTGGGCGGAGAAGGGGCTGACC
CAATCTGGGCCGTACACCAAGAGGACCTTCGACAGGAATGACCCCTCCATTTGCGTGATCTGCGCCCAACAT
GACAAGGGACGCGTTGAGCAGTTCGTCAGGAAGTTGCTTAAGGGCATTCCAAACTCCAAATACTTCAGCAAC
GGTCTCGAGGGGAAGTTTACCCTGGGCACTAGCAGGGTAGAAGTGTTCGCGACCGCTACTGACAGCGTAGAC
GCCTACAAGAACGCTATTGAAGCCGCAATACGGAAGAAGGCCGACGACGGCGGCAGGTGGGACCTGGCCCTG
GTTCAAGTGAGGCAGAGCTTTAAGAAGTTGAAAGTGACCGAGAACCCCTACTACCTTGGCAAAAGTCTGTTC
TTCCTCCACCAGGTGCCCGTCCAGGACTTTACCATTGAGCTGTTGGCTCAGTCCGACTACTCCCTCGGCTAC
TCTCTGAATAACATGGCCCTTGCATGCTACGCGAAGATGGGCGGTGTGCCCTGGCTGCTTAAATCTTCACCC
ACCCTCAGCCATGAGCTTGTGATAGGCATCGGCTCCGCCAACATCGGCCAGGAGAGAGGAGCTGATAATCAG
AGAATTATGGGCATCACCACTGTGTTCAGCGGAGACGGCAGCTATATCGTGAGCAATACATCTAAGGCTGTT
GTCCCCGAAGCTTACTGCGAGGCCCTTACCGCCGTACTTGGCGAAACCATCGAAAAGATTCAGAAGAGGATG
AACTGGCAGAAGGGCGATACCATCAGATTGATCTTCCACGCTCAGGTCAAGAAATTCAACAAGGAGGAAATC
GAAGCGGTCAGAGCCGTCATTGAGAAATATCGGGAATACCAGATCGAGTACACTTTTCTGAAGATAAGCGAA
AACCACGGGCTTCACATGTTCGATAGTGCAACCGCAGGGGTGCAAAAGGGCCGACTTGCCCCTCCGAGGGGG
AAGACGTTCAAGCTGAGCAAACATGAGATGCTGGTTTATCTGATAGGGCAGAGGGAGCTGCGGCAAGACACC
GATGGTCATCCCAGGGGCGTCATCCTTGATGTTCACAAGGACAGTACATTCAAAGACATCACCTACCTTTCA
GCCCAGCTCTACTCATTTGCCAGCCACAGCTGGCGCTCTTACTTTCCCAACCCTATGCCAGTAACCATTTCA
TACAGCGATCTGATCGCTCGAAACCTTGGTTGGCTGAACCAACTGCCCGGGTGGAACGACTCCGTGATGATC
GGAAAGATCGGGCAAAGCCAGTGGTTCCTG
183 39 ATGAAAGAGTTTAACGTCATTACCGAGTTCAAGAACGGCATAAACAGCAAATCTATTGAGATCTACATCTAC
AAAATGATGGTCCGAGATTTCGAGAAGCGACACAATGAAAATTACGACGTGGTGAAGGAGCTGATTAACCTT
AACAACAACTCCACCATAGTGTTCTACGAGCAGTACATCGCCTCCTTTAAGGAGATTGAGAAATGGGGGAAC
GAGCAATACATAAATGTGGAGAAGAGGGCTATCAACCTGGAGTCCAACGAGAAGAAAATTCTGGAGAGGCTC
CTGCTGAAGGAAATCAAAAATAACATAGACAATAACAAGTACAAGGTCGTCAAGGACAGCATATACATCAAT
AAGCCAGTGTACAACGAGAAGGGCATCAAAATTGACAGGTATTTCAATCTGGACATAAACGTTGAGTCAAAC
GGAGACATTATCATCGGGTTTGACATCTCCCATAACTTCGAGTATATCAACACTCTGGAGTATGAAATAAAG
AACAATAATATCAAGATTGGGGACCGGGTAAAGGACTACTTCTACAACCTGACCTATGAGTACGTGGGCATC
GCCCCCTTTACTATCTCCGAGGAAAACGAGTACATGGGCTGCTCAATCGTCGACTATTATGAGAACAAGAAC
CAGAGCTATATTGTGAATAAACTGCCTAAAGACATGAAGGCCATCCTGGTAAAGAATAATAAGAACTCTATA
TTTCCCTACATCCCGAGCAGGCTTAAAAAGGTGTGCAGATTCGAAAACCTTCCCCAGAACGTGCTGAGGGAC
TTTAACACGAGGGTGAAGCAGAAGACAAACGAAAAAATGCAGTTCATGGTTGACGAAGTGATCAACATCGTG
AAGAATTCCGAGCATATCGACGTCAAAAAGAAAAACATGATGTGCGATAACATTGGGTACAAGATCGAGGAC
CTGCAACAGCCCGACCTGCTCTTCGGTAACGCCAGGGCCCAGAGGTACCCCCTCTATGGTCTCAAAAACTTC
GGGGTGTACGAAAACAAGCGGATAGAGATCAAATACTTCATAGACCCCATCCTCGCCAAGTCAAAGATGAAC
TTGGAGAAAATCTCCAAATTTTGTGACGAGCTGGAACAGTTTAGCAGCAAGCTGGGCGTGGGGCTCAACCGG
GTTAAGCTGAACAACATAGTTAATTTCAAAGAAATCCGCATGGACAATGAGGACATTTTCAGCTACGAGATA
AGAAAGATAGTGAGCAACTATAATGAAACTACCATCGTAATCCTGAGCGAGGAGAACCTGAATAAGTACTAC
AACATCATTAAGAAAACATTCAGCGGCGGAAACGAGGTGCCCACCCAGTGCATCGGTTTCAATACGCTGAGC
TACACGGAAAAAAACAAAGATTCTATCTTCCTGAACATTCTGCTGGGGGTTTACGCCAAGAGTGGCATCCAG
CCCTGGATCCTGAATGAGAAGTTGAACAGTGACTGCTTTATCGGCCTGGACGTGTCTAGGGAGAATAAGGTC
AATAAAGCGGGAGTCATCCAGGTGGTCGGGAAAGACGGCAGGGTGCTCAAAACTAAGGTGATCAGCAGCAGC
CAAAGCGGAGAGAAGATCAAGTTGGAGACCCTCAGGGAGATCGTGTTTGAGGCAATCAACAGTTACGAGAAT
ACGTACCGGTGCAAACCCAAACACATTACTTTCCACCGCGATGGAATCAACCGCGAGGAACTGGAGAACTTG
AAGAACACCATGACCAACCTCGGTGTTGAGTTCGACTACATCGAAATTACCAAAGGCATTAACAGGAGGATC
GCCACTATCAGCGAAGGTGAGGAATGGAAGACGATTATGGGGAGGTGCTACTATAAGGACAACAGCGCGTAC
GTGTGTACCACCAAGCCTTACGAGGGAATCGGCATGGCCAAGCCCATCCGAATCAGGAGGGTGTTCGGCACG
CTCGACATAGAAAAGATTGTCGAAGACGCCTACAAACTGACCTTTATGCACGTTGGCGCAATTAACAAAATC
AGGCTTCCCATTACTACGTACTACGCAGACCTGAGCTCCACTTACGGCAATCGGGATCTTATCCCCACAAAC
ATCGACACTAACTGTCTGTACTTTATA
184 89 ATGTCTGTGGACGCTATGATCAGGAGTATCGGGGTCGCACGGGACCGCCCGCTTCTCGTTTTCCTCGGGGCA
GGTGCCTCAATGAGCAGTGGTATGCCGTCCGCCACTCAATGTATCTGGGAGTGGAAACGAGAAATCTTCTTG
ACAAACAACCCCGACGTTGAGAAGACCCAGTTCTCCGAGCTGAGCCTTCCCAGCGTCAGATTGCGCATCCAA
GCATGGCTGGATCGGCAACGACGCTATCCCGCTCTTGATCATCCCGACGAGTATTCTACCTACATAGGTGAG
TGCTTTGCACGCTCTGACGACCGCAGAATCTACTTCGAGAAGTGGGTCAAACGCTGTAGTCCGCACCTTGGA
TACCAACTGCTTGCCGAATTGGCACGGCAGGGGCTTGTGGCCAGCGTTTGGACTACTAATTTCGATGCCTTG
GCGGCTCGCGCAGCTACGTCCATCAATCTCACTGCAATCGAGATTGGAATTGATTCACAGCAAAGACTGTAC
CGGGCGCCGGGCGAGGCGGAACTGGCGTGTGTGAGTCTGCATGGAGATTATCGGTATGATCCTTTGAAAAAC
ACCGCTCCAGAACTCATAAAACAAGAGAAGGAGCTCAGAGAGTCACTTGTCCAAGCGATGAGAACTCACACA
GTCCTGGTTTGCGGCTATAGTGGTCGGGATGAGAGTGTCATGGCAGCGTTTTCCGATGCCTATGACGCAGCT
CATTTTAAGGGTCATCACCCCCTCTTCTGGACACAGTACGGCGATTATCCCGCCAGTGAGCCCGTAGCTGGA
CTTCTTGCTTCACCGCTGGATCAGGAACCTGCGAAGTTCCACGTGCCTGGGGCATCATTCGATGATCTTATG
CGCAGGATAGCACTCCACGTGAGTGACGGTGAAGCGCGCGAGCGGGTGCGGAAGATTCTTGAGAACTTCAAG
ACGGCACCAGTTAACCAGAAGCTCCCCTTTGCCTTGCCTAGTCTTCCTGTGACGGGTCTCGTCAAGTCAAAC
GCCATTCCGTTGATACCGCCTGGAGAGCTTATAGAATTTGATCTTGTCCGGTGGCCGCCGTCCGGTGAAGTT
TGGAGCACGCTCCGGGAAATAGGGGATAGACACGGATTCGTAGCTGCCCCTTTTCGCGGGAAGGTGTATGCT
CTGGCTACGATAGAGCAACTGACACAAGCCTTCGCGGACAATGTAAAGGATGGCGCGTTCAACAGGGTGCCG
CTGAATAATGATGACCTCCGCTACGAGGACGGAACCGCCAATCAGCTGATGCGACGCGCTACTGTTCTGGCT
TTGGCTGGGAAAGCTGGATGCGCGAACGATGGGGATGCCATTGTGTGGGACACGTCTCGCTCAAAAACCGAA
AGATTGGATAGGCAACTTTGGACTGTATACGATGCAGTACTTCTGCAGATTCGGCCGCTGGGAACTAAGCTC
GCGCTCGTACTTAAGCCTACGCTGCGGGTTACGGATTCAACTGGCGAGGTAGCCCCGAAAGAAATTGAACGG
GCAGTCAAGGTGCGCGTATTGGGATACCAGCATAACAAAGAGTTCAACCAGGCGACCGACTTTTGGAGGAAA
AGGCTCCTGCCCTCAAGAGATCTCCTTGTCAGATTTCCTGATCTGGATGGTGGAATGACTTTCACGATTTCA
GGTCGGCCAATATTCGCCCGGCTCACCGACGAAAGGACTGAAACTGTCACACTGAACGATGCCCAAGAGCGA
TCAGCATCTCAAGTGGGGTTGCAGCTTGCAGAGCCTAAACTGGTGTTTGCACGCACTGTAGGTACGGGTCCC
GCAACGGACACCCTCCCGGTTAGAGGATTGCTGCAAAATAGACCTTTCGATGCTAATCTGACAGACTTGGGC
ATCGCGACGAACCTGAGGATCGCGGTTATTGCGCCCGCTCGGGACGCCAGAAGGGTACATGACTATCTTGGG
CAGCTGCATCAGCCTATAGATCCTACAAAGTGGGATGCGGACTATCTGATGAGGTTTCCCGGCTTCAGCTCC
GCTTTTAAATGCCCTTTGGACATTCCGCAGCCGGGCCAGGCAGCTTTTGTAACACTTGACGAGCCACACGAT
GAGAGTCCTCAATCAGCGCGGACCCTTGCAGGCCGAATCACAGCGGCACTGTCTGCATTGAGGGCGACGGAG
AATCCCTCTGTTACAATAATATATATTCCGGCGCGCTGGCACGCGCTGCGAGCATTCGATCTCGAATCAGAG
CAATTCAATCTTCATGACTTTGTTAAGGCCGCCGCAATTCCAGCGGGCTGTTCCACACAGTTTCTGGAGGAG
TCAACTCTTGCAAATGGCCAACAGTGCAGAGTGCGATGGTGGCTTAGCCTCGCTGTTTACGTAAAGGCAATG
CGCACCCCGTGGGCTTTGACGGGACTCGATAGGGACTCTGCCTTTGTAGGGCTGGGCTTCTCTGTAAGACGA
AAGATCGATGGCGAAGGTCACGTCGCGTTGGGTTGTTCTCATCTTTATAGCCCAAATGGTCATGGTTTGCAG
TTCCGCTTGAGTAAGATTGATAATCCGATAATGCTGCGAAAAAATCCTTTTATGTCCTTTGACGACGCTAGA
AAGTTGGGCGAAGGCATCAGGGAATTGTTTTTTGACGCCCACCTCCGGCTGCCGAATCGCGTAGTTGTTCAT
AAACAGACCCCGTTTCTTAAAGAGGAGCGGGAAGGGCTCCAAGCAGGTCTCGAGGGAGTCGCGTGTGTGGAA
CTCTTGCAAATTTTTGTAGACGATACGTTGCGATATGTGGCTAGTCGACCAATGCCGAATGGAGATTTCGAA
ATCCATGGCTATCCTATCCGAAGGGGCACCACAGTAGTGGTCGACGACCAGACCGCATTGTTGTGGGTACAC
GGCACATCAACCGCGCTCAACCCGCGGCAGAGCTATTTTCAGGGCAAACGCCGCATACCGGCCCCCCTTGTG
ATGAGGCGGCACGCGGGGACGTCTGATCTGATGATGTTGGCGGACGAAATATTGGGACTGTCCAAAATGAAT
TTTAACAGTTTTGACCTGTATGGCCAACTCCCGGCAACCATCGAAACGAGCCAAAGAGTCGCGAGGATAGGC
GCTCTGCTGGACCGCTATACGGAACGGTCATACGATTATCGACTCTTTATG
185 29 ATGCCACACACCTCCCTGCTGTTGAACTTTCTGCCCGTCTCTCTTAGCGGCGACACACGCATCCATGTCGGC
TACCGGCCATATAACGAGGATGTGCTGCGGGAACTGAGGGAGGAGTTCGGCGAAAGCCACGTGTTTAAAAGG
GACTACCAGGAGGACACGATAAGCGAGATACCGGTCATCCCCGGAGCCGAGCCCCTTAGCGACAAATCTACT
GGCGTGGATCTTGCCGAAGCGCGATGGCTGTGGAAACCACTTCTGAACGCTGCATTGCTTCGCCTCTTCAGC
GGAAGCAGAGAGATCACCTCTGATTATCCAGTCAGCGTGCTTGGTAACCCCAAGAACAACTTCATCAGCCAT
GCCAATCTCCCCGACTGGGTGAGAATCCTGCCCCTTCTGGAATTCGAGAGCCGAACCCTGTTCGGTGGTAAA
TCCGGTCCGCAGTTTGGGCTTGTTTGCAACGCCCGAACTAGGCACCAGGTCCTGGCAGGCTGCGACCATCTC
ATTGAAAGAGGTATAAGTCCCATTGGCCGCTATGTTCAGATCGACCAGCCACAAAGAGACTCCAGACTTGCG
CCACGCGGTCTGACTGTTGGTAAGGTGAGCTCTATCGATGGGGACACGTTGATCCTGGAGGATCACCGAAAG
GGCTACGAGCGCGTGAAGGCAAGCGACGCTCGCCTTACCGGCAATCGGGCGGACTTCGACTGGTGCGTGAAC
GCGCTGTTGCCTGGACAAGGTCAAGCAACGCTGAGCAGGGCGTGGGACGCCATGAGCGCCCTGAATCAGGGA
CCCGGCCGCTTGCAAATGATCAATCAGACAGCTGAATATCTGAGGACCGTGAACCTTGAGGCGGTTCCTGGG
GTAGCATTTGAGATCGGCGAGTGGCTGAGTTCTACCGATGCTCAGTTTCCTGTGACCGAGACCATCGACCGC
CCTACCCTCGTGTTTCATCCCTCCGGCCGACCCAACGACACTTGGAACGAGAGGGGGATAAAGGACAATGGC
CCGCACGACCAGAGGACATTCACCCCCAAACAGTTGAACATCGCCGTGATTTGCCAGGGCAGATTTGAGGGA
CAGGTAGACAGATTCGTGGGCAAGCTGCTCGATGGCATCCCGGACTTTCAGTTGAGGAACGGCAGGAAGCCC
TACGACGACGGTTTCCTTAGCCGGTTTAGGCTGGAGAGGGCCAACGTGCAAACCTTTCAGGCTAACAGTGCG
TCCCGCGAGGCTTACGAAGCAGCGTGTGAGGACGCTCTGAAACATGCCGCTGATAACGGCTTTGGCTGGGAT
CTGGCTATCGTTCAAATCGAGGAGGATTTCAAGGCGCTGCCTGGGCCCCAAAATCCCTACTACGCCACCAAG
GCAATGCTCCTCCGGAACAACGTAGCCGTGCAGAACATCAGGATCGAAACAATGAGTGAGCCTGACAAAAGC
TTGGTCTACACTATGAACCAGGTTTCTCTTGCTTGCTACGCAAAGCTGGGTGGTAGACCTTGGCTCCTCGGT
GCCCAACAGAGTGTCGCGCATGAGTTGGTGATTGGACTGGGCAGTCACACCGAGCAACAAAGCAGGTTTGAT
CAGTCCGTGCGATACGTAGGCATCACCACCGTATTTTCCAGCGATGGAGGCTACCATCTGAGCGAGCGAACC
GGAGTAGTGCCCTTTGAAGATTACGCCAAGGAGCTGACAGACACCCTCACTAGGACCATAGAGAGGGTGCGA
AGGGAAGACAATTGGAAGAACACTGATAGAGTTCGCCTGGTGTTCCATGCTTTTAAGCAGATTAAGGACATC
GAGGCCGAGGCCATCAAACAGGCAGTGGAATCTCTTGATCTGGAGAACGTTGTGTTCGCATTCGTCCATGTG
GCCGAGCACCACCCTTATTTGATCTTCGACCAAAACCAAGAGGGATTGCCCCACTGGGAAAAGAACAGGAGC
AAGCGCAAAGGCGTCTTGGGACCCAGCAGAGGCGTGCATATAAAGTTGGCGGACAGCGAATCCCTTGTGGTA
TTTGCTGGTGCTAGCGAGTTGAAGCAGGCGGCACACGGTATGCCTCGGGCCTGTCTGCTGAAGCTGCACAGA
AACAGCACCTTCAGGGATATGACCTATCTGGCGAGACAAGCCTTCGATTTCACCGCCCACAGCTGGAGGGTG
ATGACCCCTGAACCATTTCCGATCACAATAAAGTACAGCGACTTGATAGCAGAGCGATTGGCGGGTCTCAAA
CAAATAGAGACCTGGGACGACGATGCCGTGAGGTTTAGAAATATTGGCAAAGCCCCCTGGTTTCTG
186 52 ATGTCCGGCCTTTTCCTGAACTTTTACCAGGTAGACATCCCCACCAAATCCGTACCGATCCACAGCGTAGAG
TATAGCCATTACAGTTCAAAGGAGGCCTTTATCGCGTTGAAAGAAAACTTCCCCTACTTTAGCTTCTACCGG
GATGACGACCGAATACTGATCTGGAAGAAAGACAAGGATGCCGAGCTCCCCGAGAAGAACTCATTGATTGAA
ATTGATTTCACCGAGAAAGCGAAGGTCCTCAGCAAAATACTCGAGAGGGCCATCATTGACTTCATCGAGCCA
AAGGGCTACAAGATATTCAAGAACAAGTACAGCAACAGCTGGGAAATAGTGAGCATGAAGGACATCCTGAAT
GGTGGGATCGAGGGACTCAGCATCAATCGAATCGTGCATTTTTCCCCCTGCTTCTTCTTCAAGGAGAACAAA
CTCATGCTGGGTTTCAGCCTTAGCACAAGCCTCAAAAACGTGTTTACCTGGAATAAGGCGGACTTCGAAAGG
TACGGCTTTGACATCAAGGGCCTTAAAGGAGACGAAGAGCGGATTTTTGCCAACAAGCAATCCCTTAAGAGG
TTCCTGGAGACCAAGGGCGCAGTTGCAATGTATGACCAAATTATCGCAAAGGAAAACAAGAACGCGAAAATG
TTTAGCATCATCGACGGCTTCTATCGGTGGCTGGAGAGGAACAAGACTGAAATCCAGCTTCCATTCGGACTG
AAGATAAATTCAGTGTCTAAAAAGTACCTGCCGTTCGAGGATGAGCTGATCAAGAGCGAGATCATCCCTAAG
CCCCAAAGGTATTTCTATAGCAATAGGAAGAACACCCAGAGCCTGCGGTACTATGACGAGATGGTGAAGACT
TATCAGCCCTACTCTCTGGAGCTCTACCAAAACAAACAGATCAACATCGGAATCATCTGCCCCAGCGAGTAC
CAGGGAGAGACGGAGGGGTTCATAAAGAAGATCGAACTGAAGCTCAAGGAAGTATTCCATTTCAACAGCCTG
ATCTTTCACTTCAAGACCATTACGAACAAGGACCTCGCGTCCTATAAGGAGGTTTTGTACGACGATGAACTG
CTGAAGTGCGACCTGATTTACGTCATCGTGAATGAGGCCCAGGAGAAACTCTCACCTAATAACTCCCCTTAC
TACGTGTGCAAGGCCAAGTTTATAGGCAATGGCATACCTACGCAAGACATTCAGATTGAGACCATCCGGCAG
AACTTGAATGCGTTCACAATGACGAACATCTCACTTAACAGCTACGCCAAACTGGGAGGCACCGCGTGGACC
ATCGAGAAGGAAGACAAACTTAAGGACGAGCTGGTCATTGGCATCGGCTCCACCCTGTCAGAAAACGGCCAG
TTCGTGCTCGGTATCGCACAAATCTTCCATAATGACGGGCGCTACATGGCGGGTGACTGCAGCCCCCTTTCT
ACCTTCTCCAACTACGCGGAGAACCTGGAGGATCACCTGTACAAGACCCTGAAGCCCCTGGTGGAGGAGATG
AGCAAAAGCGGCACCTTCCGGCTGATTTTCCACTTGTTTAAAAGTGCCTCTGAGGAGTACGAGATACGCGCG
ATCAACGGCCTGCAGAAGAGGCTGGCGAACTACAATTTCGAATTTGCACTCGTTCACCTGGCCTATGGACAC
AACTTCCGACTCTACTACAACGACGGCAACGGCGACATTAATCAGGGCACATATATACAACTGTCAAAACAC
AGCGCCCTGCTCCACTTCGTTAGCAAGTCAGACTTGCCCCTGAAAATCGACCTGGACAAGCGGTCTACTTTC
ACCAGCCTGTTTTACATCGCCAAGCAGGTGTACTGGTTCAGCCATCTGAGTCATCGCAGCTATATGCCCAGT
AAGAGGACCGTGACCATCATGTATCCGTCAATCATGGCGAAGATGACCGAGGAGCTTAAGAAGGTGGAAGGA
TGGGACTACGAGCGCCTGAAAGCAGTAAGCGATAAGCTGTGGTTCATC
187 60 ATGAAAAGCAACTTCTTCCCCATCCAGTTCAACTTCGACGACTTCCATATCCAGAGGCTTCCCTACCAGAAG
GAGGTGCTGGACAAGCTTCGGCAACAACACAATGCGACCCATAGCTTTTTCCGCAGAGACGATTTTATCTAT
ATTAGCCCAGGGGTAGAGGCCGCAGCGAACCTGGGAGACGTAGTACGCCTCTCTATTACCAAGCACCCCGAG
GTCGTTGCTTCTCTTGTTAGGCACATATTCTTTAGGACAATCAAGGATAAGGTCCCCGGTCTGCTGCCAAGC
TTTCACCCATTCACCTTTCCCGCCAAACAGGACAAATACGATCTGGCCCTGAACATGCTCCCCGAGCGCCTG
CAGAATGTTATCACCTACAAGAGGATAACCGAGGTACAGCTTCGATTCAACGAGACCGAAGAGCAACCCCAG
TTCGTCGCCGTAGTTAACCACAGGTACCAGTGGACTATCGACCGAACTTGCGAGCAATTGGTAAACGAGGGT
CTGGACATCCTTGGCCTGGAGGTGAACTCTAGTACGAGCCCTGATTATTCAGACGGAGTTGTGGCACCAGAG
CTGACACTGTTGGGCAGGGTGATGGCCGTGAACGGGGATCACGCCACAGTAGGGACCAACCAGGGTCCGACA
GAGTATGCCCTGTTCGAATTGACCTTGTTCAAGTCCAAGGAGAACATAGTGAACTACCTTGGATCTTTGGTG
GGCGAGGGTAAAGCCGAACAAATAGTCAACCATATCAAACAAGATGAAAGCAGAAGGCTGCAACCGGACGTT
GTGATGAGGGAGATCGAGGAAATGGGAGTGTGGCTGTCTAGGCTGGCCTACAGAAACTTTGACTCCTTTTGC
TTCACCATCGGAACGAACAACGCTGTCAGCGGCCAAGCAGGTATCAGACTGGAGGAGCCAAAGCTGATATTT
GACGTCTCAGGTACGAACATACACGCTACCCCCACAACCGGGCTCAACACCTTCGGCCCCTATAGTAGAAGC
ACGAGTTTCGACGTTAACTCTCCGAAGATTCTGGTTGTGTTTCACCAGCGGAACGCAGGCCACTTCGCAGAG
TTTCTCGCACAGCTGAAGGGCGGCATCGCTCAGCACGCATACTTTGCTAACGGGATGGTCAGGAAGTATGGT
CTCACGGCAATGGAGTACCGGATTGCCGAGATCACTGACTACACCGTGCCCCAATATCTTACCGCCATCAAT
AAGCTGCTTAGGGCGGAGAACGGAAGCTTTGACATCGCCATCGTGGAGACCTGTGAGGATTTCCGGAGGCTG
CCTCCCATGGATAATCCGTATTTTCAGGTTAAGAGTTTGTTGTACAGCCATGGAATCAGCACCCAATTCATC
AGAGCGGAAACCGCTCAGAAACCGATTTATTCAATAGATAGCATCGCGCTCCAAATGTACGCCAAATTGGGC
GGAACACCATGGACGGTGCCAATAGGGCCGAGCGTAGATCACGAATTGGTGATAGGCATCGGTAGCTCCATA
TTGCGCAGCAACCAGTATGCAGGTGCAACCCAAGCTCGAATAGTGGGGATTTCTACCTTCTTCAGCGCCGAC
GGGAAGTACATAAGCAATAGAAAGACCCAGGACGTGCCTTACGATCAGTACTTCGATGAGCTCTTGCATAAC
CTTAAAGTCTCCATCGACGAGATTTCCAATAACTACAGCTGGAGCTCAGGCGACCGCATCAGGATCATATTC
CACATCTTCAAGCCCATAAAACACATCGAGGCAGACGTCGTCGCAAGCCTGATGGAACAGTACCAGGAGTTC
GATATAAAGTTCGCTTTTGTGACCTTTAGCGAGTTCCACCCGTATGTGCTGTTTAATGAAAATGAAAGGGGG
GAATTTGATGCGTATAGGAAGGTTTACAAGGGCACCCATGTACCGTGGCGCGGTTACAATGTTCTGCTGGAT
CCTCGGTCATGCCTGGTCCAGATGCTGGGACCCCATGAGATGAAGACCAGCCGGCACGGCGCTTCTAGGCCC
GTCCTTGTGAGAATCCACCGCAGTTCTACGTTTGTAGACCTCGCGTACGTCGTGCAACAGGCCTTTAAGTTT
ACTAGGCTCTCATTCCGCACGTTCTACCCTGTGCATAGCCCTGTGACGCTGCTCTACAGTAATATGTTGGCC
CGACAGCTCAAGGACCTGAGGGGCATTCCGGGTTGGAACTACGATGTAGCTAGCAGGCAGTTGAGGCACAAG
AAATGGTTCCTG
188 40 ATGCAAGGCACTATATCCATAAACGAGGTGAGGATCCAGCTTAATACTATTAAGAATCTTTCAGTGTTCAAG
TGCAGCCTCAGCGGAATTAGCACCCGCCATAAGAACCAGATCGAGTTCATCCTTCGCAGCGAGCAAAACCGA
GTTAGCATCTTTGAGGGTGAAGTGATCTTTGCGCTTCCCGTCGAACAGCAGAACCTCGAAAGAGATAAGCAG
GCTCTGTTCAGCTTCCTGGTCAAACAACAAAGGGATCTCAATCTGAAACAGCTGAGCCTGGTGCCCCTGAGG
GAGGTGCCCGAGCGCGTTATCGAGCGACTGACTTTCGCAATGGTTAGCTATCAGGCCATGAAGCAGGGCATC
TTCTCTATCTATGGTCATACATTTTTTCGCCCCACCCTTATGACGGATAGGCTTGCGCACAAGGCGGTGGAA
GTCACGACGTGCATCGAGGATGGCTTCCTCAAGTTTTATCTGGACCCGACGTACATTGCACTGACATGCATA
ACGGACACAGCACGCGAAAATAGGGAGAACCTGGAACTGGTCGGGCTCTGCTCTTTCCGCAACAAAAACCTT
TGTAGCCTTGTCAGGCCGGACGGCTCATGCAACTGCCTCATACCTGGTAAGTTGGGGTATTACGTCCAGGAG
ATGGGGATTAAGGACGTTGAGGATGATAGCAAGGACTTTCTGGCCAAACGGTTCAATAGCTGTCCCCGGTTT
AGTGAGCACACGCGCTTTATACAAGTGAAGGCGAGTAAAAGAGGCACGAAGTACTCCCTGTTCCCTTCTTAC
GTAGTTTTTAGCAGGTTGTCCCGAATGGACCTGTCCGCTAAGCCAGATGTGCGGTCCAGTTATCGGAAGGCC
ACATTGATGGACTCTCACGAAAGGCTTAACTTGACCAACGACTGGATAAGACAAATTTTCATGATCGGGCAG
AAGGGCCTTCAAAATTGGGGTGTTATAAAGGTCAACCAGACCGAGATTCCCGTTGAAATTGTACTCACAATT
GCCCACGCCATCGCGCCCAAGACTTCTCAAGGCATCTATAAGGCTATATTCCTCCCGGACCAGCAAATTACG
AATGACAGCAATAACCCAACGCCTCAAACGCTGAGCGGGGGTTGGCTCTTCACGAATAGGGGTGCGTTCGAC
AGGAGGGATCCTAATAGGCCTTTTAAAGTAATCAGCCCCTACATCATCGTGCCCAACAATGAGCAAAGCATC
AGCTCTTGCCGCCAGCTGATCAACTACTTCAGCAACGGCAGGTACAAGGCCCGGTGCAAGGGTGACAGAGAC
TTTATTGGTATTTCATTGCCCGAAAACAAGGGCAAGTACAACACATCATTTGTCAATGCTTTCGAAGAGGAG
GACGGCCTGTATTTCGTTGAAGAGACGATACAGGGCTACCAGAAGGCGCTGCAAGACATTGTTAGAGACTGG
AATATCACGTCCAAGCGGGACATCAATAAACACGCTATAGTGATCATACCGGGCGAGAACGATATTGACGAC
AATCCTTTCTATTATCAACTGAAAAAGGCGTTCGTAGAGGAAGGGATTCCCAGCACCTTCATCACGTACGAG
ACTATGAACAAAATCAACGACCCCGACATCGCGTTCGGGCCAATCATGGACAGCCTGTGGTTGAACATTTAC
AGCAAAATGGGGGGCAAACCGTGGCGCCTCGCTAATAGCCTCGGCAACGTGCACTGCTTTATCGGTATTGGG
TTTGGAATTAACCCCGAGACCACCGGAAACCACATATTCGCAGGGATCGCCCACATCTTCGACAACTACGGG
AGTTGGATAGACGTAGCGAGTGATTCCGCCAACCTCTCCCAAAACGATCTGAACTCATTCGAGGGCACGGAA
AAGTACACACAGGGGAGTGCTAGCTTTAAGATCAGTCAGAGCGTGTCCCAGTCCATTGTGTATAACGCATTG
AAGCTGTACCAACAGAAGCAAACTAAGACCCACGAAAACGCCACAAACATCGTCCTGCACAAACTGGGCCAG
ATCTACGAGTGTGAGGTCATCGGGTTCCTCGAAGGAATTCGCCAAGTGCTCGGGAGTCTGGGCGACTGCAAG
CTGGGATTGCTGCAAATTGAGCAGGAGCACCACCTGCGCCTCTATGGCGCAGCAGCCCAAACCGGCAAGGAG
AACAACACGATCTTTCGCGGTTCAGCACTTCAACTCAACCCGGAGAAGCTGGTTATCGCGTCCACTGGCCGC
TCTTACCGGCAGACGAGCTCCGGGCTGTTTATGAATTATCCGGGCATCGGCACCCCCCAGCCGCTCCTGTTG
ACTTCTATCGTACCGAATCAGCAGATCCTGCAGAAGTACGGCTGTAACGCAAACCAATTCTACTCAAGCGAG
GACCTGGCGAAACATGCAATGGCCCTGACGCAACTTCACTGGGGGTCACTGAAGGATAATGTAAGATTGCCG
ATTACCACGCTTTACGCGCAAAAGGTCGCCGACTTGATTAGCAAGACCAACATGCGGATCAATCCAGGCTTG
GGCTACTTCCGACCCTGGTTTCTT
189 58 GTTCCAGTGTACCTTAATCGGTTCCTGCTGGACCACCTCACATCACCCTTGTCCTTGCCGGCGTTTCGGGTC
GAACTGGACCCTCCCCCTTCCAAAGATGAAGTGCACCCGCTCCTGGCTCTCGTCGGTCGGGAAGCGGGAGGG
CTCGTGAGGTTCCAGAACAGGCTGATCGGCTGGGAGGCTCCACGGGCCCTCGAAGGTCAGGTTAGGCGAGGC
AAGCAGTCATATAGACTGGTGCCCCTTGGCCGGCAGGCACTCAATCTTAGAAAACCCGAAGAAAGGCAGGCG
CTCGAGAATTTGTATAGGATCCGACTGGAAAACATCTTGAAAGCCCTCGCCAAACGACATAGGGCTAGAGTC
GAACGCAGGGGCAACGGCCTTTTTCTGTGGAGGCCAGAGAATCCCCGAGAGGAGAAGGAGGGGTGGCACCTT
TACCGGGGAAGCCTGTACCGCATACATCTCTATCCTGACGGCGAAGTGATACTTGAAGTCGACGTGCAGCAT
CGATTTCAACCCACTCTCCATCTCGAGGAGTGGCTGCAACGAGGCTATCCACTCCCTAGGCGCGTGACTAAC
GCCTACGAGGACGAGAAAGAATGGGCACTCCTGGGCATCGAAGAGGGGAAGGATCCCCGCTCTTTTCTCTTG
GATGGGGGCGAGTCATTGCTTGACTACCATCGCAAGAAGGGACGATTGGCAGAGGGGCAGGACCCCGGTCGA
GTGGTCTGGGTTGCTAGAGGTAAAGAACGCGAGCGGATCCCACATCTGAGCGTCTTGTTGAAGCCAGTCATC
ACCATGGAGCTGCTGGCGGAAGTCGCTGAGGTCACGCAGGAGGCCTTGCCTGCGCTTCAGCTCGAACCCGAG
GAACGGCTGAAGGACATTAGGCGCTTCGCTGAACCTGTACTGCAAGCGTTCGGCAAACGCGAAACTGCAAAA
CCCCTTGAAGGCAGAGCCCAGCGATTGCCGCGACCCAGTTTGTTGGCACGGGGAAAAAAGCGAGTGGGCAAA
GTAGCGGACGTACTCGAAAAGGGAGCATTGTCACCGGGCGAGACACGGTTGGCCCTGCTCGCATGGGAGGGA
GACGGGAAGGCCAAAGGCGGTCTCGCGTACTTGGAGGAGAGGCTTCAGGGCGTCGGGTCTGCATCCGGCATC
AAACTTGAACTTAAACGGCGATTTCTGCCCCGAGGCGATAACCTCGAAATGGCACAGGTGTTTGAGGAGCTC
TCCCAGGAAGGAGTAGGTGCCGGTCTGCTTCTGACTCCGCGCCTCACAGAAGGGGAAAGACGCGAACTGAAA
AATACTGCGGCGAGCCATGGGCTCGCTCTCCAACTCCTTAACCCGTTTGACCCTGGCGACATCTACAGGGTG
AATAACGCTCTGCTTGGATTTCTCGCGAAGGCCGGGTGGCTGTTCCTGAGACTGGAGGGAACTTATCCGGCC
GACCTGGTGGTGGCCTATGACGCAGGCGGGGAGAGTCTCCGATTCGGCGGAGCCTGCTTCGCCCACCTGACT
GATGGCACGCATCTGGGGTTCAGTCTGCCAGCCGCTCAGGGTGGTGAACGGATGGCCGAGGAGGTCGCGTGG
GAGTTGCTGCGACCCCTGCTGTTGAGATACCGGAAAGCGAAGGGCCAGACACCAGGGAGGATCTTTCTGCTC
CGCGACGGTAAGATTCAAAAGGAAGAGTTCCGAAAAGTGGAAGAGGAACTGAGAAAGCGCAATATTCCCTAC
GCGCTGTTTAGCGTCCGGAAGACGGGGGCTCCCCGACTGTTCAGCAAAAATGGGCCGCTCGGTGACGGTCTT
TTTTTGCGACTGCCAGAGGAGGAGGGCGGGTTTCTGTTGCTTAGCGCCGAGGGTGGGAAGGGCACCCCACGG
CCGGTTAAGTATGTGTTGGAGGCGGGAGAAGTGGACCTCAACCTGGAGGAAGCTGCCAGGCAATTGTATCAC
CTGAGTCGCATCTACCCGGGCTCCGGTTACCGATTCCCCAGGCTGCCCGCACCGTTGCATATGGTTGATAGG
ATGGTGAGGGAGGTTGCACGGCTCGGCGGCAGCCATAACTTGAGACTCAAAGAAGAACAACTGTTTTTCCTG
190 41 ATGAATAACCTGACACTGGAGGCCTTTCGGGGCATTGGCACCATCAAGCCACTGTTGTTCTATCGGTACAAG
CTGATCGGCAAAGGGAAAATAGAGAATACCTATAAGACGATACGCAACGCACAGAATCGGATGTCTTTCAAC
AATAAGTTTAAGGCCACCTTCAGTAAGGATGAAATCATATACACCCTGGAGAAGTTCGAGATTATCCCGACG
CTGGATGATGTGACGATCATCTTCGACGGGGAAGAAGTGCTTCCTATAAAGGACAACAACAAGATTTACAGC
GAGGTAATAGAATTTTACATTAACAACAATCTCCGGAACGTTAAGTTCAACTATAAGTACCCGAAGTACAGG
GCTGCCAATACAAGGGAGATCACGGGCAACGTGATCCTCGACAAAGATATGAACGAAAAGTACAAGAAGAGC
AACAAAGGCTTCGAACTCAAACGGAAGTTCATAATCAGCCCCAAGGTCGACGATGAGGGTAAGGTCACATTG
TTCCTGGACCTGAACGCGTCATTTGACTACGACAAGAACATCTACCAGATGATAAAGGCCGGAATAGATGTG
GTAGGAGAGGAGGTCATCAACATCTGGAGCAATAAGAAGCAGCGCGGTAAGATCAAGGAAATCAGCGACATT
AAGATAAACGAACCCTGCAACTTCGGCCAGAGCCTGATAGATTACTATATAAGCAGCAATCAGGCGTCACGG
GTGAATGGATTTACGGAGGAAGAGAAGAACACAAACGTCATCATCGTGGAAAGCGGCAAAAGCCGCCTGTCA
TACATACCGCACGCGCTCAAGCCTATCATAACGCGAGAGTACATCGCCAAGAACGACGAAGTCTTTAGCAAG
GAGATAGAAGGGCTCATCAAAATCAATATGAATTACAGGTACGAGATTCTCAAGAGGTTCGTCTCCGACATC
GGCACTATTAAAGAACTGAACAACCTGCGCTTCGAGAAAATCTATATGGACAATATAGAAAGCCTGGGTTAC
GAGCAGGGTCAACTCAAGGACCCCGTGCTCATCGGCGGCAAGGGTATACTTAAAGACAAAATACATGTCTTC
AAGAGCGGCTTCTACAAATCCCCCAATGACGAAATTAAGTTTGGCGTGATATACCCGAGAGGCTACATAAAA
GATACCCAGAGCGTTATCCGAGCCATCTACGACTTTTGCACCGAGGGCAAGTACCAGGGAAAGGATAACATA
TTCATCAATAACAAGCTCATGAACATCAAGTTCTCCAATAAGGAGTGCGTCTTTGAAGAGTACGAGCTCAAT
GACATAACCGAGTATAAGCGGGCTGCAAATAAGCTCAAAAAGAATGAGAACATAAAGTTCGTGATCGCAATC
ATCCCCACTATCAATGAAAGTGACATTGAGAACCCCTACAACCCCTTCAAAAGGGTCTGTGCCGAGATCAAC
CTCCCCAGCCAAATGATCAGTCTCAAAACTGCAAAGCGGTTCAGCACCAGCAGGGGCCAATCTGAGTTGTAT
TTCCTGCATAACATCAGCCTCGGCATTTTGGGCAAAATAGGCGGCGTACCCTGGGTAATTAAGGACATGCCA
GGCGAGGTCGATTGTTTTGTGGGCCTGGACGTGGGCACAAAAGAGAAAGGAATCCACTACCCCGCATGCAGC
GTGCTGTTCGACAAGTATGGCAAACTCATTAACTACTACAAGCCGACGATCCCGCAGAGTGGAGAGATCATT
AAAACAGACGTGCTGCAGGAGATCTTTGACAAGGTTCTGCTGAGCTACGAGGAGGAGAACGGCCAGTATCCC
CGCAACATCGTGATACACAGGGACGGCTTCAGCCGGGAGGACCTGGAGTGGTATAAGAACTACTTCCTGAAA
AAAAACATCGAATTCAGCATAGTAGAGGTCCGCAAGAACTTTGCCACGCGACTTGTAAACAACTTCAACGAT
GAAGTGTCCAACCCAAGCAAAGGTTCATTCATTTTGAGGGACAACGAAGCGATTGTCGTCACGACGGATATT
AACGACAACATGGGAGCGCCCAAACCGATCAAAGTTGAGAAAACGTATGGCGATATTGACATGCTCACAATT
ATCAACCAAATTTACGCACTGACACAGATTCACGTGGGGTCCGCGAAATCCCTTAGACTGCCTATAACCACG
GGCTACGCCGATAAGATCTGCAAGGCTATCGATTACATCCCGAGCGGCCAAGTCGATAACAGGCTGTTCTTT
CTG
191 1 ATGAACTATACCGCTGCTAACACAGCGAACTTCCCGATATTTCTGAGCGAAATAAGCTTTCTCACAACCAAT
AACATTTGCTTGAACTGTTTCAAGCTTAACTACCAGGTAACGAGGAAGATCGGTAACCGATTTTCATGGCAG
TTCAGCAGGAAATTCCCCGACGTTGTAGTGATATTCGAAGACAACTGCTTCTGGGTCCTGGCAAAGGACGAG
AAGTTCTTCCCCTCACCACAACAGTGGAAGGAAGCACTTAGCGATATCCAGGAGGTTCTTAGAGAGGACATC
GGGGACCACTACTACAGCATCTATTGGCTTAAAGACTTTCAAATAAAGGCCCTGGTGACCGCCCAACTGGCG
GTGAGGATACTCAAGATTTTCGGCAAATTTAGCTACCCAATCGTCTTTCCCAAGGATAGCCAGATATCAGAA
AATCAAGTGCAGGTCAGGCGCGAAGTTGACTTTTGGGCCGAGATCATCAATGACACCAACCCCGCAATCTGT
CTGACCGTGGATAGTAGCATTGTGTACAGTGGCGACCTTGAACAGTTTTACGAAAACCACCCCTACAGGCAA
GACGCCGCTAAGCTGCTGGTGGGACTGAAGGTGAAGACCATCGAAACCAATGGCACCGCGAAGATCATACGG
ATCGCCGGTACCATAGGCGAGCGCAGAGAAGACTTGCTGAAGAAGGCCACAGGCTCAATGTCACGACGGAAA
CTGGAGGAAGCCCATCTCGAACAACCCGTCGTCGCAGTCCAGTTCGGAAAGAACCCCCAGGAGTACATATAC
CCGCTTGCGGCCCTTAAACCTAGCGTGACCGACGAAGATGAGAGCCTCTTCCAGGTCAACCACGGAGACTTG
TTGAAGGAGACCAAGATCCTGTATGCGGAGAGGCAGGAGCTTCTGAAGCTGTACAAGCAGGAGGCCCAGAAA
ACCCTGAACAACTTTGGGTTCCAGTTGAGGGAGAGGTCCATCAATTCTCAGGAATATCCTGAGGTGTTTTGG
ACTCCCAGCATCAGCCTGGAGCAAACCCCAATCTTGTTTGGCAAGGGGGAGCGAGGTGAAAAAAGAGAGATT
TTGAAGGGCCTGAGCAAAGGCGGAGTGTACAAAAGGCACAGGGAATACGTGGACACAGCTCGCAAAATTCGC
CTGGCCATACTTAAGCCCGCTAACCTCCGCGTGGGCGACTTTCGGGAGCAACTTGAGAAGCGATTGAAGCTT
TATAAGTTTGAGACAATTCTGCCACCGGAGAACCAAATTAACTTCAGTGTCGAAGGCGAAGGTTCCGAAAAG
AGGGCCCGATTGGAAGAAGCGGTCGACAGACTCATAAGGGGGGAGATCCCCGTAGACATTGCACTGGTGTTC
CTCCCGCAGAGCGATAGGAATGCAGACAACACCGAGGAGGGAAGCCTTTACAGTTGGATCAAGAGAAAATTC
CTCGATAGGGGCGTGATTACACAGATGATTTATGAGAAAACGCTTAACAATAAGTCACAGTACAACAACATC
CTGAACCAGGTGGTGCCGGGGATTCTTGCGAAGCTGGGAAACCTGCCATACGTTCTTGCAGAGCCGCTTGAG
ATAGCCGACTACTTCATAGGCCTGGATGTGGGGCGGATGCCAAAGAAGAATCTTCCGGGGAGCCTCAACGTG
TGCGCGTCTGTCAGGCTCTATGGCAAGCAAGGCGAGTTCGTGCGCTGCCGCGTCGAGGACAGCTTGACCGAG
GGCGAAGAGATTCCCCAGCGGATCCTGGAAAATTGCCTGCCCCAAGCAGAACTTAAAAACCAAACTGTCCTT
ATCTACAGAGATGGTAAATTCCAGGGAAAGGAGGTGGATAACCTTTTGGCTAGGGCTCGCGCAATCAATGCC
AAGTTCATACTGGTTGAGTGCTACAAGACCGGTATCCCCCGACTGTATAACTTCGAGCAAAAACAGATCAAC
GCACCCTCCAAGGGGCTGGCACTCGCGTTGAGCAACCGAGAGGTGATCTTGATTACGAGCCAAGTGAGCGAG
AAGATAGGCGTTCCTCGGCCACTTAGACTCAAAGTGAATGAGCTGGGTGAACAGGTGAACCTGAAGCAGCTG
GTCGATACCACTCTTAAACTCACGCTGCTCCACTATGGGTCTCTGAAAGACCCACGGCTGCCTATTCCCCTG
TACGGTGCCGACATCATAGCCTATCGGCGGCTGCAAGGAATCTACCCATCCCTTCTCGAGGATGATTGTCAG
TTCTGGCTG
192 65 ATCACCAGCTACCCTTACGCTAGGAACAAGGCCGACATGATTCGCAAGGTTAATTGGAATCTGATCGTGTTC
(Helicase) GACGAAGCCCACAGGATGAGGAATGTCTATAAGAAGTCCAATAAGATCGCCCGAACCCTGCGCGAGGCCACT
GCCGGCTATCCCAAGATCCTGCTCACTGCAACCCCCCTCCAAAACTCCCTCATGGAGCTCTACGGATTGATA
TCTTTTATTGACCCCCACATCTTCGGGGATGAGACAACTTTCCGCAGACAGTTTAGTCGCGGCACCAAGGAA
ATGAGCGAGATGGACTTTATCGACCTGAAACAACGAATTAAACCCGTGTGTCACCGCACCCTGAGGCGCCAA
GTCACAGAGTACGTTAACTACACTCAGCGCATTCCGATCACCCAGGAGTTCATGCCCACCAACGAAGAATGG
GAGCTGTACGAGAAGGTCAGCGCCTATTTGCAACGAGAACATCTCTTCGCGCTCCCCGCGTCACAACGAGCA
CTTATGACCTTGGTAGTGCGCAAACTGCTCGCCAGCTCTTCATTTGCTATTAGCGATACCCTGCTGAGCCTC
ATCAAGAGGTTGGAACAACTGCTGGAACAGCTGGACTCCGGCAAGACGGAGATTACCGTAGAACACAGCGAT
GTCTACGCGGACGTGGACGAGTTTGATGATACAGTGGAGGAGTGGGAGGAGGACGACCAGCCTTCTTACATA
GATAAACTGAGCCCAGACGAGATGAAACGGTTGATTCAGGAGGAAAAGGAAGAACTGGAGCAGTACTACAGC
CTTGCAAAAAGCATTAAAGAGAACTCAAAGGCTGAGGCCCTCCTCATAGCGCTTGAAAAAGGGTTTGAAAAG
CTCAGGATGCTGGGGGCTAATGAGAAGGCCGTGATCTTCACAGAATCCCGACGCACACAGATGTATCTGAGA
GAATTCCTGGAGAGAAACGGCTACGCCGGGAAGATAGTGCTGTTCAACGGTGAAAACCAAGACGAACAAGCG
AAGCAGATCTATGAGCAGTGGTTGGAGAAGCACCGACACGACGACAAGATTACGGGCTCTAAGACGGCGGAC
ATGCGAGCCGCGCTCGTGGAGTACTTTAAGGAGCAGGCTAGTATAATGATAGCGACCGAGAGCGCCAGCGAA
GGCATCAATCTGCAATTTTGCAGCTTGGTTGTGAACTATGACTTGCCATGGAATCCGCAAAGGATAGAGCAA
CGGATCGGGAGGTGTCATCGCTATGGTCAAAAGCACGACGTGGTGGTAATAAACTTTCTCAATTGTAAAAAC
GAAGCGGACAAGAAAGTAGATGAGATATTGTCCGAGAAGTTTCGGCTGTTTGAGGGCGTATTTGGCAGCAGT
GATGAAGTCCTGGGGTCCCTCGAAAGCGGCGTGGATTTCGAGAAGAGAATCCAACAAATCTACCAGACCTGC
CGAACCGCGGAAGAAATTGAGCAAGCGTTCAAGAACCTGCAAGCTGAGCTCGACGAGCAAATTCAACTGAAG
ATGAAGGAGACCCGAATGCATCTTTTGGAAAACTTCGATGACGAGGTGAGGGAAAAGTTGCGAGACCATTAT
CACCAAACCTCCCTGCATCTGAATAGGATGGAAAGGTATTTGTGGAACCTCAGCAAGTACGAGGGGGCACGC
GAAGCCATCTTTGACGACGAGACGCTGTCCTTCGTGAAGGACTACGAGACCTATCAGATGATCAGCCAGGCG
AAGAAACAAAACAGTCCAAACGTGCATCACTTTCGATTCTCCCACCCGCTTGCGCAGAAGTGGATCGAACAG
GCCAAGAGCAGGGAATTGTTGCCAAAGGAGATAACGTTCAGGTACAGCGACTACAAGGGCAAAGTCTCCATC
TTGGAAAGACTCATCGGCAAGGAGGGTTGGTTGAGTCTGGACCTGCTTCACGTCCAGAGCCTTGAGAGCGAA
CAACACCTCATCTTTAGCGCCATCGACACCGAGGGCGGTCAACTGGACCAGGAGATGTGCGAGAAAATGTTC
GAGCTGCCCGCTGTGGAGGGCGAGGAAGTAGAGATATCCGACTCCATCCGAAACACATTGAGACGAATCTCA
GAGGGCCAGCAAGAGGCAATACTGAATGAGATTATGGAACGGGCGTCCGCCTACCTCGACTCAGAACTCGAG
AAACTGGAAAAATGGTCACAGGACCTCAAGAATAAGCTGGAGAAAGACATTGATGAAATGACGGTGGAGATC
GAGCATCTTAAACGGGAAGCTAAATTGACACGCAACCTGGCAGAAAAACTCGAAAAAAACAAACAGATCAAG
GAGCTTGAGAAGAAGCGCAACGAAATGCGCCGGAATCTCTATGACCAACAGGACGAAATCGATGAACAAAAG
GACCGCCTCTTCGAGGAGGTAGAGAAAAAACTTGAACAACGGACTGCGACGGAGCACCTCTTCACTATCAAA
TGGCGGATCGTG
193 44 GTGAACCATTACTATTTTTCCGAATGCAAGGCGGACGAGAAAGCCAGCGACATAGCCATCCACCTTTACACC
GTGCCCCTGTCCAACCCCCATGAGAAATACAGCTATGCGCACAGCATCGCCTATGAATTGAGAAAACTCAAC
TCATACATAACCGTGGCCGCGCACGGTCAGTACATCGCGTCTTTCGAGGAGATATGCCACTGGGGCGACCAC
AGGTACATACAGCACGAACATAGACCAATCCAGTGCAGCCTCCCGATGGAGAGGACCATACTGGAAAGACTC
CTCAAGAAAGAGCTCGAGAATAGGTGCAAAAGCAGCTATAAGATGGACAACGACCTTTTCCGGTTGGCTAAC
GAGCAAAGCATGCACGTGGGCGAGATCAGCATACACCCAGCGATCTACATCTCATTCAGCGTGGAGGAAAAT
GGTGACATATTTGTTGGCTTCGACTACCAGCACCGGTTCGAGTACCGCAAAACACTCCAAGACGTCATCAAC
AACGATCCCTCCCTGCTTAAGGAAGGCATGGAAGTGGTGGACCCCTTCAATAGAAGGGCCTACTATTACACT
TTTGTGGGCATGGCCGATTATACCGCCGGACAGAAAAGCCCCTTCCTGCAGCAGTCTGTGATCGACTATTAT
CTCGAAAAGAATGAGCTGTGGAAGCTCAAGGGTGTGCACGAAAAAACCCCCGTGGTGCACGTCAAGAGCCGA
GACGGTCACTTGCTCCCGTATCTGCCGCACCTGCTCAAATTGACATGTTCATACGAACAGCTCTTGCCCAGC
ATGACCAAGGAAGTCAATCGCCTGATTAAGCTGAGCCCCAACGAGAAGATGAGTAAGTTGTATACGGAGATG
TTTCGATTGCTCCGGCAGCAACAGGTGCTGACCTTCAAGAAGGAAAACGTGCGAGCCGTCAACCTCGGCTAC
GATGTGAATGAACTTGACAGCCCGATCATGGAGTTCGGACAAGGCTACAAGACAAACGAGATCTATCGAGGC
CTGAAGCAGAGCGGAGTATACGAGCCCAGCTCAGTGGCCGTGAGCTTTTTTGTTGACCCCGAGCTTAACTAC
GACCCCCAGAAGCGGAAAGAAGTAGGTTGCTTCGTCAAAAAACTGGAGAGCATGAGCGAGGCCCTGGGAGTA
AAACTGAACATAAGCGACCAGCCCCGACAACTTTATGGCCAGCTCCCCAAGGACTTTTTCAAGCAGGACAAC
CTCTCATATCATTTGAAATCTATCACCGACCAGTTCAGGGGAACGGTGGTGGTTGTTATCGGCACTGAAGAG
AACATCGACCGGGCATACGTTACAATCAAAAAGGAATTCGGCGGCAAGGAGGATCTGATGACCCAGTTTGTC
GGCTTCACCTCCTCCCTCGTCACGGAGAACAACATTTTTCACTACTACAACATCCTGCTCGGCATCTATGCG
AAAGCTGGTGTTCAGCCCTGGATACTCGCCAGCCCAATGCACTCAGACTGTTTCATTGGACTCGACGTAAGC
CACGAGCACGGTAAGCACGCATCAGGGATAATACAAGTGATTGGACGGGACGGCAAGATTATCAAACAAAAG
AGCGTTGCGACAGCAGAGGCCGGAGAGACTATTGCCAATAGCACGATGGAAGAAATCGTCAACGAAAGCATT
TATTCCTACGAGCAGATCTACGGGGCCAAACCGCGCCACATAACATTCCATAGAGACGGGATCTGTCGCGAG
GACCTCGATTTTCTGCAAGCGTATTTGCGGAGTTTCCAAATCCCATTCGACTTCGTAGAAATCATAAAGAAG
CCGCGACGCAGAATGGCGATATACTCTAATAAGAAGTGGGTCACGAAACAGGGAATATACTACAGTAAGGGC
AACACCGCTTATCTGTGTGCCACGGACCCCAGAGAATCCGTGGGTATGGCGCAACTTGTCAAGATCGTACAG
AAGACTAACGGATTGAGCGTTCACGAGATAGTGAGCGACGTGTATAAGCTGTCCTTCATGCACATACACAGT
ATGCTCAAGACCAGGTTGCCTATCACGATACACTATAGCGACCTCAGCTCAACGTTCCACAACCGGGGCTTG
ATCCATCCCCGGTCCCAACATGAGAGAGCACTCCCGTTCGTG
194 67 ATGAATTTCCAGCTGTGCGACCAACGCAAAGCCATTATCGCCGAACCAGGCCATCTGTTGGTCCTCGGTGGG
(Helicase) CCAGGAAGCGGGAAAACTACCGTCGCCCTCTTCAAGGCCAAGCAGAGATTTAGCACTCTGAAACCTAGCCAA
GAAATCCTGTTCCTGTCATTCAGTAGAGCTGCCATCAGGCAGGTCCTGCTGCGGTGCAAGGAGATTCTGAAG
CCCGCAGAGAGACGCGCTGTCGCCGTTCAAACCTATCATAGCTTCTGCATGGACATGCTGAGGGCGCACGGT
AGACTGCTCCTGGGCCACCCCGTGCGATTCATGTATCCCGGCGACGAGAGGCTTCAAAAGGCCGCATTCGAG
GGGGACTGGGAGGCGGAAAGACAAAGGCAAGCCAAAGAGATGGGCATCTTTTGCTTCGACCTTTTCGCGCAA
GGCGCAGCTGAGTTGCTCGAGAGGTGTGCCGCACTTAGGAAGCTTATAGGGGACAGCTTCCCCATGATAATA
GTGGACGAGTTCCAAGACACCGACGACAACCAATGGCGGATCGTGGCGCAACTTGCCAAGGTAGCGGACATC
TTCTGCCTTGCCGACCCCGACCAGAGGATCTTTGACTACCGAGACGACATCGACCCCCTTCGGATCGAGGGT
TTGCGGACCACTCTTGCCCCCAGGGAGTTCGATCTTGGCGGTGAGAATCACCGCTCCCCGAACGCAGGGATA
TTGAACTTCGCCAACGCTGTGCTGCATAACCAGAGCCCCCTGCCCGATACCAGCGACATCATGCAACTGCGG
TACTGGCCTAGAGCGTTCGCGAGCACCGTGCATGCCTGCGTAGTGTTTACCTTCAGCGAACTCAGGAAACTG
GGCGTGGAGAACCCCAGCGTGGCAGTGCTGAGCCGATCCAACGGGCTTATCAGCGATGTGAGCGCCATACTG
GCTGAGAAGCACGCGTACAACGGGAGGGAACTGCCAATCGTGGAACACGACGTGGTTTGGGACGCGGAGCTG
TCTGCGGCAGCAGCCGTCGTCGTTGCGTCCACCCTGGAGTGGCCAACAGCCGCTGCAGAGGTTGCTGTTGCC
AGGACACTTGCGCTCATAGCAGCCTATTACAAGCTGAAGAACGCCGAGGAACCCACCAAGAGCGCGGCTGAG
GCTGCCCAAAAGTACGAGGCGGCTGCAAGCAAGGTGGCCAGTGAGGAGACCCCAAGGATCAAAGCCGCGAAA
GAATTGCTGGCCGCTCACCAAAGTGGCATCCAGATGGTGGGCGACCCGGTGGCCGATTGGAAGTCTGCGAGG
AGGGTATTGCAAGAGATAAGCGCCCTGGGTGAGTTGTACAGGGAGGTCCGGCTCGTGAGGTTGTTCCGGGCA
ACCGACGCCTTGGCTTCCGGCCTGAGCAATAGGTGGTTGGCTACTGGAAGCTACGAGGGCGTGTCCGACCTG
GTGAAGGGCATCCTTGAGCAGGAGAAACTGATTGCCGTGGAAAGGGACCCAAGAGGCTGTATACTGATGAAC
ATCCATAAAAGCAAAGGTAAGGAATTCGACGGCGTGGTACTCATTGAGGGGGCATTTAAGTCCCATTTCTTC
GATGAGCGGAAGGAAGTCAGCCCCTATGAGAGGTCCAGACGGCTCCTGAGAGTCGGTCTGACCCGCGCTAGG
CATAGGGTGACAATCCTTAGACCTCAGGGAGCGAGGCCCCTTGTGGATCCCATC
195 34 GTTCCAGGCGGTAGGGGACCGCTGCTCGTGCTTAACTTCCTTCCCGCTCGCTTCGACGGCCGAGTTGATGCG
GGCACCCTCCCCTTCGAGACCCCTGATAAATTGAGGGCCATTAGGGAGGAACTGAGAACTTCCCATGTAGTT
GTAACGCGAGGAAAAGAGGTCGTATGCGTGCCCTTCGTTAGTGGCGCGAAATTGATCGGCAAACGAACCACT
ATCACCGCAGCGGGACCCGACCTCGTCGTACAAACGAGTCTTCTCGAATCCAGCCTGAGGCGGACCTTGACC
GAAAAATGGAAGTACGAATTGCGCAGGGAAAACCCGCTCACCTTTGTGTCAAGGACGCCAGGAAGGGACCTG
CTGGAGAAGGCCCTTGGTCGGGAGTTGCCGGGACTCCATGTGTTCCCCGCTTACAGCCTGGACGTGCGCAGA
TACGGTCCTGGGGGGTTCAGCGGGGTTGTTGTAGGATTGAAGACCCGCTATGAGATCGACCTGCCTGTCGGA
GTGCTGCTCAGGAGGGGCGTTCAAGTAAACGGCCTTTATGTCCTGGCTGAAAGCCCCCTCGCGCCTACGTGG
CCCTTCCAAGATCCCCACACCAGAAGGCGGCTCGTGGGACAAGTTGTCGCGGTGGATGGCGACAAATTGCGA
GTGAGGTGTAGGGACGGGGAGCTGGAACTTGATGCCGCCGAAGCATGGATTGAGCCCAACACTGCCAACTTC
TACGCCGTCCTGCGGAAGGCGTGCGGACGCTCTTACGAACGAGACTTTCACGCCCTGGAAGCCCAAGTCGTG
TCCCTGACTAACGCCCAGCAGCGAATCGCCGATACCAACAGGATCGCCGCCAACCTGATAGGCCTTGGTAAA
TTCGACATCAGTAACGGCTTGACTGCCGAGCTGGGGAAACCACTCAGACTGACTTCCACTCAACATCCACAC
GTTCGGACTCTGGCCGAGCCCACATTTGTGTTTGACCAGAGCGGAGACAAAACCGCGCCTTTTCCCGAGACC
GGGCTGACCAAGTGGGGCCCATTGGACGCTGAGAGCTTTACACCCAAGGCACCACACATCGCCGTGGTGGTT
CCGCGGCAGTTTCAGGGTCGCGTCGAAACGCTGGTTGAGCGGTTCAGGAACGGCGTGAGGGGCAGCAACGCC
TATGCCGAGGGCTTTGTCCGAAAGTTTAGGCTCACCGACTGTACCTTCAGCTTCACCGTTTTTGACGGTGAC
GCTACTGACGCAGCCGCATATAGGCAAGCGTGCCTTACCGCCCTGAGTAATGACGAGCAAATTAACCTCGCC
TTCGTCTTCACATCAGCCGTGCAGGAGCATCAAACGGGGGACGACAGTCCCTATCTTGTCAGCAAATCCACC
TTCATGAGCCAGGGTATCCCCGTGCAAGAGTATCAAGTGGAGAACATCATCGGGGATTCAAACTTGGCTTAT
CCCCTGTCCACGATGGCGCTGGCGTGCTACGCCAAACTGGGTGGCACCCCTTACGCCATAAGCGATCGAGGA
CGACCTATGGCACGAGAACTGATCTTCGGCATCGGGTCTGCCCAGGTAAGCGACGGAAGGATGGGCGAAACA
GAGCGATTTGTGGGCATTACCACCGTGTTCAATTACGACGGTAGGTACTTGGTTAGCAACGTTAGCCGCGAG
ACACCCTACGAAAGGTACCCGCAAGCCCTGCTTGACGCATTGCGGACTTGCATTGCCGACGTGAAGGTTAGG
CAGGGATGGAGGTCCGACGACTTTGTGCGGCTTGTCTTCCATATCTTCAAACCTCTGAAGGACAAGGAAGCA
CGCGCCGTAAAAGAGCTGGTGACGGAGCTGACGTCTGAATATGCCAGCGTGGAGTTCGCTTTTGTGACAGTG
GTGGACGATCACCCGTGGCTGGTGCTCGATGAAAACAGCGATGGGGTTAAGGTTGGGCGAGGGACTAAGGGC
AAGCACGTAGCTCGGAGGGGTTTTGCCCTGCCGATTTCCAAAAGGGAGCTTCTTGTGACGGTTAAAGGTCCC
CGGGAAATGAAATCCGATAAGCAAGGGGCTCCCAAGCCCCTCTTGCTCAAGCTCCATCGCGAAAGCACCTTT
ACAGACATCGACTACCTGGCTTCCCAGGTCTTTCAATTCACCGCCATGAGCTGGCGCAGGCCATACCCTACC
AGCAAACCCGTGACTATAAGCTACAGTGACCTGATTGCGGGACTTCTCGGAAAGCTGCGACACGTGACGAAC
TGGAATAGCGACATGATCTACATGAAGTTGCGCTTCAGCAGATGGTTCCTG
196 30 ATGCAGCAGGAGATCCAGCTTAACATCATCCCCTTCACCGCCCCTGTGGAAGAGGCAGAGTTCGCTTTTTAC
ACCGCCAAGCAAGACGGCTACTGCCCCATCCATAAGGATGACCTGAACGGGGCCATCGAAGGCCTCGTGGAT
GAATCAGACCTGCACTACGGCAACTGGCTGTACACTGACTTCGCTCCCGCCAAAGAGAACGCCATCATAATT
AGCGTCAATCTCAATGACTGTAAGTACTTCGCCCAGCACTACTACAGGCACCTTATCAGGACCCACTTCAAG
GGAGTGGCCGACATCATGAGGAAGAATTTCACCAACGAAATCGAGGTCTGGTTCCACAATACCAAAGCCAGC
TCTACCAAGTTTAAGGTCTATAACCAGTTTACCCTCAAGGTACAGCACAACAGGGTGACGGACGGACCGGAA
CTTGTCGTGTCCTTCGACGGGACGACGAAGGTGCTGAACAAGTCTATCGCCGAGATACACAACTTCAAAACG
GAGCTTTACAACTGGATAAACTGCAACGGCGAGCTTAATCGCTGGAAATACCTGACCGACGATCAGAAGCTG
AATCACGAAAAGAACTACCCGGTAGTGTCAAACACACTTAAACCGCATTTCGACATTGCCTTTGACGTTCCC
GATTTTAAGAACCGGTATCCCAAATACTTCACTCTTCTGAATGACTTCTACAACAACTATCTGAATACAGAC
GCCTTTACTGCGATCTTGCCGCTTTCCGCTGACGGATTCTTCAAGCCAAATGGCCTGTCAGTGCAGAGGATC
AACGGCACTAGCAATGAGCTGCAATTCGGCAATGGCGTCGGCGTGGAGCCCAAAAGGGATCTCAAGCGCCTG
AAGCCGTATAAACCCGTGCCCAAACCCAGCAACGTAAAGTTTTTCTTCATCTATCACAAGCCAGATAGGGAG
CATGCGGTCAAAAACATCTGGCAGTATTTCAAAGACGGATACAACGGCCAATACCCCTTCCCCAAGATGGAG
GAATACATATCTCAGCCCTTCGAGCTTGAGGAGAATGGATCTATCTCATTCGACAATATCGACGACGCGGTA
AGCGTTGTCCAAAAAGCCATCAAGAACAAGGATCGGCTGCCCGACACTAAATACTTTGCGGTATACATCTCC
CCCGTACCAAAATGGGAGAAGGACCCTAAACGGAATAGTATCTACCATCGGATGAAAGAGATACTCCTGTAC
GAGGGGATCACCAGCCAGGTGATCTGGAAGGAGAACATTAGCAAACCGGCTTTCAACCTCTTCTTGCCTAAC
ATCGAAACCGCCATACTGGCCAAGCTGGGAGGCGTCCCCTGGAGGCTCAAGAGGGACACCACGAACGAGTTG
ATCGTTGGCGTGGGTGCTTTCTACTCAATCACGCGGAAGTCCAAGTACGTGGGCTCTGCATTTTGCTTCAAT
AACGAGGGCATCTTTAAGGGGTTCGACTGTTTCGGTGCCAATGACACCGACAGCATCGCGGGCTCTATCAGG
GAGGCCGTGGGAAAGTTCATCGCGTCTAATTACAAGGCCACAAGGCTGATCATTCACTTCTATAAGGACCTG
TCAAAGAAGGAGCTCAAACCAATCATCGATACACTTCACGCCCTGGGCTTGCCCATCCCAGTGATAGTCGTG
ACCATCAATAAAACCGAGAGCAAGGAACTCCTGGCATTTGATACCAGCTCACAAAAGCTCATGCCCTACTCT
GGCACCATCGTGAAGGTGGGAGCCAAGGAGTACCTGCTGTTCAACAACACGCGATACGAGGAAGCATCCGCC
CCAACGGATCGCGAGCACCACTTCCCGGTGAAAATCAGCTTTTTCTCAGACAAGGCGGAGCTGTTGGACGAT
CCCGCACTGATCAACCAACTGATCGACCAGGTGTACCAGTTCAGCCGCATGTATTGGAAAAGCGTGAGCCAA
CAGAACTTGCCCGTAACCATTAAGTATCCCGAGATGGTGGCGGAGATTTTCCCATACTTTACCCACGATAAA
TTGCCCGATCATGGAAAGGAGAGCCTGTGGTTCCTG
197 47 ATGTATCTTAACCTCTACGAAATCAAGATCCCCTACAGGGTTAAACGATTGTACTACTTCAATAAGGAGAAC
GACCCCAAAGAGTTCGCCCGGAATCTGAGCCGAGTGAACAACATACGGTTCAACGACAGTAAGGACTTGGTG
TGGCTCGAAATCCCCGACATCGACTTCAAGATTACACCCCAGCAGGCGGAAAAGTACAAAATAGAAAAGAAT
GAGATAATTGGGGAGAAGGAAGACAGCGATCTGTTCGTCAAAACCATTTACAGGTACATCAAAAAAAAGTTC
ATCGACAATAACTTCTACTATAAACGGGGAAATAACTACATTTCAATCAATGATAAGTTCCCGCTCGATTCT
AATACAAACGTTAATGCGCACTTGACATATAAGATTAAACTGTACAAGATAAACGAACGGTATTACATTAGC
GTGCTTCCAAAATTCACCTTCCTCAGTGACAAGCCAGCCCTTGAGAGCCCCATCAAGAGCACCTACCTGTTC
AACATTAAAAGCGGCAAGACGTTTCCCTATATTAGCGGGCTCAACGGAGTCCTGAAAATTGACCTGGGCGAG
AACGGCATAAAGGAGGTCCTTTTTCCGGAGAACTACTATTTCAACTTTACCTCCAAGGAGGCCGAGAAGTTT
GGGTTTTCTAAGGAAATCCATAACATCTACAAGGAAAAAATCTTCAGCGGCTACAAGAAAATCAAACAGAGC
TTGTATTTCCTCGAAGACATCATCAATATAAACAATTACAACCTTACCATGGACAAAAAGATCTATGTGAAC
ATAGAATACGAGTTCAAAAAGGGCATCAGCAGAAACATAAAAGACGTGTTCAAATACAGCTTTTACAAAAAT
GACCAGAAGATCAAAATTGCGTTCTTTTTTAGCAGCAAGAAGCAAATCTATGAGATTCAACGCAGCTTGAAG
ATGCTGTTCCAGAACAAGAATAGCATATTCTACCAGACCATCTACGAGATGGGGTTCAGCAAGGTGATTTTT
CTCCGCGAGCCGAAGACTAACAGCAGCGCATTTATGTATAACCCCGAGACCTTCGAGATTAGCAACAAAGAT
TTCTTTGAAAACCTGGAGGGGAACATTATGGCAATCATTATACTCGACAAGTTTCTGGGCAATATCGACAGT
CTTATCCAAAAATTCCCTGAGAACCTCATCCTTCAACCCATACTCAAAGAGAAACTGGAAAAGATTCAGCCG
TATATCATTAAGTCCTACGTCTATAAAATGGGAAACTTTATTCCAGAGTGCCAACCATACGTCATAAGGAAC
CTGAAGGACAAGAACAAAACCCTCTACATCGGCATCGACCTGTCCCACGACAACTATCTCAAGAAGTCTAAC
CTCGCCATCAGCGCCGTAAACAACTTCGGTGACATTATCTACCTGAACAAGTATAAGAACCTTGAGTTGAAC
GAGAAGATGAACCTCGATATAGTCGAGAAAGAGTACATACAGATCCTCAACGAGTACTACGAGCGCAATAAG
AATTACCCCGAAAACATCATTGTTTTGCGAGACGGACGCTATCTCGAGGACATAGAGATCATAAAGAACATA
CTGAACATTGAGAACATCAAGTACAGCCTCATCGAAGTTAACAAGTCCGTGAATATCAACTCCTGCGAAGAC
CTTAAAGAGTGGATTATCAAGCTTAGCGACAACAATTTCATATACTATCCCAAAACGTACTTTAACCAGAAA
GGTGTAGAGATAAAGATAATAGAGAACAATACCGACTACAATAATGAGAAAATACTGGAGCAGGTGTACTCA
CTGACGAGAGTGGTGCATCCCACCCCCTACGTAAACTACCGCTTGCCCTACCCCCTGCAAGTCGTCAACAAG
GTCGCCCTTACCGAGTTGGAATGGAAGCTTTATATCCCTTACATGAAA
198 5 ATGGAGGCGTACATAACGGAGATGGTGTCCAGGGAGAGGGCCAACGAGCTGGAGGTTTACGTGTACGTGTTT
CCACGGAAGCAATCCGACAACAACTACGAGGGTGTGTATCACATAATGAGGGCGTGGCAACGGGCTAATGAC
CTGCCTCTGGCGTATAATCAACATACGATCATGGCATTTTCCCCCGTGAGGCATATGTGTGGCTACACGCCG
ATGGAGACGCAGAAACGCCATATTAACATTGACTCCCCATTCGAGAGAGCCCTGCTGGAGCGACTGATAAAG
AACAGCCTGATTTTTACAGCCGAGCGCCATTTGCATGCCAAGCGGGTAGGCCATGCGCTTCGGCTGAACCAG
GTGCAGCAAATCCGGCAGGTGATCATCTATGAGGCCATCGAGCTCTATGTAAATATCATTGAGAATAGAATA
AGCATCGGCTTTCACCTCACCCACCAGTTCGAGTACGTATACACTCTCCAGAGCATGATAGAACAGGGAAAA
ACAATCAGACCTGGAATGCGCGTCGTGCATTCTAACGGAAGGCAGCATTATACCTACACCGTGGAGAACGTA
GCAACATATGGGGTGACCGACAGATGCCCGCTGCTGCAGACCAGCATTTACCAATACTACGTCGAAAAAGGC
GCGCAGCACATTTTGCGCACCTTCACCCGATCCACCAGGGTGATCCACGTAAGAACGAAAGAGCAGAGGTTG
AGCTACGCGGCGACACTCCTGAAACCGCTGTGTACTTTTGAGACCATGCAACCCCAGGACGTGCTCAATGTC
AGCAAGTGCATCAAACTTAGCGCGAGCAAACGAATGAAATGTACTTACAGGTGGATTCAGCAACTCCGGGCA
CAGTACCGACACCTGACCTTTGCGCCGAACCCCTTCACGATCGCCCAGAATGGCTATAAACTTGATCAGCTC
AGCACCCCCAAGGTGCACTTCCACAGAGACTACGCCACCGTCGTGAGCGGAATGAAGACCGGCAAGCTTTAC
AAAGGCGGTAATATCAAGATCAGCGTGCTCTTCGACGAGGACTTTTACTTGAAACACCACATCACCAAGAAG
GACATATATCAATTCATTGCAGTCCTGCAGAAAATCGCCATCGCACAAGGCGTGAACATGACCATAAGCACG
AGCACCAAGTCCATTACGGGCAAGTTCACGGACGACTTTTTCCACCACTTCACCGAGGAGGTCGAAGCACTG
CAGCCCATCTTCGCGCAAACCACAGTTCTGGCATTCATTACCAGTACCCACCTGAGCAACAAGAAAACCAGG
AGTTACCAGCTGCTGAAACAGTACTTCGGCGGCAAGTGGGACATTGCCTCTCAAGTCATCACGGAGAAGACG
ATTGAGGCGTTCCAAAAAATCTTGCACAAGCACGGCCTGAAGAATTTCTACCCCAATGACGAACAGCACTGT
CTCCGCGTGATCGATGTCCTCAAGAATGAGAGCTTCTACTACACGGTCATGAACATCCTCTTGGGAGTATAT
GTGAAAAGCGGCATCCAGCCCTGGATCCTTGCTAATACAACCCACTCAGACTGCTTCATCGGCATCGACGTT
AGCCACGAGAACGGAAACTCTGCGGCTGGGATGATGAATGTTATCGGCAGCCAGGGCCACCTTATCCAACAG
GCGCCCCTGAACGGCATATTGGCGGGAGAAAAGATTGACGACACCCTGCTCGCAAACTTGCTTAAACAAATG
ATTAAGGCATACCACACCCAGTTCCAGCGCTTTCCCAAGCATATAACAATCCACAGGGACGGCTTTTGGAGA
GAACACACTGCACTGGTCGAGAAGATCATGAGCCACTATGAGATTACCTACGACATCGTCGAGATCATCAAA
AAGCCTAATAGGAGGATGGCTTTCTTCAACAGCGTGGACAACACCTTTAGCACCAGGCAGGGGACAGTGTAC
CAACGGGGCAACGAAGCCTTTCTGTGCGCCACTAACCCTCAGCAGAAAGTGGGCATGGCACAACCAATCAAA
ATACATCAGGTGACCAAGACCCTGCCCTTCTCACACATCATAGAAGATGTCTACAACCTCAGCTTCCTTCAT
ATTCACGCTATGAATAAGATGCGACTGCCGGCCACCATACATTATGCCGACCTGTCTGCCACCGCTTACCAG
AGGGGCCAAGTGATGCCCAGGAGCGGTAACCAGACAAATCTGCCTTTCGTG
199 45 ATGACCGGCGAGACTAAAGTGTTGGTCGGGAGGCAACCCTTCGACGTGGATCGGCTGAATGAACTCAGAGAC
GAATTCCGGGAGACGCACGTGTTCAGAAGGGATGGCATCGACGATGTCATTGTTGATGTTCCGGTCGTGGCC
GGACAGAAGCCCATCGGCAACGTCCAGGAGGAAATAGACCTGGCTAGGTACCAAAAGGTGTGGCCCTCCCTC
CTCAGTGCTGCTCTTGTCCGGGCGTTTAGCGGCGTAAGGGACATCCTGAGCGATAGGCCCGTGAGCGTGGTG
GGGAGCACACTGCGGGGTCTGGTTCAACATCCGGAACTCCCCGAATGGATGCAGAAACGCACACTCCTTAGG
TTCGACACCCGGACCATCTATGCTGGTGATAAAAGAACCTTTGGCTTGGTGTGCGAGGCCAGATTGAAAAAC
CTTATCCAAGGTAGTTGCGCGGAGCTGCTGGCACTTGGAGTTTCCCCACTGGGTCGATATGTCCAAGTCGAG
GAGCCACATTACGATCCCAGGCTTATGAAAAAACGGCGCCTTGTGGGCAGGGTATCAGCGATCTCCGGCGAT
AATCTGGTGCTGGAGGACCATGCCGAGGGCTTTCCGACCGTGAGTGCAAAGCTGGCATTTCTGGAGGCGCGA
AGGGAGATTTTTGACGACTGTGTGCGGAGGATTTTGAACTCTGATGCGGCCTCCGTGCTGAACAAGGCCGAA
GCTACTGCTGCCTCATTTCACTCAGGGCCAGGTAGGAAAGAGCAAATAGAGGAGGCTCTCAAGTATCTCAGG
GAGAAGGTGAGCCTCGAAGCTGTACCCGGAGCGAAATTCGTGATCGGGCCGATGCTGAGTAGCGGCAACAAG
GGCTTCCCCATCACGGAGATGATCCCGAAACCCATTCTCGTGTTCGATCCGAGCGGTACACGGAAGGATGAG
TGGAACGAAAGGGGCATTAAGAAGAACGGGCCCTACGACCAGAGGACGTTTTCACCTAAGCAGTTGAAGGTG
GCGGTCATTTGCCAGGCGAAGCACGAGGGGCAGGTGGATGGATTCATCGCGAAGTTCTTGGAAGGTATGCCA
GACGTTATGACGGGCAAGAACCGAGTTGCTAGATATGGTGACGGTTTTCTGCGGCGATTCGCCCTTGAGAAA
CCTTCTGTGACCTTCTTCACAGCGCCCTCAGCCAAGGCGAGCGATTACCTGGTGGCCAGCCGGGCTGCGCTG
ACCAAGGCAACGGACGAGGGTTTCAAATGGGACCTCGCGCTTGTGCAAGTGGAGGAGGAGTTTAAGGGATTC
GACGACGAGAGCAACCCCTACTATGCCACTAAATCCGTCTTCCTGAAGCGAGACGTGCCGGTCCAAAGTGTA
CGACTCGAAACCATGGCTCAGGCCGACAGCCAGCTGATTTTCTCTATGAACCACATGAGCCTGGCGACATAC
GCCAAGCTCGGTGGTACCCCCTGGCTTTTGGCGTCACAGCAGACGGTAGCGCATGAACTGGTTATCGGTCTT
GGCAGCCACAGCGTGGCCAACAGCAGGATCGGTAGCCAGCAACGATTCGTCGGGATTACGACGGTGTTCTCC
TCCGACGGGAGCTATCTGCTCTCAGACCGCACGGCGGTTGTCCCCTATGAGGAGTATGCGACTGCGCTTTAC
GATACGCTCAAACGGAGCATCACTACGGTGAGGAAACAAGACAACTGGAGGTCTACGGATAAAGTCCGCCTG
GTGTTCCACATGTTCAAGCCCCCCAAGGACACCGAGGCCGAGGCTATAAAACGGACAGTGGACGATCTGGAG
CTGGAGAACGTGACTTTCGCCTTCGTGCACATCGCCCCATCTCATCCCTACCTCATCTTCGACAATACACAA
AAGGGAATTGGTTTCCGAGACCCCAAGAAGGGGATACTCGGACCCGAGAGAGGTCTGCACTTGAAGCTGGGG
GACTACGAGTCCTTGATCGTATTCAGCGGCGCAAGCGAGCTGAAACAGGCAAGTGACGGGATGCCCAGGCCA
TGCCTGCTCAAGTTGCACCGGCTTAGCACGTTCACTGACATGACGTATCTGGCGCGACAGGCATTCGAGTTT
TCAGGTCATTCATGGCGAATGCTCTCCCCAGAACCGTTCCCTATAACTATTAGGTACTCCGACCTGATCGCC
GAAAGGCTCGCAGGTCTCAACGCCGTCCCGGGTTGGGACGCGGAGGCTGTCAGATTCGGCCAAATCGGCCGC
ACGCTCTGGTTTCTG
200 42 CTGAAAATCAAAATTCTCAAGGAGCCGATGCTGGAGTTTGGCAACGGCGCTCACATATGCCCCAGGACCGGT
ATCGAAACCCTGGGAGTGTACGATAAGAGAGATGAACTGAGGAGGAGCGAGCTGCGAATAGGCATTGTGGGT
CGGGGCGAGGGCGTGGACCTTCTGGATGAGTGGCTCGACAAGTGCAAGCGCGGCATCGTGGGTAAAGAGGAG
ACCAAGTTCCCCAACTTGTTCAGGGGCTTTGGGGGCGTCGATGAGTACCACGGTTTCTACACCAAGATTCTG
AGCAGCCCCCAGTATACCCGGACTTTGCAGAAAAGCGAGATTAACAACATCAGCAAGATCACCGCCCGAGAG
GACAGGGTAGTGAAGTGCGTGGAGCTGTACTACGAGCAGATCCGATTCCTGTCAGAGAACAGGAGCATTGAC
GTGATCGTGTGCGTCGTTCCCAATGATATTTTCGACAGCCTTACTAAGGCCACCGGAGACAAAGACACCGAG
TCCCTGGAGGCCTACCTCGAGCACAACTTTAGACGGTTGCTCAAGGCCCGCTGTATGCACCTTGGGATACCC
TTGCAGCTTGTGAGGGAGAAGACCATCCTGAGCGTGAAGCCTAGCATAGACCAGCAGGACCTTGCCACAAAG
GCTTGGAACTTCTGTACGGCCCTCTATTACAAGGGGAATAGGACTGTACCATGGCGCCTGGTGGAGGATAAA
TTCAAGCCTAAGACCTGCTACATCGGCATTGGGTTCTATAAGAGTAGAGACGGCGAAACGGTGAGCACATCA
CTTGCACAGGTATTCGACGAGTTCGGCCACGGGGTCATCCTTCGGGGAGCACCAGTTAGCCTGGACAAACGA
GACAAGAGGCCCTACATGGACGAGTCTCAGGCTTACGAACTGCTGGACAGTGCCCTGGCGGAGTACGAGAAG
GCCCTGATGCAAAAGCCCGCTCGAGTGGTGATCCACAAGAGCAGCAGGTTCCGGCCCACCGAGGTGAGCGGC
TTCAGCAGAGTGCTGAACGCGAAAGGAATCAGAACGAAGGACCTCGTGAGCATCACATCAACCGACATCCGC
CTGTTCAGCGACAAAAACTATCCCCCCACCCGCGGTACCTTGTTGTCCCTGTCTGAAACACAAGGAGTACTG
TATACCAAGGGAATCGTAGATTTTTACAAGACCTATCCGGGCATGTATATCCCTTCACCCCTGAGGGTTGAG
GCGTTCGAGTCCGACAGCTCTCTTGAAGACTTGTGTAAGGAAATCCTGGGCCTGACCAAAATGAATTGGAAC
AACACACAACTGGACGGCCGACTGCCCATTACCCTGGAATGCGCCAATAAGGTGGGCGATATCATGAAGTAT
GTGGACGCATCCGAAAAGCCACAGGTTGGTGTGGCGCTGTTTATCTTCATGTTGGAGCAACTCGTACCCGGC
TGGAAGCTGCCTAAGGTGAGTACATGGGTAGCACGGGTAATTTTCCTGAATATTGTACAGGTGTCTATCGCT
CTGCTTGCCGGGATTACTTGGAATAAATGGATGATGGGCCACAGTTTGTTGCATACCAGCGATGCCCTGCCC
CCCTTGCTCGCAGGATTCGCCGCCTACTTCGTTAACACCTTCGTGACCTACTGGTGGCACAGGGCCAGGCAC
GCCAACGACACCCTTTGGCGACTTTTTCACCAACTGCACCATGCGCCCCAGAGGATCGAGGTGTTTACTAGC
TTCTACAAACACCCAACGGAAATGGTATTCAACTCTCTTCTTGGCAGTTTCGTGGCCTACGTCGTTATGGGG
ATCTCCATCGAAGCTGGCGCGTATTACATCATGTTTGCGGCTCTTGGCGAGATGTTCTACCACAGCAACTTG
CGAACACCGCATGTTCTCGGTTATCTCTTTCAACGCCCTGAGATGCACCGGATCCACCACCAGAGGGACCGA
CACGAGTGCAACTACAGCGATTTCCCCATCTGGGACATGCTCTTCGGCACCTACGAAAATCCCAGGAGAATA
GACGAACCACAGGGGTTTGCCGGCGACAAGGAACAGCAATTCGTTGATATGCTTTTGTTTAGGGACGTGCAT
TCCCTCCCCGGGAAGACACAACCAGCTCCCGTACTCGTCAAACCCGACGTGAGG
201 78 AAAGGGCGGCACCAGGCGAAACACTACGCGGACGGCCTGGAAAAAATGCACGGGCAAAGGCCTGTGATTTTC
(Helicase) TACACCAACGGCCACGATATATGGATATGGGATGACCATCCGGCTCAGCACTACCCGCCCAGACGGTTGTAC
GGATTCTACGCGAAGTCCAGCCTGCAGTATTTGATAAGGCAGCGCAGTGAACGCAAGGCGCTGAATACGGTG
AGCTCTAAAACCGATATACTCGGAGAAAGACTCTACCAGCACGAGGCACTGAAGCGGATCTGCGAACGCTTC
GAGACCAAGCAGAGGAAGGCACTCGCAGTCCAAGCGACCGGCACGGGGAAAACCCGCTTGTCCATCGCACTT
ACTGACTCTTGCATGAAGGCCGGGTGGGTGAAAAGGGTGCTTTTCCTGTGCGACCGAAGGGAACTTAGAAAA
CAAGCTAAGAACGCCTTTAGCGAATTCCTCAGCGCGCCTATTAGCGTACTGACAACGAAAAGTGCGCAGGAT
ACCCACAATAGAATCTTCGTGGCAACCTACCCCGCGATGATGAAGGTGTACGAGCAACTGGATACGGGATTC
TTCGACCTGATCATAGCCGACGAGAGTCACCGAAGTATTTACAACATCTACGGCGACCTCTTTCGCTATTTT
GACGCCCTTCAAGTGGGCCTGACCGCAACCCCCGTGGAGATGGTATCTCGGAGCACCTGCCAGCTCTTCGGG
TGTGACTTTAAGCAACCAACTTCTAATTACACACTCGAAACGGCTGTGGAGGAGGGTTATTTGGTGCCCTAC
CAAGTCGTGAAACATACCACAAAGTTTCTGCGCGATGGGATCAAGGGCCACGCGCTTAGCGCGGAGGAACTG
GCGGAGCTGGAGGACAAGGGCATCGATCCTAACACTCTTGATTTCGACGCCGAGCAGATCGACCGAGCGATC
TACAATAAAGACACCAATCGGAAAATCCTGCAGAACCTCATGGAGAACGGTATCCGGCAGGCCGATGGCCAG
ACCCTCGGTAAGACGCTGGTATTTGCTAGGAACCACAAGCACGCCAAACTCCTCGAACAGTTGTTCGACGAG
CTGTACCCCCAGTACGGCGGTAAGTTCTGTCAGGTTATAGACAACTACGACCCCAGGGCGGAAGAGTTGATA
GACGATTTTAAGGGCGAGGGCAGCAACGAACAGCTCACTATAGCAATCTCAGTCGACATGCTCGACACCGGG
ATTGACGTCCCGGAGATCGTAAACCTCGTATTCGCACGGCCGGTTAAAAGCCCCGTGAAATTTTGGCAAATG
GTTGGTCGGGGAACGCGACTCTGTAAGAATTTGTTTGGACCCGGCAAGCACAAGACGCACTTCCTTATTTTC
GACCACTGGGGAGTCGTGGAGTATCACGGCATGAAACAACGCGAGGTAACTGTGTCCCAGAGCAAGTCCCTG
ATGCAGCAATTGTTTGAAAATAGATTGGAGCTCGCCAAGACCGCGTTGCACCACGCCGAAGCCGACTTTTTT
GAGACGATGGCGGGGTGGCTGCACAAAACGATAAATAGCCTGGACGATCGAACGATTGCCGTTTGTGATAAG
TGGAAAACTAAGCAGCAAATGTCCGACCTGGAGACGCTTAGACAGTTCGGTGCAAACACCGTCACGCTGCTT
GAGTCAGAAATCGCCCCGTTGATGCAATGGCTGGATGTCAGAGGGCATAGTGACGCATATCAGTGGGACCTC
CTGGTCTCACAGATCCAACAACAAAAATTGAAGCAGGCGGCAGCCTTCGATGATCTCGCTGGGAGGGCAATC
AATCAACTGTGGCAGTTGCAGATGAATTTGAATCAAGTTAAGGCAAAGTCCGAGTGGATTAAGCAGTGCCGA
GAGACGGAGTGGTGGCAGAAGGCGTCCCTGGATGAACTGGAACAAATGCGACAAGAACTGCGGGGCATTATG
CAGTACAGGAACAAGGGTGACATTCCGAAGACAGAGGCGCCCATCATAGACATAACGGACTCAGAGGAGGTG
CGCGAGAAACAATCCTCCTACCTGAACTCAGTTGACATGGTCGCGTATCGGGTCAAGGTTGAACAGGCGCTC
CAGGAGCTCTTTGAGAGAAACCCCATCCTTCAGAAGATCCGGAACGGGGAGGCCGTGTCTGAGCGCGAGCTT
GAGAACTTGAACGCTCTCGTGCATACACAACACCCGGATATCGATCTCAACACACTTAAAAAGTTCTATGGG
ACCGCGGCTCCGATGGATCAAATCCTTCGGACAATAGTAGGCATGGACGGGAACACGGTTAATCAGCGCTTT
GCGGCGTTCATACAACAGTACCCCTCACTGAGTGCGCGCCAAGTTCAATTCCTGTCCCTGCTGAAACGACAA
ATTGCTCAGAGTGGGGCCATAGAGATTGACAACTTGTACGAAATGCCATTCGCAGCTATCGGCGAACCCGAC
AGCGTATTTAGTAACGCGGAACAGATTGATGACCTTCTGGCGATTGTGGAGAGCTTCGGGAAGCAGCCCCAG
CAGCAGTCTACGAGACAGGCCAATGAGACA
202 64 ATGGATTACATACTTGAATTCGACGAGTTTATTCGAAGCATCAAGCAGAATATTGATACAAAGTATTCATTC
CTGTTGGGGGCTGGCGCTTCAGTCGAATCAGGTATTCCGTGTGCCAGCGAATGCATCTGGGAGTGGAAGAGG
GATATCTTCATCAGCCAAAATCCGACCCTGGCTGAGATGCACAACAACATCAAGAGCCAGAACATTAAGCGC
AGCATCCAGAACTGGCTCGATAACCAGGGCACCTACCCAAAGGAGGGCGAGGACATCGAGTATTCCTACTAT
ATTGAGAAGGCTTTCCGGATTCCCGACGACCGGAGGAAGTATTTCGAACGAAACATCACCGGCAAGACTCCG
TCACTGGGCTACCATATCCTGTGTCTGCTGGCGGAACGCGAGATAATCAAGTCCGTTTGGACAACAAACTTC
GACGGCTTGATCATTAAAGCCGCCCATAAGTACCAGTTGGTGCCCATCGAGGTCACCCTCGAGAGCCAAGAT
AGAATCTATCGGACGGATGCCAACAAGGAGTTGCTTTGCATAGCCTTGCATGGGGACTACAAGTACGGTCCG
CTGAAGAATAGTAAAGAGGAGCTGGACAGCCAGTCTGACATCTTCGTGAATGCCCTTTCCTTCGAGGCGTCT
AAGCGCTATTTTGTGGTGATGGGATACAGTGGGCGCGACAAAAGCCTCATGCAGGCTATTGAGCGAAGCTTT
TGCAGAAGCGGCGCTGGCCGCCTTTACTGGTGTGGATACGGCCGGAACATCGCGCCTGAGGTACGCGTGCTG
ATCGAGAAGTTGAACTTGTATGGACGCGAAGCGTTCTATATTCCCACGGACGGGTTTGACAAGACGATGTTG
AACATAGCCCATATGTGTTTCGAGGATAAGGAATTGCAGGAAGAAGTGGAGAAACTCAAAGCGGATCTCGGT
GCGGGGTATGAGTGTCGCACCACCACGTTCAGCCCCTACAAGGAAGGGGTGAATAAGATCGTGGACACAAAT
GTTTACCCGATCAAATTCCCCGACAAGTGCTATCAGTTCGAGGTGAAGAACAGCAGCGTAATGAACCTCTGG
GATTACTGCAAGCAGCTGATAGACTATAACATTGTGGCCGTCCCCTATAACGGAATGATCTACGCCTGGGGA
AACCGCAACAGCATCAGCAACATGTGCGGACCAAATGTGAACGGGACGATCGAACTCGTTCCTCTCACTAGG
AAAATCTTTTTCGACAACGGCACTCTCAAGTCAATGCTCCTTAAAACTTTGCTCATCGTGATTGGAAAGCAC
TCCAATTGCAAGTATAACCGAAACAAAATCTGGCGAGAGTCCAAGAAAATCAACTACACTATTAACGGCAAA
AACATTGAAGCGTACCAAGGCATTAGGTTTAGCTTGTTCATGGACTGGAAATACAGCTACCTCACCCTGACC
CCCGCTTTCTACTACAAAGACAGGAACAACGTTAGCAAGGAGGAGAACAAAGAGTTCAGCGACCGGTTTATG
GAGCAAATATGTAAGATGCAAGCCAATAAGAATTACGCCGCGTACATAAAACACTGGATTAACATTATCTTT
CCTGATGGCAAGTCCATCATTTCCATGTACCCGTGTAACAGCGAGAGCGGATTCGAGTTCACCATTGTTAAT
AAGTCACTGCTGGTCGGACTGCGGAGTAGGCAAGCACTGCATAATCCTGACGATGACATGAAGAAACGGATT
TGCATCGGTGGAGCTGAGTTGGCGGACACCGAGCTCAAGTTCTACAATCCGGCTCAGAATGCAATGCACACC
GACTTCCACCCCATGAGGGGCCTTATCAACAATAAGCCCTACGACTTCTACATGAATAACAGGCTGTTTAAA
TCTAACATCTCCCTGGGCGTGATCTCTCCTGTGGGTTCAGAGAAAAAGCTGGAGGACTTCCTGGACCGACTC
AACAAAAAGCACAAAGTGAACTACAACGTCGACTATGTCATAGATTATCCTGGGTTTCAGTCCGTCTACGGG
GTTGGCCTTTCTGTCCCTCTGATCGCAGAATGGGCGTTGTTGGATGATAAAATGCTGAATAAAGCCAACCTG
TATCAGAGCTGCCTTAACTTCGGGGATCAGATCAAGAAGAAGATTGAGTACCTGAAGAGCCGCGACAGCGTG
GACGTGATCATCATATACATTCCGAAAGAGTACGAGCTGTTCACCTTCTTCAACGACGGAAATATCCATTAT
GACCTGCACGACTACGTGAAAGCATTCAGCGTGCAGAGGCACATTAGCACCCAGTTCATACGGGAGAAAACA
ATTGACTCTGAGCTTGACTGCCAGATCGCGTGGGCCCTCAGCCTCGCTATCTACGTTAAAGCAGGCCGCACT
CCGTGGATTCTCAGTGGCTTGAGGACTGATACCGCCTTCGCCGGCATCGGCTATAGTGTGGACCATATAAAG
ACCGACAACCAGACCCTTATCGGCTGTAGCCATATTTACGGGGCAGATGGCCAAGGTCTCCGGTACAAGCTC
TCCAAGATTAAGGATGTGACCTTCGACAGCAAGAACAATCCCTACCTGTCCGAAAACGAGGCCTACCAACTC
GGCCTGAATATCAAGGAACTTTTCTTTGATAGCTTCAAGACGTTGCCCCAACGAGTGGTCATACACAAAAGG
TTTCCGTTCCAGAAGCAGGAGATCGATGGCCTGACTAAGTGTCTTGGGTCCGCGGGAGTGAAAGACATAGAC
CTCATCGAAATCACCTTGGAGGATCGATTTAGGTGCTTTGAATACGACAGGCGACTCCAGATTGACGGCTAC
CCCGTGAGGAGGGGCGTGTGCTTCGCCATCAACGAGAACACCGCCTATCTGTACACCCACGGTATTGCACCA
AGCGTCAAGAATGCCAATCTCCGCTACATACAGGGCGGTAAGAGCATCCCTGCCCCCCTGAAAATCGTTAAG
CACTACGGGAACGGCGACCTGGCCCAAATTGCGACAGAGATCTTGGGCCTGTCAAAGATGAATTGGAACAGT
TTTGGTCTGTATAGCAAGCTTCCGTGCACTATCCAATCTAGCAACGCTATCGCTCGCGTAGGGTGGCTGCTC
TCCCAGTATGAGGGCGTAGTTTACGACTATAGGAATTTCATG
203 70 ATGAACAATCTGATGCTGGAGGCGTTTAAGGGCATTGGCACCATCAAGCCCCTGGTGTTCTATAGGTACAAG
CTCATCGGCAAGGGGAAGATTGAGAATACCTACAAGACGATCAGCAACGCCAAGAATAAGATGAGTTTCAAT
AACAAGTTCAAAGCGACGTTCAGTAAGGGAGAGACCATCTACACCCTTGAGAAATTCGAGGTCATGCCCAAT
CTTAACGATGTGACCATTGAGTTCGACGGAGAAGAGGTTCTCCCGATAAAAGACAATAATGAAATTTACTCC
GAAGTCGTGCAATTTTACATCAACAATAACCTTCGAAAGATCAAACTGGATAACAAATATCAGAAGTATCGA
GCAACGAATACCAGAGAGATAACTGGCAACGTCATACTCGACAAAGACTTCAAGGAGAAGTACAAGAAGTCT
AAGTCAGGGTTCCAGCTCAAGCGCAAATTCATAATTTCCCCCAAGGTGAACGACGAGGGTAAGGTAACCCTG
TTCCTTGACCTGAACAGCAGCTTCGACTATGACAAAAACATTTACCAGATGATCAAGGCCGGGATGGACGTG
GTGGGGCAGGAAGTGATTAATACGTGGAATAATAAGAAGCAGAAGGGCAAGATTAAGAAGATTTCTGAGCTG
ACGATCTCAGAGCCTTGTAACTTCGGCCAGTCCCTTATCGATTACTACGTTTCCCTCAACCAAGCTGTGAGG
GTGAAGAACTTTACGGAAGAGGAAAAGAACACAAACGTTATCGTCGTCCAGGTGGGAAAGGGCGAGGTTGAG
TATATTCCGCACGCGCTCAAACCCATCATTACTAGGGAGTACATAAAGAAATACGATGAGGCCTTCAGCAAA
GAGGTAGAAAACCTGATCAAAATCAACATGTCATACAGGTACGAAATACTGAAAAAGTTCATCGACGACATC
GGCTCTATAACCGAACTGAACAACCTTAAGTTTGAGAACACGTACATAGATAACATCGAGTCACTGGGCTAC
CAACAGGGAAAGCTGAACGATCCCGTGCTGATAGGCGGCAAAGGCATCCTGAAGGATAAGATACATGTGTTC
AAATCCGGCTTTTACAAAAGCCCCATTGACGAAGTCAAGTTCGGCGTGATTTACCCGAAAGGCCACACCAAT
GATAGCAAGTCCACCATCCGGGCGATTTATGATTTTTGTACCGACGGGAAATACCAAGGCAAGGACAACATC
TTCATTAACAACAAACTGATGAATATCAAATTTAGCAACCAGGACTGCGTGTTTGAGGAGTACGAGCTCAAT
GACATAACGGAGTATAAGCGAGCCGCGAATAAGTTGAAAAACAACGAGAACATCAAGTTTGTAATCGCCATC
ATCCCCGCGATTGATGAGAGTGATATAGAAAATCCCTACAACCCTTTTAAGCGGGTCTGCGCCGAGTTGAAT
CTGCCCAGCCAGATGGTAAGCCTGAAGACCGCGAAAAGATTCGGCACCAGCAAGGGTAATAACGAGTTGTAT
TTTCTGCATAACATTAGCCTGGGTATCTTGGGTAAGATAGGGGGGGTCCCTTGGGTCATTAAGGACATGCCT
GGGGAAGTTGACTGCTTCGTGGGCCTGGATGTGGGCACCAAAGAGAAAGGGATCCACTACCCCGCATGCAGC
GTCCTTTTCGACAAGTACGGCAAGCTGATTAACTATTACAAGCCCACAATCCCGCAGAGCGGCGAGATCATC
AAGACAGACGTGCTGCAGGAGATCTTCGATAAAGTGCTGCTGAGCTACGAGGAGGAGAACGGGCAGTATCCT
CGAAACATCGTGATTCACAGGGACGGGTTCAGCAGGGAGGACCTGGAGTGGTATAAGAACTACTTCATCAAA
AAGAATATAAACTTCACGATTGTAGAAATCAAGAAAAACTTCGCCACCCGCGTCGCGAACAACATAAACAAT
GAAGTGTCCAACCCATTTAAAGGGAGCTTCATACTGCGCGAGAACGAGGCCATCGTTGTAACCACCGACATC
AAAGATAATATCGGCGCTCCGAAACCAATCAAAGTCGAGAAGACATACGGCGATATTGACATGATGACCATA
ATCAACCAGATCTACGCCCTCACGCAAATCCACGTCGGAAGCGCGAAATCTATGAGGCTGCCGATCACGACC
GGCTATGCCGACAAAATATGTAAATCCATCGAATACATCCCGAGCGGTAGGGTGGACAACCGGCTCTTCTTC
CTG
204 61 ATGGGCAGGCAACTCCAACTGAACTTTACCCCGCTCAGGGTTAGGGGCGACGCCATCAGACTTCAGGCGCTG
CCTTTCGAGGACGCTCAACAATTTAGGAATCTGCGCGATGAGCATCGAGCACACTACGCTGTGACGAGAAGG
AGCGACCACATCGTGGCCCTCCCACTTACACTGAATGCCTCCCCAATCGGCGAGGAGAAGATCGTGAGCGTT
GTGGAGCATGCGAGTTTGATTCGGCCCCTGCTTGAACAGAGGTTGGTGACCCTTCTGTCCAGTAACCGGAGG
CCGGTGGCCCGGTATAATCCGATCACCACCATTGGAAGAACCTTGCCAACGGGCTTCATAGAAGCCGACCGA
CACCTCCATTTGCAGTCCCGCGTGCTTATTGCTATCCGCTCCCTCAAGCTGCCGGACGCCGAGCCCTTGGGA
TTGCTCTGGGACATCGAAATCCAGAAAACATGCGCGACTAGCCTTGCCGTCCTGCACGCACAAGGGGTACGG
CTGGACGGTCTCACAGTGGAACGGCTTGTCCCGGTGGAGGACGTGCGAATGTTGCCTTATAGGCGACTGGTG
GGCAGAGTAGGCGCGCTGACCGATGGCCACGCCCGATTGAGCGAGCGGTTCCAGAACGTCGAAGAATTGCTG
CCCCTGGACGAGCTTTACCTGGAGGCCAGTCCGGAGAACCTGAGGCACCTTCTGCAGCATTTCATGCGCAAC
ACAAGCGGGCGAGTGCAAGGGAAGATAGACGAGATCGTCTTCGAGAACTCACGGGGACGCGCTCGGATGGAG
CACATTGCCCGGATCTCCGACTGGCTTAGAGGCCTGGGCGAGATTGAACTGCAGGAGGGTTTGTCTGTAGGC
ATCGGAAACCTGCTCTCTGAAAAGGACGCCCAGAACTTTCCCAGGTTCACTGAGGGAACGACCCCAACCTAC
GTGTTTGACGCTGGGACGTTGAAGAGCGAGTCAAGGGCCGCAGTGGGCCTCAGTAAATTCGGGCCCTACAGC
CGGCATGTATTTACACCGACTCGACCCAACGTTTGCGTCATCTGCGACCGCGCAAGAAGAGGACAGTTTGAG
CTGTTCCTGCGGAAATTCCGGGATGGCCTGACTGTTGATGGGAAGTCCCTGCCGTTTGGTCGCGGGTTTCTG
GGAATATATGGCCTTCAGGATATCAACCTGACCTTCGTCGAGGCGGATGCATTCACCGCGGACGCGTACCAT
GCTGCCGCAAGCAAGGCAGTACGGATGGGAGCCGAGGGCGCACCGTGGCACCTGGCACTCGTGCAAACAGAA
CGCGACAGTCGGCAACTGGCTCCCCCCAAGAATCCGTATTTGGTAGCGAAGGCGGCGTTTCTGTCTAATCAA
ATTCCTACCCAGTTTGTGGCGTTCGAGACATTTTCTATGGCGCCTCTGAACCTCGCGTACACACTGAGCAAC
CTGGCGTTGGCGGTTTATGCCAAGTTGGGCGGCATCCCATGGCTGATCAAGAGTGATAAAGGTATAGCCCAC
GAGGTCGTCATCGGGTTGGGTAGTGCCGCGATCGGGGAGTCCCGATTCAGCCGGAAGGAGAGGATTGTCGGC
ATCACAAGTGTTTTTCGGGGTGACGGCGGGTACCTCTTGTCTAACCTGTCCAATGCCGTGCCCATGAGCAAG
TACGGCGAAGCATTGACCGAATCTCTCCAGGCGACCCTGCAGAGGGTTCGCAATGAGATGAACTGGATCAGG
GGGGACAGCGTTCGGGTCATAGTTCACGCTTTCAAGCCAATGAGGAACACGGAGGTGGAGAGCGTTAAGGCT
GCGCTGAAAGAATTCAGCGAGTTCGACCTGCAATTTGCTTTCCTTCACGTTAAGCAAGACCACCCGTACCTC
CTTTTTGACGACGACAGCATCGGTACAAAAGGGCGAGGCGAGAAAACCCCCGTGCGAGGCTTGTTCGCGGAG
GTCGGACACAACGAGACACTGCTGACCCTGACCGGACCACAGCAGCTGAAGAGACCCACCGACGGGCTGCCG
AAACCGCTTCTGCTCAGCCTCCATAGGGACTCTACTTTCACAGATATAATCTACCTCACGAAGCAGGTGTAC
TGGTTTAGCAATCACTCATGGCGGTCTTTCCTGCCAGCAGCGATGCCGGTGACGATATACTACAGCGACCTG
GTGGCTGGTTTGCTCGGAAGACTGGATAGGCTGGGGTCTCGCTGGTCACCGAGTGTAATGCTGGGCAAGATC
GGAACCACAAGATGGTTCCTG
205 12 ATGGCCTATCCAATCGCTGACGACCGGCGAAAGTACTTCCACAGTCTTTTCGAGAACAAGGAGCCGTACATC
GGATACAAGGCTCTGTGTCTGCTGGCCAAGAACGACATCATCAAGAGCGTGTGGACGACCAACTTTGACGGG
TTGACTGTGCGGACCGCATTCCAAAGTAACTTGACCCCCATAGAAATAACCCTCGACAACGCAGACAGACTG
TTTAGGAACCAAAGCAAGAGAGAGCTGCTGAGCATATCACTTCATGGCGACTATAAGTATAGCACGCTGAAA
AATACCGAGAAGGAGTTGGACTCACAGGACGGCACCTTCAGCGAGCATCTGGGTAACTATCACGTCGACAAG
AACCTGATTGTGATAGGTTATTCAGGGCGCGACAAAAGTCTGATGAAATCCCTGAACGATGCATTCACCAAG
AGGGGCACCGGCAGGCTGTATTGGTGCGGCTACGGTGACAAGATCAACACTGAGGTGGAAGAACTTATACGC
AACGTACGAACCGCTGGAAGGGAAGCCTTCTACATATCCACCGATGGTTTTGATAAGACGCTGATCGACCTT
TCTAAAAGCGCTCTGGAGGACAACAGCATGAGCCTCGAAAGCCTTAATTCCATCCTGAAACTGGCAAACAAC
GAGGAGCTCTCAAAGATCGAATTTAGCCAGAGCATCACCAGGACCGACAAATACCTGAAGAGTAATCTGCAC
GCAATTGTGTTCCCCAAGGAGATATTCCAGTTTGAAGTCGAGTTTGGCGACAACAAGCCCTGGTCATTCCTT
AAAGACAAAACTAACAACACCGACATATGCGCCATCCCCTTCAAGAGGAAGGTTTACGCCCTGGGCACGCTC
AGCGGTATATCTAGCGTGTTCAAAAACGTGCTCAAAAGCGAGATTAGGAGGGTACCAATCTCCAAGTTCGAC
ATCGACAATGTGAGCAGCTTTAGGTCTCTCATGATCCAAACGGTGATCAAGCACTTTCTGTCATACGGAATC
TTCGACAGCAACCTCAAGGACAAACTGTGGCTTAGAAATTCCGACAATTCCTTCGGGGACAAGAAAATACAC
AAGGCGATTTACCTCAGCTTCTACTTCGATAAGAGCAGCAAATTCGGCTACATTAGCTTCAGCCCCAGCATA
CACATAACCTCCGATAACGAGATCAGCAAGGAGGTGAAACAAAGGATTAGCAAAGAGATCTTGGAAAAGCTC
CGAAACGATAAGTTTGACGAAATACTGGAGTACTGGAACACCATACTGTTCAATTACAAAAATCTTAAGTTC
GAGTACCCCCTTAACAGCGGGACCGGATTCGAGTTCCAAATAAGCCGAAACACTGCGTTTGCCGAAATCATG
GTGCTGGACCCGAACTATCGAGTCTATAAACCAAGCGATTACAACAACAAGCTGACCCAGTTCAGAGGTGTG
CAGTATCTGGAGCCGCAACTGATCTTTCAGAACTCACTGAGTAACTCCCACACCAAGGACTACCACCCCATG
AGGGCGTTGACCAATAACAGGCCATACGACAACAACTTGAATGGCATCATCTATTCAAACGAGGTCAATTTG
GCCGTGATTTGCGGGGAAAACTACTCCAAAAACCTCTACGACTTCCTGAACCAGCTTAACCTTAAACACCCC
ACAGACAACATCAACCCCGATTTCCTTATAGAATATCCTGGCTTCGCGAGCGCCTACAACCTCCCCATCAAC
ATCCCATACTATGAGGACGCGGACAAGTGGATTAACATAGATTTGGAGAAGAGCAACAAGTCCGACAGCGAG
AACGCCATCATCGTTGCACGCCTCATCACAAGCAAAATCGAGCAGATCATAAACATACAGTCTCAGCACACC
ATCGTCATCTTCATCCCCAAAGAGTGGCAGGCCTTCGAGAGCTTCCAGGAAAATGGCGAGGACTTCGACCTC
CACGACTACATCAAGGCGTTTAGTGCATCCAAGGGCGTGAGCACCCAGCTCATCAGGGAGGAGACACTGTCA
GACAGGTTGAAATGCCAGGTCTACTGGTGGCTGTCTCTGAGTTTTTATGTAAAGTCTCTGCGCACGCCATGG
GTCTTGAATAATCAGGAGAAAAACACCGCCTACGCCGGCATAGGCTACAGCATTAAGAAGAACAGCAATGAC
ACCGAGGTGGTGATCGGTTGCAGCCACATTTACGATTCTAATGGCCAGGGCCTGAAGTACAAGTTGAGTAAA
GTAGATAATTACATCCTGGATAAGCAGAGCAATCCCTTCATGAGCTATAATGACGCGTTTCAGTTCGGCGTG
TCAATTAGGGAACTGTTCTACAATAGCCTGGACAGGCTCCCCGAGAGGGTGGTTATCCATAAGCGGACCAAG
TTTACGAACGACGAGATAAAAGGTATTACTGCCAGCCTCAACATGGCGGGGATTACCAAGATAGATCTCATT
GAAATCAACTACGAGACGGAGGCTAGGTTTCTCTCCATGAACGTATTCAACGGCCTTCTGGGCATAGACAAA
TTCCCTATCAGTAGGGGTACCTGCATTATTACGAATAAGTACGAAGCCCTCCTTTGGACCCACGGCATCGTG
CCCTCCGTGAAGAATCCCATTCACAAGTATTACCTGGGCGGCAGGAGCATCCCAGCCCCGATCAAAATTACT
AGGCATTACGGCGAGAGCGATCTGAATACTATTGCCATCGAGATCCTCGGCCTCACCAAAATGAATTGGAAT
AGCTTTGACCTTTACAGCAAGCTCCCTGCGACGATTAACTCCTCAAATCAGATAGCCCGGATCGGTAAGTTG
CTGGCGCGCTTTGAGGGCAAGACCTATGATTATAGGCTCTTTATT
206 54 ATGAACCTGACCGTAAACCTCGCCCCCATCAGCGTGCAGGGCGACTGCTCAGTCCTGATTGGCAGACAGCGC
TACGACGAGCAGAGGCTGGCTGAACTTAGGTCAGACTTTCGGGGCACCCACGTGTTTCGGCGAGACGGTCCA
GATAGCATGATTGACATCCCCGTGGTCCCCGACGCGGCACCTCTGGGCAACCTGAGGGAGACGATCGACCTT
AGGCGGTACCAGCGGCTGTGGCCCATGCTTCTGCAGGAGTCCCTCATCCAGCTGCTTGGTAAGCGCCCCATC
CAGTCCAGCAAGCCCTTGAAGTTCCTGGGAGCTAGGTCTCCTCTGATCGAGCACCCGGATCTCCCTGAGTGG
TTGAGGCGGGTGAGCGTTACCGAGATCCACACCCGACACATCACCGTGGACGGCAAGCAAATCTACGGTATC
GTGTGCGATGTGAGGGCCAAGTCTTTTATCCTCGCCACCTGCAGCGAACTTCTGAAATTCGGCGTGACCATC
CTTGGTAGATACGTCCAAATAGAACAGCCCGCGATAGACGAGAGAACCATGCCTAAAAGGAAGCTCATCGGC
AGGGTAAGGTCCATCCAAGGGGATGATCTGCTTCTTGACGACTGTGAGGCCGGCTTCGAAAAAGTCGCTGCG
AATGAGGCATTTCTCGAGCCGCGGAAGGAAAATTTCGAGGACTGCGTGAGGCAGGTGCTGAAGCGGGACGCC
GAGAGGGTGTTGGAGAGGTCAGCTCGCGCCAGCCAAAACCTGGCCGCAGGCCCTGGGAAACTGGAACACATC
GACGGAATCATCAGGTATCTTAGGGAGAAGAAGCCCGCAGCGGTGCCCGGCTGCCATTTCGTGATCGATGCC
ATGCTCAACACAAACGGCCACATTTTTCCACCCGGGGAAACAATGGACAAACCCTTCCTCTTGTTCGACCCT
AGCGGTTCACGGAGAGAAGACTGGCCCGAGAAGGGCCTTAAAGATCACGGCCCCTATGATGAGCAGGTGTTT
TCCCCCAAGTCCCTGAAGATCGCTGTTGTGTGCCAAAGCCGGTTGGAGGGCAGAGTGGACGAGTTTCTGGCG
AAGTTTCTCAATGGGATGCCGAAGGTCTTTCAACCCGGCAAGAGCTTCGCCCGCTACGGCGACGGATTCGTG
AAACGATTCAGACTGAACAAGCCCGAGGTGCACTTCTTTCTTGCAGATGGCAACTCCGACGAGGCATACGCC
GTGGCCAGCCGCGAGGCACTCGATAAAGCGAGGGATAGCGGGTTCGAGTGGGACCTGGCGATTGTGCAAATT
GAGGAGGAGTTCAAGTCACTGGCCGACGGCTCCAATCCCTACTACACCACTAAGAGCATCTTCTTGCGGAGG
GACGTTCCGGTGCAGAGCGTCAGGCTGGAGACCATGAGCCTGTCAGATAATGACCTGGTGTTCCCCATGAAC
CACCTGAGCCTCGCTACCTACGCCAAGCTGGGGGGCACGCCCTGGCTCCTGGCTAGCTCACAAACCGTGGCG
CACGAACTGGTGATCGGACTGGGTAGCAGCACCAGCTCCGAATCAAGGCTGGGCAGCCAGATGAGACATGTG
GGAATCACCACCGTGTTCAGCAGTGACGGCAGCTACCTGCTTTCTGATAGAACCGCCGCAGTGCCCTTCGAG
CAGTACCCACAAGAGTTGAGGAAAACGTTGCGAAAAACAATCGAGGCCGTCAGGGCCGAGGACAATTGGCGG
AGTAGCGACAAGGTGAGGTTGGTATTCCATTCATTCAAGCCGTTCAAGGACAGCGAGGTAGAAGCCATAGAG
GCGCTGACCACCGACCTGGGCCTGGGCGACGTGAAGGCCGCCTTTCTGCACATTGCGCCCGACCACCCGTTC
CTTATCTTCGACCACGACCAAATGGGCATCGCCGCACGAGGGGGCAAAAAAGGCGTGTTGGGCCCTGCTAGG
CAGTTGCACATCCGGCTTAGCGACGCTGAGAGCCTTGTGGTCTTCGCAGGGGCCAGCGAGCTTAAACAGGTG
ACGGATGGTATGCCGCGACCCGCGCTGCTCAAGCTGCACCCCAAAAGCACCTTCAAAGATATGACCTACCTG
GCAAGGCAGGCCTTTGCCTTTAGTGCCCATAGCTGGCGGATGCTGTCCCCCGAACCTTTCCCAATTACTATC
CGCTACAGCGACCTGATCGCCGACCGCCTGGCGGGACTCGCGTCTGTTAAGGGCTGGGACCCCGATGCCGTG
ACGTTCGGCGCTATCGGTCACAAGCCTTGGTTCTTG
207 23 ATGATAATGAGCCTGGAGAGCAATATCTTCACTTTTAGCAACCTCGGGACACTTACCACGCAGTACCGACTG
TATGAGATCAGAGGCCTGCAGAAAAGGCACCAAGAGTACTACCAGAACAGGCAAATCCTGATCCACCGACTC
TCCTACCTTCTGAAAAATGCCGTAACTATCATAGAGCGCGACGAGAAACTGTACCTTGTTGTAGCTGCCGAT
GCCCCGGAACCACCCAATAGTTATCCCATCGTTAGGGGCGTCATCTACTTCAAGCCCACCGGCCAGATTCTG
ACCCTGGACTACAGCCTCCGAACACCCCAGAACGAAGAGATCTGCCAGAGGTTCCTCCATTTCATGGTACAA
AGTGCCCTGTTTCAAAACGCGAATTTGTGGCAACCCAGCGCCGGAAAGGCTTTCTTCGAGAAAAAGCCCTCA
TTCGAGTTCGGATCAATTCTGTTGTTTCAGGGATTTAGCGTTAGGCCCATATTCACCAAGGACAAGATCGGC
CTGTGTGTAGACATCCACCATAAATTCGTCAGCAAAGAACCCCTCCCTAGCTACCTGAACTTCAACGAGTTC
CAAAAATACAGAGGCGTGTCATGCATCTACCATTTCGGCCACCAGTGGTACGAGATCCAACTCTCTGAACTC
TCCGAGCTTAACGCGACGGAGGCAATGGTACCCATCGAGAATAAGTTCGTGACCCTTATTAACTACATCACC
CAGCAAGCCAGGAAGCCCATCCCGGAAGAGCTGGCAAACGTGTCACAGGACGCAGCCGTCGTGCACTACTTT
AACAATCAGAACCAGGACAGGATGGCGGTGACGAGTCTGTGCTATCAGGTTTACGACAACTCTTATCCAGAA
ATCCGAAAGTACCACCAGCACACCATTCTGAAGCCACACATCCGCCGCAGCGCGATCCACGGAATAGTGCAG
AAGTATCTCGCGGAGCTCAGGTTCGGCGACATAACCCTGAAGGTATCAACTATCCCCGAGCTGGTGCCCCAG
GAGATGTTCAACCTGCCCGACTATTGCTTCGGCAACGATTACAAACTGAGCGTGAAAGGAAGCGAGGGCACA
GCCCAGATTAGCCTCGACCAGGTCGGGAAGCAGCGCCTTGAGCTGCTGAGTAAGGCTGAAGCTGGTATCTAC
GTGCAGGAAAAGTTCGACCGCCAATACATTCTCCTGCCCCAAACCGTGGGGGACAGCTTCGGGAGCCGGTTC
ATCGACGACCTCAAGAAGACCGTGGACAAGCTGTACCCCGCTGGAGGAGGGTACGACCCGAAGATCATTTAC
TACCCCGACCGAGGTCTCCGGACCTACATCGAGCAGGGTAGGGCTATACTGAAAACAGTTGAAGAGAACGAG
CTGCAGCCCGGCTACGGTATCGTAATGCTTCATGACAGTCCGGATCGACTGCTCAGACAACACGACAAACTC
GCAGCTCTGGTCATTAGGGAGCTGAAGGACTACGATCTGTACGTGGCCGTCATCCACAGCAAGACCGGGAGG
GAGTGCTATGAGTTGAGATATAACAACCAGGGCGAGCCCTTCTATGCAGTAATACATGAAAAACGGGGGAAG
CTCTACGGCTACATGAGAGGGGTGGCGCTCAATAAGGTGCTTCTCACCAACGAGAGGTGGCCCTTTGTGCTT
TCTACCCCCCTGAATGCGGACGTGGTGATCGGAATCGACGTCAAGCACCACACCGCCGGTTACATAGTCGTC
AACAAGAACGGGAGCAGGATCTGGACTCTGCCCACGATCACGAGCAAGCAGAAGGAGAGGCTGCCCAGTATC
CAAATAAAGGCGAGCTTGATCGAGATCATCACTAAGGAGGCCGAGCAAACAGTAGATCAGCTGCACAACATA
GTGATACATAGGGACGGACGAATACACGAAAGCGAGATCGAGGGCGCCAAGCAGGCGATGGCCGAGTTGATT
AGCAGGTGTACGCTGCCTGTGAACGCCACACTCACGATCCTGGAAGTGGCGAAGAGCAGCCCCGTTAGCTTT
AGGCTGTTTGATGTCTCCAATACCAATTCTAAGGACCCGTTTGTGCAAAACCCACAAGTCGGGTGCTACTAC
ATTGCCAACAGCACTGACGCCTACCTGTGTAGCACGGGGAGGGCGTTTCTCAAGTTTGGCACCGTGAACCCC
CTGCACATAAGGTATGTGGAAGGTACGCTCCCCCTTAAACTGTGTTTGGAAGACGTGTACTATCTGACAGCC
CTGCCTTGGACGAAACCCGACGGGTGCATCAGGTACCCCATTACCGTAAAGATCAACGACAGGAGGCTTGGG
GAGGACGCCAGTGAGTACGACGAAGACGCCCTGCGCTTCGAGCTGTTCGAGTCTCTCGAGTCCGAGGATGAC
TTTGACGAGATGACCGACAGCGACTTTAATCAGGAGGAGACAATGGTG
208 16 GTGGGCGACAAGACCTTCAGCTTCAAGGTGTATAGGAAACTGAAACAGCAGAACGACACCAAGGAAGACGAG
ATATACCTTTACAATTTGCCCCAAGGCGAGACCCTGAATGATTACAAGCCATATTGGATCAGTTTTACCCCG
AAGGACGGATTCGAAGAATACATCGCTAATTCTTACTTGAGCATCGGCCTGTCAAAAAAGTACCTGTTCAAT
AGATTCGTGGAGACGCTCAGCAACTCAAAACTGCACTTCACCTACAAGGTCAAAAGGAAATTCACCGACTGG
TACGTCGATTTCGTAATCGCGCAGTACAGCCAGGGAGACAGGATCATCTACATGAGCCCCTACTTCCTGGAA
GAGCAAAACACCTACGGCTTCATCATCGACTTCAAGTTCAGCAAGAAGGATGGTATCCCCTTCGATAAGGAG
GTGCAAAAGCTGTCCCTTTCACTGGATAGCAACGGCCGCAGCAACAAAAACTATTACTCTGACAAATTTAGG
CTGGTGAACAATTTCATTAAGGAGATTTACACCTCCATAAAGAACATCGGGACCAGTAATAATCCTATCACC
ATTTCCAGCAACCTCATAGAGACCACCGTGTTCCACCTGAACAAGAAAGAGTACATCTTTAGCAATAACAAC
GTAAGCTCTAGCCAGTTCCAGGGCGTGAGGAATTTCGGTGTCTATAAGAATATCCCCCAGGACGTGATCTTC
GCGTTCATATTCGAGGATAGGTTCAGGAGCTTCGCCAACGAGCTGTATCTGAGCCTTACCGGAAAATTGAAC
CCCGGGACCTTTCCCGGACTGGAGCAGATGTTCGGCATCAGCATCAACACCAAAAACGTGAGACAGATCAAG
TTGGAGAACTACTCTCTGGATTCAATGCTTAGGGTGGTGAATGACGTGAAGAGCTTGCAGGAGAACAATCCC
GATAAGAAGATCGTGGGAATCTACGTGGAAGACTGCACCATCGACAGCGAGGACATCCCTGCGTCCAACAAC
TACTACTTTCTGAAGTATCACTTTATCAAAAATGACCTGCCACTGCAGGTTGTGAATTATCGGAAGCTGGGC
GAAAGGAATTCTCTGAAATGGAGTACCTCCAACCTGGCCCTGGCCATGTTCGCAAAGATGGGCGGCATCCCC
TGGGTCGTAAAACCGTCTAATAAGAACTGCTTGATTCTTGGCATCGGATCTAGTCATAAGATAAACCGGGAG
ACCGGCGATATACTTAAATACTTTGCATACACCATATGTCTCGACTCCAGTGGCCTGTACAAGGCCCTTGAG
GTGCTGGCCGACGAGGAGAGCGAGGTGAGCTACCTTGAGAAGCTTACTGCCAATCTGGTCGCCATACTGAAG
GAACAAAAGACCAATTACGGCACCTGTGTGCTGCACCTGCCCTTCAAGATTAAGAAAAAAGAGGTAGCCGCC
ATTAGTGATGCCATAAAACAAATCAACGACATCGAGCTGGTGGTGGTAAAGATCAATGTGGATAACAAGTAT
TTCGGATACTCCTTCCACAACACATTGGTGCCCTACGAGAGCAGCTTCGTGAAGCTTTCTAAGGATGAGTAT
CTGGTGTGGTTCGAGGGCCTGCTGTACGGCAAAGAGATCGTAGATAAGAGGTTGAGCAACCCCGTGCACATC
CAATTCTTGAACATCACCAACAGGAAGAACTTCGATGAGCAGGCGTTTCTGCAGGACATTCTGAATTTGAGC
GGAGCCAACTGGAGGGGCTTCAACGCCAAAAGCATCCCTATCTCAATTTACTATTCTCAAATCATCGCGAGG
TACACCGAGGCCTTCGAAAACATCGACGGTTACAAGGAGGGTACTATCTCTAACGACAAACCCTGGTTCCTG
209 53 ATGAGCGTGGCGATCGTGAGCCCCCAAATGTACAAGAGTCTGAGCGAGGTGTTTCCTCTGACCGCCTCCCAA
CTGAACTTTATGTGCTTTAGGCTGACTCCCGAAATCGAAAAGAAGGATGGTAATAGGCTCAGCTACCATTTC
AGTCTGAAGCTGCCGGAAACTGTTGTGATCTGGCACCAGCCCTACTTCTGGGTGTTGGCGAGTAGTAACAGG
CAAATCCCCAATAAGGACGAGTTGCAAGAAACTCTGATAAGGATCCAAAACGAGGTGGATGACTTCAAAGAA
CGACTCTTCGGTTTCCAGAGCGTTCGCCACCCCCAACTCACCCCCTTTATCATCAGCCTCTTCGCCGTGCAG
GTCCTCAAAAAAACAAAGTTCGACTACCCCATTGCATTCAGCAACAACGGTGTAATCGTCAGGAGGGAGCCC
GACTTTTGGACGGAGAGCATAGAGCTTCAAGACAGCCTGCATCCTGCCCTCACGCTGACCGTAAGTTCATCA
ATAGTGTTCCGCGACAACCTCGCGGAGTTCTATGAAAAACATCATCAAAGGGAGAAGCCCGAGCAGTTTCTG
ATCGGCCTGAAGGTGCAGGAAATAGAGAGGGGCAACAATGCGATCATCGTGGGACTCGTCGGCACCATCGGC
GAGCACCGGGACCAGCTGCTTGAAAAAGCAACCGGGAGCACTAGCAAGCAGGCGCTGCGAGAGGCACCGGAC
AACCAGCCGGTGGTTGCGATACAGTTCGGCAAGGATACGAAGCAGTTCTACTACGCAATGGCCGCGTTGCGG
CCGTGCGTAACCTCAGAGACGGCAAACCAGTTCGAGGTAGAGTACGGTAAGCTCCTGAAAGCTACAAAGATA
AGCCACCAGGAGCGAACCAACCTGCTGGCCTCATACAAGAAGACGGCCCAGGAGTCATTGGCCGCTTATGGC
ATCCGCCTGGAGCTGAGTGTGAATAGCAGGGATTACCCCAGCTTCTTCTGGCAACCCCCCGTGAAGATCGAA
GATACCAAACTTCTGTTTGGCAACGGCATAACCGGCAAGCGGACTGAGGTGCTCAAGGGGCTTTCTATAGGG
GGCGTGTACCGACGCCACGGGAAATTCCAGGACAAGTCAAAAGTGATCCAGATCGCGGCTCTTAAGCTTTGC
GACGTGACCGTTAGCTTGTTCCTGAAGCAACTTACTCAAAGGCTGGCAAAATACGGCTTCCGAAGCGAGATA
ATCACCAAGAAGCCTCTGTCAATCAAGAACCTTGCCACCGCCGAAGCCAGGGCTGCTGTTGAGAAAGCGGTC
AATGAGCTCGTGGAAATACCCCACGACATCGTGCTTGCCTTCCTGCCTGAGTCCGACAGGCACACCGACGAC
ACGGATGAGGGTTCCTTCTATCACCAGATCTACTCCCTTCTCCTCAGAAGACAAATAGCCTCACAAATTATC
TACGAGGACACCCTGTCCAACTCTGGGAACTACCAGTACATCCTGAACCAGGTCATTCCGGGGATCTTGGCG
AAACTCGGGAATCTGCCCTTCATTTTGGCGGAAAGCCTCGATATAGCGGACCACTTCATCGGACTTGACATC
AGCAGAATCTCTAAGAAAACGCAGGTCGGGACACGAAACGCGTGCGCCAGCGTGCGACTTTACGGACGCCAG
GGTGAATTTATCCGCTACCGGCTTGAAGACGACCTGATCGACGGCGAGGCGATTCCACCCAAGCTGCTGGAA
AGGTTGCTGCCTGCGACCGAGCTTGCGAATAAAACCATACTGATCTACAGGGACGGGAGCTTCGTGGGCAAA
GAGGCCGACTATCTTGTGGAGCGAGCCAAGGCGATAGACGCGAAGTTTATCCTCGTCGAGTGTAAGAAATCC
GGCGTGCCGCGCTTGTATAACTTGGAGCAAAAGACCGTGATCGCGCCGAGTCAGGGACTGGCTCTTCGACTG
AGCAGTAGGGAAGCAATACTCGTGACCACCAAGGTGCCCGATAAAGTGGGCCTGGCTAGACCCATCCGGCTC
ACAATCCACGAAAAGGGCCATCAAGTAAGCATCGAATCCGTGCTGGACACTACACTCAAGCTTACTCTTCTT
CACCATGGCGCGCTGAAAGAACCGCGACTGCCCATGCCCCTGTATGGGAGCGACAGGATGGCATACCTCCGG
CTGCAGGGGATACGGCCTAGCGTTATGGAGGGCGACCGCCAATTCTGGCTG
210 88 ATGGAAGAAAATCTGTATCTTGAATACGACGCTTTCTTGAGGAGTGTGAAGCGCAACGTGGACGTCCCTCAT
AGTTTCTTGCTTGGAGCCGGAGCTTCCATCTCCTCCGGAATTCAGTCTGCATACGACTGTATATGGGAGTGG
AAGAGAGATATCTACATCACGAAGAATATAAACGCCGCCGAGTACTATAAAAATCATAAAAACGAAACGGTT
CGCAAATCAATACAGAAGTGGCTGGACAACCATGGCAACTACCCCATCCTGGATGCAGCAGAAGAGTACACA
TTTTACGCCGAGAAAGCTCATCCAATCGCTGACGATAGGAGAAAGTACTTCTTTAGTCTGATTGAGAATAAA
GAACCATATATCGGTTACAAATTGCTGTGCTTTCTCGCTTCACAGGGGATTGTAAAGAGTGTATGGACGACC
AATTTTGACGGGCTGATTGTACGAGCTGCTCACCAGAATAATTTGACGCCTATAGAAATCACCTTGGATAAC
GCGGAGCGCATATTCCGAAATCAGAGTACTAAGGAGCTTCTCTGCATAGCTCTGCACGGTGACTACAAATAT
AGCACCTTGAAGAATACTGATACCGAACTGGATAACCAACACGAAATTTTTCAGGAGCACCTCGGAAATTAT
CACGTAGATAAAAATTTTATAGTAGCTGGTTATAGTGGACGCGACAAGTCTCTGATGGATGCACTCAAGGCC
GCTTATTCCAAGAAAGGATCTGGTAGGTTGTATTGGTGTGGCTATGGTGAGAAGATAAATTCTGAAGTGAAA
GATCTTCTTAAGTATATTAGAGCGAGTGGGAGGGAAGCATACTATATAGCTACGGATGGGTTTGACAAAATG
CTCATACACTTGTCAAAGGCAATATTTGAGGATAGCCAAGAGCTGAGTGAAAAAATCCAGAAAATACTCGAA
AGCACGAATCAAACCGAGACCTTCAACACAGAATTCAAGTTGGAGTTTAAAAAAACCGACAAATATATCAAA
TCAAATCTGCACCCTATTGTTTTTCCTAAGGAAGTATTTCAGTTGCAGATCGAGTATGGCAATGAAAAACCG
TGGTCCTTCCTGAAAACACTGACAACTCAAACGAACATTAGCGCCGTACCGTTCAAAGGCAATGTCTACGCA
CTTGGTACGCTTAGCGAGATCAATTCCATCTTCAAGCCGTATCTTAAAAGCGAGGTCAAGAGGGAAGCGATC
AGCCGATTCGACATCGAAAACGTCACCGCATTCAAAAACCTCATGTTGACAGCCATATCCAAATATTTTTGC
TACACGAAAGAAGTGAACTCTAACTACAAAGATAAGATTTGGTTGAAAAACATCCTGTCCAAGGTGGGGGAT
ATCACTGTTCACAAAGCAATTTTCATATCCCTGTACTTTGACAAGAATTCCCATTTTGGTTATATGGCGTTC
GCTCCTACCGTTTATTTGGATTCCGACTGCGAAATTGAGAAGAGTCAAAAGCAATCCATCAGTAAGAATTTG
CTTGAGAAGTTGTATAATAACAAATATAACGAAGAGCTCGAACTGTGGAATGGTATCTTGTTTAATCATAAG
AAAGTGAAATTTGAATATCCTCCCTTGTCTGGTACGGGGTTCGAATTTCAGATATCAAGCAACACTGCCTTC
GGGGAGATAGACGTGATTGATAACAAGTACCGCTCTTACGTCCCCCAGAATTATGATAATAAGCAGACTCAG
TTCCGGGGAATCCAGTTTTTGGAGCCGCAGCTGATATTTAAGAACATCGCAACGAACTCTGACTTCAAGGAT
TATCATCCCATGCGAGGACTGATTAACAACCGACCATATGATGTAAATCTCAACGGGATTATCCACTCCAAT
GAAATTAACCTCTCAATCATCTGTAGCCAAAAGTATGGAGAAAGGTTGTTCGCATTCTTGACACAGCTCAAT
AGTAAGCACAGTACAGAAAATATCAACACTGACTACCTGATAGATTACCCCGGCTTCCTGTCCGCCTTTAAT
CTGCCCATCAACATCCCAGCCACCAACGATGACGCTAGCTGGATGGACATCAACTTCGTAGCAGATAACTCT
AAAGAAACACACGAGAACGCTATACGACTCGCGAGGGCAATTACCAATAAGATCGAGAAGATTTCTGCTATA
CAAAGCGCCAGCACTATAGTAATCTTTATACCTTTCGAGTGGCAGCCCTTCGAAACATATATTAACGAAATA
GAGACGTTTGATTTGCACGACTACATTAAAGCGTTTAGCGCCAGCAAGGGGATATCAACGCAACTTATTCGG
GAGGACACCCTTGACGATAAGCTCAAGTGCCAAATATACTGGTGGTTGTCTCTTTCTTTTTACGTGAAGAGC
CTCAGGACCCCATGGATATTGAACAACCAGGAGCGGAAAACAGCTTATGCCGGAATTGGGTACTCCATAAGC
AAGGTAAAGAACAAGTCAGAGATCGTGATCGGATGTTCACATATATATGATTCAAATGGCCAAGGCCTTAAG
TATCGCCTCTCAAAAATTGATAACTACTTTCTCGATAAGCAAAATAATCCGTACCTGTCTTATAAGGACGCT
TTTCAATTTGGGGTTAGTATCAGAGAGCTCTTCTATCAGTCACTCGATTCTCTGCCAGAAAGGGTCGTCATC
CATAAAAGGACAAAATTCACCGAGGATGAGATCAATGGGATAAAGGCTTCACTCAACCAGGCTGGTATTAAG
AAGATTGATCTTATAGAGATCAACTACGATATAGATGCAAAATTCGTTGCCATGAACGTGTTCGATAACAAA
TTGCAGGTCGATAAATTCCCGATATCCAGAGGAACATGCATTGTGACAAATAAACGGACGGCGTTGTTGTGG
ACGCATGGTATAGTACCTTCAGTTAAGCAGCCCAATTATAAGTTCTACCTGGGCGGGCGCTCTATCCCTGCG
CCCATAAAGATTACCAAGCATCACGGAGAAAGCAACATTGATGTGATAGCTAGTGAGATCCTCGGACTCACA
AAAATGAATTGGAATAGCCTGGATCTCTACAGTAAACTTCCCTCTACGATAGATTCTTCTAACCAGATTGCT
AAGATAGGAAAACTTCTGTCTCGCTTTGAGGGCCGCTCATATGACTACAGGCTGTTTATT
211 17 ATGGACAATTTGGCTCTCTCTGCGCTTCAGCTGGACAGTAGATTGGATCACTGTATGGTATATCAATACAGG
ATCGTGTACCATAAGTTCGACGAAACAGAGGCGGGTGAAAAACTGGCAAGAAAGGCCGCCTACGAACTGTGG
AAGGTAAACAACTTCGGACTGCTCACCAACCTGGGTGCCAGTAGCATCCTGTCCCTTAAGAGCCTGAGTCAG
CTGTCTATCGATTCACCGCTGTTGCAGGCAAGTTTGAAAGCTGACGGCCAGTTGGAGCTGGATTGCGGTAAC
GAACAGCATCAGGAGGCGCTGCAGAGACTCGTGAACCAGGACATAAACAAAGCGGCTTGGAACCTCAAACAA
GCGAGCGAGGGGAAGCTTGATTGCCGAAAATCACCAGGCGGGCACGCCGAAATCTTCGAGCCAAGTCACAGT
AGTCGGATCAAGGCCCACAGTACCTATTTGGATGCCTTCTGCACCGTAAGGCTGATTCCCGAAGTGCTGTCA
GACGGGACAGTGCTGATAGGGTTGCATCTTAAGCACAGCCTGACCGCGAAGGCGGACATCTCTCTTCAGTGG
GTCATTGATCATAGGCCCGATTGGCTGATATCCATAGAGAAGGTGCGCCACAGGTATTACGAGCCCGGCAAA
GCACCCCTCGTTGCGGAGTTCGTGAAAGTCGATGATTCCATCAACGGATCATCCCTTCTCCCACACTTGGGC
AAATCCCTTGTCGCTTACCACCAGGAGAAAGGGCTGCTTTCAGCCGGACAGCTCGCAGAGGCAGCCACCAGC
TCACTCATCAAAGTGCGCTACGGACAGAAGGAGGCAGACCACGTTGCTAGCTTGGTGGAACCCATGTTTGAT
TTCGATACTCTGTCAAAGATTGACAGCCCCTTCCTGAATAGGCTCGCCAAAGACCTGAAGTGGAGCTTGGAC
GATAGAATAAAGACAAGCGCGGAGATGGTCAAGAGGCTCTACCTGCCCGGGTTTAATCGAAAGTTGGTACAA
GTTGACTACCAGAATCTGAGCAGGAAGAGGTTCAACCACAACCTTATGCTCCAGTTCGCGGATGGGGCAAGG
AGCGGCCATGAACAAGACGTCCTGAAATACAAGGCTTTCGCCGACATGACCAGGGCTAGGGTAATCCCACTC
GTGGTAGGAGAGAGGAACAACACCGAAAGCAATAGACAATTGCTCCGGAACGCCTATAACGCACTGAGGCAA
CTTACCAAGGCCGAATTGCCCCCCTTCACGTCATTTCCCCCCAGCATCGGAAACGCCGACGAGTTGGACGCA
CGGCTGCACAAGAAATGTCCCGACAACGCCATCCTGCTTATCGGGCTCACAGAGAAGAGTGACAAAGCCGCG
ATCAGGGACACGGCGTTCAACTACGGCCTGGCCACCCAGTTCATGAGGCTCGATCACAAGCCCAAGGTTTAC
GACAGCTTCTACTTCAATAACGTCGCAGCGGGCCTGTTCTCCAAGGGAGGAGGGCAACTGTGCGCCGTGAAC
GACATGCCCGGTGAGACTGAACTGTTTATCGGTCTGGACATGGGCGGCGTGAATGTAAGGGCGCCAGGTTTC
GCATTCCTGTTTCTCAACTCTGGCGCGCAACTGGGCTGGCAGCTGGCTGACAAGCAGCAGGGCGAGAAAATG
CAGGACGACGCTCTCAGCAATCTGCTGGAGAAGTCTCTCAAAACCTACCTGAGGAGCACCGACGGGCTTTTG
CCAAGGAGGATAACTCTGCACAGGGACGGCAGGTTTTACGAGAGCATCAATGTGATAGAACAGTTTGAGCAG
AAGCACGGGGTCAAGCTCGATGTTCTGGAAGTCTTGAAAAGCGGAGCCCCGGTGCTGTACCGGAGAGAACGC
AGTGCGGACGGTAAGAAAGTTTTCAGCAACCCAGGGGTTGGCGATGCCGTCTTCCTTAGCGACAGGGAGGTC
ATTCTTAGCACTTACAGCGGCGAGGAACTTGGGAAGTCATGGGGTAACAAGGTGAGTGTGAGGCCACTTCGA
CTCCGAAAGAGATACGGCGAGACCGCATTGAGCGTGTTGGCCCATCAGGTGTTGGTCCTGTCTAGGATCCAT
GGGGCCAGCCTCTACCGACACCCCCGACTTCCGGTGACCACCCACCACGCGGACAGGTTCGCAACCTTGCGG
CAAGATGCGTGCATAGACGCACTTAGTAAGATGGATAGACTGTGTCCGGTGTATCTG
212 37 ATGAATAACGTGATGCAGGAGTTTCCCGTCGCAAGCTTCCCCACATTCTTGTCCGAGATCAGTCTGCTTGAC
ATCACACCGAAGAACTTTATCTGCTTTAGGCTCACCCCCGAAATCGAGCGCAAGACCGGTAACAGTTTTAGC
TGGCGCTTCAGCCAAAAATTCCCTGACGCCGTCGTGATTTGGCATAACAAGTTTTTCTGGGTACTCGCTAAG
CCCAATAGACCAATGCCCAGCCAGGAGCAGTGGAGAGAAAAGTTGCTGGAAATCTGCGAGGAACTTAAGAAG
GACATAGGCGACAGAACCTACGCCATTCAGTGGGTTAGCCAGCCCCAAATAACCCCTGAGATCCTGTCTCAA
CTCGCCGTCAGAGTGTTGAAGATCAACTGTAGGTTTAGCTCTCCCAGCGTAATTTCTGTCAATCAAGTTGAA
GTGAAGAGGGAGATCGACTTTTGGGCCGAAACAATTGAGATTCAGACCCAGATCCAACCCGCTTTGACCATC
ACCGTGCACAGTTCATTCTTCTATCAACGACACCTGGAAGAGTTCTACAATAATCACCCTTACAGGCAGAAC
CCCGAGCAACTGCTCATCGGCCTCAAGGTGAGGGACATTGAAAGGAATAGCTTCGCGACGATTACTGACATT
GTGGGCACCATAGCGGACCACCGCCAGAAGCTGCTCGAGGATGCCACTGGAGCTATTAGTAAGCAAGCCCTT
ATAGAGGCCCCAGAAGAGCAGCCCGTGGTCGCCGTACAGTTCGGTAAGAACCAACAACCCTTCTACTACGCA
ATGGCCGCGTTGCGGCCTTGTATCACCGCCGAGACCGCTAGGAAGTTTGACGTGGACTACGGCAAACTGCTG
TCCGCCACCAAGATACCCTACTTGGAGCGGAAGGAGCTGTTGGCTCTCTACAAAAAGGAGGCGGGTCAATCT
CTGGCGACTTATGGTTTCCAATTGAAAATCAGCATCAACAGCAGGAGGCATCCGGAGCTTTTTTTCAGCCCA
AGCGTGAAACTGAGCGAGACCAAACTCGTATTCGGGAAAAACCAAATAGGGGTGCAGGGGCAAATTCTTAGC
GGATTGAGCAAGGGTGGGGTGTACAGAAGGCATGAGGACTTCAGCGACCTCTCAAGACCTATACGCATCGCT
GCGCTTAAATTGTGCGACTACCCTGCGAATTCATTTCTGCAAGAGACCCGGCAACGCCTCAAACGGTACGGT
TTTGAGACTCTGCTGCCCGTCGAGAATAAGAAAACCCTGCTGGTAGACGATCTGAGCGGGGTCGAAGCACGC
GCGAAAGCCGAGGAAGCCGTTGACGAACTGATGGTGAACCACCCCGACATCGTGCTCACTTTCTTGCCGACC
AGTGATAGGCACAGCGACAACACGGAAGGCGGCTCATTGTATAGTTGGATTTATTCCCGACTGCTGCGGCGA
GGGATTGCTTCACAGGTTATCTACGAGGACACGCTTAAGAGTGTGGAGGCGAAATATCTCCTTAACCAGGTG
ATCCCCGGAATATTGGCAAAACTCGGCAACCTGCCGTTCGTACTTGCGGAGCCCCTGGGAATCGCTGACTAC
TTCATAGGCCTGGACATCTCCAGGTCAGCAAAGAAACGGGGGTCTGGAACCATGAATGCCTGTGCCAGCGTT
AGGCTGTATGGTAGGAAGGGCGAATTTATCAGGTACAGGCTTGAGGACGCACTGATCGAAGGGGAGGAAATA
CCTCAGCGCATTCTGGAGAGTTTTCTGCCAGCCGCTCAACTGAAGGGCAAGGTAGTGCTCATTTACAGGGAC
GGCCGATTCTGTGGTGACGAGGTCCAGCACTTGAAAGAGAGAGCAAAGGCTATAGGAAGCGAGTTCATCCTG
GTTGAATGCTACAAGAGTGGGATTCCACGACTGTATAACTGGGAAGAAGAAGTCATAAAGGCACCAACTCTG
GGACTGGCCCTTAGGTTGAGTGCGAGAGAAGTGATTCTGGTGACAACCGAGCTGAACAGCGCAAAAATCGGT
CTTCCTTTGCCTCTGCGACTCAGAATTCACGAAGCCGGTCACCAAGTATCTCTCGAGTCTTTGGTAGAAGCC
ACACTGAAGTTGACCCTCCTCCACCACGGCAGCCTGAACGAACCGCGGCTGCCTATACCACTGTTTGGTTCC
GATCGAATGGCCTACCGGAGACTCCAGGGCATATATCCCGGATTGTTGGAGGGGGATCGGCAGTTCTGGCTT
213 38 ATGAACCTGACTCTGTTCAACGAGATCCTCCCCATCAACATCAGCCAACTGCCCAACCAGTACTTCTACAAG
CTGTGCACTGCCGGCGACGTGGACCTGGATTCTCTGGGCAGGAGCATCAAGTACCGGATCCAGAAATACTTC
AGAGGAATCTGGGTGTGGAGTACCAACGACCAACTCCTCATTTCAGACAAGCTCATCGAGTACCCCGAACTG
CAAAAGTTCACCCAGTATCTGTGGACCGACCAGTCTAACCTCACATTCAACCAGCTCGAGGGGATAGAAATC
GAGAACATTAGGTGTTGCACCCCCCAAGGCATCGCTGATTTCTGTAGCCAAGGTCTCATCAAAAAGTACGAC
CAGCAGATCAAGAAGATACTCGAACAGTCCAAGACAGCACGGAGAGACTATCATATCAAACTGATCCACAAG
TTCGGCTCCTGGGTGGTGAACAATCAGCCCTGCATAAGCCTGAGCCTGAAACAGGAGATCGATTTTAACGGA
ACTCTCCAGGACTACCTGACCAAGTTCCCCAACTCTAACATCATCGGCCTGCATGTGCTCGACATCACTAAG
CCTTTCAACACCGCACAGGAGGTCATCAAGATTCTCGGTATCTTGGGTGAGGGAAATCGGCGGCAGCGCCTC
CTGACTTGGGTCAAGGAGCCAACCATGAAAAAACTCGTGGAAGAGGCCCCAGATAGTGAGCTCGTAGTTGAG
ATCGGGAACAAGAAAAAATCCTATCATTACATCATTTCTGCCCTGCGCATCAGAGTCCTCAACCAAGATTAC
CTGAGGCTGGGGATTAGCGAGAAGCTGCAAATAGTCAGTGAAGAGAGGTTGAAGTACATCGAGCCACTTTTC
CGCATACTGCAATCAGAGGGCTTCCTGGACAAGGTGTATACTAGCCAGCGCAACCCCGAGCTGTTTAGGTCA
TGCAGCGAGGAATGGGGTTACAATCCCCTGCTGAAGTTCAAGAATAACGCCACTGTTGCGGCGGAATCCGTG
CAGTCCACGGTCCAGGTGGTGCAGAAACACGGCGAATTCAGGAAAGCCGACAAAAGCGAAATTAGGATCGCC
ATACTCAACACACTGAAGAGTGAAAACAGCACCAAATTGATTGAGATTTTCCGAAACAACTTTAAGCGAAGC
TTTAACCAGAATTTGGAGGGAATCGGTAATCAGCTTAAGTATAAACTCAAGTTGGTGGGCCAGCCCATTGCA
CTGGATCTCAGTAAGAACTCCCTCAGCCTGCTGGACAGCAAAATAGGAGAATTGTCTAAAAAGAAGCCGGAC
ATTGTGATCTGTGTGATCCCTAACTTCCTTAGCAAGGGCGAAGACGGGCGGACACTTTACGACGATTTGAAG
CAGACGTTCCTCAAATACAATCTCCAATCACAAATGTTGCAGGAGAAGACTCTCACGACGTCATTTGCCACA
AAGAACATCGTGTTGGGCGTGCTGGCGAAAATTGGAAGCGTTCCCTATATTCTGCAAGAACCGCTGACGTAC
ACGGACTTTGTCGTAGGTTTGGACGTGAGCAGGCGACGCAAAAAAAACCTGCAAGGAACCAACAGCGTAGCC
GCCATGACCCGAATCTACAGCAATCAAGGCGAACTGGTCCACTATAGCATCCGAGACGCAACCATCGACGGC
GAGATCATTCCCAAGAGGATGCTCTACGACCTCTTTCCACTTCACGAATATCAGGGCAAACGCGTGGTGATT
CACCGGGACGGAAACTTCCCCGAGGAAGAGCGCCAGGCACTCGAGGAAATTGCCGAAAAGATTGACGCGAAG
TTCTACTTCGTAAGCATTATCAAATCTGGCAATCCCAGGATCTACGGTAGGACCAAAAACGAAGAGGGCATC
GGCAGTTATCGCAAGGCACCTAAGGGTAGCATTTTCCTCCTCAGCGAGACGGAGGCCTTGCTTATCAGCAGC
GACTTTCCGGACCGCTTCAGGGCCACGCCACAGCCTCTCAGAATTAAGACGTTTGGCAACTTTCCCCTTCAA
AGCGCCGTCCATAGCGTTCTGTCACTCACCTACCTGCACTACGGTTCCGAGCGCCCACCGAGGCTGCCGGTG
TCTACCTACTACGCAGATAGCATTAGCACTATGGTATCCAAGGGCATTAAGCCCAAGGACGTTGACGGCAAT
ATACCCTTTTGGCTG
214 25 ATGCTCCTTAATCATCTCCCAATCGAGTTCTCCAGCGCACAGTTCGCTGGACACGAAATTGCTTATGTCGAC
GGCGAGCAGTTGAGGTCCATACGACAGAGACTCACGCGCACGCACTTCGTGTTGAGGGATGGGGACAATGTT
CTGCTCTTCCCGTACGAACATGGAACCGCGACCGAGGGAACCAGGCGAACATTCGACACGGGCGTTAATTTC
AGCGTAGCCAACGCCCTGGCGCGCAACGGCATGCTTCTGCGATTCTTCCAGCACTCTAGAAGTATTTCCGGC
GTCCGACCGGTGAAATTTGTGAAAGACAACCAGAACCTGCTCACGGGTGACGTAGGCCGGTTGTTTGCTATA
TGTCCGGAGTACAGTTTCGACATCCGACCCCTGGCACCTCAAGACGGCAGCCTTGTGAACGGGGTACTGGTA
AACTTCTCAGCCCGATTTTTGGTGAAGCCCTCCCTCGACGAATTGATTGCGCAGGGGCTCGACCCACGGGGC
CTGTATGTTGTTAAAGAGGCAGAAAGAGAATCACCCTACATCCTGCCGATGTTTAATCGGAGATTGGTAGGG
CGGATCCAGGACGTGGTCGGAGGTATCGCCAAGCTGGTGGACGAGCGCGAACAGGACCTCCCTGTACATGAA
CTTCATGTCGAGGCCAACCTGGTCAACTTCGAGAAAGTAGGCAGAGCACTGCTTGGCCGGGATTACGAGCGA
GTGAGTCGACAAGTGCTTCCCACCCTCCATAAGGTGAGCGGCGCAGAGAAACAGCTCGATCGCTTGGTCCAG
CTGCTGACGAGCTTCAAAGACCTCCAGGGTGACATCCCGTGTTGCGACGGCCTGACCGTTAGACTGGCAGGC
ATACTTACAGATGTGCCCTTCGGCAGTGAGGTGGGCCAATTCCGCAAATTGTCCGCGCCACAGTGCAGCCTC
CGCCCAGGGGGAACTATTACGGTGCCGTGGCCCGTGGACGGCAAACTCAATGCCAACGGCCCCTTTGATGCA
GACGCCTTCAGCAGGAAGGAACCAACAATCGGCGTTCTGTTTCCGGAGCAGCACAAGGGTAGTGTAGAAGAG
CTGGCCGCTAAACTCAGAGACGGCGCACCGAGCGATGGAAAGTACCCAAGTCCATTTCCCCAAGGAATGCCC
CGGAAGTATAGACTTAGGAAGATGACATATGAGCTGACGCCCACGAAAGTTTCAGGGGACAGGGCCGCAGCC
TACAAGAATGCCGCGCTTGCAGCCGCCCAACAAGAGCTTGATCTCGCTCTGGTGGTCATATCTGAATCAGAT
AAGGCGTTGCTTGGAGCCGCCAGCCCCTACTACACTGCGAAAGCCACATTGATGAGCCAAGGCGTGCCGGTG
CAGGCTATTACCATTGAGACTATCAACAGGCTCAACCCCTACACCTTGAATAATCTGGCACTTTCCCTTTAC
GCAAAACTCGGCGGGATACCTTGGACCCTGTCAGTTCAACAGCGACTGGTCCACGAGATAATTGTAGGGATA
GGGTCTGCGAGAGTGGGCTTCGACCGCCTCTCAGAGCGGGAGAGGCTTGTCGGCATCACGACCGTGTTCTCC
GGGGACGGATCATACCTTCTTGGCAATGCAACGACGGAAGCCAGCAGTACCGAATATAGGTCTCGCCTTCTG
GAGAGCCTTAGGGCGACTTTGGCAGAGTTGCGAAGACGATTTGGCTGGCAGCGGGGAGATAAATTGAGGATT
ATCTTCCACCAAAGCTATAAGCGGTACAAGGAGACCGAAGCAACCGCCGTTAGCGACCTCATCGCCGAACTT
GATGAATTCGATGTGGAATTCGCGTTTGTGCAGATCAGTAGCGATCATGACTGGAAGTTGTTCGATGAGAGT
GCCACAGGCGTTACGTATCAGTCCCGGCAAAAGGGAGCGAAGGTGCCGGAACGCGGAGTCATAGTCCCTCTC
GGACCTCGCGCTGCGCTGATCACGTTGGTGGGTCCGCATCAACTGAAAACCGACCTGCAAGGGTGCCCCTCC
CCCATACTGGTGTCTATCCACCCGAGCTCAACTTTCAAGGATTTGAGTTACGTGTCAAAGCAGGTGTTCGAC
TTGACCTTTATGAGTTGGCGAAGCTTTAACCCAAGCACGCAGCCCGTTTCCGTGAGTTATCCCAACATGGTG
GTGGATCTGCTCGGTAACCTGCGGCAAATCCCCAACTTCAATCCCGACATTCTGACGACAAAACTGAGGGAG
TCTAGGTGGTTTCTG
215 20 TTGGACAATTACATACTGACCGAGTACAAGGCCGGCATCCACGCCAGCGAGATCAAGATACACATCTACCGG
ATGCCCGTCAAGGATCTTGAGAAAATCGACTATGAGTACGGGAAGTACACACGCGACCTCAGACAAAAAAAC
AGGAAGACGATATCCTTTTACCGCTCTCTGATCGGCAGCTTTGAGAAGCTCACCATCGTGCCCAAGGGATAC
GAGAAGTACGAGTATAGATCAATTAAACTCGACCAGAGTGAGGAGTCACTCCAGGAGAGGAAACTGCTGGAG
AGGCTGATCTTCGACGGCCTTAGGGACAGCAATAGGAACCACTTTATGAGCACCGAGCAGAGCATCATCGAG
AAAGAGCCCATCAAGTCCCTGAGCAAGTGCAAAATCCACCGGGGTATCTACATAGACATCACCGTGAAAGAG
AAAGGCGACATCTTCATCGGTTTCGAGCTGAAGCACTCCATCCAGAGCACCCACACGATTATCAAGGCTCTG
AAGGAGAAGAAACTGAACAAGGGCGATAAGGTGTTTGACTTTCTGAACAGCGCCCACTACGAGTTCGAGGGG
ATTAGCGACAAAACCATCAGCGACCCCCTTCCCGAACTGGGCAACAAGAGCATTATCCAGCACTACAAAACG
AAACCCAGCATCTACTGCCACCTCGTGAAAAAACCGAACATGCCCGCCATCCTGGTACGCAGCAAGAGCGGC
AAGGTGTATCCTTACCCCCCACAGCTGCTTAAGAAGGAGTGCCTGATGAAGGATGTGCCGGCTAAGGAGCAC
AGCTCTATCAAGCTGAACCCCAACGATAAGATCAACTACAGCATTGAGATCATGAAGAGAATCATAGATGCG
TTCGAGAACAGGTATTTCCCCATCGGCTTTGAAAAGAACAACCTGAACATCGCCAAGCTCGGATACAGGAGG
AGGCTGGTCCCGGATCCCCTGCTGAGGATTGGCAACGGAGCCACCTGCAACCACAGAGACCTCAAGGGTGCC
TTCCTTAGGCACAAGATTTATGACAGCGTGAGCTCCCCTATCTACTACCAGCTTCTGCTTGACCAACCCTTC
GAAAGGGAGTGGCAGAAAAAGATGAGCGAAGCGTTCATTACGAAGATGGAAAACCGGAGCAGGCAGTGGGGC
ATAAAGCTTCAGTGTACCGGGAACCAGATCCTCCCTACCTCTAACCCGTACGCGCTGAGACTGCATCTTAAG
GACATCAACCTGGATACCGACATCATTAGCGTGGTCCTGTTGGACGAGACCAAACAAGAAGGCGAGGAGGTT
TACTCTACCATCAAAAAAGAGCTGGGTGGCACCAGGGGCGCACATACCCAGGTAATCCTGATCGATAGCCTG
AAGAACGAATACACTATCCCCCAGATACTGTTGGGAATCTACACCAAGGCTGGATTGCAGCCCTGGGTCTTG
CACCAGCCGTTGCACGCCGACTGCTACGTTGGCTACGACGTGAGCCATGAAAATGGCAGGCACACCACTGGC
ATAGTGCAAGTGTTCGGCAAAGACGGGTCACAGATCTTCAGTCAGCCCATTAGCAGCGCGGAGGCCGGAGAG
AAGGTGTCAAAGGAGACCATTCAGACTATGGTGATACACGTTCTTTACTATTACCAGAAGAAAGTTGGCAAG
ATGCCACAGCACATTGTCTTCCACAGGGACGGCCGAGGATACGTAGAGGAGATAGACTGGATTAAAGACATA
TTGAGTAATAGGGACCTCACCAACGGCCAAAGCATCGCTTTCGATTACATCTCAGTGATCAAAGAGTGTGGT
CGGCGCATGGCTTACTTTGACGACATAAAGAAGAAGTATGTGAACGTGCCCGGGATTGCCTACCTGGACGAC
AACGCCCAAAAGGCCTATCTTTGCAGCACCAATCCATACGAAAAAGTAGGGATGAGCAAACCTATTAAGATT
GTGAAGAAGATTGGCGAGATGACCCTGGAGCAGATCGTAGAAGACATCTATCACCTGAGTTTTATGAATATC
GACACCGATAGGAAGGTGAGGCTGCCCGTGACTACCAATTACGCCGATAAGTCTTCAACGTTTTTCTCTCGC
GGCTATCTGTCATCACAAAAGAAAGGAATTGGCTTCGTA
216 69 ATGGTCGGCGGCTATAAAGTCAGCAATTTGACAGTGGAAGCGTTCGAAGGTATCGGGAGTGTCAACCCGATG
CTGTTTTACCAATACAAAGTCACCGGAAAGGGAAAGTACGATAATGTGTATAAGATTATCAAAAGCGCACGG
TACAAGATGCATTCTAAGAACCGATTCAAGCCCGTGTTCATCAAGGACGACAAACTGTACACCCTCGAGAAG
CTCCCGGATATAGAAGACCTGGATTTCGCAAACATTAACTTCGTGAAAAGCGAGGTTCTCAGCATAGAGGAT
AATATGTCAATTTATGGCGAGGTGGTGGAATACTATATCAATCTCAAGCTGAAAAAAGTGAAGGTGTTGGGA
AAATACCCCAAGTACAGGATCAATTACAGCAAAGAGATTCTCAGTAATACGCTGCTGACACGAGAGCTCAAA
GACGAGTTTAAGAAATCAAATAAGGGTTTTAACCTGAAACGGAAGTTTAGAATTTCCCCCGTGGTGAATAAG
ATGGGCAAAGTGATACTCTATTTGTCCTGCAGTGCTGATTTCAGCACCAACAAGAACATTTACGAAATGTTG
AAAGAGGGCTTGGAGGTTGAGGGGCTGGCCGTTAAGAGCGAGTGGAGCAATATCAGTGGCAACCTGGTGATC
GAGAGCGTACTGGAAACCAAGATATCCGAGCCCACTAGCCTGGGCCAATCCCTGATAGACTACTATAAGAAT
AACAACCAGGGCTATAGGGTGAAGGATTTCACCGATGAGGATCTGAATGCCAACATTGTCAACGTGAGAGGA
AATAAGAAGATCTATATGTATATTCCGCACGCGTTGAAGCCGATAATCACCCGGGAGTACCTGGCCAAGAAC
GATCCAGAGTTTTCTAAGGAGATCGAGCAGCTTATCAAGATGAATATGAACTACCGATATGAAACCCTCAAG
TCATTTGTGAATGACATCGGGGTCATTGAAGAGCTGAACAACCTGAGCTTCAAAAACAAATACTACGAAGAT
GTGAAACTGCTGGGTTACTCCAGCGGCAAAATAGACGAACCCGTCCTGATGGGGGCAAAAGGGATCATAAAG
AACAAAATGCAGATTTTTTCCAATGGATTCTACAAACTCCCCGAAGGCAAGGTACGATTTGGCGTTCTGTAC
CCAAAAGAATTTGATGGCGTGTCAAGGAAAGCTATCCGCGCCATTTATGACTTCAGTAAGGAGGGCAAATAC
CACGGCGAAAGCAACAAGTATATCGCGGAACACCTGATAAACGTGGAGTTCAATCCAAAGGAGTGCATATTT
GAGGGATACGAACTGGGCGATATCACCGAATACAAGAAGGCGGCTCTGAAACTTAATAACTACAACAATGTC
GACTTCGTAATCGCAATAGTCCCGAACATGTCCGACGAAGAGATAGAGAACAGCTACAATCCGTTCAAGAAA
ATATGGGCCGAACTGAATCTGCCCAGCCAGATGATTAGCGTCAAGACGGCCGAAATCTTTGCCAATAGCAGG
GATAACACGGCGCTTTACTACCTGCATAACATCGTCCTCGGTATCCTGGGTAAGATAGGAGGGATTCCCTGG
GTGGTTAAAGACATGAAGGGCGACGTGGATTGCTTCGTTGGACTCGATGTCGGCACCAGGGAGAAGGGCATA
CATTACCCCGCCTGCAGCGTTGTGTTTGACAAGTACGGCAAGCTTATTAACTATTACAAGCCTAACATCCCG
CAGAACGGAGAGAAGATTAACACAGAAATACTTCAGGAAATTTTCGACAAGGTGCTCATAAGCTATGAGGAG
GAGAATGGAGCCTACCCGAAGAATATCGTGATCCACAGGGACGGCTTTAGCCGAGAGGACCTTGACTGGTAT
GAGAACTACTTCGGTAAGAAAAACATAAAGTTTAACATCATCGAAGTCAAAAAGTCAACTCCGTTGAAAATC
GCCAGTATAAACGAGGGAAATATCACGAATCCTGAAAAGGGTTCCTACATCCTGCGCGGCAACAAAGCCTAC
ATGGTGACCACAGATATTAAGGAAAACCTGGGAAGCCCAAAGCCCCTGAAGATAGAAAAGAGCTACGGCGAC
ATAGACATGCTCACAGCTCTCAGCCAAATATACGCACTCACGCAAATCCATGTGGGGGCGACCAAAAGCCTG
CGCCTCCCAATCACCACCGGCTACGCCGACAAGATTTGCAAGGCGATCGAGTTCATCCCCCAAGGGCGCGTG
GACAACCGCCTTTTCTTTCTG
217 76 ATGGACCGCGAGATCATTGAAAACTTCAACCCCAGCGACCCCAGGACCGAGGGCGAGAAGTATCTGATGGAT
(Helicase) AACTTTTCAACCTCCCCCAGGTTTAATGGCTGGACAATATTTGAGCAGCCCCACATCAACTCAATGAAGCCC
GACTTCATCTTGCTGCACCCCCACAAGGGCATCATAATCATAGAAGTGAAGGACTGGAACCTCAGCAGCGAG
ACATATGAGAACGGCGGTTACATCTGGGGGGAAAACGGCGAGAGGATTAAGAAAAACCCCATCAATCAAGTA
GAAAACTACAAAAACTCTATACTCAAGATGGAACTTACAAACAGCATCGAATTTAGTGAAGTGTTCGGCGAC
AAATACTTCGCGTGCATAGAAACGGTGGTATACTTTCACAAAGCCAACAAAATTCAAGCCGAGAACTTCTGC
AGGAGGAACAATAACTACACCAAGATCTGGACCAAGGACGAGTTCGACTACATATGCAATATCAATAACAAA
CTGAAGGGCAGTTGTCACACCTATGCCCTGAGCTACGAAAAAAGCACCCTTGAAGACAACAGAGGTATGCTG
AGTAAACTGGTGGAGGAGCTCAAGTGCAATCTCCAGTACAGTGACTACAACTATGAACGACGCCAACCGATT
AAGTTGACCTATGAGCAAGAGAAGTTGGCGAGGCTGCAAAAGAATTCAATCAGGAGGTGGAGCGGCGTGGCA
GGCGCTGGCAAGTCCCTGAGTCTGGCGCAAAAAGCCGTGAACGCCCTGAAGGAGGACCATAGCGTTCTGATC
CTGACCTACAACATAACCCTGAGGCACTACCTGCGCGATCTGTGCTCTCAACAGTTCGGACCCGGCTCCTAC
AAAGGCGAGCGCAAGAAGCTGAGGAGCGACCTGACCATCTGTCACTTTCATGACTTTTTGAGAATCATCATG
GCCGAGTACGAGATCGAGGTCGAACATGACGAAGACGACAACTTCACCCAGCACTGGATAAACAAGATCGAC
AGTTGCATAAAGGTGAACGGCATCAAGAGCCACCTCAAGTACGACTATATCCTGATCGACGAGGGCCAAGAC
TTTGAAGGCGAATGGATTAGGTTCCTGAAGCAGTTCTTCACCGAGGTGGGTGAGATCTTTATCGTGTACGAC
AAGGCCCAGGATCTCTACGAGCATGGCGTGTGGATCGAAGACAGCAACCAAATCAAAAACATCGGCTTTAAG
GGCAAGCCCGGGAACCTGAAAATCAGTATGAGGATGCCTGAGAAGATGGTGTACCTGGTGCAGGACATCAGA
AATGAGTTCAAGATAGATGAGGAGGAGATCACCCCAAACGTGAACAGCCAGCAGAGCTTCATCGAGATAACC
AAGTGGATTAACTGTATGCCCCTGACGCTCACTGAAAAGCTCGACCAGATTGAAATACAGGTGGACTTTCTG
CGCCGAAACAACAACAGCCTGGAGGATATCACGATCATTACGACCAACGAGGAGACCGGAGTGGAGATAGTG
AATAGGTTCAAAAGCAGGGGTATCAAGACCAGCCACGTCTACGATATGGAGAAGCGGGGGAACCAGGCCAGG
CGAAGGATGGAAAAATGGAAATTCCAGGGCGGCACCGGCAGACTGAAGATTTGTAGCTATCACAGCTATAAG
GGCTGGGAGACTCCGAACATCATCCTTGTGCTGGACGAGCCGAGCACAAAGTATGAAGACGGCATAATTAGT
AAGGGGGAGTATAACGAGAAGAACATTTTCGACGCTATCTTCATTAGCATGTCCAGGGTGAAAAGGAAAGCC
CAAACCGGTGAGTTTAGCTTTACGTGCCTGAATTATCTTAGCGAATACAATAAGATTGAGGGCCTCTTCCAC
218 75 CTGGGGCTGAATAATGAGTCCAAAGAGTTCTTTAAGGGCATTAGCCGCATTTGGAGAAATTACAAGGACTAC
(Helicase) ACCTACCTTGACGGGATTAAGCTGAGCCAGGCGCAGATCGATATCATCGAGAAGGAGGAAGACCAATTGCTT
ATAGAGGGCTACGCCGGCACCGGTAAGTCCCTGACCCTTATATACAAGTTCATTAACGTGCTGGTTCGGGAA
GATGGGAAGAGGGTGCTGTATGTGACTTTTAACGATACGCTGATCGAGGATACGAAAAAACGCCTTAGTTAT
TGCAACGAGTACAACGAGAATAAAGAGAGGCACCACGTAGAGATTTGCACATTCCATGAGATCGCCAGTAAT
ATCCTGAAAAAAAAGAAGATCATAGACAGGGGTATTGAGAAACTGACGGCTAAAAAGATAGAAGATTACAAA
GGTGCCGCTCTCCGCAGAATTGCGGGAATCCTGGCTAGGTACATCGAGGGGGGAAAGTATTATAGCGAGTTG
CCTAAAGAGGAACGCCTCTACAAGACACATGACGAGAACTTTATCAGGGAGGAGGTGGCCTGGATCAAGGCC
ATGGGCTTTATAGAAAAGGAGAAGTATTTCGAGAAAGATCGCATTGGGAGGTCCAAGAGTATCAGGCTGACG
CGCTCACAACGCAAAACTATATTCAAGATATTTGAAAAGTACTGCGAAGAGCAAGAAAACAAATTCTTCAAA
AGCCTCGACTTGGAGGATTACGCCCTGAAGCTCATCCAGAACATAGATAATTTCGATGACCTTAAGTTCGAC
TACATTTTTGTGGACGAGGTACAGGATCTCGATCCCATGCAAATTAAGGCGCTGTGTCTGCTGACCAATACG
AGCATCGTGCTGTCAGGCGACGCGAATCAGCGGATTTACAAGAAATCTCCCGTGAAGTACGAGGAGCTCGGC
CTCAGAATCAAAGAGAAGGGGAAACGGAAAATTCTGAACAAGAACTATCGGTCCACGGGTGAGATTGTCAAG
CTCGCGAACTCAATCAAGTTCTTCGACGAGTCCATCAATAAGTATAATGAAAAGCAGTTCGTAAAATCCGGT
GATCGCCCGATCATCCGGAAGGTGAACGACAAAAAGGGTGCGGTGAAGTTCCTGATCGGCGAGATCAAAAAA
ATCCACGAAGAGGACCCCTACAAAACAATCGCCATCATCCACCGAGAGAAAAACGAGCTTATCGGCTTCCAA
AAGTCCGAGTTCCGAAAGTACCTGGAAGGCCAGCTGTACATGGAAAAATTCAGTGACATCAAGTCCTTTGAG
TCAAAGTTTGATTTGAGGGAAAAGAACCAGGTGTTCTACACCAACGGCTACGATGTAAAGGGGCTGGAATTT
GATGTGGTGTTCATCATAAACTTCAACACGGCCAACTACCCACTGAGTAAAGAGCTGAAGAAAATCAAGGAC
GAAAACGACGGCAAGGAAATGACGCTCATTAAAGACGATGTGCTCGAGTTTATCAATCGCGAGAAGAGGCTG
CTGTACGTAGCTATGACCAGGGCCAAAGAAAAGCTGTATCTCGTGGCCGACTGCAAAAACAGCAACATCAGC
AGCTTCATCTACGACTTTAACACCAAGTACTATGAGGCACAAAATTTCAAGAAGAAAGAGATAGAGGAGAAC
TACAACCGGTACAAGATTAACATGGAGCGCGAATACGGCATCATCATTGAGGACGACGACTCCAACAACGTT
AAGAACAATGACACGAAACAAGAGAACAAGTTTAATACCGAATCTAAGGAAAAGGGCAAAGATGACATCGAC
AAGATAAAGGTGTTTTTCATCAACAAGGGAATCGAGGTGGTGGACAACCGAGATAAGAGCGGGTGCTTGTGG
ATCGTCGCCGGGAAGGAAGCGATCCCTCTTATGAAGAAGTTCGGTGTCCTGGGCTATAACTTCATATTCATC
GCAAACGGCGGTCGGGCATCTAAGAACCGGCCAGCCTGGTACCTCAAGAATAGC
219 14 ATGAACAACACCATAAACAAAATAGACTTCGGCGCGTTTCTGAGATCATTCAAGCAGAACCTGGACGGTAGC
TTTTCTTTCCTTCTGGGAGCAGGCGCGAGTGTGAGCAGCGGCGTACAGTCTGCAAGCGACTGCATTTGGGAC
TGGAAAAAAGACATTTTTCTGGCCCAAAACCTTCAATTTGAGGAGTTTCTGGACATCCATAGTGACTTCTGT
AAAGATAAAATCCAAAAGTGGTTGGATGAGCAGGGCGTGTTTCCCAAGCGAGACTCAGAGGAAGAGTACGTG
TTTTATGCCGAGAAAGCGTACCCAATGGAACAGGACAGGACCAAGTATTTCGAGAACCTTTGCGCGGACAAA
ACCCCCTACATAGGGTATAAACTGCTGATGCTGCTGAACAAATACGGAGTTCTGAAATCCGTGTGGACAACG
AATTTTGACGGTCTGATAGAACGCGCAGCGCACCAAGCCGATCTGACGCCCATCGCCGTTACCCTCGACAAC
CCCGAAAGGATTAGCCGAAACGAGAGTAAATCTGAGCTGCTCTACGTGGCACTCCACGGTGACTACAAGTAT
AGCAAGCTGAAGAACACAGCCCAAGAGCTGGACGCGCAAGAAATTCTCTTCACCGAACGCCTGAAGTCTTAC
TTCATCGATAAGAATTTGGTGGTGATCGGTTACAGCGGTCGAGACAAAAGTTTGATGCACACCTTGTGCGAG
GCTTTTATGACGAAGGGGTGCGGTCGGCTTTACTGGTGCGGCTACGGTAACAAGATTACCTCTGAAGTGCAG
AACTTCCTCAACAGAATAAACGATTCAGGTAGGGAAGCCGTGTACGTGGACACCGATGGGTTCGATGCCACC
CTCGTGTCTATTATGAAGTTTTGCTACGAGGATCAATTCGACAAGAAAATCGAAATCGGCAAGTATCTCAAG
GGCCTGTCAAGGGTGAAGCATATTATCCCTTTCAGCGTTGAGAATACCACGTTCACCGGCTGCGCCAAGACC
AACCTGTACCCCTTGATCATCCCCCAAGACATATTCCAGTTCGAGATAGAGAGCCCCGAAGGTAGCAGCAAA
TGGACCTTCATTAAAGAGAAGATTAAGGGCAAGGACATTATCGCTGCCCCTTACGAGAAAATAGTCTACGCA
TACGGGCTGCCAAACTCAATCTACAACGTATTCAGTAAGGAGCTGATCGGCGAGATCAAGAGGGTTCCCATC
AGCCTGAGTAACATCAAAGACAACAGCACCCTCAAGAATATCATCCTGAAGGTGCTGATATGTTCTCTGAGC
AGTAACGCGGGACTCAGGGCGAGTATGAGCAAGAAGATCATCTGGAATGAGAAAGAGAGGTTCCAGAGCAAC
GTTTTTAAGGCAATAAAGATCGACATCGTTTTCATCAATAGCGAAAAGTACGCCCTCATCTCAATCACCCCT
ACCCTCTATTTCAACAAGGAGGGCAACTACACGACGCTGCAGAAGCAGGAAATTACGCGGAGCTACATTGAC
AAGCTGTACAATAAGATTTATGAGGAAACCCTTTGTTACTGGGAGGCCATCCTGTTTAAGCAGCAGACCAAG
ATCTGCTTCGACTACCCGCTCAATTCCGGGAACGGCTGTTTCTTCAAGGTTAGCTCTAACAGGGGCGAAGCC
CTGTTCAATAATCCGAATAAGCCGTACGTGATTACTAACGACATCATACTTAAACGCAAAATCTACGAAGGC
ATCATAATCGACGAGCCCCTCCTGAACTTCTCAGGGTCAACCAGCGCCCACATCATTATGGACTCCAATCCG
ATGCGCGGTCTCAACAACAATAACCCATATGATCACTTCATTGCAAGCAAGTTTAGGGACGTTTCTATCCAC
ATCGGAGTCGTGTGTCCCTGTACATATAGCGACAGGTTTTTTAGCTTTCTGAACGAGCTGCAAAGTCCGATA
AAGAATAACAATCCTAACTCAGACTACATCCAGAACTATAACGGATTCAGCCAGATATACGCAAGCATTCTT
AATATCCCAGCGATCAACAGCCAATACTGGATCTCATGCCGCGAAGAGCAGGATAACAGCATCTCTTTGGCT
AGGAACCTGTGTAAATACGCGAACCAGATGGCCACTAACATGCCAGGTATAATAGTTACCTTCTTCATTCCT
AACAGCTGGAGCAACCACAAGAGTTTCAAAGAATGTGGCGAGGTATTCGACCTCCACAGTTACATCAAGGCT
TTCGCCGCACAGCACGGTTTTACAACCCAAATCATTGAAGAGCGAACTCTCACAAATCTCTCCATGAAAAAG
GAGATCTATTGGTGGCTGAGCCTGGCGTTCTTTGTAAAGGCTATGCGAGTACCATGGACCCTGGCCAATCTG
GACCAGAACACCGCCTTCGCCGGCATCGGCTACTCCCTGAGCAAAAAGCAAAGCGGCAAATTCAATATCGTT
ATCGGCTGTAGCCATATCTATAATTCTGAGGGCCAAGGCCTGAGGTACAAGCTCTCAAAGATAGATAATCCA
ATCTTGGACCGGAAAAACAACCCGTACCTGACCTATAATGAGGCGTATAAGTTGGGCGTGAACATACAGAAT
CTGTTCATTCAGAGCATGGACAAACTCCCGAAGCGAGTAGTGATCCACAAAAGGATCCCGTTCCTGGAGGAC
GAGATAAAGGGCATTACCGAGGCGTTGGCCCAGGCCAACATCACGAATGTTGACCTCATCACTATCACGATC
GAAAAGAACATCAGATGCCTGGATCAGTTCTTCTACAATGGTCAAGCCAAGAACAGCAACTTCCCACTGCAT
AGGGGCACCTGCATGAAGCTCAGTGATACCGAGTGTCTGTTGTGGACCCACGGCGTGGTGGACTCAATTAAG
GCGGGCAGGAACTACTACTCTGGTGGCAAGGGTATCCCCTCCCCCCTCCGCATATCAAAGTTTTACGGCGCA
GGCTCTATGAAGACTATATGCAACGAAATCCTGGGGTTCACAAAGATGAATTGGAATAGCTTTAACTTCTAT
ACCAAGCTTCCCGCGACCATCGACACCAGCAACACGCTGGCGCAAGTGGGGAACATGCTCGATAATTACAAC
GGTATTACATACGATTACAGGTATTTCATC
220 26 ATGATGGGAGCCAGCGATGAGTATTCCTTTTACGCTGAAAAGGCCTATCCCATAGAAGCGGACAGGCAAAAG
TACTTCGAACAGCTGGCGTACAACAAAGCCCCCTACATTGGCTATAAACTCTTGTGTCTGCTGAATAACGCG
GGGCTGATAAAGTCTGTTTGGACCACAAATTTTGATGGCCTGACGGAAAGGGCCGCTCACCAAATGAACATC
ACCCCCATCTGCATTACCCTGGACGACCCCGAGAGGATTTTTAGGAATGAGAACTCTCACGAACTGCTGTAT
ATCGCCCTTCACGGCGATTACAAATATAGCAAGCTCAAAAATACCACCCACGAGCTGGACACCCAAAACAAT
ATCTTCAGAGACGCACTGAAGCGATACTTCGTGGATAAGAATCTTATTGTCATAGGATACAGCGGCCGAGAT
AAAAGCCTGATGAACGCACTTAAAGAGGCATTTTCCCAATCCGGCTCCGGGCGACTGTACTGGTGTGGCTTC
GGGGACGATATATGCAGCGACGTTAAGGAATTGATAGACATCGCCAGGAGCAATAATCGGATTGCCTACTTC
ATCCCGACGGACGGCTTCGATAAGACCATGCTCCAACTTAGTCGCGCCTGTTTCGAGGACGACATTGTGAAG
CAGGAGGAAATCAAAAAGCTGATCAAGTCCACGATCAAGAAGGACGAGACGAAGACCAGCTTCCGAATCGAG
AGCAGCAGGAACGATAAACTTATTAAGTCTAACCTGCATCCCGTGGCGTTCCCCAAGGACGTGTACCAGTTC
GAGATTAAGACTAACGGCGAGCATCTGTGGAACAACATAGACCAGATCATTGGCGGCAATAAGGACATAGTT
GCCGTACCGTTCAAAGGTAAGGTGTTCGCTGTCTCAAGCATTGCGAAAATCAAGGAGAGGTTCGGGGGCTAT
ATCAAGGGGGAAATATTGAAAGACCCGATTGGCGTCGATGACATCCGCAAAGTATCTGTGTTCCAGCGGCTT
ATGATGAAGAGCATCCTGATTGGAATCTCTGAGTTGGCAAATCTGGAAACTGATGGAAAGTGGCGCCTTTGG
AAAAAGAACACCCTGAGGCGAATCGTAAACGGCACGGAGTATTTCATCGCCGACGCTGTAGAGCTGTCCTTT
TTCTTCGGAAAAGATACCAAGTTTGCCTATCTCAGCATCAAACCGACCATTTACATTTATACACATAGCGAC
GAATTCATACCGAAGGATATAAAGCTGCAATTCACAAAGGAGAAGTTCGACCGACTCTATAATGCACAATAC
GACCAATCCCTGGAGGAGTGGAATAATCTCATCTTCCACAACAACAGCCTGAGGTTCACCTTTCCCGTACTG
ACCACCTCCGACATGAGCTTTAGCATCAGCAACAATGTGGCCTTCTCAGGAATTAAGGTTTTGAGTGACAAG
TATAAGAGCTACCCCGTTTCTATCGAGCAGAAGCGCATAGTTTTCAAGGGCGTGGAGTTCCTGGAGCCCCAG
CTGCTGTTTCAAAATAAGAACAGCAACTTCAAGTCACGCGACTTCCATCCCATGAGGGGATTGATTAACCAC
TACCCCTTCGACTACCAGAACAATGGGATCACCAACACGTTTAATGTCAAACTCGGCGTGTTGTGCTCCTCT
AAGTACTCTACTAGGCTGTACGAGTTTCTCATGAAATTGAATGCCCAACATAAAGCGCCCGAGAAAAACGAG
TACATAATTGACTATGCTGGATTCAACCAAATCTACAACATCCCTATTGAGATACCGCTGGTAAACGACGAG
AAGTGGATGGACGTAAAGTTTAATAGCAGCGTGAGTATCAAAGACGACGCTCTCAACCTGGCAAGAATCATA
TGCACCCAGATCGAGGCGCTTCACGAGTCTTACAAAACTGACATGACCATCGTGATCTTCATTCCCAACGAG
TGGCAACCCTACAGACATATCGAGGAGGACACATGGGTTTTTGACCTCCACGACTACATCAAAGCATATAGC
GCTCAGAAAAGAATTTCCACGCAGTTCATAGAGGAAGATACTCTGAACGATTCATTGACGTGCCAGATATAT
TGGTGGCTCAGCCTTAGTTTTTACGTGAAATCCTTGCGGACGCCGTGGGTTCTGAATGCTAACAATAATGAG
ACCGCTTACGCGGGCATCGGCTACAGTATAAAGAATAACAACGGTGAGGCGTCAATTGTCCTCGGGTGTAGC
CATATTTACGACAGCCACGGCCAGGGCCTCAAGTACAAATTGAGCAGAGTGCAGGACTGCTACATCGACAAC
AAGCGGAACCCCTACCTGAGCTACAATGAGGCCTACAACTTTGGCATAAGTATCAGGGAGCTCTTTCTGCAC
AGCATGGAGTACCTGCCAAAAAGGGTAGTAGTGCATAAACGCACCGAGTTCAAACCCGACGAAGTGAATGGC
ATTGTCGACTCACTGCAGATAGCGGGTATCGAGAATATAGACCTTATCTCCATCAACTTCGAGCGGGAAGTT
AAATTCATGTCCACTAAATCCAACTACGGGCAGTTGCAAATCGATAACTTTCCCATACGCAGGGGCACCTGT
ATCGTGGTGAACGACTATGAAGCCCTTCTCTGGACCCATGGAATTGTGCCGAGCGTTAAGTCCGATAACAGG
ACCTTCTATCTGGGCGGACGATCTATTCCTAGCCCTCTTATCATTAAGAAGCATTACGGTAAGAGCGATATC
AACGTTATCGCTACAGAGATACTGGGTCTTACCAAGATGAATTGGAACTCTTTTGATCTCTACACGAAGCTG
CCGGCCACCATCGATAGCTCTAATCAAATCGCGCGGATCGGGAACCTGCTGACTAGGTTCGAGGGCAAGACC
TATGATTACCGGTTTTTCATT
221 46 ATGCGATTGGGGCACATAGGCAACGGCTGTTACAGGGAAGGCGTTAAAGCACAATTCCAGACACGAGAGAGG
GAGGATGCCGGTTCAAGGGCTGCGGCTGCCCAACCCCCGATTAAGCAATTCGGATACACCGATAGACTCGGC
CTGAACCTCGCCCCCATAAGGTTTTCTAGCGAAGAGTTTGAAGCCGGACGGACGGTGTACCGCGACGAGGAA
CAGTACCGAGCTCTTAGGGAAGCCCATCAAGCCACCCATGCCTTTAGGTATGACGCAAGGGACGCGGCTATA
TACGACATCCCTATGGCAGAAGGGGTGGCGCCTCTGGGTACTCCCGTGAGGATCAAAACTAAGGACCACCTC
GCTCTGCTCGGCAAAGCGGCTAACCACGCGCTGCTCGATTGGCTCGCACCACGCAGAACCATTCTGCGGAGG
GCGAGACCTCTTCAGTGCTGGGGCAACAGGAAGGCCTCACTGTTGTCAGCCGCCGTGCGGGATCAAGGACTT
GCCGAAACAAAGGGTCTGGATGTTCTGGTAAGGCATTCTTTTGATTTGAGGGCTTTGGGCGCACCTCACCAG
GGTGCTGAACCGTACCTTGCCCTGATGTTGGACGTGAGTACGAGCAATGAGCTGGAGATACCTGTGGGCGAG
CTTCTGCGCGAGAGATTCGACCCCATCGGTCGATACGTTTGTGCCAGAGCCGACTCTGGCCAAGATAACGTA
CTTGCTAGGTTGGAAACACTGGGTAGGGTCGTGGGTGTGGATGGTGGTAAGCTTCAACTGAACGACTTTACC
GGAGAAGAATTCGTGGACGCTGATTCAGTCACGTTGGAGCCTAGATTGGAGAATCTCGATGCGCTCATTCGC
CACTTCTATCCCAGGGATGCGCCAAAAATCCTGGAGGGCCTTCGCAAAAGGAGAGTGCCTTTCTCCACCGCG
AACGACAAGCTGGCGAAGATACGAGAAGTGCACGGAGGAGTAGCCGGCCACCTTGAAACGATTAGGATCGCT
GGCATGGCTATAGAGGTGGGTGCCCTGCTGCAGAGAGGCTCTAACCTGTTTCCCCCACTCATAAGCACGGAC
CGGCCTGGATTTCTGTTCGGCGCTCAAGGTAGGGAAACTGGCGCGTTCCCCGACGTGGGGGTGAAGCAGCAT
GGGCCCTACAAGTACATGCAACACGAGCGCAATGAACCTGTGATCGCCATCATCTGCGAGAGCAGGTTTCGG
GGTCGGATAGACCAACTCGCCCGAACACTTCGCGATGGTGTCGCGGAAGATGCCTGGCAAGACGCGATGAGG
GGCAGAAATAAGGTGCCGGAAAACCCCTTTAGAGGCGGGCTGATCGGTAAATTGAGATTGTCTCGGGTGCAG
TTTGAGTTCGAAGAAGTAACCGAGCCCACTCCCGAAGCCTATCGCGAGGCCATCCTTCGGCTGCTTGCGAGA
CTCCCAGAGACACCCGACCTCGCGTTGGTTCAAATACGAGCGGATTTTAAGCAGCTCCGCAACGACAGGAAC
CCATACTTCGCTGCAAAGGCCGCATTCATGACGGTGGGAGTGCCCGTGCAGTCCGTACAAGCCGAGACTGCG
GACATGCAGCCCAGTAATTTGGCCTACATGGCCAACAACCTGGCCCTCGCCGCCTACGCAAAATTGGGCGGT
AGTCCGTTCGTGATCTCCACACGCATGCCGGCGACGCATGAGCTCGTGGTTGGCTTGGGCTACACAGAGGTG
TCAGAAGGACGCTTTGGACCGAAGTCCCGATTTGTAGGCATCACCACCGTGTTCCAAGGCGATGGCAGGTAC
TTGGTGTGGGGGCAAACTAGAGAAGTAGAATTTGAAAACTACGCCGACGCTCTCTTGGCGAGTCTGAAGACT
ACCATCGACACAGTGCGCAAGGACAATAACTGGCAGCCACGCGATCGAGTGAGGTTGGTATTCCACGTGTAT
AAGCCCCTTAAACATGTCGAGATCGACGCTATCAAACAGTTGGTGCAGGAGTTGCTGAAGGGCGAACATGAA
GTGGAGTTCGCATTTCTGGACATCTCCCGCTTCCACGATTTTGCCCTTTTCGATCCTTCCCAAGAGGGCGTG
AATTACTACGCTGACCGCAGACGACTGCTGAAAGGCGTGGGCGTCCCCCTTAGGGGTATCTGCCTCCAACTG
GACGAAAGGAGCGTGCTCTTGCAGCTGACAGGCGCTAAGGAGGTGAAGACCAGTGAACAAGGTCTGCCCAGG
CCCCTGCGACTGACGTTGCATTCCGAGAGTGATTTTAGGGACCTCACATACTTGGCGCGACAGGTGTACAGC
TTTAGCTACCTCTCCTGGCGCAGCTACTTCCCGGCCATAGAGCCGGTGAGCATTACCTACAGCAGACTTATT
GCCAATGCACTTGGCAACCTTAAGAGCATCCCGAACTGGAACAGCACATTCTTGACAGCTGGCCCACTGAGG
TCAAGGATGTGGTTTCTG
222 49 CTGGAGAACCTCACCATAAACATAATCCCCTTCAAGCACCCCAGCATCCAAAAAGAATTTGGCTTCTATACC
GAGAAGAAGGAGGGCTATTTCCCCATTCATAGGACCGAGTTGCCCAACGAGCTGTGGGACAACCAGAAAGAG
GAAGTGGTGAAGCACAAGTTCTACTACACGAACTTTGAAGACACGGAGGATTGCGTTCTGAAGACCAAGGTG
GACCTGTATAGTAGCACTAAGTTTGCCAAGCATCTGTACACGCGATTGGTGTACCAGTATTTCATTGGGATA
GCGGATGCAATCCAGTTCAACTACGTGGGTGACATAGAGGTTTGGCTGCTGGATGCGAAAGCCAGCACCACC
AAATACAATAGCTACAACAAGTATACCCTGAAAATAGAGTTTAGCGGTCTGACCAAGAGCCCCGCTCTCCTC
CTCAGCTATGACAACACTAGTAAGGTAGCGACTACGAGCATAGACGAAATCAACATTCCCACCGAGTACTTC
AAGACCGTCGTGTATAACAAAGAAATCCAGAGGTTCAAGTACCTGACCGAGGACGCGAAACAACACCTCGAT
CAAGTGTATCCCCTGCTCAACATACCGTTGAAAAACCATCTTGAGATTCCTCACACCGTTCCCCGCAAGGGC
AACAGGTATAAGCCCTACTTTAACCACATTACGACTTTTTACAATAACTATTTGAACACCGACGAATTCAGG
GCCATCCTGCCCCTTGATGAGAATGGATTCTTCAATATCCCAGAGGACAGCATTTTGAAAACTAGCAAAAAT
TCTAACAACCTCCGGTTCTATAAGAAAGTCGGAGTAGATCCCAAGGCTGGAATGAAGAAGCCCGGTCCCTAC
AAGGCCTCCCCCCACGACAACGTGAACCTGTTCTTTATCTATCACAAACCCGACGCACATGAATACGCCAAA
ACGTTGCATGACTACTTCATGGAGGGGTACAAAAAGTTCTTTCCCCCCCTCAAGAACGTTATCCGGCAGCCG
CTGTTCCTGGACAAAGGCACCTCACTTGCATTTGAGAGCTTCGACAGCTGCATCGCCGAGCTGAAAACCCAT
CTGTTCGACCTCAAAAAAAAGCCCAATACCCGGTACGTGGCCATCTACGTGAGCCCCATCCATAAGGAGGAC
GAAGACAATAAACACCTGTACTACCAGGTCAAAGAAGAGCTGCTTAAACATGACATCACCAGCCAGGTGATT
TACAAAGAGTCCATCAAAGATAAATACTTCGGCGCTTTCCTCGAGAATATCGCACCAGCTTTGCTTGCAAAG
ATCGACGGCATTCCCTGGCGACTGGACAGGGAGTTGAAACAGGAACTGATCGTAGGCGTCGGCGCCTATAAA
AGCAGCGTCACCAACACAAGGTTCGTTGGAAGCGCCTTTTGCTTTAACAACAAAGGAGAGTTCAAGAGCTTT
GACTGCTTCAGGGAGAAGGAATTCGATCTGATTGCCGGGAAAATCGGCAAGCAGGTGCTCACCTTCATTGAG
GAGAACGAGAACAAGTTGGAGAGGCTGATCATCCATTATTTCAAGCCTTTCAACAAGGATGAGATAGATCTC
GTGCAGGAGACCCTCGGCCTGCTGAAGCTGGAAATCCCCATCATCATCGTGACTATCAATAAGACCGAGAGC
TCCGATTACGTCGCTTTTGACACCAACGACGACGCCCTGATGCCCCTGAGCGGCACCATTATCGAGATAGCA
CATCTGAAGTATCTGCTGTTCAATAACGCGAAGTACAGCAGCATCGGCTTCGCCAAAGACCACCCCTTCCCC
GTTAAGCTCAGTCTGTACTGCACCGACCAGGATTACTTCGAGGACATCGCCATCGTCAAGGAGCTCATAGAT
CAGGTTTATCAGTTTTCTAGGATGTACTGGAAGAGCGTCAAGCAGCAAAACCTGCCCGTGACAATCAAATAC
CCCGAGATGGTGGCCCAAATCTTCCCACACTTTGAGGGCGATAAACTGCCTGATTTTGGAAAAAACAATCTC
TGGTTTCTG
223 77 ATGCTGACCAATAATCAGATTGTGCTGGAGCAGGAACTTCTGGGAAGCATATTCAAAAACAATAACCTGATG
(Helicase) CTGAAAGCCCGAGAGAAGATAAAACCGGAGATGTTCCTGTATAGCAAACACATGAACATTTACCTGGGCATC
CTCGACATGGTGGCCAACAAGCTGGAGGTGGACCTGATCACCTTTCTCGAGCACCATAAGAAAAGGGTGGGG
GATATGGATGGCGTAACTTACGTGACCGAGATCTACACCTGCAGCGCGTCCGACATTGGCTTCAATACAAAA
CTTGACATGCTGGTGAACAACTACAAACGGCATCTGTATGTGGAGATGAAGGACAAAATCAACAGTGATATG
AGTCTTGAGGAGATCGAGAGCGAGGTTGAAGGGGTGAAGGTAAAGGTGCACAAATGCAACATCAAGAAAGAA
CTGGATATAGACAAGCAATATGACGATTACATCAACTGGCTTTACGACGAAAACAGAGACAAGGGGATGAAA
AGCGGCCTGACCTATCTGGACAAGTATCTCGGCAACTTCCAGAAGGGCAGGCTCGTCACCGTGTTCGCCAGG
AGCGGCGTCGGCAAGACCACGTTCAGCTTGCAGCTGGCCGCCAATATGGCTCTGAAGGGCCACAAGATATTC
TACGGGAGCGCAGAGATGACCCGCAACCAGGTCTTTAACAGGATCGTGGCCTCAGGTTTGAGCCTTAGCGCG
AAGGCGATTGATGAGGACACCATCCTGAAGGAGGACAAGGAGAGCATCGCCAAGTTTATGACCAAGGTTATC
AACAACAAGTTCTACGTGTCAACCGAGACCGACTTCGAAAAGTTCATCGACGAGATAAAGGTTTATAAGCTG
CAGAACAGTCTGGACGTGGTGTTCGTGGACTACATTAACAAGTACATCGACTTCACCGACAGGGACATGTTG
ACCAACAAACTGGGGAAGATCAGCGGCATGCTCAAGAGCCTGGCCATGGAAGAGGATATCTGCGTGGTGCTG
ATGGCCCAGGCCAATAGAGTGATTGACAAGAAGGTGGGTGACAATGCCGTCGAAAAAATCGACAGCAGCGAC
ATCCAGGACAGCGCCAGAATCGAGCAAGACAGCGACCAAGTGATCGGCCTGTACCGGAACGTGAAGCTCGAT
GATAAAATGTATAGGGAGAACCTGTTCAATCAGGGCAAGCTCAAGTATAATTCCAAGAACGCCGACGACAAT
CCGGAATGCATGAACGCTGTGATCATTAAGAACAGGCATGGCGACCGAGGCACGTGTGCACTGAGGTGGCAC
GGCAGGTACAGCAGGGTCAGCGACTTC
224 66 CTTCACCTTAACTACCTCCCATTGCGCTTTACCGCCGATATATTCAAGGGTGGTGCTTTGACATTTCCCGAA
GGCAGCGAGAAAAACTGGACCAGCGACGATCCAATCAGCAAGGAGCTGAGCAAGTTGCGAGAGAAACACGGA
GATAGTCATGTCTTCCACCGGATGGGAAACAAAATTGCATGTATCCCCGTTGTGGAGAACGCCATTGCTATA
GGCACCGAGACGGATTTCAACATCATTAGTGACTTTCAGCTGGCTAATGCTCTTGCTCGCAGCGCCCTCCAC
AGGTACTTCAAAGCTGCGGGAAGGGAGACTGTAATTGGGTTCCGACCCGTAACCCTTCTCTTGGAAAAACAC
AACTTGGCCAGCAACAGGAAGGACGTGTTCGGCATTTTCCCCGAGTACACTCTGGACGTCAGGCCTCTTGCA
CCACATGAGGGCGACATAGCGAGCGGAGTGCTTATCGGCTTTGGAATAAAGTATGTTTTCCTTCAGAACGTA
GCCGAGCTGCAGGCACAAGGGGTGAGTGCCGCAGGGATGTACGCCGTGAGGCTGGTAGACGAGAGCGAACAT
CAATTTGACCGGGCCTACCTGGGAAGGATTGATCGGTTCACAAAAGATAACGTGACGCTCGTTGACAGCGAT
TACGCGGAATATCCCGCCGACCAGTGTTACTTCGAGGGAAGCAGGACCAACATCGAAGCCGTGGGCCGAAGT
CTCCTGGGGAAAGACTATGATGCCTTCAGCTCAAGCCTTTTGCAGGAGAGCTACAAAGTGACCGGAGCCCCC
AACCAAACCCAACGACTGCACCAGTTGGGCGCGTGGCTCGAGGCCAAGAGTCCGATCCCCTGCGCCGTTGGT
CTGGGAGTACGGATTGCAAAAAAGCCGCATGAGTGCTCACGAGGCAACGACGCCGGGTACAGCCGCTTTTTC
GACAGCCCCAAGTGCGTGCTGCGGCCTGGCGGCTCTCTGACCGTGCCCTGGCCGGTCGACAAGCAGATAGAT
CTCAATGGCCCTTACGACGCTGAGAGCTTTCCCAACAAGAGGGTACGAATTGCCGTCATCTGCCCTCAGGAA
TTCACCGGGGATGCGGAAGAGTTCCTCCGGAAGTTGAAGGAGGGCCTTCCTAACGCACCGGACGGCAGTCCG
TTTCGCAAGGGCTTTGTTCGAAAGTACCATTTGTCTAGCTGTGACTTCACGTTCCATGAGGTTAAGCGGAGC
TCAAACAGTGACGACATCTACAAGGATGCGTCCCTTGAGGCACTGAAGCAGAAGCCAGATATGGCAATCGCC
ATAATCCGGTCCCAATATCGCGGGCTGCCCGATGCTTCTAATCCCTATTACACGACAAAAGCTAGGCTGATG
GCCCAGGGCGTACCAGTTCAACTGCTGAACATAGAGACCATCAGGAGGAAGTCTTTGGACTACATTCTGAAT
AACATCGGTCTTGCGATGTATGCCAAACTTGGAGGAATCCCTTGGACCCTCACCCAGAATAGCGACATGGCG
CACGAGATCATCGTCGGGATAGGGTCAGCCCGGCTCAATGAGAGCAGGAGGGGTGCTGGCGAGAGGGTCATC
GGGATCACGACCGTGTTCAGTGGTGACGGACAGTACCTCCTCGCCAACAACACCCAGGAAGTTCCCAGCGAA
GAGTACGTAGACGCATTGACTCAGTCTCTTAGCGAGACAGTATCAGAGCTTAGGAGCCGGTTCGGTTGGCGC
CCTAAAGATCGAGTGAGGTTCATATTCCACCAGAAGTTTAAGAAGTACAAAGACGCAGAGGCGGAGGCGGTT
GATAGGTTTGCACGCTCACTGAAAGATTTTGACGTGCAATACGCCTTCGTGCATGTGTCTGATTCTCATAAC
TGGATGCTGCTGGACCCAGCTAGTCGGGGGGTGAAATTCGGCGATACGATGAAGGGCGTCGCCGTCCCTCAG
CGGGGACAATGTGTGCCCCTGGGGCCAAACGCTGCGCTGCTTACTTTGAGCGGTCCGTTCCAGGTAAAGACC
CCACTGCAAGGCTGTCCGCACCCCGTGCTGGTGTCAATTCATGAGAAGAGCACTTTTAAGTCTGTTGATTAC
ATAGCCCGCCAAATCTTCAATCTCAGCTTCATCAGTTGGAGGGGCTTTAACCCTAGCACCCTCCCAGTGTCC
ATTTCCTACTCCGACATGATCGTAGACCTCTTGGGACATCTTAGACGCGTTAAGAATTGGAATCCGGAAACC
CTGTCTACCGCTCTTAAGGAACGAAGGTGGTTTCTG
225 15 ATGCAACTGAACTATTTCCCCATCCAGTTTGACTTTTCTGACTACCAGGTCATCACGCAGCCCTACTCCGAC
GAGAGATTGAAAGAACTCAGGCAGGCCTACAACGCCAGCTATTCCTTCTTTCGGGACGGCAACCTTATCGTA
ATTTCCAATAAAGAGGACGAGGAAAACCAATTGACGGGCAACGTCGAAAACCGCAGCGTGTTCGACGATGCC
AAAGTTACCGCCAGCATGGTCAAGCATATATTCTTTAGGACGTTCAAGGACAGGTTCCAAGGCTTCATCCCC
GTGGACTTTTACCCCTTCCGATTCTACAGCAGACAAGAGAAGGACGACCTTATTCTGAACCACCTGCCCGAA
AAACTTAAGCATAAAATCGCCTTTAAGAAACTGATCGAGGTGCAGCTCAGGGAGACGAATCTTAATTCAACC
CAGGGCTTTGCTTTCGTCGTCAACATCAGGAGAAATTGGGTGTTTAACATTTCCTGTCTCGAGCTTTATCAG
GAAGGCTTTGACCTCACAGATTTTGAAGTGCTCCATGCGGAGACGCTTCCCGGGTTGGACAATATCCTGGCC
CCGAACGAGGACTTCGTTGGCCTTCTCAAGAGCATCAACGGCGAGACTGCCATTGTGAGCACTAGCGAGGGT
GCCCGCTCCTATTCACTGCAGGAGCTCTTCATTCGCAAGACTAAGCACAACATACAGGCGTACCTCAACTTC
GCCACCGGGGAAAAAAAGTGCGACCAGATCCTTGCAGCCGTGTCCCAGGAACGAATCCGGAAGCAGAACCCC
GTGAATCAATTCAGCGAGATATCCAACATCGCGAAGCATCTTTTTTCAGACAAAGGCAATCCAGTGCTGTTC
CAGAATATGGATGGCTTTTGTTTTAAAGTTGACACCACGCCGATGCAGGTACAAAACTCCATGAACCTGCAA
ACTCCCACGTTCATCTACGACCACGCGGGTACCAAGACGAACACCCGCAACGCGGACCAGGGGCTGAGCTAC
TACGGCCCCTACGATAGCCTCACCTTCGACATTAAGAAGCCAAGAGTTCTCTCTATCTGCCATAAGACCAAC
CGAGGCTCCTTTACGCGCTTCCTCCACGACCTCAAAGACGGGCTCCCCAATAGCAGCTGGTTCAAGAAGGGC
CTCCTGAAGAAGTACGAGCTTCAAGAGGTGAATTACCTCATCCAGGAGATCAGCGACTACAGGTTGGAGGAC
TACCTGGAAGTGATCTCAAACTACGATGATGAGAAGCCGCACCTGGCAATCATCGAAATTCCAGATAGGTTC
AAAAAACTGTCCGACCGGGACAACCCCTATTTCAAGATTAAGGCAAAGCTGCTGAGCCTTGAGATTCCCGTA
CAATTTGTGCGCAGCACGACTTTGAGCAGCTACAGCGAATACATACTTAATCCGCTTGCATTGCAAATCTAT
GCGAAACTCGGCGGCACGCCTTGGGTTCTTCCGGCCCAACGCTCCGTTGACCGCGAAATCGTTATTGGCATA
GGTCACTCATGGCTTCGGAGTGGCATGTATAAGGGTGCTGAAAACAGCAGGGTGGTCGGCATTACTACGTTT
ATGTCTAGCGATGGCCAATACCTCCTGGGCGACAAGGTGAAAGACGTGCCTTACGAGTCTTACTTCGAGGAG
TTGCTGAAGAGTCTCAAAAGTAGCATAAGCAGACTCTCCGATGAGTATGCCTGGCAGGATGGCGACACAGTG
CGCCTCATTTTCCACATCTTCAAACCCATCAAGAACGTTGAGTTCGATGTCATTAGCCAGCTTGTGAAGGAC
ATCAGCCAGTTCAACATAAAGTTCGCGTTTGTGACCATTAGCAAGTCACACCCGTCTATTCTCTTTGACACG
AGTCAGCAAGGCGAGAAAAAGTACGGCTCTAACCAGGTGATAGGGCAGTACATCCCTCAGAGGGGTAGCAAT
ATCTTCATAGATGACGAAACCAGCCTGGTGCAGATGCTGGGCGCCAGGGAACTTAAAACTGCCAAACACGGG
ATGAGCACCCCAATCCAAATCAAACTTAGGACACCGCAGGGTAACCATAACGACCAAGAACTGAAGGATTTG
ATGTTTTACGATCTTAACTACATTACCCAGCAGATCTATAGTTTTACTTACTTGAGCTGGAGGAGCTTTTTG
CCACGCGAGGAACCGGCCACAATGCTCTACTCCAACTTGATATCCCGACTTCTTGGGAAGATGAGGAGCATC
CCTGAATGGGATGCGGATAAGCTCAATTATACCCTTAAAAGGAAGAAATGGTTCCTG
226 22 ATGTTGGAGACGAATATCAGGGTGGTGCGGCCTGGTCCGCAGCTGTGCGTTCCTGTACGCAGGGTGATCGTG
TCCGGTCAAACCTTGGCTCCCGACCTCCTGGAGAGGCTGTGTAACCTGCTGCGAAGGAGGTACGGCATTAGC
GCCGCAAGAATACCGGGCTCCGTGAGCGAGCTGTTCGTTGCGACCGACCGGCAGGTGGAGAAGGTGACACTG
GAAGAAGATAACTGGCAACTGACCGCCGTGGACTCCAACGACCCTACTCGAATCATGTCCATCTCTAACACG
GACGATGAGAGCTTTATAAGCATCCTGATCGAACGCGCGCTCCTTGCCCAGATCGCCAGTCGAAGCCTCTTT
TGGACCCTCGACTCTCCTCGAATTTGGTATGAGAAGAACCCGTTCCAAAGGAATGAAGGCGTAGCCGTCTAC
CACAGGTACGAGGTGGATGCGCTCCCCCTCGGCGACGCAGGCATTGGCATCTCAGTGGATGTTTCAACGGCC
TTTTTTAGCGAGCACACCCTGGAGTACTACTTCGCCCCCAACCTGATTAGCGGCGAGAGCAAGACGCGACAG
GACGAATTCCACAAGTTCACCGGCCGACAAGCTGGTCAAAAGGGGACGCTGCTTTACAATAACGGCAGGAGT
AAGGTGAAGTGCTATTTCGAGAACAATAGGGTGGGCCTGACATGTGGCGCAACCGGCCAAATGAAACTCGAG
GGAATCACGTATCCCAGCCTGTACCACTACTATGCGAGCAAGTATAGCGCATTGCAGATCAACGAGAACGAT
GCCGCAGTGCAAGTGTCTTTCCCTGGCTTGGACCGCCCAGTTCCGGTAGCCGCCAGGCTCCTGTCCCTCCGA
GTGATGAACGACGACGTGCCCGATGGTCTGAGCTCCGTCGACAAGATCCCTCCAAGGAACCGCAAGTACCTT
ATCGAGCAGTTTTGGAAGTGCCTGGAGCCGAGACCCTTCGGGAATGTGGCCCCTGGTGTCTTCGACGGCTTC
TGGAGACCCAACAACGAAAGGGTGCATTACATCCAGCTGCCCGAGATTAACTTTGGACAAGGCCAAAAAGCA
GAACCGCCTGACGTACGCTCCGTTGCATCCATCAAAAACTATTTTAGGCGACGACTGGAATTGCTGGGTCAC
GCGGGGTGTTACCACTTTCCGCCCTCAGCCCCCAGGACAATCTTCTGCGCCTACCCGCAGTCATTGGGTGAG
GAGATCCCGGAAAAGTTGGTGAACGGGATCGTCAATGTGCTGAACAAGTGGACCGGCCTCAGCTTCTGTAGC
AACCTGGTAAGCTACAGCACGGCCAGCGAGGCGTACGGTAAATTGAGGAGGGCCGAGAGTGCCGGCGTGGTC
CTGTTCATCTTGGACGAGGAGCCGGCAGTCTACTACGACGCGAGCTTCAATCTTGAGGGCTGGAGGGTAAAG
CGCGTAACCGAGCCTGTGCTGCGCCAGCAGCATAAGTATCTGACCAACGGCGTGTGGGACCGGAAGAGGCAA
GAGTATAGTTTGGGGAGGGGGCAGAGTCGCTGGGAAAGCTTCATCAATTTGATCGGATTGGACGTTATCCAG
CAACTCGATGCCATTCCGTATAGGATCCCCAACATCGGCCCCTACGAAGGCCAGCTGATAATCGACGTGGGG
CATGACAGGCAATTCTTCGCCGTGTCACTGCTTATTGTGAGATCAGAAGACAAAGTGCCCGCATTTAACATC
AGCAGCCAGGTCCAGCACAAGGCGGATCATAAGCACGAAAGCATTAACCCGGTGCTGTTGAAGGACACCATC
ATTAACGTGTTCAAGACCGCCAAACGGAGGACTTTTGATCCTCTGACTAGCCTGTTGATCATGCGGGATGGC
AACGTGCAGGGCAGCGAGATCGGCGGGATAGACAACGCCCTGGTCGAACTTAGGCAACTTGGCATAATCTCC
CCCGATGCGAGGCTGGACATCGTGGGCGTACACAAGGAATCTGTAAGCTCCATCAGGCTCTGGGACGTTGAC
GTAAGGGGGGAGGTAAGCAACCCGATCGAGGGCACCGGTCTGTCAGTCAACTCATCTCTGTACCTGGTGGCG
TGCACAGGTGAGGCCACGCTGACCCAAGGCACCGCAGAGCCCGTGGCCATCGTCGCAAACAACAGGTGCCTG
AGTATTGCCGATGCAGCCCTGAGCGCCTTTCTGGCAGCCCAACTGAACTGGAGCAGCCCGGGAGTCGCCCAG
CGCCTGCCCCTGCCTCTGAAAAGAACAGATGAGGAACTTACCGCTAGGAGCGATCAAGAAATTAGGAGGATA
AGG
227 32 GTGCAGCAGACAGTGGAGCTCACCCTCTACACAGAAAAACATCCCGACACCCACCCAGAGCTCGTTTATGCC
GACGAGTGTCCCGACCTGTGGCAACAGCACAGCGAGCTTACGGGGGACAAATCTCTGTTCTACTCTCTTACG
AACCCGGCAGAATGCAAGGGAACCCAGTACACAGTGCAAATCAACCTGAATAACCAGAAGCAGCGAAGGATC
GCCAAGCACATAATTAGCCAGCAACTGTATAATCACTTCCGCCAGACCCAAATCGCTACCTTCGACAAGATC
GACAATGTGGAGGTGTGGACCAAGAACACCCAACAGCCTACCCAGAATTGCACGGAGTACCTGAGGTTCAGC
CTTATACCCCAATACGCCGTGTTCTCTGACTCATGGGAGCTGGTCGTGTCCTCAAATGGCATATCCACCGTG
TATAACAAGCCTTTGAGCGCACTGGACCTTCAGACCGACCGATTCAAGGTCGTCGTTGGAGGGGAAGTGGTC
AAGTACAAGAACCTGAGCCCCAATCAAAAGCAACAAATAGACGAGGCCTTCCCCAAAATCAATAGGGAACTG
GCCGCTGAACTGCATATTAACGAGAAACGCTTTCTCAATAAAGACAAGTATACGACCACCTACAACCACATT
AACAACTTCGTGCGACAGCACCTTCTCACATCCGAGTTCCAGGCACTGTTTTGTCTGAGCGGCGAGATGTTC
AACGTACCCGAGGAGCGGATCGGCCAAGTGGCGAAGGGGGCGAACCTGTTGCAGTTTAAGGACGGCAAGACC
GGCATTGACCCATTCAGCTGTGTGTTCGGCAGCAAGAGCATGGACGCACTCGGCATCTACCAACCCAGCCTG
AAGCCCCAGGTGAAATTCTTTTTCATCGCCCAGCAAAGCGATATCAACGTGTGCAAAAGCCTGTACGATATT
TTCACGAAGGGATACAAGCCCTACGTGGACACAGCCACTGGCGAGCAGAGGTACGTGTTCCCACCCCTGGCG
ACGTGCATCAAGCAGCCCTTTTCAACCGACCCCAAGGGGAGCATTTACTTCAGCGACCCTCAAAATGCCCTG
AGCGAGATCAAGAGCCAGCTTAACAATAAGCCTCTTGACCCCCAAACGCAGTATGTGAGCATATACGTGTCA
CCCATCCCTCGCGACGCCGTCAACAATCCCTACTACGGTCTGTACTTTCAGATTAAGGAGCTGCTGCTCGAA
AAGAGGATAACGTCTCAGGTGATCTATAAGGACCGCCCCAACAACCAGTACTTCAACTTCCATCTGCCCAAT
ATCGCGACTGCCATCCTGGCAAAAATAGGCGGCATCCCGTGGCAGTTGAACTCCCACACGACGAACAAAGAT
CTGGTGATAGGCGTGGGCGCCTTCCTTAGCGAAAAAGTTGGCGAGAGGTATGTGGGCAGCGCGTTCAGCTTT
AACCCCAACGGCCTGTTTAAGAACTTCGACTGCTGTAAAGCGAACGATCTCGAATCTATCGTAGCCGGGATC
AGAAAGGCCATCGGACACTTCGTTGTGGACAGCGAAACAAACCCCCAGAGGCTGATCATCCACTACTACAAG
ACCATGTCAAAGAGGGAGGCCAGGCCCATCACGCAGATGCTGAACACGCTTGGCCTCAACATTCCTGTATTG
ATCGTCACAATAAACAAGACGGAGACCAGCGACATTGTTATGTTTGATGAGAAACAGCAGGGCTACATGCCC
CTTTCAGGCACCGTACTGAAGATAAGGAACGATGATTTCCTGCTCTACAACAATAGCAGGTACAAAGAGAAC
GAAAAGTCAGATATGCTTTTTCCAGTGAGGATCCGCCTGAGTAAGATCGTAAACCAATCCGACAAAGACATC
CCAATGACAGACGCCTTCAATTTGCTCAACCAAGTGTACCAGTTCTCACGCATGTATTGGAAGAGCGTTAAG
CAGCAAAACCTGCCGATCACGATAAAGTATCCAGAGATGGTGGCCGAGATAGTGCCACACTTTTCAGAAGCC
GAATTGCCGCAGTTCGGAAAGAATAATCTGTGGTTTCTG
228 91 GACCTGTTCCTGGGCGCTGGCGCCTCCATATCTAGCGGTATCCCTTCCGGAGGCGACCTCGTCTGGCATTTT
AAGCGCGAAATACTGAATTCCAACGGGAAGATAAATATTAAAAAATTTCAAGATCTTAAGATAGAAGATAAT
AAGAAGGTTATACAAAGTTTCTTTGAGGAGACTGAGGAGAACAACATTATTAATCCTTATTCCTATTATTTT
AACAAATGTTATCCAGACCCCTTGATAAGAAAAGAATTCTTGACGAATCTTGTGAGGGACAAGAAGCCTTCC
ATAGGATTTATGTGCCTGTCTGCTCTCGTGGAGCAGCAAAAAATCAACACAGTATGGACAACTAACTTCGAT
GACTTGATTGAGAAGGCGATTAACGGATTGAATTACAAGTCCTGTCAAATTGTCTCACCCGAGAATGCGGGC
AGCGTGAATAACTTTCGAACTGATATCCCCACTGTTGTTAAGCTTCACGGAGATTTTAGGTATGACCCACTG
CAGAATACTGACGAAGAGTTGCAGAAACTCGAAGAGTCCTTGCATAAGTATTTCGTAGAGGCAAGCACAAAG
AGGGGACTTCTCGTAATGGGCTATTCTGGGTCAGATGAGTCTGTGCTGCAAAGCCTTGAGAAGGCGCTGGAA
GAGAACAACGCGTTCCCTAAGGGACTCATTTGGTGCATCCCCAAAAGTGTCACCCCAAACCAACGACTGGTC
CGAATTATATCTAAGGCTAATGAGCAGAACCAGCGGTCCGGATTTATGATTATCGACAGTTTCGATTATTTC
TTGCATGAACTCTACAAAATATGCGACCTTACGAATGACTATATCGACTCTATTACCAAGGAGAGATTTGAA
AAAAGGCAGTCATTTAGGCTTAACCAAACTCCGTCCTCTACTCTGCCAATCTTGCTGAACGCAATAAAAGCA
AAGCACTTCCCGAAAAGTACCTTTCTGACTAAAACGAATATCTCAGGCATAGGTAAGTGGAAACGCTTGCGA
GACGCTATAGGAAATAGCTCTATAGTCGGATCTTTCGGTAAGAACGATTCTCTCAGACTTTTTGGAAGTGAA
CAAGACATTAATAATGTACTTAAGAACTACTTGATTGATGATTTGAAGATCAGTGATATCCCAGAGCACCTT
TTTTTCCATTCTGATTCATTCTACATTGGCATGCTTTATGAACTGATTGAAAAGTGTTTGATTAAAGATTAT
GGGCTGTCAGTATATGCAAAGGGGAGAACTATCAGAAAGTTCTATTCAATCAATAACCCGCTGCCGGAATCT
GAAATCGCAGATATTAAGAAGAGAAACAATAATTTTAACATCGACAAAAATATAAATGTATTTGAGGCGTTC
GAGTTCTCCATAGAATTCATTAATAAGGAGCTGTTCCTGTTGCTGTGTCCCACCATACATATTCAGACTAAA
CTCGGAGGTGAGGTCAATCGCAATATCTCTCAGTACCTGTCAAACACAATCATCAGCAATAGGTATAATAAC
AAATATGGGAAAAAGCTGAATTGGTGGATTAACGAGCTCAAGAAGTATAACAAGGACTTGGTTTTTAAATTG
GGGGACTTTGAGATACGATTGACAGATTATTACTCCACGAGCGCTAAGCGCGTTAAAGATGACATCTACTGT
TTTGACGGATTTACTAAGTTGAGTGAGCCCAGTATATATTTCCACTATCAAGACGAAGCAAAGCAGAGTATC
CATCCCATAAGTGGACTGAAGATACTCGGTCCATTGGAAGAATCATTCGAGGCAAACGGTACATCTTCCACA
GTCAACCTTGCCATCATTACTCCGGACTTTGGCTTCTCCAAACTCAAGGCGCACCTCGAAAGTTTGCTTAAT
ACAATTTCCCCTATATGGGAGAAGGAATACTTGAAGGAGTTCCCTGGTTTCGATAACGTTTTTAAGAAGCAC
CTGATAATACCCAATTCTATTCAAAGCGAGTATGTAATCAGCATACCTAATAATGATGTAAAACAGTTCTCA
GCAATTCAATTCTACGACTACCTGAAGAGTAAGATCGACCGACTCGCTCTGAAGTCCAATGACATTGATTGT
CTTGTAATATACATACCCGACCAGTGGAAGAACTTCCGAGAGCTGAAAAATGAAAACACATATTATGACCTT
CACGACAGTCTTAAACTCTACTGCGTAAAAAAGGGGTTGCGAATCCAGTTCATCGAAGATAAAAGCATTAAT
TATAAAGACCAAGCCAAGATCCGGTGGTGGCTGTCTCTGGGGCTCTACGTGAAGTCTAACGGCACTCCCTGG
AAGATCAAAACAGATAATACAGAGACTGCCTTTGTGGGCCTCGGTTACGCTATACGACAAAATGTTAAGAAT
AAGGTTGTTCTCGGGTCTTCACAGATTTTCGACGGTTATGGGAATGGTCTCAAGTTTCTTTTGCAGCCCATA
GAGAAGCCAATTTTTTACAATAAAAACCCCTTCATGAGCAAAGAGGACTCTTTTCGGCTTATCAGTAATATA
CGAAACACATATCATAAGATCGATCCAGTTATCGGACTTAAGAAACTCGTGTTGCATAAGACAACTCATTTT
ACTTCAGAGGAGATGGAGGGGATCTCTAATGCTTTGGAAGGCATAGACAATATTGAACTCTTGCAGATTCAG
CAATTCTCATCATGGAGGGCAATTAAGCTTATGAAAAATGCCACAAAGCACGATTTTAATGGTTATCCGATC
GATCGCGGAACTATAATTCAACTCGACGACTTCTCTTTCCTTCTGTGGACACACGGGCTTATAGAGAACCAA
GAGCTGAACGGTAAGTACTACCAGGGAAAAAGAGGAATACCGGCTCCGCTTCTTATTAAGAGATTTAGAGGC
ACGGATCCAATAGAGACGGTGGCAAACGATATTCTTAAGCTGACCAAGATGAATTGGAATGGTGCAGAGCTC
TATAAAACCTTTCCTGTAACTGATTTCAGTAAAAAACTTTCAGTCATGGGGAAG
229 0 ATGCCTTCAGCTCAACGGTGCATCTGGGAGTGGAAGAGGGATATCTTCGTGACCAAGAATCCGACGCTCCGG
GAGTCCGTGGATGAACTTAGCTTGCCAGGGACCAGGCGCATCGTACAGGGATGGATCGACCAGCAAGCCCAA
TACCCGGAAGATGGGTCAGCAGACGAATATAGCTTTTATGCCGAAGAGTGCTACCCAACCTCTCATGACCGG
CGAGCGTTCTTCCATCGCTTCATTGCCGAGGCGAGACCGCATATCGGCTACAAGCTGGTTGCGCAGTTGGCA
GAAGCAGGGTTCTTGAGAACCATTTGGACGACCAACTTTGACGGACTGGTTAGCAGAGCGTGCACAGCGGCT
AACGTCGTGTGCGTGGAAGTGGGCATGGACACACCCCACAGGGCCTCACGACCGCAAGGGGATGACGAAGTC
AGACTGGTGTCCCTCCACGGTGACTTTAGGTATGACCTGCTGAAGAACACCGCCAATGAGCTGCGCGAGCAG
GATTTGGCCCTTAGGGAGGAACTGCTGCACGAACTCAAAGACTACGACCTGGTGGTCATCGGATATTCAGGG
CGGGACGACAGCCTTATGCAAGTGCTCTCTGCTGCCTACAGCGACCGCGCATCTTGTAGGCTCTACTGGTGC
GGGTTTGGCGCGGAACCAGCACCGGAAGTGAGGCACCTTATTAAGAGCATCGACCCAGCCCGAGAGAGCGCG
TTCTACGTGGATACCGCCGGATTTGACGACGTAATGAGCAGGCTTGCACTCAGGCGACTGAGCGGTGAAAGC
CTCGAAAGGGCCCAGAAGCTCATAGAAAGCGTCACCCCGGTTGCTGGCAAAAAGATGGCCTTTAGTGTTCCA
CCATTGGCCCCTAGCGCCTTGGTGAAGGGTAATGCCTACCGATTGACCTGTCCGGCAAACGTCTTGAAACTT
GATATCGAACTTCCCGAGCACGGTTCCTGGCGCGATTGGCTGTCCGAACGAATGACTCCAGAAAGGGGGCAG
GCCGTTGTGTTCGAGAAGGGAGCACTGGTTTTGGCCGACATGGCGGTTACCGCTAAAGTTTTCGATGGATTT
CTTAGGGTGAGCCCGACACGGGTGGAGATAAGTGACGAGAACATCATCGCTGACGGCCGGATCGCCAGTCTT
TACCGACGAGCTCTCGTGAGCAGTGCCGCAAAAGCGCTCCAGATCCAAACCGACCACAGGAGGAGGATATGG
GAGCCCGTGCACTATGATACAAGGCAACTCGACGATGTGACGTACCGCGTGCATCGAGCCGTCTCCCTGACG
ATAGTAGGGATAGAGGGAGTGCCCCATGTGGTGCTGATGCCAGAGGTCGTCGCATCTACGTTGGCGGGCGAC
CTTGCGCCGGTTGACAGTCAAAAGACTCTCCGCAATGCCATTTACGGGTTCCAACATAACGATAAGTTTGAT
GCCGACCTCAGCTATTGGACCCACCGCCTTGTTGAGAAGGAGCTGGCTTCCAGCGGCGAGGGCGTTTTCGTA
TTGAGCAAAGTGCCACTTTATGCGGGCCTGGCACAAAAAGGTAAAGCTCCTCTCCCACACAGGTTTGCACGC
CACGCTAAACAGCATGGAATTATTGTGCCCGACGCACCGCTTGTTTTCAGCGCCAAGGTTGGCTCTGGAGAG
GTACGAAACCCCAATCCGCTGCATGGGCTGGTGCAAAACCGGCCATGGGACCACTCTCTTACGGCGTCTGGT
TTGTGTCCGAGTACAGATGCTAGCGTGATCTGCCCCGCAGACGCTGCTCCGAGGTTTGAGAGATTCCTCCAA
TCTATGCAGGAGGTAGCAAGACCAAGCCAGAGCGAGAGGGACTATTTGCATGATTTTCCCGGCTTCCCTGCG
GCCTTTGGACTGCCACTCCGAATGCCCGTGAGAGGGGACGCAAACTGGATTACCATCGACGACGGAGTGAGC
ACCGATGCCCTGACAGGGGCTAAGCAACTGGCGCACCGAGTGTGCCAAGCACTCGACCACCTCCGCAGAGCA
AGGCCCTCTGACACGGCGATCGTGTTCGTTCCCAGGAGATGGGAACCATATAAGGTAGTGGACACGCAGCAC
GAAAGATTCAATTTCCACGATTACATTAAGGCCTACGCGGCCAGGCACAGTCAGAGCACGCAGTTCGTCAGA
GAAGAGACCATCCAAAGCCAATACGTGTGTAGGGTCCGGTGGTGGTTGAGTTTGGCACTGTATGTTAAGGCT
ATGCGGACCCCCTGGCGGCTGGATGCGCTTGATGAGAATACGGCTTTTGTTGGTATAGGGTACTCCCTGGAC
GCAGAGGCAGGGAGGGGCAACCATGTACTGCTCGGCTGCAGCCACCTGTATTCTGCGAGGGGTGAGGGATTG
CAGTTTAGGCTGGGCCGAATCGAGAATCCCGTGGTGCGAGGAAGGAACCCCTTCATGAGCGAGGACGACGCA
AGGAGGACCGGAGACACCATCCGGCAGCTTTTCTACGATAGCAAAATGCATATTCCGACAAGGGTGGTGATA
CACAAGAGGACAAGGTTCACTGACGAGGAGCAGAGGGGGTTGGTACAAGGATTGGACGGTGTGAGGAATATC
GAGCTGATAGAGATCAACCAGGAAGAGAGCTTGCGATATCTCAGCAGCCAGATGAAGGACGGCAGATTTGAG
ATCGACAAGTTCCCCCTGTTCAGGGGTACCACAATAGTTGAGTCAGATGACACTGCATTGCTGTGGGTGCAT
GGAGCCACACCCAGCGCCGTGAACAAGTACTGGAGGTACTACCAGGGGAAGCGCCGCATTCCGGCGCCATTG
AGGATTCGAAGGTTCCTCGGGCAAAGCGACGTAGTGCAGATCGCGACCGAGATCTTGGGACTGTCTAAAATG
AACTGGAATACGCTTGACTACTATTCAAGGATGCCTGCGACTCTGGATTCTGCAGGCAGTATTGCCAAGTTC
GGGTCATATCTTGATGGGTTTACGAGCGCACCCTATGATTACAGACTTCTGATC
230 6 GTTCACGCATTGCTCGCTCTGCTCGCGAACCGAGCCGGTGGAAGGACCGCCAGAATGGGAGACAGCTTGCTC
ACGTGGAGCCCTCCTGAGTCTCTGCTGCTTGAAGGGACCCTGAGCTGGCGCGGCAACACCTACACATACCGG
CTTCGCCCACTGGCGAGAAGGGTGCTCAACCCTAGGAATCCCAGTGAGAGAGACGCCTTGTCCGCGTTGGCG
CGACGACTCCTCCGAGAAGTGCTTGAGCAATTCAGGCGCGAGGGGTTTTGGGTTGAAGGTTGGGCCTTTTAC
AGGAAGGAGCACGCACGGGGTCCCGGGTGGCGCGTGCTGAAAGGTGCGGCGCTGGATCTGTGGGTTTCAGCC
GAGGGGGCCATGGTATTGGAGGTGGATCCGACTTATCGAATCCTGTGTGACATGACACTCGAGGCGTGGCTT
GCACAGGGACATCCACCCCCGAAACGCGTCAAGAACGCGTACAACGACAGGACATGGGAACTCCTGGGTCTG
GGTGAGGAGGACCCGCAAGGCATTCTTTTGCCAGGCGGGCTGAACCTCGTCGAGTACCACGCTAGTAAGGGC
AGAATCAGAGACGGCGGGTGGGGTCGGGTTGCGTGGGTGGCAAATCCTAAAGACGCCAAAGAGAAGATCCCG
CATTTGACGAGCTTGTTGATCCCCGTCTTGACCCTGGAAGACCTGCATGAAGAGGGGGGCTCTAACTTGGCC
CTCTCCATCCCGTGGAATCAAAGGCAAGAGGAAACCCTTAAAGTGGCCCTGTCCGTGGCTCGCCGACTCGGC
GTCGAACACCCCAAGCCCGTCGAGGCCAAAGCCTGGAGGATGAGGATGCCAGAGCTTCGCGCACGACGCAGG
GTGGGTAAGCCAGCGGACGCCCTTAGAGTGGGGCTGTACCGGGCTCAAGAGACTACCCTCGCACTGCTTCGG
CTCGATGGCGGCAGAGGATGGCCTGACTTTCTGCTTAAAGCATTGGAGAACGCTTTTAGGGCCAGCCAGGCT
AGGCTTCATGTTAGGGAAATCCACGCGGATCCTAGCCAGCCCCTTGCATTTAGAGAAGCCTTGGAAGAAGCG
AAAGAAGCAGGTGTGCAGGCTGTCCTCGTACTCACCCCCCCACTGAGTTGGGAGGAGCGACACCGCTTGAAA
GCACTGTTCCTCAAAGAAGGACTCCCAAGTCAACTTCTGAACGTCCCCATACAGAGGGAGGAAAGGCATCGG
TTGGAAAACGCCCTGCTCGGGCTCCTGGCGAAAGCGGGTCTCCAAGTAGTCGCCCTTGAGGGCGCATACCCT
GCTGATTTGACAGTTGGATTTGATGCCGGAGGCCGCAAGTCCTTTAGGTTCGGAGGTGCCGCATGTGCTGTC
GGCTCCGACGGAGGTCACTTGCTGTGGAGTCTGCCGGAAGCCCAAGCGGGCGAACGGATACCAGGCGAAGTA
GTTTGGGACCTGTTGGAGGAGGCGTTGCTGGTGTTTAAGAGAAAAAGAGGGCGGTTGCCCAGCCGGGTGCTT
CTGCTGAGGGATGGCAGGCTTCCCAAGGACGAGTTCACCCTGGCACTTGCAAAGCTGAGGCAGCTCGGCATT
GGCTTCGACCTCGTGTCCGTAAGGAAGAGTGGAGGCGGAAGGATTTATCCGACCCGGGGAAGATTGCTTGAC
GGCCTTCTGGTGCCCGTTGAAGAGAGGACTTTTTTGCTCCTGACGGTGCATAGGGAGTTCAGAGGCACCCCA
CGGCCCCTCAAATTGGTACACGAAGAAGGTGAGACACCTCTGGAGGCTCTCGCAGAGCAGATCTACCACCTG
ACGAGGCTGTATCCTGCATCAGGTTTCGCATTTCCCAGACTGCCCGCACCCCTGCACTTGGCAGATAGGCTC
GTGAAAGAGGTGGGCCGATTGGGCGTGAGGCATCTCAAGGAAGTAGACAGGGAAAAGCTGTTCTTTGTA
231 50 GTGAGGCTGGTAAACCAGAAAGAGAAACCGGAAGGCGACTACGTGTATGGCTACACTCTCCCAATAGACCCC
AGTAACAGGAACATGAGGCAGCCCTTCTGGATAAGCATGGATAAAAAGGAGGGCTATGAAGCTCATTTCGTT
GGCCCCTATGAGAACATTGAGTTGACCAAGAGCGTGATCTTCTGGGACCTTCTGAGGAGGACCAGGGAGCAA
CTCAGCAGCGATAAGTTCACGGAATCAAGAAAAAAGTTCTTTAAGGAGATCTACTTCCCCCTTAACCTCTAC
AATGAGGGCAGCCAAGGGCTCGCCGTGCAACCCTACTACCTGAAGATTGATCAGCAATTTGGACTGCTGGTG
GATTTTCAATTCAAACTTGACAAAGATTTCACCTTCAGCCGGAAGATTCAACAGCTCAGTCTGACATTGGAT
GGGAAGAACCGGAGGAACCTCAACTACTACGTCGACAGGATAACCAAAACCAACCAATTCATCAAGGCCCTC
TGGAACATCATTGGCACCTTCTCCCATAATGAAAACAAGGAAAACTACACGCTGAGGAACGACTTCTACCCC
TGCGCCGCAAGCAGGCTGCGGTCTCGAATGTATCTCTTTTCCAATGGCAGTGAATCCAGGAGCCAGTTCAAT
GGCTTGAAGGAATACGGCCCACTCCGACCCCTGACAGCCAATCCGACACTGCTGTTTGTGTTCCGGGAACAA
GACCGCGACGCCGCGAGAAAACTGGCGATGGCACTTAAAGGCAGCAAAAAGCAAGATCAATACAGCTTCCCC
GGGTTCAACTCCCTGTTTAAAGCGGACCTGTTGATCGACGGAAATCCCATGGTCTTGAAAGACTTTTCTATC
GAGAGCAGCAGGGAGGTGTTGGCCAGGGTGACAACATCAACATCCAGCTTGTTGCCCATTTTCATCCTGCCC
AACCGCGAGGGCGACGGCTACCTGGAGCACAAAGCCATCTTCGCCGAGAACGGCATACCTACTCAAGCGTGC
ACACTCCAAGTCATTCAGGACGACGTGACCCTTAGGTGGAGCGTCCCCAACATCGCCCTGCAAATATTCTGC
AAAGCGGGTGGCTGGCCCTGGAAAGTGCAGAGCCCCGTAACCGACAACGCCCTGATTATAGGCATAAGTCAG
AGCCACAAGTTGAATTATAGTGACGGTAAGACAACTGTGGACAAGCACTTCGCTTTTAGCGTGCTGACTGAT
TCAAGCGGCCTCTTTCAGAAAATTCAGGTGCTGAGCGAGCAGAAGACGGAGGAGACCTACTTCGAACAACTG
AAGCTGAATCTCAAAAGCATCCTGAACGCCAATAGCAAGAACTACCAACGCATCGTGATCCACACCTCATTT
AAGCTCAAATACAAAGAAATAAGTGCAATCGAGGAAGTTGTTAGCGAATTTGCAAGGAACAGCAACAGCGCC
GACTGCAAGTTCGCCGTTGTGAAGGTTAATCACAAGCATAGGTACTTCGGGTTTAATCGGGAAGTGAATAGC
TTGGTGCCCTACGAGGGAACCGTGTGTAAGCTGGGCGATAGAGAGTACCTGGTCTGGTTCGAGGGTATCTAT
CAGGAGAAGCCGACCGTTACCAAAGCATTTCCGGGTCCCACCCACATCGAATTTCTTAAAATCGGGTCTAAT
AACGTGATTAGCGACGACCTTTTGTTGCAAGACCTGATGAACTTGAGCGGAGCGAACTGGAGAGGCTTTAAT
GCGAAGAGTGCTCCGGTATCCATCTTTTACTGCCACCTGGTGGCCGACATCGTGCATGATTTCCAAATCAAA
GGCCTCCCTATGCCCGCCATAGATCTTATACGACCCTGGTTCATC
232 11 ATGCAAGAACACCTGAAGACGAACATACTGAACTTTAAATGGCCCAACTCTGCTCCGACCATCTACCTGACA
TTGGAGGACATTGAGGGGAGCCACCCTATCCACAAAAGCAAATTTTCTAGACAGATAAAAGAAGTGTTCCCC
GACGCGGATTTGAGTAACAAGGACCAGATCTTTACGACATTCACGACCGAAATCCCAGACGCCCCAAGCATA
AAACTGAACCTTGTGGACGGCCGAGAATTGCGGATCTATAAACAGTTCCTCAAGCACAAGCTGCGGTCATAT
TTCAAATCTAAGGACTACATCGTGGTCAAGAATTTCGTGGGCGACGTTCAAGTGTGGATGCCGAGCAAAAAG
GGTAACACCGCAGATTACAACCTGTACTATAAGTTTAGCTTTAAGATCCAATTTGCCAAACTGACGGACCTC
CCCGAGCTGATCGTAAGCTACGATGGCACCTCCAAGGTGCTCACGACGTCCGTTAAGGACATCGAAGATTCA
GAGCTCATCAAGCGATGCGTCTACGGCCAAAAGACGTTTAACTACCAAATGGACTTGGACACCGAAGAGAAG
CAAGAGTTTTACAACGCGATACAGTTTGACCAGGCCTACCCAATTTTCAACCTTTCCCTGGCAAGGGCACTC
GACATCCCCATAGAGGAGCCAATAAGGCCGATCAACAAATACCAAAAATACGTAGCCCTGATTAACAATTTC
GCAACTAATTACCTTTTCAAGGAGGACTTCAAGGTTATCTTCCCGTTTAAAACAGACACGTTCATCGACGTG
CCTATAAATCGGATAAATCACATCGACCCCCAAGTCGGCCTGTTGGAATTCGGAAAAGATCAATATGGCAAC
AAGAAAACCCACCTGGTACCTAAAAAGGCAATGAACATCTTGAATCCATACCGGCGACCTAATAATCAGAAC
ATCAAAATCTTTTTCATCTGTCACACAAGCCACAAAGACTCCGTGCTCAGCTTCTATCAGAATCTGAAGGAA
GGAGTAAACACGGAGAAGAACTACTACAAAGGACTTGAAGCCTACGTGAACATTAAGGCAAGTAGTAGCAAG
GAGCATTTTATCGAGTTCACGAACGAGAATGACCCCATCCCGGAGATCGTGGAGAAGCTTGAGAGCCTCACA
TTTGATCATGACAATGTTCTCTACGCGGCGTTCTATCTCTCCCCCTTCGACAAATTCACCCAGAATCCGGAG
GACCGGGAAATTTACATCCAAATAAAGGAGTTGTTCCTGAACGAAGGTATCGTGACCCAAGTTGTCGATTAC
GAGAAAATGGTCGTCAATATCGAGAATCAGTATAACTTCCAGTTCAGCCTGCAAAACATGGCCCTCGCCATT
CATGCTAAGCTGGGCGGTGCCCCGTGGAAGCTGGCCGTGACCGACAAGAAGGAATTGGTCATCGGGGTTGGA
GCGTTTACAAATCAAGGCGAGAACAGACGCTATATTGCTTCCGCCTTCTCCTTTCAGAATAACGGCCTCTTC
CGCAAGTTCGAGTACTTCGATCAAAGCGAGACCGACCTCCTGGCTGGCAGTATCTGCAAAGCCATCCGCGAC
TTCACCAGCGTAGCGGAGGCAGATAAGGTCGTTATCCATTTCTATAAGGAGATGAGTTACGAGGAGCTTAAA
CCCATCATTCGGGGCATGCACACGCTTGGGCTGAAGATACCCCTTTACATACTTAACATAAACAAGACTGAA
GCCGAGGATATTATCGCCTACGACCTGAATTGGAACAAAAAGCTGATGCCCGTCAGCGGCACCTACATTCGC
ATCTCCGAAAATCATTTCCTGCTCTTCAATAACGCACGATATCCTAATTCCCAACGGTACGCCGACACGGAT
GGTTACCCGTTTCCCATTAAGATTAAGGTCAGCTCTCCGGACGAGGATGCCTTTGAAGATGCAGATGTGGTC
CTGGAGCTGCTTACTCAGGTTTATCAATTTAGTAGACTGTATTGGAAAAGTCTTCGCCAACAAAATGTACCT
ATCACCATCAAGTACCCAGAGATGGTAGCCCAGATTGCCCCCCATTTCAACAACGGGGTGCCCGACGATGCC
AAGGATGCTCTGTGGTTCCTG
233 48 ATGACTGAGGACTTGTACCTCGACTACGACGCGTTCCTGCGGAGCTTTAAAAGAAACATAGATGTGCCGCAC
TCCTTTCTCCTGGGAGCAGGTACATCCATTAGCAGTGGCATCCAGACCGCCTACGATTGTATCTGGGAGTGG
AAAAAGGACATTTACCTCTCCAAGAACATCAACGCCGCTGAGTTCTATAAGAACCATAAGGACGAGGCGGTA
AGAAAGAGCATCCAAAAGTGGCTGGATAACCAAGGTGAATACCCAGTTCTCGACAGCACGGAGGAGTATTGC
TTTTATGCCGAAAAGGCCTATCCCATCCCCGAGGACCGCCGCAAGTATTTTCTGTCTCTTATCGAAAATAAG
GAGCCCTACATAGGGTATAAGCTCCTCTGTCTGCTGGCCGAGCGCAGCATTGTAAAGGCTGTCTGGACTACT
AATTTCGATGGCTTGACCGTCAGGGCTGCTCATCAGAACAAGTTGACGCCCATTGAGATAACCCTCGATAAC
TCTGATAGAATATTTCGCAACCAGTCTACCAAGGAATTGCTCACAATTGCGCTGCATGGTGACTACAAATTC
TCTACGCTGAAAAATACGGAGAAGGAGCTCGACAACCAGAACGACACATTCAAACAGCAGCTGGGGACGTAT
CACGTGGACAAGAATATGATCGTAATAGGCTACTCAGGGCGCGACAAGAGCCTCATGGACGCCATCAGCGAG
GCCTTCAGTACGCGGGGTGCAGGGAGGCTTTATTGGTGCGGCTATGGCGAGACGATCCCCAACGAGGTTAGC
GAGCTCATACTGAAAATCAGGTCCCAGGGTCGCGATGCATACTACATATCAACGGATGGATTTGACAAAACG
CTGATACACCTGTCTAAAAGTGCGTTCGAAGACAACCCCGAGATTACGAAAAACATCCAACTCGCGCTCGAA
AACAGCGCGGACGAAGAGTACTTTAAGACTGACTTTTCACTGAACTTTAGCAAGCCGGATAAGTTCATCAAG
TCAAACCTCCACCCCATCGTGTTCCCGAAAGAAATCTTTCAATTCGAGCTTGACTTCAAGGAGGACAAGCCT
TGGCAACTCCTCAAAACTATTTCACGCGAGACAAACATTTGCGCCGTGCCGTTCAAGGGTAAGGTGTTCGCA
CTGGGCACGCTTACTGACATTGGGAACGTCTTCAAGAACCGCCTGAAGAGTGATATAAAGCGCGAAGCAATT
AGCACCTCCGACGTGGATAATGTGAGTGCCTTTAAATCTCTGATGCTGCAGGCTGTGCTGAAGTTTTTCATT
GGTATCGAAGGCGTGGAGTCCAACCTCAAAGACAGATTGTGGCTTACCAACGCGGAGCAGCTCGTGGGTGAT
ATTAGTGTGCATAAGGCTATCCACCTCAGCCTGTACTTCGACAAAAACAAAGGATTCGCTTACCTGTCCTTC
ACCCCCACCGTACAACTCATCTCTCCTGAGGAAATCAGCAAAATCCAGAAGCAGAGAATCTCTAAGAGTAAA
CTCGAGAAGCTGTTCAATGACAAGTATGACGAGATATTGGAGTTCTGGAACCAAAAGCTCTTTAACAATAGC
CAAATCAAGTTCGAGTACCCGATCAGCTCAGGTAGTGGGTTTGAGTTCAAAATCTCCGCCAACACCGCATTT
GGGGAGATAAACGTATTGGACCCCAACTTTCGCTCCTTTTCCCCTAGAAATTATGACCCGAAGCGCACACAG
TTTAAGGGCGTGCAGTTCCTCGAACCGCAGCTGATATTCCGCAACATCAGTACTAATGTGGAATTTAAGGAC
TACCACCCGATGAGGGGGCTGGTGAACAACCGACCGTTCGACGTGAACCTGAACGGTATAATTCATTCTAAC
GAAATAAACCTCACGGTCATCTGCGGCAAGTCATACGCCAACGACCTGTATGAATTCCTGAGCAAGCTCCAA
GTGAAGCACGCCACTGAGAATGTCAACCCGGACTATCTTATTGAGTATCCGGGCTTCCAAAGTGTGTTCAAC
CTGCCACTCAACATACCCCACTTTGACTCTTCCGAGAAGTGGTACGACATCGACTTCGTAGCTGACAATAAC
GGGGAGAACCACGAGAATGCCATTAAGCTTGCCAGACTCATCACCACCAAGATCGACCAGATTGCCTCTACA
CAGAACCAGAGCACGGTCGTGGTGTTTATTCCAAATGAATGGCAGTTGTTTGAGGGGTACCTGAATCAGGGG
GAGAGTTTCGATTTGCACGATTACATCAAGGCATTCAGCGCTAGTAGGGGCATTTCAACGCAGCTCATCCGC
GAGGATACACTGGCGGATACGTTGAAGTGCCAGATCTACTGGTGGCTGAGCCTCTCATTTTACGTTAAAAGC
CTGCGAACTCCTTGGATTCTGAATAATCAAGAAAAGAACACGGCCTACGCCGGGATCGGTTATAGCGTGACT
AAAATACAGGACCGGACGGAAACGGTGATCGGCTGTTCCCATATTTACGATTCCAACGGCCAGGGGCTCAAG
TATCGGTTGAGTAAAATTGACGACTACTTCCTTGACAATCGCAATAATCCATTTCTTAGCTATAAGGATGCG
TTCCAATTCGGTGTGTCCATACGGGAATTGTTTTACCAGTCCCTGGACAAATTGCCTGAGCGGGTAGTTATA
CACAAGCGGACCCGATTTACCGATGATGAGATCAATGGTATTAAGGCGTCTCTGAACAAGGCGGGGATTAAG
AAGATTGACCTGGTGGAGATTAACTACGAGACGGACGCCCGCTTCGTGGCCATGTCCGTATACCAGAATGCA
CTGCAGGTAGACCGATTCCCTATCAGTCGGGGTACTTGTATAGTCACAAATAAGTACACTGCCCTTTTGTGG
ACGCACGGGATTGTCCCAAGTGTACGGCAGCCAAACTACAAGTTCTACCTTGGCGGTAGAAGCATACCGGCT
CCGATCAAGATCACAAAGCATTATGGTGATAGTAATATAGACGTTATCGCCACCGAAATCCTTGGGCTGACC
AAAATGAACTGGAACTCCCTTGACCTTTATAGCAAACTTCCCTCTACGATCGACTCCAGCAATCAGATCGCT
CGGATTGGCAAACTGCTCTCCCGGTACGAAGGCAAGACGTACGACTATCGATTGTTTATC
234 31 ATGGAAAATCTGACCCTGAATATCATCCCTTTCAGCCACCCCGTGCAGGAGCTTGAGATCGGCTTCTATAAG
CAAGAGAAACAGGGATGCTACAGCCTGTGGAAGGGCGAGTACCCGCAGTCATTCTGGGACGACTTCAACGAG
GAAATGCAAAATTGCGACAAACTCTACACCAACTTCATTGACACGGAAAACTGTGATTACAAAGCCAGTGTG
GACTTTAGCAAAAACAGACGCCTGGCGGTCCATTACTACAGCAGGCTGATCTACAACTACTTTGAAACAGTG
GCAGATGCCGTGAAAATCAACTTCGTGAAAGATATCCAGATATGGTTCAAGGACGAGACCAAGAGCACCGCC
GTCTATACCAGTTACAAGCGGTTCACGATCAAGGTCCAGTTCCATAAGGTGACCGAGTCCCCAGAGCTGTTG
ATCAGCTTCGATGGCAATACCACGGCCTATAACAAAAGTCTGGCCGAGTTGGACGATTTCCCTCCCGAGCTG
ATTAACTACGTTAAGTACAATACCCAAGTGGTGAAGTACGAGTTCGCCGAGGACGCTATTAAGCAGCATATC
GAGGAGCTGTACCCGATCCTGAGCAACCCCATCAGGGACTACCTTAAGATTGCCAGGCCCGATTTTAAGAGG
GGCAACAAGTATAAGCCCTACTACAAGAACATTACAGACTTCTATCACAACCACCTGAACTCCAAAGAGTTT
AAAGCTATCCTGCCTATCTCCGAAGACGGTTTCTACAAAATGCCTAAGCACAAGGTTCACAAAACCAGCTTC
AATAGCAATAAACTGAGATTTTTCAATAACACGGACATCGTGCCCCACAACGGGATGAAAAACATCGGCCCC
TATAAGGCGTCCCCCCACCCCAACGTGAGGTTCTTCTTCATCTACCATAAGCCAGACCGAAACTTCGCCGTC
AAGACGCTGTACGAATACTTTACGGAAGGGTACAAGAGCCCAGAGGGCTACCTTTACTTCAAGCCTCTCAAA
ACCTACATTAAACAGCCCTTTCTCATCGACAAGGATACCAGCATCGCGTTCGAAAGCCCGGAAAGCGCTCTG
CGCGAAGTCAAGCAGGGTTTGCTTAACCTGGAAAAGCAGCCCAATACGAAATACGTCGCTATCTATGTGACC
CCCATACATAAGACCGAGACCGACGAGCAGAGGAAGATGCTTTATTACCAGGTCAAGGAAGAATTGCTCAAG
CACGACATATCAAGCCAGGTGATATACAAGGACAACATTGGACATAAGGATTTTAGTTTCTATCTGCCCAAC
ATCGCCATCGCCCTGCTGGCCAAGATCGATGGAATCCCCTGGAGGCTGGACAGAGACACTAAGGAGGAACTT
ATCGTGGGCGTAGGCGCATTCACAAGCCTGAACCACAATATCAAATATGTAGCTAGCGCCTTCTGCTTTAAC
AACAATGGGGAATTCAAGGGATTCGACTGCTTCAAAGCGAATGAAACCGAACTTTTGGCTGGCACCATCGGC
AAGCAAATCCTGAAGTATGTGGTGGACAACGGCGAGAGCGCCAAGCGCCTGATAATCCACTTTTACAAAAAG
ATCAGTAACAAGGAACTCGAGCCCATAAAGAAAATGCTGAACAAGCTGAACCTGACCATCCCCGTAGTGATA
GTGACTATCAACAAGACGACCTCAGAAGATAACGTGGCGTTTGACACCAGCAGCCATAACCTGATGCCCGTG
AGCGGCACCTACCTCAAAATAGGATGGGACCAGTACCTCCTTTTCAACAACACGAGATACAACGCCAGCGAC
ACCGAGAAGGATAACCCCTTCCCTGTAAAGCTGAGCTTCTCTAGCACCGTAGACAATTACTTCGACGACAGG
AAGGTGGTCGAGGAATTGATCGACCAGGTGTATCAGTTCTCCCGCATGTATTGGAAGAGCGTGAAGCAACAG
AACCTGCCCGTTACCATCAAGTACCCCGAGATGGCGGCAGAGATCTTCCCATTTTTTGAAGGCGATAAGCTG
CCCGACTTCGGAAAGAATAACCTTTGGTTTCTG
235 2 ATGAACACGCCTTTGACGCATTACGTGCTCACCGAGTGGGAATCCGATACAAATACTAATGTATTGCACATC
CACCTGTACACCCTCCCCGTTAGGAACGTGTTCGAGCAGCACAAGGAGAACGGTAACGCATGTTTCGATCTT
CGCAAGCTGAATAGGAGTCTGATCATCGACTTCTACGACCAATATATCGTGAGCTGGCAGCCTATAGAAAAC
TGGGGCGAGTACACCTTCACCCAGCACGAATACCGCAGTATAAACCCAACAATACTGGCCGAGAGGGCCATC
CTCGAACGACTCCTCTTGCGGACAATCGAAAGCGTCCAGCCCAAGAAGGAGATCGCAGCTGGTTCCCGCAAG
TTTACCTGGCTGAAGGCAGAGAAGGTCGTGGAGAACATTAGCATCCACAGGGTAATCCAGTGCGACGTAACC
GTGGACTACGCCGGCAAGATCTCTGTGGGCTTTGACCTCAATCACAGCTATAGGACAAATGAGAGCGTGTAC
GACCTCATGAAGTCTAACGCCATCTTTAAGGGAGACCGCGTGATAGACATTTACAATAACCTGCACTACGAG
TTTGTAGAGATTTCCAACTCCACAATAAATGACTCCATCCCCGAGCTCAACCAAAGTGTCGTCAACTACTTT
ACGAAGGAGCGAAAGCAAGCATGGAAAGTGGATAAGCTGGAACAGAGCATGCCAGTCGTGTACCTCAAGGCA
TTCAACGGCAGTAGGATTGCATACGCGCCTGCGATGCTCCAAAAAGAGCTGACCTTTGAGAGTCTCCCGACC
AACGTAGTACGGCAGACGTCAGAAATATTCAAGCAAAATGCCAATCAGAAAATCAAGACCTTGCTGGATGAA
ATCCAAAAGATTCTTGCCCGCACCGACAAGATCAAATTCAACAAGCAGAAGCTGTTGGTTCAGCAGGCCGGC
TACGAGATACTTGAACTGTCCAACCCAAACCTCCAGTTTGGGAAGAACGTTACTCAGACGCAACTGAAGTAT
GGACTGGATAAAGGCGGAGTTGTGGCCTCCAAGCCGCTCAGCATCAATCTTCTGGTCTACCCGGAACTTATA
GACACCAAGCTCGATGTGATCAACGATTTCAATGACAAACTGAACGCTTTGTCCCACAAATGGGGCGTGCCC
CTGAGTATCCTGAAGAAGTCTGGAGCGTACCGCAACAGACCCATTGATTTCACTAACCCCCACCAGCTCGCG
ATTCTGTTGAAGGAACTGACCAAGAACCTTTTCCAGGAACTCACGCTTGTGATAATACCGGAAAAGATCAGC
GGCATGTGGTACGATCTGGTTAAAAAGGAATTTGGCGGCAATAGCAGTGTTCCGACGCAATTTATCACCATC
GAGACACTTCAGAAGGCAAACGACTATATTCTGGGGAACCTGCTCCTTGGCCTCTATAGCAAGTCCGGCATC
CAACCATGGATTCTTAATAGCCCCCTTAGCTCCGACTGCTTCATCGGTCTGGACGTATCACATGAGGCGGGT
CGCCACAGCACCGGGATAGTCCAAGTCGTAGGAAAGGACGGGCGCGTGTTGTCATCCAAGGCGAATACGAGC
AATGAAGCCGGCGAGAAGATCCGCCACGAGACCATGTGCCAAATAGTGTATAGCGCCATCGACCAGTACCAG
CAACACTACAACGAGAGGCCTAAGCACGTGACCTTCCACCGCGACGGTTTTTGCAGGGAGGACCTGCTGTCA
CTCGACGAGGTGATGAACTCCCTGGATGTCCAGTACGACATGGTGGAGATCATCAAAAAAACCAATCGGCGA
ATGGCACTGACCGTCGGCAAACAAGGATGGGAAACCAAGCCAGGACTGTGCTACCTGAAGGACGAGAGCGCC
TATCTGATCGCCACCAATCCGCACCCGAGGGTGGGCACCGCGCAACCCATCAAGATTATCAAGAAGAAGGGG
AGCCTCCCTATCGAGGCCATTATACAGGACATCTACCACCTGAGCTTCATGCATATCGGCTCACTGCTTAAG
TGCCGACTCCCCATCACAACTTATTACGCCGATCTGTCTAGCACCTTCTTTAACCGCCAATGGCTTCCGATC
GATAGTGGCGAGGCCCTTCACTTCGTG
236 35 ATGATTAACAAACTGCAATTCGACGAGTTTCAGAGGGCCATAGGTATTTCTAAGAACGACACCTTCAGTCTT
TTGCTCGGAGCGGGTTGCAGCATCAATAGTGACATCCCTAGCGCGGAAGACTGTATATGGGAGTGGAAGCGA
GATATTTACAAAACAAATAACAGTTCTAGCTTCGGCTGGATTGACAATTACAAGAATCCCAAGACTCAGGAG
ATCATTCAGAACTCGCTCAACAACCAAGCCATCTATCCCGAACGCGCCTGCAAAGAGGAGTACACCTTTTAC
GCCTACAAATGCTATCCCATCGACGAACATAGGCGACAGTATTTTCAGAAAATCTGTAGTGGTAAAAAGCCA
TCCATCGGGTACAAACTTATTCCCCTGCTTGCCCGAAAGGGCATGCTTGATAGCGTGTGGACCACGAATTTG
GACGACCTCGTGGTGACCGCCTGTATAGGCAACGGGATCCAGGCGATCGAAATCACGCTCGACTCCGTGCAA
AGGTTGAACAACCGGCCTCAGAACCGACATGAGCTTCCTGTGATCAAACTCCACGGAGATTTTAAGTATGGC
GATCTTAAAAACACCGAGGAGGAACTCCTCAATCAGGATAAAACGTTCAGGGAGAGACTTATTGAATACGTA
CAAGACAAGCACCTGATCGTGCTCGGCTACAGTGGCCGAGACACCAGCCTGATGGACACACTTAAAGAGGCC
TACTCAAAACAGGGGGGTGGAATTCTGTACTGGTGTGGATATGGTGACAACATAAACTCCGACATCGCCGAA
CTGATTCAAATAGCCACTAAAAATGGCCGACGAGCCTTTTACATCCCCACTGATGGTTTCGATTCTACGCTC
CGGAAAATCACACAGATAGTGGTCGAGGATGATAACAACCTGAAAAAAGAGCTTCTCGAGCTTCACCAGACC
AGCAATATCAATGACACTATCACACCTTTTGATCTGAAGTGCGAGAGGGTGAATAAGCTGTTGAAGTCAAAC
ATATTCCGGATTAGCTTTCCAGACGAAGTGTTCGTTTTCGATGTGAGCATCAGCGATAAACCCTGGAAGTTC
GTGGACGAAAGGACTCTTGAGCGCAACGATATTAGCGCCGTTCCCTATAACAAGCAAATCTGGGCATTCGGT
AGGCTTGACATCATAAAAGACATCTTCAAAGACGTGATGAACTCAGACATTCAGCGAAAACCCCTGGCAAAC
ATCAAGATATACAACACGGCGGTTAGTCGGCTGTTGCTTACTACGATTTGCAAGATACTGGCGCTGCAGAGC
AACCTTAAGACCGACTATAAGGGTAAGATATGGACCGAGAACAACAGTAAGTCCATTTCCGGCCACATAGTA
TACAATGCCGTGCTGCTGTCCTTTGATCGGATAAGCGGTGACTATTACCTTAGCCTCAACCCCGACTTCGTG
CTGGCTAACCCCAACATTGAGAAGAGTACCATACAGACCATAGGACTGTTCTTCTTCCAGAAGCTGTGGAAT
CAGCAGTTTAACGAGTACATTAACTATTGGAGGCAAATTTTGTTGAAAAAGAATAATGAGTACGAGTTCCCC
ATAAATAGCGGAACCGGCTTCAAGTTCAAGATCAAGAACATCCCAGTGTTCACTAACATCTGCGACCTGAAT
AACCCTCGCATCAACAATCACAACGTCTCCAGCCACCACCTGCTGCTTCAGGGGGTGCAATTTAAGGAAATC
CCGCTGCTTTTCAGCACCAACAATGGCAACCGCACGGCCACCGACACCCACCCTATGAGAGGACTTCTCATA
AACAAACCGTATGAAACGGGCGTCAACGACTTCCTCGAAAAGTCTATCACCCTGGGAATCATAAGCCCCAGT
CAGGACGCCCTCAGGTTCTACCAATTCCTGGAAAACCAGAACTCTAAAATCAAAAAGCACAACGACAAGGAC
AACTACATAATAGACTACGAAGGGTTTTTCGCCATCTACGGCGTTAGTCTCAGCTTCCCAACACCTAACGAC
AACGAGTGGGAAAGGATCAACGAACCGCTGATTATGGGCATCAAGGAGACCGCCCAACAGATAAAGCAACTG
ATATGCGACAGCATCGTGAAGATCTCAAGCACGACCAGGAGAAAAATCATCGTCATCTATATCCCCCAACGC
TGGGAGCCCTACACCTCTTACCAGCTCGATGGTGAGTCATTTGACCTCCATGACTACGTGAAAGCGTTCTGC
GCGGAGAAAGGGATTATGAGCCAACTCATTCGAGAGAAGACCATTAACGATACTATCCAAAAATGCCAGATA
CATTGGTGGTTGTCTCTGTCATTTTTCGTAAAATCCTTCCGGACCCCATGGATTCTCGCAAATACTAACAAC
ACCACCGCCTTCGCGGGTTTGGGGTACAGTGTAGAAAACAAGAAGGATATTAACGGACATATTGTGCTGGGG
TGTAGCCACATTTACAGCTCAAACGGAGAAGGGCTCAAATACAAGCTGGCCAAAATAAGTAATGATAAGATT
CAGTGGAGGCATAAGAAGCCGCACCTCTGCTACGACGACGCGTATGAGTTTGGCAAGTCAATTGTGAACCTG
TTCTACGAATCTATGAACGAACTGCCAAAAAGGGTGGTCATCCACAAGAGGACCTTCTATACCGATGAAGAG
AAACAAGGGATCATAGACTCCATTAGCGACAATAAGAAAATAGAGAGCATCGACCTCATCGAGATCAACTTT
GAAAACAATATAAAGTACGCCTCTAGCAAAATCCACGACGGAAAGGTAGACATTGACGGATTTAGCGTATCT
AGGGGAACCTGCATACAACTCAGCTCTAAGGAGGCGCTCCTGTGGGCGCATGGAGTGATTCCTAGCGTCATT
AACCCTAACTGGAACTTCTACCCTGGCGGCAGGTACATACCTAAACCACTTAGGATCATTAAACATTACGGT
ACAGGTAGCTTGGAACAGATCGCGAACGAGATTCTGGGCCTGACTAAAATGAATTGGAATAGCCTGAACATG
TACAGCCAATTGCCTGCCACAATTTCAAGCTCCAATGATATAGCTAGGATAGGTAAATTGATAGGGGCGAAC
AGTATGCACGAATACGACTACCGATACTTCATC
237 9 ATGAATAACATACCCATCAGGCTGAACTTTTTCGCCCTGAAGAACCAGAACATTAGCTTCAGGATCTACAGG
CAGGACTTCAACGGCCAGAAAAAACAGGACGGGTACTACAGGACCAAGCTGCCCATCAACGACTCTTCTGAC
ACCTACGCGGAGTACTGGGTGACAACCCAGCCCAAGGATGGCTTCGAGAGGGTGTACTGCCTGGGTTCCTCA
AACCCTAAGCTCACCGTCCGAATCATGTGGGAGAGCTTCCTGGATAGGGTCCAGAAGTCCCTGAGCTCCGAC
GAATATATCCTTTACGGTAACGGATTTAGCCGGAAGGTCGCCGTGATCATCGGCAGGCACAGGGAGGGCAAT
GAGGTGATCCAGATAGAGCCCTATTACCTGAAGGCCGAGAAGAAGTTCGGCTTTCTGGTGGACTTCGCATTT
AAGAAGGCCAAGGACGTGCCCTATAGCATCAGGGTTCAGCAGCTGAGCCTGTCACTGAACAAGTATGGGAAG
AGCAACGCCGACTACTATAGCGACAAGCTGGATAAGATAAAGTTCTTTATGCAGAAGTTTAAGCAGAGGCTT
TTCCCATTTAGCTTGGATAACGAGGATTACGACATCGAGAACGAGCTGTATCTGATGAGGAGCTACCCGCTC
AAGATGAAGACCTACATATTCTCTAATGGCAAGGAAAGCAACAGCCAGGTGCAGGGTCTCAAAACCTACGGA
CCGCTGGCGAATCTCGATAAGGAGCCACTGTTCGTGTTCATGTTCGAGTCCCAGGACAGGAACGAGGCCCTG
GAGCTCTATTCTAGCCTGCTGGGCAAGACGTACACCAACATATTTGCTGGCATGGAGAGCGTGTACAAAATC
AAACTCGCAAAAGAGAATGTGAAGCACATCATCATCCCCAGCCTTACCAAGGAGGGTCTGCAAGTGGTGGAG
CAAGAGCTGCAAACTATCGTGGAGAGTCATCAGGACAAGAAGGTGATTGGGATATTTGTAATGAATGAAAAG
GTGCCCTCATCCATCACCGGTTTCAGCCCCTACCACTACGTCAAGTACATCTTCACAGAGAAACGCATTCCC
CTCCAGACAGTGAGGTGCGAGAGGATCGCTGCCAGGGATGGCCTCAAATGGAGCGTTGGCAACATCGGCCTC
CAAATTTTCGCTAAATTGGGCGGCATCCCCTGGAAAGTCAAGCCGAGTAACGATAAGTGCATCATTTTTGGC
CTGGGCTGCGCCCACAAAAAAGACGAACTGGGAAACATTAACAAATACTTCGCCTACAGCGTGTGCATGGAC
AGCAGCGGCATTTACCGAAAGATTAATGTGCTCGGCGATGCAAAGGAGCGCACTGATTACATCCTTCAACTG
CGGGAGAACATCAAAAGCGTGATAAGCGAGAATCTGGACGGGAGCATTGAAAAGTGCGTGATTCACCTGCCC
TTCAAAATTAAGAACGACGAGATCAGGTACATAAAATCCAGCGTGCAGGAGATCGCGCACCTGTATTCCGAC
ATAGAATTTCAATTTATCAAGATCAACACGGACAACAAGTTTTTCGGATACGCTGAAAACAACAGCAAGGTA
CCCTACGAGAGCAGCTACATACAACTGAGCAGCAACGAGTTCCTGGTGTGGTTCGAAGGCCTGCAGTACGGG
AAGGAGCTGGTGAAGAAAAAGGTAGGTAACCCCGTGCACATTGAGTTCATGCAGATCGATGAGTTGGATCCC
GAAAAGAAGCGGCGATATCTGCAGGATATCATAAACCTGAGCGGTGCCAACTGGCGAGGTTTTAACGCCAAA
CTGTCTCCAATCAGCATCTACTACCCCAACATCATAGCCAATTTCATTTCAGAGTTCAGGGAGTTCCAGCCC
GAAGGCGACGTGGACCTGACCAACTTTTACATTCCCTGGTTCCTG
238 10 ATGCATAACATCGAAATCAACACCTTCGTCAACAGCTTTGCCATTAAACCCAACAACTCCATGTCCTTCCTG
CTCGGCGCAGGCGCGTCTATATCCTCCGGGATCCTGTCTGGCGGACAGATGGTGTGGGACTTTAAACGGAAC
CTCTATTGTGCGTCCAAAAACATACGCACCAGCAATTTTCCCGATATGAGCAAAAAGAATGCGCAGGACGAG
ATCCAACGCTTTTTTGATGGGCAGGCCGGAAATCCTAGCCTGTGGTCCTCCGAGGAGTATAGTTTCTACTTC
GAGAGGTGTTATCCGGCGAGGAAAGACAGGGAGCTGTACATACAGAACAAGGTACGAGACGTCAAGCCGTCA
TTGGGGTATCTCTGCCTCGGGGAATTGATCATACACGAGAAGATCGGTGTAGTATCAACCACAAACTTTGAT
GACCTGGTGTTGGCCGGCATCCATTCAATAAGACCGGACCTGAGTGTGAAGACCATCAGCAGTGCCCTCAAA
AATAGCACGGGATTCTTCGTGAACGACGGGTTCCCGAACATCATTAAGCTGCACGGCGATTACTTGTACGAT
AAGCTGAAGAATACCGATAAGGAGCTGCAAAAGCTCGAGACGGAGATCAGCGGAATTTTTCGAGATGCCGTC
AAGAGTGGCGGGCTCATCGTACTTGGCTACGCCGGCAACGACAACAGCGTGATGAGCGTCCTGGAGGAGCTC
GTAAGCTCCGGGCAAATCAGGTACGGCGTGTTCTGGTGCCAACCGAAGGGCTTCCCCCTGTCCAAGCGAGCG
CGGGAGTTTATTGAGAAGGCTTGCGCCTACAATGAGGAATCCGGGGTTGTCGAGATCAACAATTTTGACGAC
TTTATGTACCGCCTGTTCCTTACACTCAACATCCAAAACTCATTTATCGACAGCATGTGGGAACAGAGCGGC
ATGAAGCAGCCGATCCTCTATGAGAATATCGGACGACACAAGTCCACCGCCGTGACGAACGCCCTGTGCGCC
CTGCAGTACCCCCGAAAATGCTACGTCTTCAACGCGAATATATCAAGCTGGAAGGAACTGCGCGAGACGATA
AACGACACGTGCGTGGCAGTGCTGTATAAGGGCATGGTTTGGGCGCTGGGCAGCAAAGCAGGCATCGTGCAT
GCGTTCGCCGGGAAGATCAATGGAGACATATACGAACTCGACATCCCGTTGTACATGATGAAACTCGAGGAT
TCTGACATCCTGGGCATGTTTTACGACATCATAGGACGCGGCCTTCAGCGAAAGGGGCTGGTGAGCTACGGT
AATAGGAAACATCACAAATACTTCAACCCCTCCAGCAAACGGTTCAAGAACGGTCAAAACATCTACGACGCG
GTCAAGATATCACTGAGTTTCGTGGACGATCAGCTCGTGCTCATCCTGCTGCCTACGGTGCATCTGCTGAAA
CGCGACGGGACGGAGCTGGAGAAATTTGACTACCAAAAATTGGTGTCCCAGGAGATGGCAACACACTACAAC
AAAGTGGTGGACAGCGAGATAGAGATCTGGCTGAAATTCATCTCTAATAACGGCAAGATAATCTTTGAGCTG
GGGAACGCAATACTGGAATTTAACAACGTCCGCATCCAGTACTCTGGTAACGGTAACCTCAGCAAGTGCTAC
CAGGTGAGCGAGCCCGAGCTCACGTTCAGTTACGAAAAGGACAACTGCATCGCTACCAACCAACTGCGGGGT
CTGATCAACTATGGACCCATAGAGACTTACGTGAACAAAGCCATCAGGTTGGCTGTACTCAGCCCTAAGGAG
TGTGCCGCGGACATTTGGAAACACCTGCAGAAGTTGAATGAGCATCACGTCACCTCCCTTATTCAGGATGCA
AATTTTCTGCCGGAGTACACCGGCTTTCAGAACGTTTTTAGGTGCAACCTTGACATTCCCAATGGGAACGAT
GTGCATAGGTTCAAAGGCTACAGTATAGACAAGGTCATGCAACTCAACGCAAAGAGCTACTTTTACGGGATC
TGCAAGTACATTGATGCATTCGAGACACAAAGGAGCCAATACGACCTCCTCGTCATCTATATACCTAAGCAG
TTGACCCACATCCGAGAGGCCAAGAATAACTTCGAATATTTCGACCTGCACGACAGCCTGAAGATTTATTGC
GCTGGTAAAGGTATAGTCACGCAGATCATCGAGGAACACAGTGTTTATACTAACAATGACACCGCCAAGATC
ATATGGGGTCTCTCAACGGCCATATTCACCAAGACCGCCGGAAGGTTGTGGAAACCCAGACGCTATTCCATG
AACACCGCTTACGTCGGCCTGTCATATGTGCAGAGCGTTAAGAACAACGAGAAAGTCAGCATCGGTTGCAGT
CAGCTGTTCGACGCCGAAGGCAATGGAATGAAGCTTTACCTGAGACCCTTGATGAACCCCCAGATAATTCAA
AATAACCCTTTTATGCGGAGCGACGACGCTTGCAGGCTTATGTCAAACCTTAAGCGGATGTATGACGACAGT
GTCCCGCTCTACAAACTGAATAGGATCGTGATCCACAAAACTACGTTCTTCACTAAAGAAGAGATGGAAGGC
ATCACCAAAGGGCTGGCTGGAGTGGATGACATAGAGTTGCTCCAGATCCAGGAGTTCACAGCTTGGCGAGCA
ATACGCTTCGACTACGACAAGATCGCACCGTTTCCGATACAGAGGGGCACAGTGATTCTGGGGTGGGGCCAC
TTTAGTTACTTGGATACCTGGAAGTGTACCACC
239 7 ATGAACGCCGTGACCGTGGGCAGCACCCCAAGCGCCCAGGTACTCGTCGGTGTTCAGCCATACGACGAAACC
ACCCTGGAGAGCCTGAGAAGTAAACACCGCGGAGACTATCTCTTTAAAAGGGGGGGAGAGAACGGCGATAGC
ATACTTGCTGTGGCCCTGAAACCGAGTCTGCCGGTCATCGGAGCAACCGAGGAGGATGTAATTCTTGCCGAG
AGCCCATGGTTGTTGGCTCCACTTGCCTTGGAGACTTTGCTGCAATGCTTCGTGAGGCTTCAAAGGCCCATC
CTGAAAGCTAGGCATCCCCTGAGAGTGCTCTCACAAAAACCGGCAAATCTTTTCCCAGCCGATGCGGGGGTC
CCCCAGTGGCTGCAGAGGAGACTGGTGCTGGAATTCGACACGCGCACTGTTAGGGACAGGTCAGACGCTGCC
TCTGTCGTGCTGGCATGTGGCGTGAGGACTCGGAATTTGATTGATGCCGACTGCGCGACACTGATAGCAGCC
GGTGTCCCCCTTGTGAATCGATACGTGGTGACGAGGCACCCTGCGGATGATCCCCGAGTGCAGGGCTATTTG
AGGCTCGCCGGGAGGGTGACCAGGATAGATGGCCCCAACCTGTACTTGGAGGATCATGGCGATGGAGCAGCT
GTGATCAAGGCCTCCATGGCCTATCTGGAGCCCAGGAGGGAGAACGTGATTTGGTGTGCCCACCATTTGCTG
GGGAGAAATGCGGATAGAGTACTGGCGGAAGCGGATAACGCAGCCGCAAAGCACTTGAGCGGTCCCGAACGA
TTGGCCGTAGTGAAGAAGACTTTCGACTACCTTAGGAGCCAGAACATCGAGCTTGCGCCTGGAGTGCCCCTC
ACTCTGGGTAACGTTGTGGGGAATGACAAGGGTTCTTGGATCTTCCGGACGGAAACTCTGCCCAAGCCCCAC
CTGGTGTTCGACCCGAGCGGGACCCGGATCGATAGGTGGAATGAGAGGGGATTGGACGCTCACGGGCCCTAT
GATCAAAGGACCTTCACCCCTAAACAACTGAGGATTGCCGTCATATGTCAACTGCCCTACGAAGGCCAGGTC
GATGCGTTCCTGGCAAAATTTCTCGACGGCCTTCCAGACGTGAAGACCGGCTACGGGGACCGGGCCAGGGCG
CCTTATGCCAAGGGGTTCATCAGGAGGTACGGTCTGGAGAAGCCCAAGGTGAGCACCTTCGCAACAAAAGGC
GCTACTGCTAAGGACTATGCCGCTGCATGTAGGGCGGCTGTGGAGGACGCAACCGCAAGCGGCTTCGAGTGG
AATCTGGCTATCGTGCAGATCGACAAGGATTTCAAGGAGCTGAGTGACGTGGAGAATCCCTACTTCACCACC
AAGGCCCTGCTGCTGAAGCATCGGGTGCCCGTCCAAGAGGTGACGCTGGAGACGATGAGGTTGGCAGACGAA
CAGCTGGTGTACGTGTTGAACAACATGAGCGTAGCCACCTACGCCAAAGTGGGCGGTACTCCCTGGCTCTTG
AAAGCGCAACCAACCGTGGCCCATGAGTTGGTAGTTGGAATCGGAAGCCAGACTTTTAGTGCCTCAAGGCTG
GGTGAGAAAGAGAGGGTTGTAGGCCTTACCACCGTGTTCTCCTCCGACGGGAAATACCTGCTGGACGACCGG
ACTAGCGCCGTTGATTACGACAACTATAGCGAAGAGCTGTTTAAGAGCTTGTCCCGGTCAATAGAATCAGTA
AGGATCGCCGATAACTGGCGAAGTACGGACAGTGTCAGGCTGATTTTCCATGTTTTCAAGCAGATGGCGGAC
GAGGAAGCCGACGCGGTTGACAAGTTGGTGCAAAAGCTGGGTTTGGCACAGGTTAAGTTCGCGTTTCTGCAC
ATCGTGGATGACCACCCATTCGCCCTGTTTGACGAGAAGAACATAGGTACAAAGACATGGGGTGGGATATTC
AAGGGCGTCTTGGCACCGGAAAGGGGCCTCGCGGTAAACCTCTCTGGGGCCGAAACCCTGTTGTGCTTCACA
GGCGGCAGGGAACTGAAACAGGCGAAGGATGGCCTGCCCGTGCCTAGTCTGCTGCGACTGCACCACAGGAGT
ACGTTCAGGGACATGACCTACCTGACGGGGCAAGCCTTCAACTTCAGCTGTCACACCTGGCGCATGTTCACA
CCCGCTCCTGTTCCCATCACAATACATTACAGCGAGCTGATGGCGCGACTCCTTACGGGCCTCAGGCACGTC
CCGGATTGGGATCCAGACACAATGCTGACCCCCATCAGTCGAACCCGGTGGTTCCTG
240 13 CTGGACAGTTTCCACCTCGTGCAGACAGAGAAAAAGGCCATCGCAATGCCAAAGCAGAAGCTTGCGGTTAAT
GCACTCCCCATTAGCCTGAAAGAGCAGGAGCAGCACAAGCTGTTCTTTTTTAGCAAGGAAAAGCAGGGCGAG
CGAGCCCCGCTCACCAGGAAAGAATATCCTGACAGCTTCGCCAAGAGGTACCCCAAGAGCTCCAAAGAGTAC
GACGTGCTGTACACGGACTTCACCCCAGAGCCAGCTGAGGATGGGTTTGAAATTGATATCGACCTGGAGGAG
GCACCTGGCCTTGCCAAGCACTACTTGCACAAAAGGATCTTTGAGGCCTTTAAGGGAGTAGCTGACTTCAGA
AAGCGGGATTTCATCAACGGTGTGGAGCTTTGGTTCAGGGACAAACCCGCCGACGAAGTTAATTTCCGGGCC
TACAAGAAGTTTAAGATTACCACCCGCAGAACTTGGTTCTCCGCAGGCTGGGCCCTGTTCATACAATACACC
GGCCATTCCTTTATTCACCCGGTGGCGATCAATAGCGAAGAGGCCGCAGTGGACACTACGGAACTCACGCGG
GTTGCTTATAACCGACACATCTTCCACTACGAGGAGATCCCCGAAGACAAACTGAGTGAGATAGATTTCAGT
AAGATGTACCCCGTGGTGAACTTCAACATTAGGGATAAAATGCAGCAGTTCCCCGTTATCGATCCATTCAAA
AACAAGGTCAAGGAATATGTCGACGAAATAGACAGGTTCAAGAACATGTATCTGATCGCGCCAGCGGTTGAG
GAGGTGCTTCCGTTTACTTTCAACGACGACAACTGGTGCGAGATCAAGATCGGCACCTACCATACCGTGCCC
AATGCCGGTTCCAAATTGGTTTTCCGCGATGGGCAAACCGAGATACACCCGTTCTACGGTATCAGGAACCAC
GGCCCTTTCATGCCCCCCAAACACAGCCACATAAGGTTTTTGTTTATCATGAGCAAGAGGGACATCAAGGGC
GCTGGTAAGCAATTCTATGAATACTTGAAGGGGGAGGTAAAAGGAGTGGACGGGTTCAACAGGTATGCTAAT
ATACCGTCATCCCTGAGGGGTGAGATGATCGAGTTTGAGAACGAGCAAAACCCCCTGCCGGAGATTATCGAC
GGCTTGAACAACATGGAGCGAGAAGCGGGCGTGGCCTACTTCGCCTTCTATATCAGCCCCATCGACCGAGAA
GTGAGGAACAGGAAGGAGAGGTTGGTGTACTACAGGGTTAAGGAGGAGCTGCTGAAGAGAAAGATTGCCTCA
CAAGTGGTAGAAAGGAGCACTATCGAGAAGGCCGACTTCCGCTACAGCATCCCCAACATCGCCGTTGCCACA
GTGGCCAAGCTGGGAGGCATCCCGTGGAAGCTTACTCAACCCCCAGAAGCAGAGCTGATCGTGGGCATAGGC
GCATTCCAGCCACGCGAGTTCGACAAGCGATATCTGGGCAGCGCCTTTTGCTTCCAAGGCGACGGAACCTTT
AGCGGCCTGAGGTGTTTCACCAAGGACGAACCCCATATGCTTGCTGGCAGCATCAGGGAAGCGGTTCAAAGG
TACGCCGATGAAAACAGGCAAGTGGAACGGCTGGTTATCCATTTCTACAAAACCATGAGCTATGACGAGAGG
AAGCCGATCCTGGCCACCTTGAAAGAACTCGGCCTGGACATTCCCGTTGTGGTGGTCACTATCAACAAGACT
GAATACGAGCAGACAATCCTCTTTGACCTGAATTCTAGCATGAGGCTGCCGCTGAGTGGTACCTATTTCAGC
CAGCGCAGGGACGACATCCTGCTGAGCAACAACACCAGGTACCGCAAAGACAGCGAGGTGAAGAGGGGTTTC
CCTTTTCCCGTGAGACTGCAGCTGTGGTGCTCCAAGGAGGGCCTGCTGGACGACGAGGGTTTTAGGGAGCGA
CTGATCACCCAAGTGTATAGGTTTTCTCGGCTTTACTGGAAGAGCGTGTCTCAACAGAATCTGCCCGTGACC
ATTAAGTATCCCGAGATGCTGGCCGAAAAGTTCCCATACTTTAACTCAAGGAGCCTTCCTAGCTTCGGCGAA
AAAAGCCTGTGGTTCTTG
241 3 ATGCTTATCTGGCAATTCAAGAGAATGCTCTACTGCCAGGCCAACAACATCAAAGAGGAAAAATTCAAAGAC
CTGGAGAGCGAGCGAAATCAAAACACTATCCAGAGCTATTTTGACCTGAAGGGCGGCTATCCGGAAAGATAT
AGCCAGGAGGAATACTCCGCTTATTTCGAGCATTGCTTCCCGAAGTCTATCAACCGGAAGTATTTCATGCAG
AAAATAGTAGAGGGCCGAAATCCGAGCATAGGTCACAAGTGTTTGGGTGCCCTGTTCGACTGCAAAAAGGTA
AACCACATCTGGACAACCAACTTCGACGAGCTCATCGAGAATGGGATTAAAAGCGTCAACAATGCCAGCAGC
TTCGAGGTCATTAGTATCGACAATCAGAGGCAGCTGGCCAACCTCAACAACTACCCAAGGGTGGTAAAACTT
CACGGCGACTACAGGTACGACAAGCTCCAAAATACCGTTGACGAACTGCAGACGCTGGAGAAGGACCTCCAT
AAGTACTTCGCCGATGTGCAAAGCAAGACCGGCTTGATTGTGATAGGCTACGGCGGAAACGACCAGAGCATC
ATGTCCGCCTTTGAAAAGACTTTGGAGGCCGACAACCCGTTCCCGTTTGGGCTTTACTGGTGCGTGAGGACG
GGCCAGAAAACCAACAAGAAGGTAATCGAATTCATAGAGAAGGTTCACCAGAAGAACAAGGAAAAGCTTGCT
GCGTTCATCGAAATCGACTCTTTTGACGATTTTCTTTATGAGCTGTATAAGACGAACAACCTTGCCAACGAT
CACATTGAAAATATCGCCAAAAGCCGCTTCGAAAAAAGGAAGGCTTTTACAGCCCCCCAGATCGGCACCTCC
TTTACGCCTATAAAGCTTAACGCCATAAAGGCCAAGACTTACCCGAAAAGCATCTATTCCTTTAAAACTGAC
CTCAAGGGGGGCAAGGATGACTGGGATAAACTCAGGGAAATCATTAAGGACCAACCGGTGAGCGCGGCTCTG
ACCAATGAAAACACGGTCGCCTTCGCAAGTGTCAACGACATCAAGAAACTCTTCTCACACACACTGAAGTCA
GAGATCACCACCGTGGACATAGATGACAAGTTGATCTATCGGCAGGAGTCTTTCTACCTGGGCATGCTTTAC
GATCTGATAGAGCACAACCTCCTGAAGAAGTTCAAGTTGGAGAAAGTGCCCAACAATAGGCTCCGCAAGTAT
TATAGCAAAAACTACAAGCTGAATACCGAGGAGCTTCAGAAGTCCAAGATCAAGACCAGCCTGTCCGTCTAC
GAAGCGTTCGAGATTCAAATAGAATTCCACAATAAAGAGCTGTTCCTCATTATCCTTCCGTCCATCCACATA
GACGACAAAGCCGGGCTGAGCCGATTTGAGAAACAGGAGATAGCCAATAAGATCATAAGCAAAAGGTGGAAC
CGCATGGTTAACAACCAGCTTAGGTTCTGGCTGGGGCTCCTTAAGAACGATAACACTAACATAGAGTTCAGC
ATCGACAGTTTCAAGATTGATTTGGAAGAAAAGTTCTCCGGCGTCGGGAGCTTTACATCCTCTTACTACATC
TTTAAGGGCGCGTTTATTTCCAACGAACCCAAGCTTAGCTTCCATATCTCCGACAGCAATTACAAAACAGTG
CACCCCCTGAAAGGCCTCAAGAACTTCGGTCCACTGGATTACTCATTTGAAAGCAAACAGACCAATCAGCAG
GCTATTAAACTTGGTATAATCACTCCGATCAGCGGCATGCAACGGATACTCAAACACCTGAACGAACTTAAT
AACGAGATCCGCGCAGCTACGGAAAAGGAGTACCTGACCGATTATTACCCCTTTAGCAACATCTACAAGAGA
TACCTTGACATCCCGCAGAATAAGGATAGTAAATTCTTGGAACTCGTGAATGAAGCCGAAGTGAACAAACTG
AACCACCTCGAGTTTTATGACTTCCTCAAACGCAAAATTGATTACTTCTATACAATTAGGGGCGAGTTCGAC
GTGCTTGTGTTGTATTTTCCCAAAGGCTGGACTAAGTTCCGCGAGCTGAAAAATGACAGTGTCTACTTTGAT
CTGCACGACTCCATCAAGCTGTACTGTGCTAAGAAGAATATCAAGATCCAATTCGTGGAAGATAAGAGTATA
GACTACCTCGACCCGGCCAAGGTTAAATGGTGGTTGAGCCTCGGCTTGTATGTCAAAGCGAACGGGCTGCCC
TGGCGGAACGTGGTCGTAAACGAAAGCACCGCGTTTGTCGGGCTCGACTTCGCGGTCCAGCGAATAAACAAC
AGTAACAAGTACGTGCTGGGTAGCTCACAGATCTTCGACAGCTCCGGACAAGGACTCAGGTTTCTGTTGCAG
CCCATCGAACACCCTGTGTTTATCGGTAAAAACCCCTTCATGAGCAAGGAAGATGCGCGACGGATGATTCTT
AAATTGAAGGAAGCGTATTTTAGGATTGACGGTAACTCCAAGCTGGAAAAACTGGTGGTGCACAAAGTACTG
CATTACACAAATGATGAGATGACCGGCATTTCCGAGGCGCTGGAAGGTATTGAGAACATTGAGCTTCTGCAA
ATACAGAAGTATAGTAAGTGGAGGGCAATTAGAGGGGACATCGATCGGTATACGGGAAAGGTGAAGACCGAC
CCGCACAATTTCCCGATCCAACGGGGGACAGTGATCCAGCTCGACGACTTCTCTTTCCTTCTGTGGACACAT
GGAAGTGTACAGGAAGACGACGTGGCTGGTAGGCACATGAATTACTACCAGGGTAAGCGCGGGATTCCCGCA
CCACTTCTCATACGGAGGTTTCGCGGCACCGATCCGATTGAAATGACCGTGCGAGACATCCTGTCACTCACC
AAGATGAACTGGAACGGAGGCGAACTTTACAAGACTCTGCCGGTGACCCTGGATTTCTCTAAACGGCTTTCT
AAGTATGCGAAGCAGGCAGAGACCCTCCAGGCAATACCCTACGACTTTCGGTTCTTCATG
242 51 ATGCTTCAACTGAACGGCTTTAGCATCGAAATCGCCGGAGGTTCCCTGACTGTCTTGAAATCTAAAATCGCG
CCTACCGACGTTAAAGAAACCCGCAGGAGCCTGGAAGACGACTGGTTCACCATGTATCACGAGGGCCACTTG
TACTCACTTGCAAAAAACAGCAACGCATCCGGCGGATTGGGTGAGACCGAGCTCCTGGTCCTGTCTGATCAT
CTGGGTCTTAGGTTCGTTAAGGCTATGTTGGACCAAGCCATGAGGGGCGTATTCGAGGCCTACGACCCCGTT
AGAGATAGGCCCTTCACATTTCTGGCGCGAAACGTAGATCTCGTAGCCCTCGCGGCAGAAAACCTCGAGTCC
AAGCCCAGCCTTCTCTCCAAATTCGAGATCAGGCCCAAGTACGAACTGGAGGCCAAGGTAGTGGAATTCAGA
CCGGGCGAGCTGGAACTTATGCTGGCGCTCAATCTGACTACACGGTGGATCTGCAACGCCTCCGTAGACGAG
CTCATTGAGAAGAACATACCGGTCCGAGGAATGCACCTGATCCGACGGAACCGGGAGCCGGGACAGAGAAGC
TTGGTTGGCACCTTCGACCGCATGGAAGGCGACAACGCCCTGCTGCAGGATGCTTACGACGGACAAGACAAG
ATAGCAGCCTCACAGGTGAGGATCGAGGGGAGCAAGGAAGTCTTCGCGACCTCTCTGAGGAGGCTCTTGGGC
AATCGCTATACCAGTTTCATGCACTCCGTGGATAACGAGTACGGCAAGTTGTGCGGGGGTTTGGGGTTCGAC
GGCGAACTTAGGAAGATGCAGGGATTTCTCGCGAAAAAGAGTCCTATACAACTGCACGGAGGTGTAGAAGTG
TCCGTGGGGCAGAGGGTACAACTTACCAATCAGCCTGGGTATAAGACAACAGTTGAGCTTTTGCAGTCAAAG
TACTGCTTTGACAGAAGTAGGACGAAGCTCCACCCCTACGCCTGGGACGGGCTTGCTCGATTCGGCCCATTC
GACAGGGGCAGCTTCCCGACGCGATCCCCCAGGATTCTGCTCGTGACACCCGACTCCGCGAGCGGTAAGGTC
TCTCAAGCTCTGAAGAAATTCCGCGACGGGTTCGGCAGCAGCCAGAGCAGCATGTATGACGGCTTCCTCGAC
ACCTTTCACCTCAGTAATGCTCCTTTCTTCCCCCTTCCCGTGAAGCTGGACGGCGTGCAGCGCAGCGACGTG
GGCAAAGCTTATCGAAAGGCGATCGAAGATAAACTCGCACGAGACGACGACTTCGACGCCGCCTTTAACATT
CTCCTGGACGAGCACGCCAATCTGCCGGACAGCCATAACCCCTATCTGGTCGCCAAGTCCATCCTCCTCTCC
CACGGCATCCCAGTGCAAGAAGCACGAGTGAGCACTCTGACGGCCAACGAATACAGCCTGCAACACACCTTC
AGGAATGTCGCCACAGCCCTGTACGCCAAAATGGGTGGTGTCCCATGGACCGTTGACCACGGGGAGACCGTG
GACGATGAGCTGGTAGTAGGAATCGGAAACGCGGAGCTTAGCGGGAGCAGGTTCGAGAAAAGACAGAGGCAC
ATCGGAATCACGACAGTGTTTAGGGGGGACGGCAACTACCTGCTTAGCAACCTCAGCAAAGAGTGCCGATAC
GAGGATTACCCGGACGTACTCCGGGAGAGTACCATCGCCGTGTTGAGGGAGGTTAAGCAAAGGAACAATTGG
TTGCCGGGTCAAACCGTGCGAATCGTTTTCCACGCCTTCAAGCCTCTGAAAAACGTGGAGATTGCCGACATC
ATCGCGAGCTCTGTAAAGGAGGTAGGCTCCGAACAGACCATAGAATTTGCATTCTTGAATGTTTCCCTCGAC
CACTCCTTCACCCTTCTGGACATGGCTCAAAGGGGAATAACGAAGAAGAATCAGACCAAGGGGATATACGTT
CCCAGGAGGGGCATGACAGTCCAGGTTGGGCGCTACACCAGGCTTGTAACCAGCATCGGTCCGCACATGGTA
AAAAGGGCAAACCTTGCCCTCCCGCGACCCCTGTTGATTCACCTGCACAAGCAGAGCACCTATCGGGACCTG
AGCTATCTGAGCGAACAGGTTCTGAACTTTACCACCCTGTCCTGGAGGAGCACCCTCCCCAGCGAGAAGCCT
GTTACCATTCTCTACTCATCACTGATAGCCGACTTGTTGGGAAGGCTCAAGTCAGTGGATGATTGGAGCCCC
GCAGTGTTGAATACCAAACTGAGGAATAGCAAATGGTTCCTG
243 28 CTGGGAGCCGGTGCCAGCATCAGTTCCGGCATCCAAAGCGCTAATGACTGCATTTGGGACTGGAAGTACTCT
ATCTACCAAACTAACTCCGGCAGTCAACGAGTGGCCCTCGTGGACCCTAAGAAATCCGACGCCTCCAAGTCT
ATCATCCAGAAGTGGCTGGATAATCAACCGAAATTCTCACAGATCGAAGCCCATCAGGAGTACAGCTTCTAC
GCCCAGGCGGCTTACCCCATTGAGGCGGACCGAATCAAATACTTTCAGAATCTCTTCCAGGGGAAGTCCCCC
TATATCGGCTACAAATTGCTCTGCCTGCTGAACAAGTACGGTGTAGTGAAATCTGTGTGGAGTACCAACTTC
GACGGCCTGGTCGAACGGGCAGCACAGCAAGCCAACATCACCCTGATCGCCATCAATCTTGACTGTGTTGAC
CGCATATATCGAGCAGAAAGCGTGAATGAACTTCTGTATATCGCGCTCCACGGGGACTACAAGTTTAGTACC
ATAAAGAATACCGCGAATGAGCTCGACAGCCAGCACACCGAGTTCGTATCTGCCATGTGCCGGTACTTCGTC
GATAAAAACTTGATCGTCATGGGATACAGCGGACGCGACAAGTCACTTATGGACGCCCTGGTCCAAGCGTTT
AGCAAGAAGGGTGGGGGGAGACTTTATTGGTGCGGCATGGGCGAGACCATCACGATCGAGGTGCAAAACCTG
ATACAGAGAGTGAGGACCGCAGGCCGGTCAGCTTATTATGTAGATACCTCTGGGTTTGACAACACCATGCTG
TCACTGGTAAAGTACTGTTTTTCAGAGGACGTCGCCAAACAGCGAGAAATAAACGAAATTTTGAAAATTGTG
GAACCGGAGCAGATTACTCCGTTTGAGATTCAAAAGAGCCAGAACAAACGGTATCTCAAGAGCAACCTGCTG
CCAATCGTGCTTCCCAAGGAACTCTTTCAGTTTCAGATCTCTTATAACGACACGGCGGACAGGTGGGGATTC
TTGCGCGAGAGGATTAAGGAGCGGGAAATCATAGCAGTCCCGTACCAGGACAAAGTATACGCAATCAGCACG
GTCTCCATCATTAACGACGTTTTCAAGGACTGTCTCGTAAGCGAGATTGAGCGCACGTCCATCTCTCTGAAT
GAGATCGAGCGCAATGGCTGCTTCAAAGAGCTGTTCCTCAAGGCTATTCTCTACGGGTTTAGCCAAATCCGG
AATCTGGGCATCAACTACCGCCACGGCATCATTTGGAAGAAGGAGGCGCTCTACACTGAGCCCGGCAAGACC
GTACACGAGGCCATAGAATGCGGCTTGTCTTTTATACCGCAAGCGAACTACGCTTTGATTAGCATCACACCA
AGTTTGCACATCGAATCCAGCAGCCCGATCGAAAAAGAGAAGAAACAAGAGTATAACAGGCGGTACCTTGAC
AAGATGAGGAATAAAGAGTACGAGGAAAAGATCCAGGAGTGGTGCAACATACTGTTCTCCGGTAACAAGCTC
GTTTTTGACATCCCGCTGCAAAGCAACAACGACTTGAAGTTCTTCATTTCCAGTAATAGGGGTTTCGCCGAG
GTATACAATTACGGTAAGGACATCGAGAAGAGCTACACGCCCAATGCTTACAATACGAAACAGACCATTTAC
TACGGCATGCAAATCGAAGAGCCTCAGTTGGAGTTTATCAACTCCATAATCAGTAGGCCGTTCTATGACGTT
AACCCAATGAGGGGCCTCTCAAATCACAAACCATTCGACGCGGACTACTATGACAAGTTCCCCCAGGATGTG
TGTTTGGGCATTGTGTGTCCGACCAGCTACAGCCTGATGTTCTCAGAATTCCTGAAGCGCCTGAACACTAAG
ATCCCAGCACCGAAGTCATCCGACTACATCCACAACTATATTGGCTTTAACAGCATCTACAACTGCAGGCTG
GACATACCGGACATCAATGCCGATCGCTGGGTGAGCATCGGCGACAACCCCCAGAACGCGGAGGAATTGGCC
CGCAACATCTGTATGGAAGCAAAAAAGCTGAGTGAACAATATCCGGGCATCGTGGTTAACATATTCATCCCT
ACTATCTGGAGCAACTACAGAAACTTTAAACACAACGGTGAATTCTTCGACCTGCATAACTACATTAAAGCA
TTTGCGGCACAAAATCGCTTCACCACGCAACTCATCGAGGAGAAAACTGTTTGTAACACGATGATGTGCGAG
ATATCCTGGTGGCTTTCCCTTGCCCTTTTCGTTAAGACCCTGAGGACTCCGTGGACACTGGCTGACCTTAAC
CCCAACACCGCCTACGCGGGGATAGGGTATTCAGTTAAAAAGCAGGCCAAGGGCAGGACAGAGATCGTACTG
GGGTGTAGCCACATTTACAATGCGCAGGGACAGGGACTCAAGTACAAACTGAGCAAGGTCGAGCACCCACAG
TTCGACAAAAAACGGAACCCATTCTTGAGCTTCGAGGAAGCCTTCAAATTCGGGATGGATATTCTTAATTTG
TTCCAGAGTGCAATGGAAAAACTGCCGCAGAGGGTGGTTATTCATAAACGGACGCCTTTTAGGGAAGAGGAA
ATAGAAGGGATTACCAGCGCCCTCAAGCGGGCAGGGATCACGGAGGTGGACCTGATCACTATAACGCAGGAG
CGAAACATTAAGTTTATAGCACAGGTTGTCTCCTTCGGCCAACTCAATACCGACGGCTATCCCGTCAACAGA
GGCACTTGCATCAAGCTTAGCTCTCGCAATGCACTCCTTTGGACCCACGGCGTCGTCCAGAGCATTCGAGAC
AAAAGACGGTACTACCAGGGGGGCAGGTGCATTCCGAGCCCGCTGAAAATCACTAAGTATTACGGCAACGGC
GATCTCCAGACTATAGCTAAGGAGATCATCGGTTTCACGAAGATGAATTGGAATAGCTTCAACTTCTATACG
AAGCTGCCAGCGACCATTGACACTAGCAACACCCTGGCCCAAGTGGGCAACCTTCTCAGGAACTATAATGGC
ACCACCTACGATTATCGCTACTTTATC
244 43 ATGGCCAACCATACCTTTAACATCCTGACTTTCAACCACCCCCAGGAGGAACAGACCTTCTACTTCACGGAC
CAGGAGCAAGACAACCTGACCCGCATCTACAAGAGCCTGGTGCCCGACGAGGTCATCGAGAAATATGGCGAG
CAGGATCACTACTACACCTCTTTCACCGTAGAGAAGGATGGTTTCCTGGCCGTCAGCAAGCCCACAACGCCC
CTGTTCGAGACCAAGACTACGGAGGCGGGCGAGGAGAGGAGCTATACCATCAGGAATTCAACGTTCAGCAGC
AGCGTGTTGAAACGGTACTACAACAGCCTTATCCACAGCCACTTCAAGGAGAAGGGCTTCCTGGTGAAGCCC
AACTTCGTGAGCGACACGGAGGTGTGGCTGCCTAGCGCCAAGCAGGACACGACCGGCAAATACAAAATATTC
GACCGCTTTAGCCTGAAGGTGCAGTTCAAGACCGTCTCTGATTCCCTGGAGTTGCTCGTCACGTTCGAGGGG
AAGTCAAAGATATTCAAAGTACCTGTTAGCACCCTGCTGGAGGATGTGAGCCCCACGGACATCAACTGGGTT
GTGTACGAAAAGGGATTGTACAGGTTCGACGAACTCCCGGACAGCGGCAAGAGGGAGTATGACAAGGTTTAC
CCCGTGTGGACCTTCGAGATCAGGGACGCGCTTATGCAGGGCACCGAAGCCCCAGACAAGACCAACAAGTAC
AAAAAGTTCAGGGAGGGCATCGACAAGTTCTATAACCAGTATCTGAACACAGAGGAGTTCAAAGCCATCATT
CCAATCACGTCTAATGGCTTCATCCCGGTCAATAAGATCAATGTCGGTAGTGTGAATAATAGTAGCAACAGG
CTGCTGTTCGGGGAACAAAAGAGCGGTATCGTGCCAATGGACGGCATGAAGGAACATGGCCCATTCGACTTT
TCCAGCACCAGCAAGATCCATTTCTTCTTTATCTTTCATAAAGACGACCAGCACATCGCCCAAAAGATGGAT
GGCTATTTCAAAGGCAGCGAGTTCGGGTTCAAGGGACTCACCAAATTCATACACACCCCCTATCACACCGAG
AAAGGATTCTCAATCAGGTTTGAGGACCGCGACAATCCGTGGCCCGAGATCTACGAAGCCGTCACTAACAAG
CACTTCGAGTCCGACATACAATACATTGCGATCTACATCAGCCCCTTCAGCAAAAACAGCCCCGACAAGAGT
CGGCGCAAAATCTATTACAAGCTCAAAGAACTGCTCTTGAAAGAAGGCGTGAGCAGCCAGGTGATTGACGGC
GAGAAGGTGATGACCAACGAGAAGTATTACTACAGCCTCCCCAACATAGCAATCGCCATTCTGGCCAAGTTG
AATGGCACCCCTTGGAAACTGGACACCAAGCTGAAGAACGAACTGATCGTGGGAATCGGCGCCTTCCGCAAC
AGCGAGGTTGACATTCAATATATCGGCAGCGCGTTCTCTTTCGCAAACAACGGCAAGTTTAATCGCTTTGAG
TGCTTCCAGAAGGACCAGACGAAAGAATTGGCGGGAAGCATCATACGGGCGGTGAAGGAGTACGCCAACGTA
AACACCGGCATTAAGAGGCTTGTGATCCACTTTTACAAAAGCATGCGACAGGATGAGCTCCAGCCGATCGAG
GACGGCCTTAAAGACCTCGGCCTGGACATTCCGGTATTCATCGTATCTATCAATAAAACAGAAAGCAGTGAT
ATCGTGGCGTTCGATAACAGCTGGAAGGATCTGATGCCGATGAGCGGCACATTCATTAAAGTGGGGTACAAC
AAATTTCTCCTGTTCAACAACACCAGGTATAATCCAAAGTTTTACAGCTTCCACGACGGGTTCCCCTTCCCC
ATCAAACTTAAGATTTTTTGCACTGAAAAGGAACTCGTGGAGGAGTATAAAACGGTTAAAGAGCTGATCGAC
CAGGTGTACCAATTTAGCCGCATGTACTGGAAGTCTGTCCGCCAGCAGAACCTGCCCGTGACCATTAAGTAT
CCGGAAATGGTGGCCGAAATGTTGCCTCACTTTGACGGGAATGAGATACCTGAATTCGGTAAGGACAACTTG
TGGTTCCTG
245 74 GTGAACCATTACTATTTTTCCGAATGCAAGGCGGACGAGAAAGCCAGCGACATAGCCATCCACCTTTACACC
GTGCCCCTGTCCAACCCCCATGAGAAATACAGCTATGCGCACAGCATCGCCTATGAATTGAGAAAACTCAAC
TCATACATAACCGTGGCCGCGCACGGTCAGTACATCGCGTCTTTCGAGGAGATATGCCACTGGGGCGACCAC
AGGTACATACAGCACGAACATAGACCAATCCAGTGCAGCCTCCCGATGGAGAGGACCATACTGGAAAGACTC
CTCAAGAAAGAGCTCGAGAATAGGTGCAAAAGCAGCTATAAGATGGACAACGACCTTTTCCGGTTGGCTAAC
GAGCAAAGCATGCACGTGGGCGAGATCAGCATACACCCAGCGATCTACATCTCATTCAGCGTGGAGGAAAAT
GGTGACATATTTGTTGGCTTCGACTACCAGCACCGGTTCGAGTACCGCAAAACACTCCAAGACGTCATCAAC
AACGATCCCTCCCTGCTTAAGGAAGGCATGGAAGTGGTGGACCCCTTCAATAGAAGGGCCTACTATTACACT
TTTGTGGGCATGGCCGATTATACCGCCGGACAGAAAAGCCCCTTCCTGCAGCAGTCTGTGATCGACTATTAT
CTCGAAAAGAATGAGCTGTGGAAGCTCAAGGGTGTGCACGAAAAAACCCCCGTGGTGCACGTCAAGAGCCGA
GACGGTCACTTGCTCCCGTATCTGCCGCACCTGCTCAAATTGACATGTTCATACGAACAGCTCTTGCCCAGC
ATGACCAAGGAAGTCAATCGCCTGATTAAGCTGAGCCCCAACGAGAAGATGAGTAAGTTGTATACGGAGATG
TTTCGATTGCTCCGGCAGCAACAGGTGCTGACCTTCAAGAAGGAAAACGTGCGAGCCGTCAACCTCGGCTAC
GATGTGAATGAACTTGACAGCCCGATCATGGAGTTCGGACAAGGCTACAAGACAAACGAGATCTATCGAGGC
CTGAAGCAGAGCGGAGTATACGAGCCCAGCTCAGTGGCCGTGAGCTTTTTTGTTGACCCCGAGCTTAACTAC
GACCCCCAGAAGCGGAAAGAAGTAGGTTGCTTCGTCAAAAAACTGGAGAGCATGAGCGAGGCCCTGGGAGTA
AAACTGAACATAAGCGACCAGCCCCGACAACTTTATGGCCAGCTCCCCAAGGACTTTTTCAAGCAGGACAAC
CTCTCATATCATTTGAAATCTATCACCGACCAGTTCAGGGGAACGGTGGTGGTTGTTATCGGCACTGAAGAG
AACATCGACCGGGCATACGTTACAATCAAAAAGGAATTCGGCGGCAAGGAGGATCTGATGACCCAGTTTGTC
GGCTTCACCTCCTCCCTCGTCACGGAGAACAACATTTTTCACTACTACAACATCCTGCTCGGCATCTATGCG
AAAGCTGGTGTTCAGCCCTGGATACTCGCCAGCCCAATGCACTCAGACTGTTTCATTGGACTCGACGTAAGC
CACGAGCACGGTAAGCACGCATCAGGGATAATACAAGTGATTGGACGGGACGGCAAGATTATCAAACAAAAG
AGCGTTGCGACAGCAGAGGCCGGAGAGACTATTGCCAATAGCACGATGGAAGAAATCGTCAACGAAAGCATT
TATTCCTACGAGCAGATCTACGGGGCCAAACCGCGCCACATAACATTCCATAGAGACGGGATCTGTCGCGAG
GACCTCGATTTTCTGCAAGCGTATTTGCGGAGTTTCCAAATCCCATTCGACTTCGTAGAAATCATAAAGAAG
CCGCGACGCAGAATGGCGATATACTCTAATAAGAAGTGGGTCACGAAACAGGGAATATACTACAGTAAGGGC
AACACCGCTTATCTGTGTGCCACGGACCCCAGAGAATCCGTGGGTATGGCGCAACTTGTCAAGATCGTACAG
AAGACTAACGGATTGAGCGTTCACGAGATAGTGAGCGACGTGTATAAGCTGTCCTTCATGCACATACACAGT
ATGCTCAAGACCAGGTTGCCTATCACGATACACTATAGCGACCTCAGCTCAACGTTCCACAACCGGGGCTTG
ATCCATCCCCGGTCCCAACATGAGAGAGCACTCCCGTTCGTG
246 68 ATGGAGAACCTGGCTCTTAGTGCGCTGCAACTGGACTCTAAGCTCGACCGCTACATCGTGTGCAGGTACAGA
ATCGTGTACCAGAAGCGAGACGAGACCATTCCCGGCGAACAGTTGGCCCGGAAGGCGGCCTACGAGATCCAG
AAAGCGAATGACTTCGCCCTTTTGACCAACCTCGGCAATCAACACATCGTTTCCCTCAAGCCCATCTCACAG
AGGGGCATTGAAAGCACCCACCTTCAGGCGAATCTCATCGAAGACGGGGACCTGGAGCTCGATTGCTCCATC
GAACAACATCAGCAGGCACTCCAGCGGCTCGTGAACCAGGACATCAATAAAGCTGCGTGGAAGCTTAAGAAG
AGCTCACAGGGCAAACTCGATTACAAAAAGGCAGCTAGCGGGAACACCGAGATCTTTGAGCCAATTCATAGC
ACTCGAATCAACGCCCGAGCCACGTATCTTGACGCTTTTTGCTCACTGCAGCTTAGCCCCGAGGTGCTTGCT
AATGGAACCGTACTGATAGGGCTGCATCTCAAGCACAATCTGGTAGCAAAGTCTGACATCTCTTTGCAGTGG
ATCATTGATAAAAGGCCCGATTGGCTGCAGAGCATCAAGAAGGTGCGGCACAGGTACTTCGATCCCGGCAAA
GCGCCCCTGGTCGCCGAATTCCTGAGGGTGGAGGACTCCCTGAATGGCAACAGCGTCTTGCCCCACATGGGC
CAGAGTCTTGTTTCATACCACCAAGCGAAGGGACTCTTGTCAGAAAGACAGCTCGCAGAGGCCACGAAGAGC
GTGCTGATAAAGGTAAAATACGGCAAAAACGAGGCGGACCACATCGCATCTCTGGTTGAACCAATGTTTGAT
TTCGACACGCTCAGCAAGATCGATAGTATCTTCCTTAACAAGTTGGCAAAGGACCTGAAGTGGAGCCTGAAC
GACAGGATACGCACTTCCGCGAAAATGGTGAAAGGCTTGTATCTCCCAAACTTCAACTGCAAGCTGGAACAG
GTTGACTATCAGATCCTTCACAGGCAGCGACTTAATCACCAACAGATGCTTCAATTCGCCAACGGGGCGAAA
TCTTCAAGAGAGCAGGACGTGCTGCGACATAAGGCGTTCGGCAACATGACGCGCACACAAGTTATCCCGCTT
ATTGCGGGCGAGAAGAACAATACAGAACAAAATAAGCAGCTCCTGTGCAACGCATACCAAGCATTGCAACAA
CTGACCACCACGGAATTGCCTCCGTTCACCAAGTTCCCCAACCCCGTAGAGAACGCAGCCGAGCTGGACGCA
AGACTGAATGAACGGTGTCCCCCAAATGCGATACTGCTCATCGGCCTTATCGACAAAAGCGACAAAGTGGCG
ATCCGCGACACCGCGTTTAGCTACGGTCTTGCAACCCAGTTCATGCGCCTGGATCACAGACCGAACGTCTAC
AGCCCCTCATATTTCAACAACGTGGCGGCTGGTTTGTTTTCCAAAGGTGGCGGGCAGCTCTGCGCCATTGAT
GACATGCCGGGTGAAACCGACTTGTTTATCGGTCTCGACATGGGAGGGATCTCTGTAAGGGCACCAGGCTTC
GCGTTTCTGTTTCTGCGATCTGGTGCGCAGTTGGGGTGGCAACTCGCGGACAAACAACAGGGAGAAAGGATG
CAGGATGAGGCCCTGATGTCACTGTTGGACAAGTCTCTCACCACCTACCTGAGAAGCTGCTCTGGTGAGCTT
CCTAAGCGCATAACCCTCCATAGGGATGGCAAGTTCTACGAAAGCATAGAAGTGATCGAGCAGTTTGAGCAG
AAGCACGGCGTGAAAGTAGATGTGCTGGAGGTTCTGAAAAGCGGTGCTCCGGTTTTGTATAGACGAAGCCGC
ATGGCCGACGGAACCAAGGAGTTTAGCAACCCCAATGTGGGCGACGCGATCTATCTCAGTGATCATGAGATG
ATCCTGAGCACGTATAGCGGCGAAGAACTCGGAAAGATATGGGGTGACAAGGTCAGCGTCAGGCCTCTTAGG
CTGCGCAAGAGATACGGTGATGTGAGCCTGGAGACCCTGGCACATCAAGTGCTCGTGCTGTCTAGGATACAC
GGCGCTAGCCTGTATCGCCATCCTCGACTGCCCGTGACCACGCACCACGCCGACCGATTCGCAACACTGAGG
CAGGAAACATGCATAGACGCCCTCTCTAAGATGGACCGGCTCTGTCCGGTCTACCTG
247 56 ATGCAGCTGAACTACTTCCCCATAAAGTTTGAGTTTGAAGAGTACCAGATAAAAACTGAGCCCTACAGCGAA
GAACGACTTAAAGAGTTGAGGGCCAGTTACAACGCCACCCACTCCTTTTTTAGAAATGGAGACAATATATGC
ATTAGCAACAAGGAAGGCGAGGACATTAGTCTGACCGGCGAGGTGATACCGAAAAGAATTTTCGACGACAGT
CAAGTGACCGCCTCATTGATAAAGCACTTGTTTTTCAGGACGTTCAAGGAGAGGTTCCCCAACTATATTCCT
GTGGACTTTTACCCCTTCCGCTTCTTCTCCGCCCAGGCTAAAGACGACATCATCTATAACGCCCTGCCCGGC
AACCTCCGGAAACGAATCGCTTACAAAAAGCTGATCGAGGTTCAGTTGCGGCTGACGGAAATAAACGGCATC
AAGCAGTTTGGCTTCCTGATCAACATTAAACGAAATTGGGTGTTCAACAAGTCATGCTTCGAGCTCCACTCC
GAGGGCTACAACCTGATCGGGGTGGACGTGCTGTACGCCGAGGAACTGCCGGGGTTGACCGAGGTGCTGGCC
CCAAACGAAGAGCTTTTGGGCGTAATCGCGGAAATCGTGGACGACAATGCCAGGATAGAAACCAACGAGGGC
ATTAAGGAGTTCCCTCTGAACCAGTTGTTCATCAAGAAAAGCAAGTACAACATTGGCAATTACCTTAGCTTC
GCGATCTCTCAGCAAAAGAGCGACGAAATAATGAATCTTATCGAGAGCAAACGCTCCGACATCTACAATACC
AAGGGTCTTTACGACGAGATCTTGAAAATTGCGAACCATCTTTTTTGCGAGAACAGCGCACCCATACTGTTT
CATAATAAGGACGGATTCTGCTTTACTGTCGATTCCCAGCCGCTCAGTGTGACGAACAGCATGGAATTGAAG
ACTCCAACATTCATATACGATCCAGCGGCCACGAAGACGAATTCTAGCAATCCCGACTTGGGCCTGTCCAAT
TACGGGCCCTACGACTCCAGCATTTTTGACATAAAGATACCCAACGTGTTGTGCATCTGCAATAGGAATAAT
CGAGGCAACTTTACAAAGTTTCTGTCTAACCTGAAAGACGGGATACCTCAAAGCCGCTATTTCCAGAAAGGC
CTCCAGAAGAAATACGACCTCCAGGATGTGATCCTCAATATCCGAGAAATCCAGGCCTATAGCATCGCCGAC
TACCTTAACGCCATCAGGGACTACGATGAGAACAAGCCTCATCTGGCGATCATCGAGATCCCTGCCAGCTTC
AAGAGGCAGGCCGACGTGGCGAACCCCTACTACCAAATTAAGGCCAAGTTGTTGAGCCTGGAGATTCCCGTG
CAATTCGTTACCAGCGAGACCATCGGTAACCACAACGAGTATATCCTGAACTCTATCGCGCTGCAGATCTAC
GCAAAGCTCGGCGGGACCCCGTGGGTCCTGCCCTCTCAACGCAGCGTTGACAAAGAGATAATCATCGGAATA
GGCCATTCCTGGCTTAGGCGCAACCAGTACGCTGGCGCAGAACAGAATAGGGTAGTGGGGATCACGACCTTT
ATGAGCTCCGATGGCCAGTACCTTCTGGGTGACAAGGTCAAAGATGTTGCCTTCGAGAACTATTTTGAGGAG
CTTCTGAAAAGCCTGAAGCAAAGCATCCAGAGGCTCAGCACAGAGCAGGGCTGGAGCGATGGCGACACCGTG
AGGCTGATATTCCACATATTCAAACCGATAAAGAACACTGAATTCGACGTGATCAGTCAGCTTGTCAGAGAC
ATCACGCAGTACAAGATTAAGTTCGCATTCGTAACCATCAGCACTGTGCACCCTTCCATGTTGTTCGACATT
AATCAGTCCGGTATCGCCAAATACGGTTCCAATATCATGAAGGGACAATACATACCAAACAGGGGCAGCAAC
GTTTTCCTGGACGAGAAGACATGCATCGTACAGATGTTCGGCGCGAACGAACTGAAAACGGCCAAGCAAGGC
ATGAGCAAGCCCATCCTTATAAACATTCGCACCCCCCAGGGGAACTACAATTCAAGCGACCTGAACGATCTC
CTGTTTTATGACCTGGGGTACATCACACAACAGATATTTAGCTTTACCTACCTCAGCTGGCGGTCCTTCTTG
CCCGGTGAAGAGCCGGCGACTATGAAGTACAGTAACCTCATTTCCAAACTTCTCGGGAAGATGCGGAACATC
CCTAACTGGGACGCCGACAATCTTAACTACGGCCTGAAACGGAAAAAGTGGTTCCTG
248 4 CTGAAGCTGAACCACTTCCCCCTTAATCCCGACCTCCCCCTGTACATCACAGAATATGCCCACCGGAACCCG
CGAGCGTTGCTCGGATTCGTTAGGGGCCAAGGTTTCTGGGCGCAACAGGTCGGAGAACAGGTACAAGTGTAC
CACGGTAGACCGCAGCCCACGTTCAGGGGAGTTCAGGTGATCAGCCATACCAGGTTGGACCCCGACCATCCG
GCTTTTGACCAAGGCGTTTTGAGCCTCATCCGACAAGCACTGGTGAGGGCGGGATACGTGCTGACCTACAGG
GAGAGGATGGCTATTCATCCCAGACTGGAGAGGGTTGTGCTGAGACCCCCGGACCGGCACCCAGCAGAGTTG
ACCGTCCATGCACATCTGCGATGGGAATGGGAGCTTGAAAGGCACAGCGGACAACGCTGGCTGGTTCTTCGA
CCCGGCAGGCGACATCTGAGCGCCCTTCCATGGCCCGCAGAAGCAGTACAAATGTGGTCCGCCGCTCTTCCG
GCCACCTGCCAGAAGCTGCACGCCCTTTGTCTGGACCGAGGCCAACAGATGGCCCTTTTGCGGCAAGAGGAC
GGCTGGCACTTCGCCAATCCCGGTGCTGCCACTCAAGGAAGGTGGCACCTGTCCTTTAGCCCCCAGGCCCTT
CACGAGCTGGGACTGGCACAGGCTGCGCACCATGCGGCTGCATTTAGGTGGGACGAGGTACAGCGACTCGTG
CAACTGACTGACCTGTGGAAGCCCTTCGTGACCTCTCTGGAGCCCCTTGAGGTAGCTGCCCCCATCATTGCC
GGGAAAAGGCTGAGGTTTGGACGGGGTCTTGGCCGCGATGTCACGGAGGTGCACAAGCGAGGTATCCTGGAA
CCACCCCCACTGCCCGTGCGACTGGCTGTCGTGTCTCCCCATCTTCCTGATGAGCACGCGAACGCCCAGTTG
AGGCGGGAGTTGCTTGCTCACCTCCTCCCGCGACACCAAGTACTGAGATCAGCGGAGAGCCGGCAAGGCCTC
CACGAGCACCTGAGGAGGCAAGATCAGGACGATACCCTGTATACCTTTTGGTCAGGCGGCGAGTACAGGAAG
CTGGGCTTGCCCCCCTTCGATCTCGCACGAGGCCTGCACACCTACGACCCAGCTAGCGGCCAGCTGCAACAA
CCGGCTGCCCTGGCACCAGCACCCGCGCAGGCCACGCAAGCGGGTAGGCAGCTGATAGCCCTGGTGGTGTTG
CCCGACGACCTGACGCGGTCTGTCCGGGACACCCTGTTTCAGCAGCTCCAGCAGTTGGGCCTTAGGTGTCTG
TTTAGTGTGAGCAGGACCCTGCTGCACCGACCACGCACAGAGTATATGGCATGGGTAAACATGGCCGTCAAG
TTGGCTAGGACTGCAGGGGCCGTGCCTTGGGACCTGGCAGACCTGCCCGGTGTCACCGAGCAGACGTTTTTC
GTAGGCGTTGATCTGGGGCATGACCACACCCACCAACAGTCCCTCCCGGCCTTCACCCTGCACGACCATAGG
GGACGCCCTCTTCAAAGCTGGACGCCTCCCCGACGCACCAATAATGAGAGGCTGTCATTGGCCGAGCTTAAG
AAGGGGTTGCATAGGCTTCTTGCACGCAGGAGCGTGGACCAAGTGATCGTGCATCGAGACGGCCGATTCCTT
GCTGGCGAGGTGGACGACTTCACTCTGGCGTTGCATGATCTCGGCATCCCGCAGTTTAGCTTGTTGGCAATC
AAAAAAAGCAACCACAGCGTGGCGGTGCAAGCAGAGGAAGGATCCGTGCTTAGCCTGGACGAACGACGATGC
CTTCTTGTTACTAATACCCAAGCCGCGCTTCCGCGGCCCACGGAGTTGGAACTGGTCCATAGCGACAGGCTT
AGTTTGGCGACCCTGACCGAACAAGTATTCTGGCTGACCCGCGTCTTCATGAACAACGCGCAGCATGCGGGC
AGCGATCCAGCCACCATCGAATGGGCCAACGGCATAGCCAGGACTGGACAGCGAGTGCCCCTGGCCGGGTGG
CGGCTG
249 27 ATGCCCACCCAGTTCCAGGAGGTGGAAGTGATACTCAACCGCTTCTTTGTAAAGAAACTGTCTCGGCCCGAC
CTTACGTTCCATGAGTACCAATGCCAGTTCACCCAGGTTCCAGAGCAAGGCAGCGAACAAAAGGCCATCAGC
AGCGTGTGCTACAAGCTCGGTGTGACCGCCGTGAGGCTGGGCTCATGCATCATCACCAGGGAGCCCATAGAC
CCTGAAAGGATGCGCACCAAAGATTGGCAGTTGCAGCTGATCGGATGCCGAGAGCTGAGCTGCCAAAACTAC
CGAGAGAGGCAAGCTTTGGAGACTTTCGAGCGAAAAATCCTGGAGGAAAAGCTCAAGGAAACATTTAAGAAG
ACCATCATCGAGAAGGACTACGAGTTGGGCCTGATCTGGTGGATATCAGGCGAAGAGGGACTGGAAAAAACC
GGTCACGGGTGGGAAGTGCACAGGGGCAGGCAAATAGACCTCAAGATCGAGACGGACGAAAAGTTGTACCTG
GAGATCGACATACATCACAGGTTCTACACCCCCTTCAAGCTGGAGTGGTGGCTGAGCGAATACCCCAACATC
CAAATCAAGTACGTGCGCAACACGTACAAGGACAAGAAGAAATGGATACTGGAGAATTTCGCCGACAAGAGC
CCCAACGAGATTCAGATAGAGGCCCTTGGCATCAGCCTTGCGGAATACCACCGGCAAGAAGGTGCTACCCAG
CAGGAAATCGACGAGAGTAGGGTTGTGATCGTCAAAAAGATCTCTGACTACAAGGCGAAACCCGTGTATCAC
CTGTCTCAGAGGCTGTCCCCGATACTGACCATGGAGACCCTTGCCCAGATCGCCGAGCAGGGTCGGGAAAAG
AAGGAGATACAGGGCGTGTTCGATTACATTAGGAAGAACATCGGCACGAGGCTGCAGGAGAGCCAGAAGATC
GCGCAGGTCATTTTCAAGAATGTTTATAACCTTAGCAGCCAGCCCGAGATCATGAAGGTGAACGGTTTTGTA
ATGCCACGCGCGAAGTTGTTGGCAAGGAACAATAAGGAGGTCAACCAGACCGCTAGGATCAAGAGTTTCGGC
TGCGCTAAGATCGGAGAAACGAAGTTCGGATGTCTCAATCTGTTCGACAACAAACCGGAGTACCCGGAGGAG
GTACACAAGTGCTTGCTGGCGATTGCGCGGAGCAGTGGGGTCCAGATAAAGATAGATAGCTACTTCACGGGG
AGCGACTACCCGAAAGATGACTTGGCCCAGCAAAGGTTCTGGCAACAGTGGGCGGCACAAGGAATAAAGACG
GTGCTGGTCGTGATGCCCTGGTCCCCTCACGAGGAGAAGACAAGACTGCGGATCCAAGCTCTTAAAGCCGGC
ATCGCAACTCAATTTATGATCCCCACGCCCCAGGATAACCCATACAAAGCATTGAACGTTGCTTTGGGTCTG
CTCTGCAAAGCCAAATGGCAACCCGTTTACCTGAAGCCCCTGGATGACCCCCAGGCCGCAGACCTGATCATC
GGCTTCGACACTTCTACCAACAGGCGGCTCTACTACGGTACAAGCGCCTTCGCGATTCTGGCGAACGGCCAG
TCACTGGGCTGGGAGTTGCCTGACATCCAGAGGGGCGAGACATTTAGCGGCCAAAGTATATGGCAGGTAGTG
AGCAAACTTGTGCTGAAATTCCAAGACAACTACGACAGCTACCCTAAGAAAATTCTGCTTATGAGGGATGGA
CTGGTTCAAGACGGCGAGTTTGAACAGACCATAAGAGAGTTGACCCACCAAGGGATCGACGTGGACATCCTG
AGCGTGAGGAAGAGCGGTAGTGGCAGGATGGGAAGAGAACTGACAAGCGGCAATACTGCCATCACCTATGAC
GACGCCGAAGTGGGAACCGTGATATTCTATTCTGCCACCGACTCATTCATACTGCAGACAACCGAGGTAATT
AAGACAAAAACGGGCCCACTCGGTTCCGCGCGACCGCTCAGAGTGGTTAGGCACTACGGGAACACCCCGCTT
GAACTGCTCGCGCTGCAAACGTACCACCTGACCCAATTGCATCCCGCCAGCGGCTTTCGGAGCTGTAGGCTC
CCCTGGGTTCTGCACTTGGCAGACAGGAGCAGCAAGGAGTTCCAACGGATCGGTCAAATTTCATTGCTCCAG
AACGTGGATAGGGAGAAGCTGATTGCAGTG
250 24 ATGCTCACACAAGAACAATTTATACGCAACTTTAGCGTTATGGCCAATGGTGAAGTAGACTTCTTTCTTGGT
GCCGGTGCATCTATTGCGAGTGGAATCCCAACTGGGGGTGGCTTGATTTGGGAATTTAAGAGGACACTGTAC
TGTAGCGAGTGCGGCATCAGCGCCGAAAAGTACAAGGACCTGTCACTCCCAAGCACGCGCAAAACGCTCCAG
GACTACTTCGACATTAAAGGGTATTGCCCCAAACAATATGCGCCTGAGGAATACAGCTTCTATTTCGAGCAA
TGTTACACCGATCCCATGGCCCGAAAGAGGTTCATCGAGAATATGGTTAGTGGGAGGGAGCCAAGTATAGGT
TACCTTTGTCTCGCGGAGGCCGTTATGCAAGGCAAAGTTAAAAACATTTGGACTACCAACTTCGATAGCCTT
CTGGAGAATGCCCTCCATAGGCTTTACCCCATGAACAACGTTTTGGTGTGCTCCGAGGCTAATAGAGGCAGT
GTGTGCCTGCTCAACCCGACGTACCCAGTCATAGGCAAGCTCCACGGCGACTATCGCTATGATTGGCTCAGG
AACACCGAGGACGAATTGCAGCGACTCGAGACCAGCCTTAAAGGTTACGCGTCCAGCCAACTTACAGGGAAA
CAACTCGTCGTTATAGGATATAGCGGGAACGATGAGAGCATTATCAGTTTCCTCAAGGATTGCATAGATAAC
CCGGCACTGCTTACCAAGGGTCTGCTGTGGGCTGTACGACGCGGTTCCTGGGTAAACCCGAGGGTTAATGAG
CTGATAGAACGGGCGCACAAAATTGGGAAACCAGCCGACGTGATCGAGATCGATGGCTTCGACCAATTGATG
TTCTCAATATACCAGATCCAGAACTACCATAATGAGATTATCGACGGCCAAGGCAGGCTCCTCCAGGTCGGA
TCTGACATCCGCCTCACGGGGAAGCCCGTGGACAGCTTTGTCAAGCTGAACGCTTACAAGGCTGAGTACTGC
CCCCTTTGTAACGTGTTCGAGACAGACATCACATCCTGGAAGGAACTTCGGACCATAACCGGCAGCAGTGAC
ATCATCGCCGGTCTGTTCTCCAAACATATCTATTCTCTGTCTTCCGCAGACAAATTGAAGACCGTGTTCAGC
AAGCACTTTCTCTCTAGCATTAACAAGGAGGAGGCTCCCGAACGGGACATTCGACGGAACGAGAGTGTGTAC
ATTGGATTGATTTACCAGCTTATTAAGCGGACCCTGCTTTCAAAAGGGATGGTGTCCTTCGCTAAGAATAAG
GTCTATAACCCCGACAGCTGCCGCAGCGAGCAAGGCTACCAAGTTTTTGACGCCCTGGAGATCGCGGTCAGC
TTCGTTGATGGAAACCTGTACCTGAATCTTATGCCCACGGTACATGTGAGAGGCTCAAATGGCGAGAGTCTC
GACAAAGAGTCCTACCAAATACAAGTCAACCATGTGGTCAGCACAATCTACAATAAGCAATACAATGAGAAA
CTGCGGTTCTGGGAGAGCTTGTGTCTGGACAGTGGTAGAATAATCTTCGAGAACGACGGCTTCAGCATATCA
TTTGTCGCTCCCGCTGTCTCCCTGGGCGGCAACAATCGAAGAGCTAAGTGGCTTTCCATGCCGTCCTGCAAG
TATGACGAACCACTCATGTGCTTCTCAGACACTGACAAAAGCAAACGAGTTATTAACCAACTGAAGGGACTC
TGCCAGTACGGGCCAATCGACTGCTCTTATATGCGGGATAGCACCACAAGGCCCAGCGTTAGGCTGGCCGTT
CTGAGCCCGAACCAGGACATGGACCGAATTCTTGCACACCTCAATAAACTCAACACCCACGTCCAAAACAGG
GGCAGCGATAATTTCCTGCCCCACTATGAGGGCTTTGAGCAAGTTTACAGAAGGGCTCTGAGCGTCCCTACG
AAGGAGCAGAGCAACATCTGCATCGGATACAACGTGAACGCCATCCTCAAAATGTCTCCTGCAGAGTTTCTG
GCTTTTATGAAGCGGGGTATAGAGAAATACTCCCTTCGGTCAAGCGATTTCGATATACTCGTTATTTACATC
CCAGAGTCATTCGCGCATTTCCGGACAGCAACCGAAATTAGTAGCGACTACAATCTGCACGATGCGCTCAAA
CTGTATGCCACGGATAAGGGGATTATCCTTCAACTCATAGAGGAGAAATCTGTGAAGTCATACGACCCCTGC
AAAGTAATGTGGGGCTTGTCCACCTCACTCTACGCGAAGGCGACAGGGGTACTTTGGCATCCAGAGGCAATT
AGAAATGACACGGCCTACATAGGGATAAGCTACGCTTTCAGCGAAGAGAAAAGGATTTGTATAGGCTGCAGT
CAGCTGTTCGACTCAACCGGGACAGGTATTCGGATGGTCCTTAGAAAGATAAACAATCCGATATTTCTGGGG
CGATCCAACCCCTACATGAGGGAAGACGACGCTCGAATTATGATGACCGAGCTCAGGGAGCAGTATTACCAC
AGCGCACCTGTGAATACTCTCAAGAGGGTCGTGATCCATAAGACCACGCCCTTCATACGGGATGAGATAGCC
GGTATAATGCAGGCATTTAACGGCATCGAGGTCGAGCTGGTTCAGATTCAAGACTATTGCTCTTGGAGAGGC
ATACGCTTCGGCGGTGAGCCTGGGAAAACGGCGTTTGGGTTCCCGGTGAAGCGAGGTATGGCCGTAAAACTC
GACCGAGAAAGCTTCCTGCTCTGGACCCACGGCTGCGTGATTCACCCGGAACTGTCAGGCACGCATAACTAT
TTCAAAGGTTCACGCGGTATCCCAGCACCCCTCCTGGTCCGCAGGTTTGCGGGTAACGCAAGTGGCGACACA
TTGGCAAAAGAGATTCTGATGCTTACGAAGATGAACTGGAACTCCGGTGACAGTCTGTACAAAACCCTTCCC
GTGACCCTGGATTTTGCGAAAGTTCTCGCCCGCATGTCTAAGCAAGATGAGGCGATCTTTGATAAGGCGTAC
GACTTCAGGTTTTTCATG
251 62 ATGAGGGAAACCAACATCTACGAGCTCAGCGGCCTCGAAACCGTGAGTACCAGCTACAGACTTTTCGAGTTG
CAGGGCGCGCCAGAGTTCTCTCCTGAGTATTATGCTGGTGTGAGCCGCCTCGTGAGGACGCTTAGCAGGAGA
CACCAGGCACCCTTCACCAGTATCCAACGGGGCGAGACCATGTTGCTCGCTGCACCCGAGGCCCTGAGCGGT
GATCTCGCAGAACACCATAATCTGGCACGCTGGGTGGCGACCCTGAAGTCACTTGGAGATAGCATAGAGATA
GACTGCAGCGTGAGCGGAGATGAGCTGGACCCCATAAGGCTGCGATTCCTGAACTTCATGATCCAATCTCCA
TTGTTCAACCACGGCGAGCTCTGGCAGCCCAGGGCCGGTGATGCCTTCTACTACCGGAAGCCTGCCGACACG
TTCGACGGAATCGAACTGTTTGAGGGTATTGCCGTGAGGGCCGTGCCCTACCCAGGAGGCGGGTTCGGCGTT
ATGCTCGACGCGAGGACTAAGCTGATCTCACAGCGGGCTGTGGGCGCCTACGCGGACCCGAATTTCATAAGG
AGGCTGAAAAACACTAGCTGCCTGTACCGAATGGGAGACATCTGGTACGAGATAAAGATCAGTGGCGCGAAT
CAGACCGTTTCTCACCCCATCCTGTTTAAGGACAACCAGCCCGTGTCACTCAAAGCCTACCTGCACGAACAA
GCACGGCAGCCAATCCCCAAGTCTCTGATTGATCTTAAAGGTGACGGCGTGGTGTTGACCTATCGCGGCAGC
GATAGCGCCGAGGTCAAAGCGGCACCCGCGGAACTTTGTTTCCCCATAGTAGACACCCATAGCAAGAGGGGT
GCCCGGCACCAGAGAAGGAGCATCCAAGCCCCACACATCCGACGCAGCAAGGCTTACCGATTCAAGCAAAGG
TTCTTGCGGGACATCAAAATAGGAAATGCCGTGTTGAGCGTGGCCGACCAACCCGCAGCCCTCAAGACCAGG
CCCATCGACTTGCCCGAGCTGCAATTCGGCTCCAATAGGATTCTGTACGGCACGGACAGGGGCGGAGACCGA
ATCGACCTTCGCCAGTATGCCAAGAATCGGCGAACGCTGCTGGAGCGCGCAGACGTGGGCTTCTTTGAGACT
TCTCCCCTGGAGCCCCAATGTTTGGTACTTCCTAAGAGCGTGATGAACGCATGGGGCAACGAGTTCGTTCGA
GACCTGACTGCCGAAGTGAAGCGACTCCACCCCACCGGTAACTACAAGCCAACCGTAATCGCGTTTGATGAT
GTCAGCGCAACCGTGGACGCCAGGAGCCAAGCAGAAGCCATCTTCAAGCTCGCGGAAGACGGGGATCTCCCT
CCAGGCGACTGCGCCATTATGATACACCGAACCAAAGGAAAGGCAAGAGCGCAGGAGGAGCTGCCCGCACTT
CTTATAAACAAGCTGAGAAAGAGCTACGGAGTGAATGCCGCCATATTCCACGCGACTGTCCCCGGCAACGCC
TACCGAAGGGAAAGCGCCAGCGATGGCGCTCGCTATGTGCGCAAGCGGGATGAGAAGGGCAGGTTTAGTGGA
TACCTGACCGGAGCGGCGCTTAACAAGATTCTTCTGCCCAACGCCAAGTGGCCCTTCGTGCTCAAGGACGAG
TTGGTGGCAGATATAGTGGTGGGCATAGATGTGAAACATCACACCGCAGCTCTCGTTTTGATCGCCGAAGGC
GGGAGGATTATCAGGCACACTCTTCGCCTCAGCACCAAGAACGAGAAACTCCCTGCTGGTATCGTGGAAACG
AAGCTGGTGGAACTGATTTCAAATGAAGCACCACACCTGAGCAGGCTCACCAAAACAATCGCCATCCATAGG
GACGGCAGGATTTGGCCCTCCGAGCTTAAGGGATTGCGAGCAGCCTGTAGGAAGCTTGCCGACGACGGCCAC
ATCGATCCTGCGTTCGATCTGAACGTCTTCGAGGTGAGCAAAAGTGCCCCTGCTAGGCTTAGGCTGTTTAGC
GTCGACCGCAGTGCTGGCAGAAAGCCGAGGATTGAAAACCCGGAACTGGGGGACTGGATGATGCTGACAGAA
ACCGACGGCTACGTTTGCACGACCGGTGCTCCGCTGTTGAGAGGTGGTGCGGCTAGACCCCTGCATGTAAAG
CAGGTCGCAGGTGATATGAGCTTGCAGGACGCCCTTTCCGACGTGTTCCGACTGAGCTGTCTGACCTGGACT
AGGCCCGAGTCATGTAGCAGGTTGCCTATCAGTTTGAAGCTCTGCGATATGCTGCTGATGGACGAGGGAACT
GCCCACGACGAGGACGAAATCCTTCATGCTAACGACGACACCCCAGCCGTTAGCGCC
252 55 ATGGCGTTTAGGCCCGGTGAACGAGTCAGACCGCAGCTCGCGCTGAATGCGATCAGGGTCCTTACACCCCCT
GGCACCATCCCCGCCAGTGTAGTCCAATTCGACAGAGCGCTGCTGCACGCATATCTTGACAGACCCGAGAAC
GACGTATTCGCTACCCGACACGGGGAGACTGATATGGCGGTCGTACCCCTGACCAGCGGTGCGAACCTGCCA
ACGGACAGAATGGGGCTTCCAGCTGCAGAGCACCTCAGGCTGGTATCTGCGCTGACAAGAGAAGCTGTGTTT
CGCCTCCTCGCGGCCAGCCCGGAAGCGGATCTGCTGATCCGGCGACGCCCACCGACCGTCGCGGGGAAGAGA
GAAAACGTACTTGCAGAGGACATTGGGCTCCCGGACTGGTTGAAGAAAAGACTTGTGCTGGAGTTCGACACG
CGCATATTGCAACCACCGAGAGGGGACGCCTACGTGGTGCTGACGTGTAGTAAAAGGCTGCGCACGACAATA
GACGCGAGTTGTCGCACCCTTCTGGAACTCGGTGTACCACTGACGGGTGCCGCAGTCAGCTCCTGGAGGGAA
GATCCTGACCCCAAGGTGAGCCGGCGATTGGCCTACGCTGGGCGCGTTGTAGAAGTAGGGCAGGACACGCTC
ACTCTGGACGACCACGGAGCTGGTCCGAGTGTTGTCTCCAGCGAAGACGTGTTCCTCGAGCCGACTCGAGCA
AACTTCAACAAGGTGGTGGAAGTGATAACCCAGGGTAACTCCGAACGAGCCTTCAAGGCCGTACAAAAAGCA
GAAGCCGAATGGCACGGCGGGAGGCGGACAATCGAAATAGTGCATGGTGTCCTCAACCAACTCGGCAACCGG
TCAATGGTTCTTGCCGATGGCGTGCCTCTGCGGCTCGGGGGCTTGATAGACCAAGCGGTCGATAGCGACGCA
TTCCCCCCAGCCGAGGCGGTGTGGCGCCCTAAGCTCTCATTCGACCCCGTGCACAGCCCCGAGACATCAAAT
TCCTGGAAACAGCAGTCACTGGACAGGACGGGCCCTTTCGATAGGCAAACCTTTGAAACAAAGAGACCGCGA
ATCGCGGTTGTCCATCAGGCCGGAAGAAGGGAGGAAGTGGCTGCGGCGATGCGCGATTTCCTCCACGGAAGG
CCTGACATCGCCAGCGATACGGGCCTGGTTCCCCACGGTTCAGGACTCCTCGGACGCTTTAGGCTCCACGAA
CCCGAAGTGAGATACTTTGAGGCCGCAGGCAGGGGGGGACCCGCTTATGCCGACGCAGCACGGAGTGCGCTC
AGGGACGCGGCGTCAAGGGACGAACCATGGGACCTCGCAATGGTGCAGGTAGAGCGGGCGTGGCAAGATCGC
CCACATGCCGATAGCCCGTACTGGATGAGCAAGGCAACGTTTCTCAAGAGGGATGTGCCGGTGCAAGCCCTT
AGCACAGAAATGTTGGGTCTTGATGCATTTGGGTACGCGAACGCACTTGCGAACATGTCACTTGCAACGTAT
GCGAAACTGGGCGGTGCCCCGTGGCTTTTGTTTGCCAGGTCACCAACCGACCATGAACTGGTGGTCGGGCTC
GGAAGCCACACTGTAAAAGAGGGCCGAAGGGGTGCGGGTGAGAGGTTTGTCGGTATCGCGACCGTATTCAGC
AGCCAGGGCCATTATTTCTTGGATGCCAGGACAGCCGCGGTCCCGTTTGAAGCCTATCCTGCTGCCTTGAGC
GACAGCATCGTTGACGCGATCAAAAGGATTGGACGAGAGGAAGCCTGGCGACCAGGCGAGGCCGTCAGGTTG
GTCTTTCACGCCTTCACCCAGTTGAGCCGAGAAACCGTTCAGGCAGTGGAGAGAGCAGTAGCAGGCATCGGG
GCCACCAACGTAAGCTTCGCGTTTCTGCACGTTGTCGAAGATCACCCGTTTACCATGTTTGACCGAGCGTGG
CCAGACGGAAAGGCGACATTCGCCCCTGAAAGAGGTCAGGCGCTTCGACTCTCCGAGCGCGAATGGTTGTTG
ACACTTACCGGCAGGCGCGAAGTTAAGAGCGCCAGTCACGGGCTGCCTGGGCCGGTTCTGTTGCGACTTCAT
GACAGCAGCACCTATAGAGACATGCCCGTGCTCGTCCGACAAGCATCCGACTTCGCCTTCCACTCTTGGCGC
AGTTTTGGACCCAGCGGACTCCCCATCCCGTTGGTTTACGCGGACGAAATTGCAAAACAGCTCAGCGGCTTG
GAAAGAACCCCCGGATGGGACACGGATGCGGCTGAGGGTGGCCGGGTTATGAGAAAGCCTTGGTTTCTG
TABLE 19
Argonaute nucleic acid sequences containing 2 nuclear localization sequences
and a cloning sequence
SEQ
ID NO Argonaute Sequence
253 36 GGTGTCGTGAGGATCCATGCCTAAGAAGAAAAGAAAGGTGGAGGATCCAAAGAAAAAACGCAAGGTGGGTAG
CGGCAGCATGCCATCAGCCGAGAGGTGCATCTGGGAGTGGAAGAGGGAAATCTTCATCACTAAAAACCCCTT
GCTCAGGGAAACCGTCGGCGAGCTGTCCCTCCAGGGCACGAAGGACCGAATCCAAAAATGGCTCGATCAACG
CGGCGAATACCCCGCACTGAACTCCCCAGAGGAATACTCATTTTATGCCGAGGAGTGCTACATCACCGAACA
AGACAGGCGGAGCTTTTTTCAGCAGTACGTAGAGGTCGCCAAGCCGCACATAGGTTATAGATTGTTGCCCCT
GCTGGCACAGACCAAGATCATAAAAACTGTATGGACGACTAACTTTGACGGGCTTGTCGCCAGGGCCTGTCA
TTCCAACGACGTGGTGTGCATCGAAGTCGGTCTCGACAATACCCAACGCATTACGCGCCAGCATTCTGAGGG
GGAGCTGCGGGTTGTAAGTCTCCACGGCGACTACCGATACGATGAGCTTAAGAATACAGATGAGCAGCTCAG
GTACCAGGAGGAGGCGCTTAAAAACAATATAGAGCACGAGCTGCAGGACTACGACCTGGTAGTGATCGGTTA
CTCCGGCAGGGACCGGAGCCTCATGAACGTACTCGAAAACATATTCAGCAAGGCCGTGAAGAGCAGGTTGTT
TTGGTGTGGCTACGGCGAAACGATAAGCCAGCCCGTTATGGAGTTGTTGGAGCTGGCCCGCAAGAATAATCG
AGACGCATTCTATGTCAGCACCGAAGGCTTCGACGACACCGTTGAAAGAATCAGTAGGAAGCTGCTTGACGG
CAACATGCTGTCCAAAGCCTTGGCTGAGATACAGGAGACCACTTGCATCACCAACCAATCTGCCAAATTCAC
CGCACCTGAAAACGACATCAGCAGCCTTATTAAGTCAAACGCATACCCCCTCCTGAAGCTCCCGTCTCAGTT
CCTTAAAGTGACCCTCAAATACCCGGAGGGGTCCTTTAGTTACATTGATTGGCTTAACTCCAAGGTTGACTT
CAAGGAGGTTGTGTTGTCTAAGATAGACAAGGAGATCATCGCGTTCGCGGATGTTGATAAGCTGAGGAAGTA
TCTGGGCGAGTTCTACCTGTCTACGCCCACGGTGGTGAACTTTAGCAAAACGGACGTGCTTAACGATACTCG
CATTCAGAGTCTGGTGAGGCGCGGACTTATACAGTCCATCGTAAAAAACCTGAACCTGTCCAGCGACCAGAA
CAAGCGAATATGGAATCCAGACGTGAGCTCCATCGAATTCTACAACGGCAAGAAGTACAAAATCATCGACGC
GCTCATCCTCAATCTTAGTTTTATCAAAGATGACATCTACCTCACGTTCAAACCCGATCTGCTGGTCCTTAA
CCTCGACGAGAGCCTGCCAGACAACGATATAGTTTAGACTATCAAGAACAAAAAGTTCGGCTACCAGCACAA
CAAAGAGTACAGTCAGATCCTGGAGAAGTGGGCCAACCTTATAACGAAGAAGGATTTGGTCGTGAGTGGCGG
GAGCGTGTTCTTCCTTGGGAAGAAACCGCTGTATGCCGGACTTGTGTCTTACGCCGCGAGGAAACTCCCAAC
AGATTATAACAAGCACGCCACCCAGAAAGGACTGATCATTCAAGACGCGAAACTGATTTTTTGCAGCAATTC
CATCTCCAATGAGATTTCTCACATCAACCCCCTGAAGGGGCTCGTGGAAAATCGCCCGTGGGACTACAAAAA
CACCAGCTCTGGGCTGTGCCCCGAGATCTGCATTAACGTGATCTCAACCAGGCAGGACGCGGGTGTGGTGAG
CAACCTTCTCCGAGGTATTCACGAGAAGTCCTTCCCGGAAAAATCCGAGCAAGATTACTTGCACCCCTTCCA
TGGGTTCACAAACGCTTTCGGGGTGCCCATCACGATCCCTAAGATCGGTGAGAATACGTGGCGCTTTGTGGA
CGAAGCACTGAGTGCACAGAAGGCCATCGATAACGCGAAGAACCTCGCGAACCGCATTTGCTATGAACTTGA
CAGCCTGAAGAAGCTTGAACTGCGGACGGGCACCGTCGTGATCATATACATCCCCAAGAGATGGGAAGCATT
GACATCCATCAAGTCTGAGCATGAGTACTTCGACCTGCATGATTACATCAAGGCCTATGCTGCGCAACAGGG
CATTAGTACGCAATTCGTGCGCGAGAAAACGGTTAATTCAAGCCAAAGCTGCCGGGTAAAATGGTGGCTCAG
CCTGGCGTTCTACGTGAAGGCTATGCGCACTCCGTGGCGGTTGGAGAGTATTGATAACCAAACGGCTTTCGT
GGGGATAGGGTACAGCATCAATCGCAATATGCATCCCGAGAATTCCAAGCGGATAATTCTTGGATGCTCCCA
CATATACTCCGCCCGAGGCGAAGGCATGCAGTTTCAACTTGGGCGAATTGAAAATCCCATTATCCACCATCA
CAATCCCTACATGAGCGAGGAGGACGCTAGACGCACCGGCGAGAAGATACGACAAATGTTTTTTGATGCCAA
GATGCAACTGCCACGCAGGGTCGTCATCCACAAGAGGACCGCTTTCACTGAAGAGGAACAGCGGGGGTTCAT
ACAAGGATTGGAAGGCGTTGAGGACATCGAGCTGATCGAAATTAACTTCGAGGACTCCCTCCGCTATTTGTC
TAGTAAGTTTGTAAACAGCAAGCTGGAAATCGACGGGTTCCCCATCGCTCGGGGGACCGTAATCGTGCAAAG
CAGCAACACCGCGCTCCTGTGGGTGCATGGTGCAACCCCTAGCGCGCAAAATCCAACGTTTAAGTATTTCCA
AGGCAAACGACGGATCCCCGTGCCCCTTGTCATAAAGCGCTACGTGGGGCAGAGCGACATTAGCCAGTTGGC
GAACGAAATATTGGGCCTCAGCAAAATGAACTGGAACACCTTTGACTATTACTCCAGGCTTCCTGTAACCCT
TGAGAGCGCCAATGATATTGCCCGGATCGGCGTGTATTTCAACAATTTCTCCCCCATGAGCTACGACTATCG
GCTCCTCATATAGTAACTCGAGGTTAACTTGT
254 90 GGTGTCGTGAGGATCCATGCCTAAAAAAAAAAGGAAAGTCGAAGATCCGAAAAAGAAACGCAAAGTAGGGAG
TGGTAGCATGATCAAACACCTCAAGTTCGACGAGTTCCTTCGCAGCGTGTCAATTAGTAAGGATAACACGTA
CTCCATGCTTATCGGTGCCGGGTGCTCAATCACTAGTGATATCCAATCTGCCTATGACTGCATATGGGAATG
GAAGAAAATAATTTACAAGTCCAATAACTTGAATACTCAGGACTGGATAGAGAATTACAAATCCCCCAAAAC
ACAAGACGTGATACAAAAATGGCTTGACAACCAGGGAAACAACCCTGAGAAAGATAATATCGAAGAGTACTC
ATTCTACGCAAAGAAATGCTTTCCGATAGATGAAAATAGACGCCAGTACTTCCAAAAAATCTGCGCTAATAA
GAAGCCCAGCGTCGGATATCGAGCCATTCCTCTCCTGGTGAAGCAAGGCATGCTCGACTCAATTTGGACAAC
CAATTTTGATGATCTTGTTAATGTGGCGTGTATAGGTGGTGGCGTTCAGGGGATTGACATATCCCTTCAGAC
GGTAAACCGCATAAATCAACGCAATCAAAGCAAAAATGAACTGCCTATTATAAAGCTCCACGGGGATTTCAA
GTATGGCGACCTTAAGAACACGAGTGAGGAACTTCAGAATCAAGACGAAACGCTTAGATCAAAACTTTTGGA
CTACTTGAGCGATAAGAATCTCATAGTCATTGGCTATAGTGGTCGGGACAACTCACTCATGGAGAGCTTGAA
AGAGACTTATTCAAAACCTGGTGCGGGAATATTGTTTTGGTGTGGGTATGGGAACAGTCCATCAAACCAAGT
GAAGGAACTCCTTAAATTTATCAAGGATAAGGGGCGCAGCGCATTCTATGTTTCCACTGAGGGATTCGATAA
CACCATGCTGAACCTGACCAAGCATGTTATTGAGGACGATGATAACCTCAAAGAGGAATTCAGAGAACTCAA
GAAGAGTATCATTAATAAAAATACAACGACCCCGTTTACGTTGAACCCGGAACGAATCAATAAGGTACTGAA
AAGTAACCTCTTTCCTATTACATTCCCCAAAGAGATCTTCGTATTCAATGCGACCTTCGATAAGAAACCTTG
GGAGCTTGTTAAGGAAAAAACTCTGAGTGACTATGAAATTTCAGCGATTCCATTTGAAAAAGACATATGGGC
ATTTGGGACTGCTAATAACGTCTACGAAAAGTTTGCAGATATCATTAAGGGCGAGATCCAACGGAAGCCCCT
GACCGATATCCGGCTTTATAATCACAACATAAAGTTCCTGCTCCTGTCAAGCCTCTGCAAGCTGTTCTCAAA
AACCTACAATCTGAAAACGGACTTTCGGTCTAAGATTTGGGATGAGAGCTCATACAAAACGGTTCACAACCA
AAAGGTCTATAACGCTATAAAGATCGATCTCGTCAAAATACAAGAACAGTCATATTTGTCACTCAATCCAGA
CTTTCAATTGGCAGATGATAACGTTCCCAATGATATCAACCAGCAGGTTGGACTGGAATTTTTTCATAAGAT
CTATAACGACAAATTTAACGACTATATAAACATCTGGAGAAAGAAGATCCTCGAAACTACGTCATACGAATT
GCCACTGAACTCCGGCACCGGGTTCGTATTTAAAATCTCTAAGAATCCAATTTTCACAAATATAGATGACCT
TAATTCCAACTATACGAACGAGCACAATATACCCATAAACATGATTAAACTTAAGGGGGTTCAATTCAAAGA
GACGAACCTCCTCTTTAGTTCACAAAATGGAGATAAAGTGGTTAAGGAGACCCACCCAATGAGAGGCCTCGT
CAATCATAGCCCGTTCGATAAGGGATTGAGTAGTCTTAAAAACACTACGATCAACCTGGGGATCGTATGCCC
CCAACAGGATAGCGAAAATTTTTATACTTTTTTGAATAAACAAAACCAAGAGATTAAGAACGTTAATATTAA
GGATCAATATGTAATCGATTACAAAGGATTTCACAACACATACGGTTTGAGTCTGAACATACCTACTACGAG
CAGTCCTAATTGGGAAATGACTAACGAGCCTGTCTCAAGGGACTCAAAGAAAATAATTCATGAAATCAAGAA
TAATATTTGCGACAAGATAAATAAGCTTTGTAGTATAGGCGGACAGAAGACAATAGTAATATTTATCCCTAA
ACGCTGGGACAACTTCGTACACTATAATGATGCCGTGGAAAGCTTTGATCTTCACGATTATATCAAAGCGTT
CTGTACCGAAAAAAAGGTTACGTCTCAGTTGATACGGGAAAAGACGATACTCGATAATAACCTCGAGTGCCA
GATCAACTGGTGGTTGTCACTCAGTTATTTTGTAAAGTCCTTCCGAACACCGTGGGTAATCGACAACACCGA
CAATAAAACAGCTTTTGCGGGCATTGGTTATTCAGTAGAGTCCAAAAAAGAGGATAAGGGGCACATTATACT
TGGCTGTTCCCATATTTACAGTAGTAACGGGGAGGGTCTCAAGTATAAGCTTTCCAAGGTTAATGATAAAAT
AGAATGGATCAAGAAAAAGCCGCATCTGTCCTACGACGATGCTTACGAATTTGGTAAAAATGTGATCAACCT
GTTTTACGAAAGCATGAATGAGGTGCCAAAACGAGTGGTAATTCACAAACGCACCTTTTACACTGAAGATGA
GAAGCAAGGCATACTTGACTCTTTGCACGATAACAAGAAAATAGAAAACATAGACTTGATAGAAATAAATTT
CGAAGACAACATAAGGTACGTCTCCTCTAAGATATATAATCGGGAGGCAAAAATCGACGGTTACTCAGTATC
ACGCGGTACCTGTATCCTTCTTAACGAAAAAGAGGCACTTTTGTACGCCCATGGCGTAATCCCGAGCGTGAA
GAATCCGAGTTATAATTTTTATCCGGGAGGAAGGTACATACCGAAGCCATTGAGGATAATAAAGCATTATGG
AGTTGGTTCCCTGGAACAAATAGCAAATGAAATACTGGGTCTCACTAAGATGAACTGGAACTCTCTGAACAT
GTATAGCCAAATGCCTGCCACGATCGACTCAAGTAATAAGATAGCCAAAATAGGGAAACTCATAGAGAATAG
GGATAAAGTAGAGTACGATTATCGGTATTTTATCTAGTAACTCGAGGTTAACTTGT
255 18 GGTGTCGTGAGGATCCATGCCTAAGAAGAAGAGGAAAGTGGAGGATCCCAAAAAGAAACGAAAGGTCGGCAG
CGGTTCTATGAGCGAGCTGGAGACCAACATCTTCCCAATCACCAACTTGCATGAGCTTGAAAGCAGGTTCAG
GTTGTATAGGGTGAGGGGCCTGAGCATCAACCAAGAGGAGTACGACCCCAACACCCAGACATTGGTGAGGAA
GCTGAGCTACAGCATGAGGTCTCCCGTAGCTGTGATACTTAGGAACAGCGACCCGTTCCTGGCTCTTCCAAT
CGACGCACCCGAGCCCATCTCTCCGTACCCGCTCGTGAGAGCCACTGCTGTGTTCGAGAAGACGGACGAGGT
ATTTACTCTCGATTACGAAAGCCCAACTCCCGAGACAGATGCGCTGCGAATAAGGTTCCTGCAATTTATCAT
CCAAGGCGCGCTGTTTAGGAATCCCAGCCTGTGGCAGCCCTCAGCTGGCACCCCCTTCTTCGAGAGGAGCCC
CGTGTTGGAGAAGGCCGGCATTTGCGCGTACCGAGGCTTCTCAGTGCGAGTCGTGCCCATAGAAGGTGGTAA
ACTGGGAATCTGTGTGGACGTTAAGCACAGGTACGTCAGCAAAAACCCCATCGAAGCAAACATCAAGCGCGA
GGAATTCAGGAAATACAAGAACGGCAGGTGCATATACCACTACGGCCACAACTGGTACGAGATCAAGTTGCA
AGACCACACTGGGCTGTCCGTGTCAGAGCAGATGATCAGCAACGGGACGGCCAAACCCATAAGCTTGTATCA
GTTCATTATGAATAACGCGCCCAAGCCCCTGCCCAGGGAGGTCATAGACATGCCTCCCGACTCACCCGCAGT
CAAATACATGACCAGCAGGGATGAGGTGCGCTACGTGCCCTCCATCCTTTGTTATCCGGTCTTTGACACCTC
TGACCCCAGGGTGAAGCCGACGCATAGGGGCACAATCCTCCTCCCTAACGTGAGGCGACAGTATATCCACAA
TTTCGTGAACTCACACCTGACCGATGTGCGATCCAAAGACATGGCAATCCGAATCAGCAGCAAGCCAGTTAT
CGCCCCTACCAAGATTTTCCTGCCGCCTGACCTGGCATTCGGCAACAACACCGTGTTCAGCGTAAGAGGCAC
ACCCGGGACCACGTATGTTAGCCTGGAGCAGCTGGGCCAGACGCGGATAAGCGCCCTCTTCAATCAGAAAAT
AGGCCCTTATGACAGCAGGCCGCTGGATAGGCAGTACATGATTCTGCCGAAAAGCGTGTGGGACTCCCACGG
GCCAGTATTTCTGAATGACTTTAAGAAAATCATGAACGAGCTGTACCTGCACGAACTGCCCTACAATCCCAT
CGTCGTGACCTACAACGACTTGAGCGCCAAGACCTACGCGCTTCAGGGAAGGGCTATTCTGGACGCCGTGGA
CAGCGAACTGAGAGAGCCGGGATACGGCGTGGTTATGATACACGAGACGGTGGACCGCCGGAATAGACAGCA
CGACCAGCTTGCCGCGATGGTGATGAGGGAGCTGCGGAACAGGAGGCTGTATGTGAGCGTGATCCATACCAC
GGTGACGAAGGACTGTTACCAATTGCCCCAGAACGCCCCCATTGGCAAGGCCTACTGCCCGGTAGCAGGCAA
GCAGGGCAAACTCAATGGCTACTTGAGGAACGTGGCCATTACCAAGGTGCTTCTGACCAACGAGAGGTGGCC
CTTCGTTATATCTACCCCGCTGCATGCGGACTTTACCGTTGCCTTCGACGTGCAGCTTAACACCGCTTGCTT
CACATTCATCGGCAAGAGCGGCTCCGACATCCGGACCGTTTTGAAGACCAGTAACCAAAAGGAGAGGTTGAG
CAAGGCACAAGTAAGGCAGACGCTCCTGGAAGTGCTCCGCCAGGAGGTTGGCTTCGGTCGACGGACCATGCA
GACCATAGTGGTTCAGAGGGATGGCAAATTGTTTGCCAGTGAGATCGCGGGAGCAAAAGACGCTATAGAGAT
AGTGAAGAAAGAAGGCATCTTGCCCAGCGATGTGTCACTGAATTTCATCGAAATCCCCAAGAGCAGCGTCGC
CCCATTTAGGCTGTTCGATAGCAGCCCCAGGCCAGGGCAGCCTGAAATGGCGAACAACCCAAGAATCGGCTC
CTACTTCATCGCGACGAATTACGACGGTTACATTTGCACCACCGGCAAGGAGTTTTACCATCCCGGTACGGC
AAATCCTCTCCACGTGAAGTACATCGAGGGAAATATGCCATTTGAGAAGATCCTGGAGGACGTGTACGCCTT
GACTTGCTTGGCGTTGACCAGGCCCGAAGACTGCACAAGGGAACCCTTCACCATGAAACTGGCCGATATCCG
ACTGAGGGAACATGCCGGAGGCTACGACGAAGATGCATTGGCGTATGATGATGAAAATGAGAACGACGAGGA
TAACGAGAATGAATAGTAACTCGAGGTTAACTTGT
256 57 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGAGGAAAGTGGAGGATCCAAAGAAAAAGAGAAAGGTGGGTAG
CGGAAGCATGACCGAGGCCTTCCTCACAACCAGGAGGGGCTTCGTGCAAAAGCTGACGCTGACCAGGTACGA
TTACCTGAACTGGATCATCGAGTCCGAGGCGCAGAAAGCCAAGCTGAAGAACTGGCTTAAGAACAAGAGCGG
GTTTCTGACCCACGAGATCGAGGATACCTGTTTCTTCACCTTCGAGAGGCTTCTGGAGGAGAGTACTAAGCA
GTATAGAGCCTCCGGCGAGAAAACTCTGTCTGCCCCGTTCAAGAACACGCAACTGATCTCAAATCTGATCGG
TACCATATTGAAAAAGGAGTTGAGCAAGAAATACAAGCAATTCTTTAGTCAAAACATCTTCATCGTGAGCAC
CATCGATCTGTATCCATTCAATCTCTTGAAGGCGTTCGAGTTCAACATCGAAGTGTTTGACAGCGGCCACTT
CCTTATCCACGTCAACCCAGTGTCTAAAATTGTAAGCAGCAAGGTTGTGGACAAGGAGTATCTGGACTACCT
CAAGAAAAGCAACCTCAACAACAGCAAAACCACCGAGATGGAGTTCGCGGTGATCAACCATGAAAGGAATTT
CAGACTTAAATTCGACCTGCTTGACGAATGCATCTTTGAGAAGATAGAGAAGCTGCACAGCGAGAAGAATAT
GTTTACAGCCACTTTTGATTACCATTTCCTGGCCAACTTCAGCCCCGAGATCTTCGGCAAAATCGTGGAACA
TACTAGCAAGGATCTGAAGCAGGCCATCATGTTCCTGAATGACATACTGAGCAATATCAAGCTGCCGAGCTT
TCTCAACCTGCACGAGGAACGATACTTTAAGGTCAATATCTCCGAATTGGACCGAAAGAATAATCTTCTGAT
TGGAAGCAGTTTCGAGGTAATAACCATATACTCAAAAAGCCAGACCCAGTATGGACTGAGGATTGAGTTCAC
TCGCGACAGCATAAGCCGGGACGAGCTTATAACAATCTTTCTGAAAAACGAAGAGCTGATCGAGAAACTCAA
CGACATTAAAGTGGTCCCCGCCACCATCAACGCAAAAATCGAACAGAAGACCGGCTGGAAAAACCCCTACAT
CACCAATGTTTTCATCGATAACGTGGGTGCCTTCAGCACCAGCAGCCTGCAAAGCGCCTCATACTTCCACGG
CATCTACAAGGCCGTTAACAACTGGAATATCCTGCCCATCGTGTACGAGGACCTCGACATCAAAGTATTCGA
GAACCTGATGCTGCACGCCTTTAACAAGAACGCCACCGAATTCAAGATCCTGGAACCCATCATAATCAAGTC
CACGAACGAAATCGACAAACAGGAGGTGCAGAGGAGCATCAAAAACCAGGCCGGCAAGACCATGATCGCAGT
GTTCTGCAAGTACAAGATACCCCATGACAGCTTCGCCCCCCTCAAGGGCTTCAAGTATCAGATCTATCAAGG
CGACACCACGGACAATAAGCAGAATAGGGCCAAACTGAGTAACTTCACGTGCAAGTGCCTGGAGAAAATGGG
AGGGGTGATTGCGGCAATCGCGGACACAAGCATAGCCGAGGATGGATATTTCATTGGCATCGACCTTGGCCA
CACCACAAATGGCAAGGAAAAGTTCTCCAACCTCGGAGTGAGCTTGTTTGATAGCCTGGGCATCCTGTTGGG
CGATTACGTGGAGAAGGAGATTCCAAGAAGGGAAAACCTCATCGACACGAACTGCCTCAATGCTTTTAAGAA
ACTTGACAAAATGCTGGAAGCTAAAAAACTGAACAAGCCCAAACACCTGATCATCCATCGGGACGGCAAACT
GCACTTCAAGGATATCAACATTCTCGTAAGCTGCGTGGAAACCGTGTGGGGTAAGATAAACGTCGATATAGT
CGAGATCATTAAGAGTGGCTTCCCCGTGATGGCTATAAAGGACGAGACCAACAAACCAATCAATCCCATAAG
CGGGACCAGCTACCAGGACGACATCCATAAGTACGCCATACTCGCCACAAACGTACAAGCCGACGAACAGTC
AGCCGTAATAAACCCGATAATCATAAAACACAAATACGGAGAGCTGGAGTTTAGCAAAATAGTTGAACAGGT
GTACTGGTTCACGAAAGTGTATACCAATAACCTGTACAATAGTACCAGGCTCCCAGCGACTACACTCAAGGC
CAACAACGTGGTTGGCACGTCTAAGAAGCTCCACAGAAGTACATACTTGGGCTAGTAACTCGAGGTTAACTT
GT
257 59 GGTGTCGTGAGGATCCATGCCGAAGAAGAAACGAAAGGTGGAGGACCCAAAAAAGAAGCGGAAAGTGGGGAG
TGGCAGCATGTTCGTGGAACTGAACGCCTTCCCCATCGACATCCGCAATATCGGTATCGTGGAGGCCTGCGA
GGTGCCGTACGACAAGGAGGTGCTTTATAGCCTGCATGATAACCCACAAAAAGATTACCATGCTATCAGAAA
CGGCAACCAGATATTGATATTTTCTAATAGCAAAAACTACCCCATCCAGGGTACAATCAAGGAGATAAATCT
TGCACAGGACTACCGCATCCTGTTTTTCCTTATTAAGGAGTCCATTATCAAGATCCTGACGCAGATCAAACG
GGAGCCTTTCAAGTTCAACCCGATTGAGTTCATCTCACCAAAGGAGAACATCACCGAGAATATCCTGGGAAT
CAATTACCCATTTCAAATAAACGCCAAATATTCAATCGATACCAGAATCATTCAGGGGGTGCCCTGCCTCAC
CATTGATTGCAGCACGAAGAAATACAACAAGGAATCCCTGATCTACTTCATTAACGACGGCTTCAACCTGAT
TAACAGGTACGTGATCTCAAAGCAAAACGAGAAGTATAAGCGCGTAGGTAAGATACTGAGCATTGACAACAA
CATCGTGACTGTTCAGAGCTGCGACAAGATAAAGAAGTACTCCGCCGAGGAAATCACCTTGGAGGCGAACTC
TAAGAACACCAAGGACTATCTGGCATACAAGTTCCCCTATAAGTTCGAGCAGATCCAAGAAAGCATTAAGAA
GGCGATCAGTACCTTCACCCAGGGGACCTCTAAGCAGATAAACATTGGCAAGATCTGGGACTTTTTCAGCCA
GAAAGGCATCTTCCTGTTCAACGGCCACCGAATTAACATAGGGCTGCCTCCCGACATCTCCCAGCAATGCAA
GAACCTTGTGTACCCGCGCTTTTTCTTTAGCAACTCCCGAGAAAACAATTCCAAAGAGAACGGCCTGAAGGA
TTATGGCCCTTACACCAGGAATTACTTTGACAGGAATAACCCCAGCATTTGCGTGATTTGCAACGCTAAGGA
ACAAGGCAAAGTGGAACAGTTCCTGCACAAATTTCTGAAGGGCATACCCAATAGCCATAACTTTAAGACGGG
CTTCGAGGGCAAGTTTCATATTGGCCTCTCTCAGATAGAATTTTTCACGACCAGCGACGACAGCCTGGGCAG
CTACCAGTTGGCTATCCAGAAGGCAATCCAAACGAGGACTAACCAAAACTCTAGCCAGTGGGACCTGGCCCT
GGTGCAAACCAGGCAGTCCTTCAAGAAATTGTTGGTGGAGCAGAATCCGTACTTTATTAGCAAGAAAATGTT
CTTTCAGCATCAGATCCCCGTTCAAGACTTCACCATCGAGCTGACCAATCAGAACGACAAAAACCTGGAGTA
TTCTCTGAATAACATGGCTCTGGCGTGCTATGCGAAGATGAATGGAAAGCCCTGGCTGCTTAAATCAAGCCC
TACTATCAGTCATGAGCTGGTTATTGGCATCGGGAGCAGCAACATCATCATCGAGGAGGACAGTCTGAACCA
GAGGATCATGGGCATCACCACCGTGTTCAGCGGCGACGGGTCTTACATGGTCTCAAACACTAGCAAGGCGGT
GGCGCCCAATGAGTACTGTTGCGCCCTCATAGACACACTTGAGCAAACGATCAAGAAGCTGGAGAAACTTAT
GAACTGGCAGAGCAATGACACCATTAGGCTCATCTTTCATGCCGCCGTGAAGACCTTCAACAAAAATGAAAT
CCTCGCCGTAAAGGAAGTGATCAAAAAGTATAGTGAGTACAAGATCGAGTACGCTTTTCTCAAAATCAGCAG
CGACCACGGTCTGCACCTGTTCGACCACTCAACTAAGAATGAGAATAAGGGTAAATTGGCTCCCAAGAGGGG
TAAGTATTTTGAACTGAGTAGCCATGAAATTTTGCTGTACCTCGTGGGGCAGAAAGAGCTGAAGCAGGTGAG
CGATGGCCACCCCCAGGGCGTGATCGTGTCCCTGCATAAGGACAGCAGCTTTCAGGACCTTAAGTACCTCTC
TAATCAGATTTTCAGTTTTAGCTCCCACAGTTGGAGGAGCTACTTTCCCTCTCCCCTGCCCGTGACAATTCA
TTATAGCGATCTCATCGCGGAGAACCTGGGCTGGCTTAACAAGCTGAGCGGCTGGGACGATACAATCCTGCT
GGGCAAACTTGGACAGACCCAGTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
258 73 GGTGTCGTGAGGATCCATGCCTAAGAAAAAGAGGAAAGTTGAGGATCCAAAAAAGAAACGAAAGGTAGGCAG
CGGCAGCGTAAAGCTTAATCACTTCCCCCTGAATCCCGCTCTTGCAGTGTTCAAGACTACCTACAGGCACAG
AAACCCCAGGGGCTTCCTGGGATTCGTTAGGTCACAAGGGTTGACCGCGGAGAGAGTTGGCGAGGAAGTGTG
TGTCTATCACGGTCTTCCCCACCCGGCTTTTAGAGGAGCCACCGCCCAAGGACACACCAGACTGGCGCCTGG
TGACACCGATTACGACAGGGGCGTACTTAGTCTGATCGGAGCCGCCCTGCTGAAAGCGGGTTACGTGCTTAC
TGAGCGCGAAAGGGCCGCAGTGCACCCCACGCAGCAGAGAGTGCCCCTGCACACCCCTAGGAAACTCCCTGC
CGAAATTGCGGTGAATGCCCATCTTCGATGGGAATGGGAACTGGAACGGCACAGCGGGAAGTCTTGGCTTGT
GCTTAGGCCCGGACGCATGTTTTTGAGTGCGCTGAGCTGGCACGATTTGGACCTGAGGGCATGGGCACAGGA
GTTGCCCCAGAGCGTACAGCAACTGCACGCGCTGTGTCTTCGCTCCGGACGACGAGAACGACTGAGGCGCAT
GGGTAACACGTGGGCGTTCCAACGAGAGGATAGGGAGCAAGAGGGCAGGTGGCACCTGAGCTTTAGCACTAA
GGCGCTTTCCGACCTGAACCTGTCCGGCGATGCTCACCATGCTGCTAGCCTGAGCATGCCCGATGTGCAGAG
GCTCGTAAATCTGCCGGGTCTGTGGCAGCCCTTTGTGACAAGCCTTGAAGTCCTTGAGGTGCCTGGTAAGGT
GATCGAGGGCAAAAGGCTGAGGTTCGGACGAGGAACAGGGCGCGACGTCACGGATGTACACAAAAGGGGCAT
CCTTCACCCTCCGCCGCAGCCAGTGCGCCTTGCGGTCGTGCCCCCCATTCAGGCGGACGAAGAGGCGGATGA
GCAGTTGAGACGCGAGCTCCTTGCCCACCTCCTGCCACGGGAAAAGGTGTTGGCCCACCCCGAGGCTTCCCA
GGGCCTCAAGAAGCACTTGAATCGAAGGGAAACCGACGACACCTTCTACACCCTGTGGAGCGCTGGAGACTA
CTGCAAACTGGGGCTGGAACCCTTTGATCTGGTGCGCGACCTCCATAGGTACGACCCCGGCACGGGTCGCCT
GCTGGCTCCAGAGAAGTTGCATGGAGCAGCAGCCGCCGCGAGAGAGGCTGGCAGGCAATTGATTGGCCTCGT
GATCCTGCCCGACACCATAGGGCGAGATGAGAGGGACGCACTGTCCGACGAACTGGCCAAGCTGGGTGTGAA
GAAACTTCAGCACATCCGCAGGGACATGCTGAACCGGCCCAGGACGCAGTATATGGCCTGGGTGAACGTGGC
CGTGAAGCTCGCCCAGAGGGCCGGAGCAGTCAGCTGGGACCTGGAAAAGTTGCCTGGAGTGTGCGAACAGAC
CTTCTTCGTTGGCGTGGATCTGGGCCATGACCATCGGGAGAAGCAAAGCGTCCCGGCCTTCAGCCTGCACGA
GTTCCGAGGCAGGCCGGTCGACTGCCTCACCCTTCCAAGGCGAGCCGGAAATGAAAGGTTGAGCCTGGCGGA
GCTGAATCAAGGCCTGAGGAAGCTGCTTAAGGGTAAGAGGCCAGCCCAAGTGATAGTGCATAGGGACGGCAA
GTACCTGGAGGGGGAGGTTGATGACTTCATAATCGCTTTGAACGACCTCGGCGTGCCGCGCGTCAGTCTTCT
CGCCGTCAAAAAGTCCAACCTCTCCATGGTTGCCGGCGCTAAGGAGGGAGCGTTTTTGCCACTGGACGAGCG
GCGGTGTCTGCTGGTTACCAATACCCAAGCCGCGGTAGCTAGGCCGACAGAGCTGGAGGTGATGCACTCAGA
TCATCTGACTTTCGCCGAGCTGACCGAGCAAGTGTTCTGGCTGACCCGAGTATTCATGAACAACGCACAGCA
TGCGGGTAGCGACCCTGCTACCGTAGAGTGGGCGAACGGGATCGCTAGGACCGGAAAGAGAATTGCCCTGTC
TGGGTGGTCCGCCTAGTAACTCGAGGTTAACTTGT
259 72 GGTGTCGTGAGGATCCATGCCGAAGAAAAAACGGAAGGTGGAGGACCCCAAAAAGAAACGCAAAGTGGGTAG
(Helicase) CGGCTCAATGCTCGACTTTAGCCTTACCCAGAAAGGTTGGGTGCTGCCCATCGTACTGAACGCCTTTCCGCT
CAAGGTACCGGACATGGAGCTCAAATTCGTGCAGATCCCCTACGACAAGACGACCCTGGACTCACTGAGGTC
AAGCCACAAGATGACCCACGTCTTCAGGAGGCAAGGCGACAGTATCCAGATCTTTTCTAGCGACGGCACCTT
TCCAAAGAGCGGCACCCCCCAGACCCTCCAACTGAAGGATAATCTGGGAATCTTTTTCTCTCTTGTAAAGGA
CGGCCTCCTCAAGCACTTCGCCGGTTTGGGCCGAACCCCGTGCGGATTCAACCCCATTGAGGTCGTGTCAGC
TCAGGCCAAAGACAATCTTCTGGCTAGCATCCTCGGAGAAGCCTACCCGCTGAAAATTTGCGCCAAGTACTC
CATCGACACCAGGACAGTGCAAGGTCAACCGTGTCTCATCATCGACTGCAGCACTAGGAGAGTGGTTAAAGA
GAACTGCCTCTTCTTCCTTAAGACCGGCTTTAACGTGATTGGCCGCTATGTAGTGACCGAGCAGGACGACGG
GTTTCGGAAGCTGCTGGGTTTTGTGGAAAACTGCCACGAAGGCAGGACACTGAGCGTTATAAGGCCAGATGG
CCAAGCCGTGCATGCCGAGGCCAAGGACGTGTATCTCGAGGCATCTAGGGCCAACTTCGACGACTACATCCT
TTATACGCACGGAACTAAAAAGGATAGCATCGTGGAGCGAATCAGACAAAGCGTGAGTATCTTCAACGGCGG
TAAGAACAAGAAAGATAGAATCGACGCGCTCAAAAAGTACATCCAGGCCACCAATATAAGCCTTTTGGATGG
GACCAGGATCGAAATCGAGGAGCCCAGCGACATTCAGAAGGACTGCGCCCAGATGCAGAAGCCCGTGTTTGT
GTTCAATGACAATGGCGAGGCCGACTGGACCGAGAAGGGGCTGACTCAGAACGGCCCCTACACCAAGCGCAC
CTTCGACCGAAACGACCCCAGCATCTGCGTGATCTGCGCACAACACGACAGGGGGCGAGTGGAGCAGTTCGT
TAGGAAACTGCTGAAAGGCATGGCTAACAGCAAATACTTCAGAAACGGCCTTGAGGGCAAGTTCGCGCTGGG
AACGTCCCGGGTAGAGGTGTTTGAGACCAGCACAAATAGCGTGGACGCCTATAAGAGCGCGATCGAAGCCGC
CATCCGCAAGAAGGCCGATGACGGCGGCAGGTGGGACCTGGCATTGGTTCAAGTTAGGCAGAGCTTCAAGCA
GCTGAAGGTGACTGACAACCCCTACTACTTGGGAAAAAGCCTGTTCTACATGCACCAGGTGCCAGTGCAGGA
TTTCACTATCGAGCTCCTGAGCCAGTCCGACTATTCACTGGGCTACAGCCTTAACAACATGAGCCTCGCTTG
CTACGCCAAAATGGGAGGAGTGCCCTGGCTGCTCAAGTCCTCTCCCACCCTTAGCCACGAGCTGGTGATCGG
CATCGGCAGCGCCAACATTGTCCAGGAGAGGGGGGCACACAACCAGAGGATCATGGGGATAACCACCGTATT
TAGTGGCGATGGCAGCTACATCGTCAGCAGCACGTCCAAAGCTGTGGTTCCCGAAGCATACTGCGAGGCGCT
GACTAGCGTGCTGGGCGAGAATATCGAAAAAATCCAAAGGAGAATGAATTGGCAAAAGGGTGACTCAATCCG
ACTGATCTTCCACGCCCAAGTGAAGAAGTTCAACAAGGAGGAGATTCAGGCAGTGCGAGCCGTGATAGACAA
GTATAGGGACTACCAGATCGAGTACGCTTTTGTGAAAATCAGCGAGAACCACGGCCTGCACATGTTTGACAG
CTCAACCGCCACCATGCCCAAGGGCAGGTTGGCCACACACAGGGGTAAGACCTTTAAGCTGTCCAAAAACGA
GATGTTGGTCTACCTGATCGGACAGAGGGAGCTGAGACAGGAAACCGACGGCCACCCCAGGGGTGTCATCGT
GAACGTACACAAGGACAGCACTTTCAAAGATATCAAGTACCTGAGCGCCCAACTGTACTCTTTTGCGAGTCA
TTCTTGGAGGTCATACTTCCCCAACCCTATGCCCGTGACCATCACCTACAGCGACCTTATCGCCCACAACCT
CGGCTGGCTGAACCAGCTGCCCGGGTGGTCTGACAGCGTAATGATAGGTAAAATCGGTCATAGCCAGTGGTT
TCTGTAGTAACTCGAGGTTAACTTGT
260 92 GGTGTCGTGAGGATCCATGCCGAAAAAGAAAAGGAAGGTTGAGGATCCTAAAAAAAAAAGAAAGGTCGGCAG
(Helicase) CGGGTCTATGTTCGACATTGGATCAATGGTGAGAGTTAGGGGTCGAGACTGGGTCGTGTTGCCTGGCAGTTC
CGCAGACTTTCTCCTGCTTAAGCCACTCGGCGGATCAGATGCAGAAACGACAGGGGTTTATGCCGGTCCCGG
CGGCGAAGTTGTGAGATCAGCGACTTTTGCGCCACCCGATCCGCAAGCGTTTGGAACAGCCTCTGGCGCTCG
GCTTCTCCTGAATGCAGCTAGATTGGCCGTTAGGTCCGGCGCTGGACCGTTCCGCTCCCTTGGCAGGCTGGG
GGTAGAACCACGCCCATATCAACTTGTCCCCCTCCTTATGGCCCTGAGACAAAGTACCGCCCGGCTCCTTAT
TGCCGACGATGTAGGTATAGGAAAGACAGTTGAAGCGGCACTCATCGCCAGGGAGCTGCTTGACCGCGGAGA
GATAGAGCGATTCGCTGTGCTTTGTCCGCCCCATCTGGCTGGTCAGTGGGTAGGTGAGCTGAGGAGCAAGTT
TGGGATAGATGCCGTCGCGGTCCTCCCCGGAACCGCGCGAAGACTGGAGCGCGGCTGTAACCCAGGCCAATC
TGTGTTCGCCAGATACCCTTTCGCAGTTGTCTCTCTCGACTTGGTCAAATCAGACCGATGGCGCCAGGATTT
TTTGCAGAACGCCCCCGAGTTTGTTATCGTCGACGAAGCGCACGCCAGTGCTGAGGGCGAGGGGTTGGGCGC
GCGAAGACATCAGAGATATCGCCTTTTGGAGGACCTTGCGCGAGACCCAGAGCGACACTTGATACTCGTGAC
AGCTACGCCACACAGCGGAAAGGAGGACGCATTCAGATCCCTTTTGAGATTGCTCAACCCTGAATTCGCCGC
TCTGCCACTGGATCTCTCCGGCGCTCAAAACGAAAGAGCTCGGGCAGCTATCGCTCGACACTTGGTGCAGCG
GAGGAGGGGTGACATCACTGCATACCTTCACGAGGACACCCCATTTCCAGTCCGAAGGGACGCCGAGGTTAA
GTATACTCTGCACCCCGATTATGCGGCATTGTTCGAGGACGTTCTGGCCTATGCAAGGGAGTCCGTGCACGT
TCCAGGCGAGGCGCATAGTCGGACGCGGATACGCTGGTGGGCCGCCCTGGGACTGCTTCGGGCTTTGGCTTC
TTCACCCCAAGCAGCCGCAGCCACTCTCCGGGAAAGAGCAAGCACCGAAGGCGAGACTGATGAAGCAGTTAT
TGAAAGACTTGGCAGGGAACTGGTGCTTGACCCCGAAGACGGTGAACATGGGCTGCTGGACGTCACCCCTGG
AGCGCAGGTCGACGGTGAAGAAAGCGGGACCACGCGACGCCTTCTCGCACTCGCAGAGAGGGCCGACGCTCT
GGCTGGGGCCAAAGACCGGAAGCTCGCACTCCTGACCGCACAGGTCAGGGATCTTCTGCAGGAAGGTTTCGC
GCCGATAGTTTTTTGTAGGTTCATTGCGACCGCGGAGGCAGTAGCGGAGCACTTGAGGGGAGTTCTGAAAGG
AGCTGAAGTCGTGGCTGTCACAGGAAGGCTGACGCCAGATGAGCGCGTCGCCCGCATCGAAGAGCTTGCACC
CCACGAGCGACGGGTTCTTGTGGCAACGGACTGCCTTAGTGAGGGCATTAATCTCCAAGCTGCCTTCAGCGC
AGTAGTACACTATGATCTCCCCTGGAACCCTACCAGGCTCGATCAAAGGGAGGGCCGAATTGACCGATATGG
TCAACGATCACCAGAGGTCCGAGTGCTTACATTGTATGGGGAGGATAACAGGATAGATACTCTGATACTGGA
TGTTTTGATCCGAAAGCATCGGCTGATCCGGGCTACCTTGGGAATGGGTGTCCCCGCTCCCGACGAGGCAGA
AGGATTGCTTGACGTGCTGTTGGCGCGAGTACTGGAACCCGAACGAAGAGGTTCTATTCAGCCATTGCTTCT
GGATGAAGTGCAGGCTTTTGATTTGAAATGGCGCGATGCGGCTGAAAACGAAAAAAGGTCAAGGTCACGATT
CGCCCAGAACTCTATAAGGCCCGAAGAAGTAGCAGGGGAACTCGCAGCGGTACGGGAAGCGCTCGGAGACGC
TCGAGCCGCTCAGGACTTCGTTCTTGATGCACTGCGAGGGGCCGGTGTTCAGGTGACGCCGCGCCCCGACGG
AAGCTTCGAAGCGGACCCCACCCAAGCCGATGTAGCACCGGAGGTCCGCGACTTTCTGCGGGGAGCAAGGCG
CTTCAGATTTGACGCACGGGTAGAACGAGGTGTGACGCCCTTGGCGCGGAACCACCCATTGGTCGAGCAACT
TGCAAGCACTGTACTGGGTCAGGCTCTGGAGTCTCCGCAGGAGGCCGCAGCCAAGCGCGTAGGCGTCATTCG
GACCTCTGGCGTAAGTACTCAGACCACTCTTTTGCTCCTTCGATGGAGATTTCATCTTTCCGGACGAAAGGG
AAACCGATCTTGGCAAACTCTTGCTGAAGAACTTGATCTTCTGGCTTACGCAGGAAGGGCAGAGGATCCGCA
GTGGTTGGACGCTGAGGCCACCAGAGCTTTGCTCGATCTGACCCCTCAGGGTAACTTGGATCCGGTGCAGAA
AGAGGAACGCCTTACTCGGACGCTTGAGGGACTTAGCGCTTTGGAGGGGGTTTTGGACCAGCGAGGAAGGGA
TAGAGCCGCAGCTCTGCTTGACGCTCACGAGAGAGTACGGGGAGCAGCGCGAGGGCAAGGGGTGACCTATTC
TGCGGAGCCTCCTGGCCCCCCGGATCTGCTTGGTGTCTATCTCTTTCTCCCCGCACCAAGACTCGGAGGCCT
CGCCTAGTAACTCGAGGTTAACTTGT
261 71 GGTGTCGTGAGGATCCATGCCGAAAAAGAAACGGAAGGTGGAGGATCCAAAGAAAAAACGCAAAGTTGGCAG
CGGCAGCATGATAGCCGTGGAAGAGTGGCAACCTGCGGACGGACTGACCCTTGAGCCTAATGCAAAGAGGGC
TGCGAAGGCTAGAAAGAGGTGCCTGGCCCTGACAGCGGGTCCCGGTGCCGGAAAGACAGAGATGCTCGCACA
ACGCGCCGACTTCTTGTTGAGGACCGGAACCTGTCGGTACCCCAAGAGGATACTGGCCATCTCATTCAAAGT
GGATGCAAGTAGAAACCTGAAGGACAGAGTGGAGAGGAGGTGCGGCTATGATTTGGCGTCAAGGTTTGACAG
TTATACTTTCCACGCGTTCGCCAAAAGGATCATCGACCGCTTTAGGCCGGTGCTGACAGGCAAGGACGCCCT
CGACGCAGGCTACACCATCGTGGATAAGAAGAATGGCCCCTCTAGGACCCAGATCGAGTTCGGCGACCTTGT
CCCCCTTGCCATACAAATCCTGCAATCAAGCAAAATTGCACGAAACGCGATCCGCCAAACTTACAGCGACAT
CTTCCTGGATGAGTTTCAGGACTGTACAAACCTGCAGTACGACTTGGTAAAACTTGCGTTCCAGGGTACGTC
AATACGGCTGACGGCTGTTGGCGATACCAAGCAGAAGATAATGGCCTGGGCTGGAGCCCTGGACGGCATTTT
CCAGACGTTTGCCAACGATTTCAACGCCGTGTCCCTGAACATGTATAGGAATTTCAGAAGCAAGCCACAACT
GCTCAGGGTTCAAAATGAAATTATCAGGAAGTTGGACCCCGATTCCGTGATGCCTGACGAACAACTTGACGG
TGATGAAGGCGAGGTCTATGCGTGGAGGTTCGAGGATAGCTGCAAGGAAGCCGTGTATCTTGCGGACCTTAT
CAATGGCTGGATCAACACCGAACAGCTGCCCCCAGCGGAGATCGCCGTACTGGTCAGCAAACAGCTCGACCT
CTATGTCGACCACTTGATGACTGAGCTCGAGGCTCGGGGAATCCCCTACAGGAACGAGCAGCAGCTTCAAGA
CATCACCATAGAGCCGGCAGCTAGACTCATTGTGGACTACTTGAGTTGCCTCTACGGCAAGAGAGAGCCGAA
AGCATGGATCCGGCTCATGAACCAGCTGATCCCATTCGCGGACGAGGAGATCCAATCTAGTGCTCGAAAGGA
CCTCGACCAGTTGATAAAGAAGCAGAGAAAAAGGGTGAGCGACGCGAAGCACACCGATTCACCTTTCAGCGA
TTGGGCACAACTCGCAATTGAATTCCTGAAGTACATAGGCAGTAAGATGCTGGTGGCACTGAGTCCAGATTA
CGAGACGCGCGAGAGGCTGAATGACGTGATCAGGGAAACTTTCGCGAGGATCAAGGAACTGTTGAAGAGCGA
GCCCGACCTGCCCAAGGCGCTGGGCCGGTTTGCCGATGACCAGGCGGTGCGAATACTGACCATCCACAAGAG
CAAGGGCCTGGAATTCGACAGTGTGATCATCATGGCCGTCGAGAACGAGATATTCTTCGGGAACCAGGACGA
GAATAGGTGCGCTTTCTTCGTAGGTGTGAGCCGAGCAAAAAGGAGGTTGATACTTACCCACGCCGACCAGAG
GGAAAGGCCAGCGTCTGCCAAGCGATGGAATGTTAGTAGAACCGCTCAGACTGAGTACATTAGTTACGTCAC
CCCTTTCGTGAGGCCACAGTAGTAACTCGAGGTTAACTTGT
262 21 GGTGTCGTGAGGATCCATGCCGAAAAAGAAAAGGAAAGTGGAGGACCCCAAAAAAAAGCGGAAGGTCGGGAG
TGGCTCCGTGGCCGCTTTGAAGCGCTACTTTAATGACAAGAACCTGATCGTGATAGGCTACTCTGGCAGGGA
CAAGAGCCTGATGAGTGCGCTTACCGAGGCTTTCTCTGAGAAGGGCTCTGGCCGCATCTACTGGTGCGGCTA
CGGCAGCCACATTTCCCCCGAGGTGGAAAGCTTGTTGAGGACCGCGCGAGAGGCAAACCGCGACGCCTACTA
TATCGACACCGATGGGTTCGACAAAACCATGTTCAGCCTGGTAATAAACTGCTTCCAGGCGGATATCGAAAA
GAAGAAAGAGATAATGAGCATCCTGGAGTCTGCTCCCGAGGACAACGATACCAGCCCGTTCTCAATTCACAT
CACCAGGACGGATAAATACCTTAAGTCCAACCTCTACCCGATCATCTTTCCTAAGGAGCTGTTTCAGTTTGA
GATAGAATATCATGAGGGCGAACGACCATGGACCCTGCTGAGAGAGATCACCAAAGACCAGAACATCATCGC
CGTGCCCTACAAGCAAAAAGTCTACGCCTTGTCAACGGGATCAGCTATCAACAACGTGTTTGGTAGCCGGTT
GAAATCAGATATAGAGAGGATTCCCGTGTCTATGGATGACATTGAGCGCAAGTCTAGTTACAGGGAGCTCTT
CCTGAGGGCCACCCTTCAGTCTATAGCCATTATAAGGGGCCTGAACGTGGACATACGACACAATACCCTTTG
GCGGAGCGACATCTTTAGGAACGACAATGGCACCCTCATCCACGAAGCGATCGAGTGTTCCCTGGTGTTTGT
GCCCCAACAGAAGTATGCCCTGTTGAGCTTGAGGCCCACCATCTACATAGAGAACTCTCATACGGTTAGCAA
GGAGAAAAAGCAGGAGTACGCCAGGATCTACCTGGATAAGATGTGGAATAAAGCGTACAGCACGAAGTTGGC
CCAGTGGGAATCTATAATCTTTGGAGACACGAGGCTCGCCTTCGAGGTGCCGCAAAATTCAGGATCCGGGTT
TAAGTTTCTGATAAGCCACAACTGCGGCTTCAGCGAAATCCAGTATCAAGACAACACCGAAAGGGGATACAG
TAGCAAGAGCTACGACAACAAGAGGACGATCTATAGGGGCTTGCAGCTGAAGGAACCCGAGCTGGAATTTGT
CAATACGTTTGCAGACCGGCCCTTCCTGGACAGCAACCCCATGCGAGGCCTGAGCAATCACAGGCCGTACGA
CAGCTGGCAGAAAGACGTTCTCTTGCAGAACGTGCGGTTGGGCGTGATTTGCCCGAACACGCACACCGACCG
ATTCCACTCTTTTCTGCAGCAGCTTAACACCACAATTCAAGCCAATGACGATAGCGACTACATTCAGTCCTA
CACCGGTTTCCATAGCATTTACAAGACTCTGCTGGAAATCCCCGATAACGGGACCGACAAATGGATAAACAT
CGAGGATACCCCCAAGGACACCATCAGTCTGGTTCAGAGTATATGTCACCAAGCGAACCGACTGGCCGACAA
GTACCCGGGCATCGTGGTGGTGATTTTCATCCCCGCATTTTGGTCTATCCATCGACAGTTCAAACACAACGG
GGAGAGCTTCGATTTGCACAACTACATCAAGGCCTACGCCGCACAACATAGCTTCACTACCCAAATCATTGA
GGAAAAGACGCTGCGCGACCACATGGTCTGCGAAATTTGTTGGTGGCTGTCACTCGCACTGTTCGTTAAGGC
TATGCGAATCCCGTGGGCACTGGCCAATTTGGACTCTGACACCGCTTACGCGGGTATAGGGTACTCAGTGAA
GACCAACAGCAAAGGCAACGTCGACATAGTGCTTGGATGTTCACATATATACAACGCAAAGGGCCAGGGTCT
CAGATACAAACTCTCTAAGGTCGAGCAGCCCCAATTCGATGGCAAGAAAAATCCTTACCTTACGTATGAAGA
GGCCTTCAAGTTTGGAATTACCATACGCGAGTTGTTCGTCAAAAGTATGGACCGGCTTCCCAGGAGGGTTGT
GATTCACAAGCGGACGCCGTTCAAAAAGGAGGAAATAGAGGGAATCACTCACGCGTTGACTCAGGCTGGCAT
TAAGGACATCGATCTCATTACGATCAATTACGAGTACGACGCCAAGTTCATAGCGCAGAAGGTATACTATGA
CAACATCAGCGACGATTCATATCCCGTAAGTAGGGGCACCTGCATCAAATTGTCCAGCCGAAATGCGCTGCT
GTGGACACACGGCGTGGTTCCCTCAATCCGGGAGAGACGACGCTACTACCCCGGTGGGCGCTGTATTCCCGC
ACCCCTGAAGATAACAAAATACTACGGTAAAGGCGATCTTCCGACAATCGCCAGCGAGATTATTGGATTTAC
TAAGATGAATTGGAACAGTTTTAATCTGTACACGAAACTGCCCGCCACCATAGATACGAGCAATACATTGGC
GCAGGTCGGCAATCTGTTGCATCAGTATAACGGCGCAACTTACGACTACCGATATTTCATCTAGTAACTCGA
GGTTAACTTGT
263 63 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGAGAAAGGTAGAGGATCCCAAGAAGAAACGAAAAGTAGGCAG
CGGCAGTATGGTCGCGCTGAGGCTGAACGGCGTACCCATCTTGTGCGCCGCTGACGTAACCGTGGCCGTGGC
GAAGTTGCCGTACACGAAGGAGAGCCTGGACGAGTTGAGGAAGGAGCATGCGGGGAGGTATTTGATTAGGAG
AGGCGGAGATGACGGGCAGGAAATCATGTCTGTTCCCTTGCTTGCTGATGCTCCGCAGCTGAGCGATGCCGT
TGTGGAAGTTAAGCTGTCAGAAGCCCACTGGTTGCTCGCCTCACTCGCGGTGGAGGCCCTCACCAGGTTGTT
CACAGAACTTGGTAGACCTATCCTGCGGTCCCGGCCATTGCGGCTGCTCTCCCAAAAGCCGGCCAATCTTTT
TCCGGAGAACGTCGGACTGCCAGACTGGCTGCAAAGGAGGGTTGTGCTGGATTTGGAGACTAGGAAGATCTG
GCGGCAGGATGGAGACCCGACATTGGTGCTGCTGTGCGATGTGCGGACTCAAAACTTTATCGACGTGCCAAC
GGATAAACTGATGGCCACCGGCGTAAGCGTTATGGGTCGCTACGTTAGCCGAATGGTGAGCTCTGATGATCC
CCGGATCACCTCACATCTGAAGCTCGCCGGCAGGGTCATTAGCATAGAGGGCGACCGACTGCTCCTCGCCGA
CTTTGGCGAGGGACCGGATAGTATAAGCATTGCTCATGCCTATCTGGAGAGACGACGGGAAAATGTCGACTG
GTGTGTTCAACAGCTGAACCCCGCGAAAGCAGGGCAAATCCTGATGAGCGTGCAGGCCGAGGCTGCGAAATT
CTTGAACGGACCTGGCCGATTCGAGCTGATCAAGAGGACATTCGATTACCTGCGCACGCAGAGTATAGAGCT
TGTGCCCGACGTGAAGCTGGAGTTGGGGGACTTGATTGGCATGGGAGCCGCACGCTGGCCCTTCCGCCAGGA
AACAATTAAGAAGCCTACCCTGGTGTTTGATCCGTCTGGTGTCAAGACCGATACCTGGAACGAGCGAGGGCT
TGACAAACACGGACCCTACGACCAGAGGACCTTCAGCCCCAAGGAAATGAGGATCGCCGTTATCTGCAGGGA
AGCAGACGAAGGTCGGGTTGAAGGATTTCTGGCCAAGTTTCTGGACGGGATGCCACACGTTATCGTCGGGGA
GAACCGAAAACCCTATGAAAAGGGATTCATAAGGAGGTTCGCCCTGAGTGCCCCGAAGGTGCACACTTTCAC
CGCTAAGTCTTCTAGTGTGCCGGACTACCTGAATGCGTGCCGAGCGGCCCTGAAGTTTGCCCACGACCAAGG
CTTTGAATGGAGCTTGGCAATCGCGCAAATCGACAAGGACTTTCGGGAACTCCTCGGTCCTGACAATCCCTA
CTTCGCGATCAAGGCCGCGTTTCTCAAGCAGAGGGTGCCCATCCAGGAGTTGACGCTCGAGACAATGAGCAC
CCCCGACAGGCAGCTGGTGTACATTTTGAATAACATAAGCCTCGCAAGCTACGCCAAGATCGGCGGCATTCC
GTGGCTGCTTAAGAGCGGTCCTACCGTGGGCCACGAGCTGGTCATTGGTATTGGTAGCCAGACCGTTAGCAG
TAGTCGATTGGGCGAGAAGCAACGGGTGGTGGGCATTACCACCGTATTCACCCACGATGGCAGATACCTTTT
GGACGACAGGACGCGAGCCGTGCCATACGGCGAGTACGAAGCAGCTTTGTCCGAGACGCTGACCAGGGCCAT
AGAGAGGGTAAGGACGGAAGATAACTGGAGGTCAACCGACGCGGTGCGACTTGTATTCCACGTGTTCCAGCA
AATCAAAGACTACGAGGCCGACGCAGTGGGGAAACTGGTCGAGAATCTCGGCTTCAGCGATGTCAAGTACGC
CTTTGTGCATGTCGTTGACAGCCACCCCTACACCCTGTTTGACGAACACATGCCAGGCGTTAAGTTTGGCTA
CGAGATGAAGGGCGCCTACGCACCTGAGAGAGGCCTGTGCATCAGTCTTGGCAGGGACGAACGCCTCCTCAG
CTTTACCGGGTCTAGGGAGGTTAAACAAACCCATCATGGCCTCCCAAGGCCAACCCTTCTTCGACTGCATAG
GAACAGTACCTTCCGGGACATGACCTACATCGCCAGGCAGGCTTTCGACTTCGCAAACCACTCATGGAGGAT
GCTCACCCCAGCGCCCCTCCCCATCACCATCCACTACGCCGAACTCATCGCCCGGTTGTTGGCTGGTCTGAA
AGACACACCCGGCTGGGACGAGGACACAATGCTCGGCCCAGTAGGTAGAACCCGATGGTTTCTGTAGTAACT
CGAGGTTAACTTGT
264 33 GGTGTCGTGAGGATCCATGCCAAAGAAAAAACGGAAGGTCGAGGATCCCAAAAAAAAGAGAAAAGTCGGTAG
CGGCAGCATGAACTACACAGCCGCCAACACGGCCAACAGCCCATTGTTTCTCAGCGAGATTAGCAGCCTTAC
CTTGAAAAACAGCTGCCTCAACTGCTTCAAACTGAATTACCAGCTGACTCGCGAAATAGGCAATAGGTTCGG
CTGGCAGTTCAGTAGGAAGTTCCCTAACGTTGTGGTGGTGTTCGAGGACAACTGTTTCTGGGTTCTCGCTAA
AGATGAGAAGAGCTTGCCCTCTCCTCAACAGTGGAAGGAGGCTCTGAGCGACATCCAGGAAGTGCTGCGAGA
GGATATCGGAGACCACTACTACAGCATCCACTGGCTTAAAGACTTCCAGATCACCGCCTTGGTGACCGCCCA
GCTCGCCGTGCGAATTCTGAAAATCTTCGGTAAATTCAGCTACCCCATCGTGTTCCCCAAGGACAGTGAAAT
TAGTGAGAATCAAGTGCAAGTAAGGCGAGAAGTCAACTTCTGGGCCGAGATCATTAACGATACCGACCCCGC
CATTTGCCTCACCATCGAAAGCAGCATCGTCTATTCCGGCGATCTCGAGCAGTTCTACGAAAATCACCCGTA
CAGGCAAGACGCCGTGAAGCTGCTGGTGGGCCTGAAAGTTAAGACCATTGAGACCAACGGCACCGCTAAGAT
CATCAAAATCGCTGGCACTATAGGGGAAAAGCGCGAATACCTGTTGACTAAGGCCACGGGAAGCATATCCCG
GCGAAAGTTGGAGGAAGCCCACCTCGCACAACCCGTGGTTGCGGTGCAGTTTGGTAAAAACCCTCAGGAGTA
CATATACCCCCTGGCTGCCCTCAAACCTTGCATGACCGACAAGGATGAGAGCCTGTTCCAGGTCAATTACGG
CGACCTCCTGAAGAAAACCAAGATCTTCTACGCTGAACGACAGAAATTGCTTAAACTGTACAAGCAGGAGGC
GCAGAAGACTTTGAATAACTTCGGTTTTCAGCTTCGGGAAAGGTCCATCAATAGCAGGGAAAATCCAGACTT
CTTCTGGACGCCCCCAATTTCATTGGAGCAGACCCCCATCCTGTTTGGGAAGGGTGAGCGCGGTGAAAAGAG
GGAGACCCTCAAGGGCCTTTCAAAGGGCGGAGTCTACAAAAGGCACAGGGAGTACGTTGATCCTGCCAGGAA
AATTAGGCTGGCCATCCTTAAACCGGACTCTTTTAAAGTGGGCGACTTCAGGGAGCAGCTGGAGAAGCGACT
CAAGCTGTATAAGTTCGAGACGATTCTCCCCCCTGAGAACCAAATCAATTTTTCTGTGGAGGGTGTTGGGAG
CGAAAAAAGGGCCCGACTGGAAGAAGCCGTAGACCAGTTGATAGGTGGCGAGATCCCCGTGGACATCGCCCT
CGTCTTTCTGCCCCAGGAGGACCGGAACGCGGACAACACCGAGGAAGGCTCCTTGTATAGCTGGATCAAAAA
GAAATTCTTGGATCGGGGGGTGATAACACAGATGATATATGAGAAAACTCTCAACAATAAGAGCAACTACAA
TAACATCCTGCACCAGGTGGTTCCCGGCATATTGGCAAAGCTCGGAAACCTGCCGTATGTGCTGGCCGAGCC
TCTTGAAATCGCCGACTACTTCATCGGCCTGGACGTCGGAAGGATGCCTAAGAAGAATCTCCCTGGTTCACT
GAACGTGTGCGCGTCCGTTAGGCTCTACGGAAAGCAAGGTGAATTCGTCCGATGTAGAGTCGAAGATAGCTT
GACCGAGGGGGAGGAAATCCCCCAAAGGATTCTTGAGAATTGTCTGCCGCAGGCAGAACTTAAGAACCAGAC
CGTCCTGATCTACAGGGACGGGAAATTCCAGGGTAAGGAGGTGGAAAACCTTTTGGCTCGGGCACGAGCCAT
CAACGCCAAGTTCATCCTGGTAGAGTGCTACAAGACCGGCAGCCCGAGACTTTACAATTTCGAACAAAAGCA
GATTAATAGCCCCAGCAAGGGGCTGGCGCTTGCATTGAGCAACCGGGAGGTCATCCTCATCACCAGCCACGT
TAGCGAACAGATCGGCGTGCCTCGGCCTCTCCGCCTGAAGGTGCACGAACTGGGAGAACAGGTGAACCTCAA
GCAACTTGTGGACACGACCCTGAAACTGACTCTGCTGCATTATGGCTCTCTGAAGGAACCTCGGCTTCCAAT
CCCCTTGTACGGAGCCGACGCCATCGCGTATAGGAGGTTGCAAGGAATCTATCCAAGCCTGCTGGAGGACGA
CTGTCAGTTCTGGTTGTAGTAACTCGAGGTTAACTTGT
265 19 GGTGTCGTGAGGATCCATGCCGAAAAAAAAGCGCAAGGTGGAGGATCCAAAAAAGAAACGGAAAGTGGGATC
TGGCTCCATGAACTACACAGAGGCCAAGACCGCCAATAGCCCCTTGTTCCTTAGCGAGATTAGTAGTTTGAC
ACTTAAGAATAGCTGCCTGAATTGTTTTAAGCTGAACCATCAGGTCACCCGGAAAATAGGCAACAGGTTCTC
TTGGCAGTTCAGCCACAAGTTCCCTGACGTCGTGGTAGTGTTCGAGGACAATTGCTTTTGGGTGCTGGCTAA
AGATGAAAAGAGTTTGCCTAGTCCACAGCAGTGGAAGGAAGCACTGTCAGACATACAGGAAGTGCTGAGGGA
AGACATTGGGGACCACTACTACAGCATTCACTGGTTGAAAGACTTCCAGATAACCGCCCTGGTCACCGCGCA
GCTGGCTGTGCGGATTTTGAAGATATTTGGGAAGTTTAGCTACCCGATCGTGTTCCCCAAGGACAGTCAGAT
CTCTGAAAACCAGGTGCAGGTGCGAAGGGAAGTGGATTTCTGGGCTGAGATAATCAACGACACGGACCCAGC
AATATGCCTGACGGTGGAAAGCAGCATCGTTTACTCTGGCGACTTGGAACAGTTTTACGAAAATCATCCGTA
CCGACAGGACGCCGTGAAACTTCTCGTAGGGCTGAAAGTGAAAACTATCGAAACCAACGGCATCGCGAAGAT
TATCAAAATTGCCGGGACCATCGGAGAAAAGCGGGAGGAACTGCTGACCAAGGCAACCGGGTCCATAAGCAG
GCGCAAATTGGAGGAGGCACACCTGGGCCAACCTGTGGTGGCCGTGCAGTTCGGCAAGAATCCGAGAGAATA
CATCTATCCCCTTGCCGCGCTCAAACCGTGTATGACCGACAAAGACGAGAGCCTGTTTCAAGTGAACTATGG
CGAGCTTCTGAAGAAGACTAAGATTTTCTACGCCGAACGGCAGGAGTTGCTGAAATTGTATAAACAGGAGGC
GCAGAAGACGCTGAACAACTTCGGCTTCCAGCTCCGGGAGCGGTCAATCAATAGCAGGGAGAACCCCGACTT
TTTCTGGACCCCCTCAATTTCCCTTGAACAAACGCCCATCTTGTTTGGCAAAGGTGAGCGAGGTGAGAAACG
AGAGACCTTGAAAGGCTTGAGCAAAGGCGGCGTGTACAAGAGACATAGGGAGTACGTCGACCCCGCGAGAAA
GATTAGGCTGGCCATCCTGAAGCCGGCCAATCTCAAGGTTGGGGATTTTAGGGAGCAGCTCGAGAAGCGACT
GAAGCTCTATAAGTTCGAGACCATCCTTCCCCCCGAGAATCAAATCAATTTTAGCGTAGAGGGCGTGGGCTA
TGAAAAACGAGCCCGCTTGGAAGAGGCCGTGGACCAACTGATTAGGGGGGAGATACCCGTGGATATCGCTCT
TGTCTTTCTTCCGCAGGAGGACCGAAACGCCGACAACACCGAGGAGGGGAGCCTTTACTCATGGATCAAGAA
GAAGTTCCTTGACAGGGTTGTGATAACGCAAATGATCTATGAGAAAACGCTTAACTATAAGAACAATTACAA
GAACATCCTCGATCAGGTGGTGCCTGGAATCCTTGCGAAACTTGGTAATCTGCCTTACGTGCTCGCAGAGCC
ACTGGAAATCGCCGACTACTTCATTGGCCTGGATGTGGGTCGCATGCCTAAGAAAAACCTCCCCGGGTCACT
TAACGTGTGCGCGTCCGTAAGGTTGTACGGGAAGCAGGGCGAGTTTGTGCGGTGCCGAGTCGAAGATAGTCT
CACCGAAGGTGAAGAGATCCCCCAGAGAATCCTGGAGAATTGTCTGCCCCAAGCCGAGTTGAAGAACCAGAC
CGTGCTGATATACAGGGACGGTAAGTTCCAGGGCAAGGAGGTGGATAACTTGCTGGCCCGAGCCAGGGCCAT
TAAGAGCAAATTCATACTTGTCGAATGCTATAAAACGGGCATCCCCAGACTGTATAACTTCAAGCAAAAACA
GATCGACGCGCCCAGTAAGGGCCTGGCGTTCGCTCTGAGTAACAGGGAGGTGATCCTGATCACGTCCCAGGT
TAGCGAAAAGATCGGCGTGCCGCGACCTCTGAGGCTTAAGGTACATGAGCTGGGAGAGCAGGTAAATCTGAA
GCAACTGGTGGACACCACACTCAAGCTGACCCTGCTCCACTATGGGTCTCTTAAGGACCCGAGGCTGCCCAT
CCCCCTTTACGGCGCTGACATCATCGCGTATAGGAGGTTGCAGGGAATATATCCCTCTTTGCTGGAGGACGA
TTGTCAGTTCTGGCTGTAGTAACTCGAGGTTAACTTGT
266 85 GGTGTCGTGAGGATCCATGCCTAAGAAGAAAAGAAAGGTGGAAGATCCAAAGAAAAAACGCAAGGTGGGTAG
CGGCTCCATGACTAACAAAACCAAACAAAAAAGCAGGAAGCAGAGGTCCCTCATAGAATTTCTTAAGGTGAA
GAAGATCAACAAGGAAGATGGTAAGAACCATAACCTGATCAAGTATAGCACCGAACGGATCGATACAGGAGT
GACCCAGAGCCTCATTGACATCAATATATCCAGTAACATCCTTAAGCTGCGGGGCAGCATTGCTCAAGAGGT
GTTCAAACGGAAAATTGGCGTTTACTACGGGCTTGGGAAGTATTACGTTGCCGAAAACAAGCTGAAGAACAC
CGATCGAATGGATTTCTTGAAGAGGGTCTACGAGACCTTCCCCTATAACTACCTCGATAAACAGGACCCGCA
CAGCAAGATCAGCTTTTACGAGTACTACACATTCCAGAAGTCCATCGACAAAGACGTGATAAACCTGCTTGA
GCTGCAGAAGATAAACGAGTATAGTTGGGACATACTGGACCCACACATCGCCACGCGCCTTCTCACAAGCTA
TGTGAAGCTTTACTTGGGCGACTACTTGAAGCCAATCCTGTCCTCTTTCGAGTACGTCCGGGCTCGAATCAA
GACAAAGCAAAAGACCGTTCCAATCAAAATCCCCGTGACCAAGAAGTTCGAGATCCGAACTTTGGGGTACGA
CCCGACGCAGAGCGAAATTACTCTCGCCATAAAACGACACGCCAGCATGAACGCTGTGCTGTTGAGCAGCTT
TCCCCCCGACATCCTCGCGGTTGTGATAACTAAGCTCAAACGCCTCGTGAACGAGGCCGTGAAGCAAGACTA
CCGAAAGGTCAGAATATACTCCGAGACCCAGCCGGGGAGCGGTACTGCCGCAGTTGTTGAAATCATCAGCGG
CAGCCAAAACGTGATGAAGTTTCTCGAAGAGCATCCGAAGGGGGCCATCCACGTTGAAAAGCGACTTAAAGA
GCTGGGTAAATCACTGCAGGAGGTCCGGTACCTTCTTATCGGCGTCTATGACAACAACGTCAGCCTGGAGCG
GGCAAAAAAAGACGAAAGATACCACTACTACTTCACCGAGCATAACGCTTACCTTGTACTTACGCCCGAGGT
GCAAAAGGCGCTCTTTGGCAAGTTGATCGACGACTGGAAGACAAGCATTCTGAATGAGTACCAAAATAAGCT
CCACGAGATCACGAGTCTTGGGATGTTTAAGCATTTGGAGACCATACGGGGCATCCCGGTTTCCTTGAAAGA
GAGGCTTGTGGTCCGCACCAGCGAGGGCTTGCAAACCGTAGATGACATTAGGGACATTTTGACCAACCCCAA
GATTCTTAGTAATATGTTGCCTATATCCGAGGACGCGCTCAAGGAGACGCGAAAGCATAAACTGCGAATCAC
CCTGTTCTGTCCGGAGAAGTTTAGTGAGAGGATTCACCGGACTATTTTCTACGACAAATTGAACCAGTTTCG
AGACGGTCTGCTTAGCAACAGCTTCGCAAGCGTGGACGAAATCGAATTGTTCCAGGTCAAAGGCGAAAACTC
TAGCGATTATGAGGAGATCATGAAGGACGCTGGCCTTGATAAAATCCACGATTATACCCTGGCGGTCATCAT
ATTTCCCGAACATTATAGTAAGCGCAACCTTGAGTTGCGCATCTTTTACAACTGGCTGAAAATGCGGTTCTA
CTCAGAGAACAAGCCACTGGTTTTCCAGGGCGCTCGGATTGACAGCGTCTTCGGCCGGTATGCGAAGTACGC
ATCATACAACCTCATCTTGCAGATCCCACCTAAATTGGGCATCTACCCGTACTCACTGGAGGAGCACGAGGA
CTATGACTACATCATCGGCATTGATTACACCTATTGGTACGAGAGAGATACGCCTAGTCTGGGCGGTGGCGC
CGTGTTGACCAGCCCGTCAGGGCTGATTGAGAGCATATACCCCATCGCACTCCCGAGCCGCACTGAATCCCT
CAACATGTCCAAGATACTGAGCGAATGGTTCACGCGAACAGTCAAAACGAACCGGCATATCATAGATAAGGG
CCACGTGACCGTGCTTATCTCCAGGGACGGCATGATTCCTAAGTACGAACGCCAGACAATCCAGGAGTTCCT
GAGTGAATATAGCGGCGACATGGGCATGACCATAGAGGCAGTAGAAGTTAGGAAACGCATCGCCGTGAGGAC
CTGGGCTACACAAGAGCCCGTGGCCTACTACAGCCCGATAAAGGTTGGCGACTGTACCTACTATCTGGTCGA
CGCGCACACCGGATACCCGCTGGGGGAGAAAGGGAACCGAACCTTCTACAGCTCACCCTATCTCATAGGAAG
TTTTTACAGGTTCGAAAAGGGCAAATCCTCCCCCGTGCCAGGTAGCGCAAAGAAGCACGTGATCGAAAGCCT
GATAAGACTTCAAAAAATCAATTACGCCACCACCCGCATGGATAACATCAAGTTGCCCCTGCCCGTCGACAT
CACCCACAAACTCATTAACTTTATCCGGGACACCAAGATGGAAATCAAGGGGGTCGGTATCCCAAACAGTCT
CTTTATGATATAGTAACTCGAGGTTAACTTGT
267 79 GGTGTCGTGAGGATCCATGCCGAAAAAGAAACGGAAGGTAGAGGACCCCAAGAAAAAGCGGAAAGTTGGGAG
TGGAAGCATGCCGTTCAATAGCAACCTGATCTTCGTGAAGCTCGACGACCTCAAGAGAGCCTTTCTCGAGGG
CGTCCACAGTGGTCACGCCGTGGTGTATGAGGTGAGCGAGGGACTGAGCACCGAGGATCTGAAGAAAAGGCT
TATCAAGGCCAGCGTGATGTACCACTATAGGTATGGAAGGAACGTGTTTGTCTTCGGCGTCAAGGAGGGCAC
TAAGGTTGACGATCTTGTACCAGGCCGACGACTCGGCGAGCACGAGGTGAAGGAGGTTCTCAAGGGCATCCC
GTCTAACAACCTGGTGTCCATGATGAGCGCCATGCTCAATTACCAGCTCTCTGTGCTTCTCACCAGCAAGGG
CTTCCAGTATAGCTACGAAGAGATGCGGAGGGGCAAGTATCTGTGTGTCAGCAACTATTACGGCAAGCTGAT
ACGGAACCCCGTGAAGGTTTGCCTCAAGGTAAATGTCATAAGGAGCCTCATTGACGAGCAGGATCAGTACCT
GCCCATCGCGCTTAACTACAGGGTGAAGAAGAGCAGGCGGCTTAGCCCCGAAGTAATGAATGAGATCCACGC
GGAGTTCATGGAGGCCTTCCCCAGCTACCTCAACGACCTGAAAATCATAACTCGCGTCTTGAACGACGATAT
GGTGAGGAACAGGGAACTGAAATTCCTGGAGATCGAGTACAAACCCCCTGCTATCATTACGTTCCGGTTTCG
AGGCAACAGCACCGGCGAAAACGTGACCGACATTCTGAAGCTGGGCCCCTACTTCCTGCCTGGGGAGGAGGA
GAAGATCGATGTGGTCTTTGTGTACGAAAATGCTCTCGCTAGCCAGGCGAAGAAACTCACCAAGGTTTTGGA
GGATACCATCAAGGACGGGCTGGGCATAAAGCTGAACATAGACGACGAACATAAGTTCAGCCACGACAAGCC
GCTGGGCGACGTTATTAAGCTGGTGCGCGACCGATTCATCAACAGCGGGAGTTGTCTGCTGGTCCTTAGCAA
GGAGAACCGCCTCGGTCCTATCTTCATGAGCATTAAACCGCTCACGCTCAAGAAGAACTTCTACTTCAAGTC
TCAATTTATCACCAACGAAACGATTAGCAAACTGGACTCTTATGCGGTCAAAGCCAATATCGTGAATAGCAT
CCTGTTCAGGGTTGAAGGTACCCCGTACATGCCCGTTCTGCGGGGCAATATAGACGTACTGGCAAACAATTT
GTTCGTGGGCATCGCCCTGAGTAAGCCTCTGAGGAAGGGCTACACCAAAGGAGGCATAGCCCTCATAGACCC
CTACAGCGCCCGAATTATCACAAGGGCCATCGTGTTGAAGCGCAAGATGAGGAGCGGCAAATTCGAAGCCTC
AGACATGCACGAGATCGTGTCCAACATCAAAGGCGTGCTGAAGGACTACAAGGAGCTGTACAACGTCAACGA
ACTTGTTATACATATCTCCAAGTTTCTGAGCGATGACGAATACGGCCTTTTTTACGAGTACTTGCAGGACCT
TAATGTCAACGTGCGACTCCTGAGCATCAGGAAGAGGGACGACATTACACTGGTTAGGGACGGGAGGATGGA
CAGCCTGACCATGATCAAGCGCGGCAAGAGTCATGTCGAGGTCATGTATTGGCCTCACGAAAGGGCCTACCA
CCCCCTTACTATCAGGATCTACGGCGACAATGTGGACAGGGACGTGATGATGCGACACCTGAGGTTTATCGA
GCTGCTCCGGCACATGTACTACCCGGCCAGCAGCCGCTTCATAGTTGAGCCCGCGACCATTAGCTACAGCAG
GAGGGTCGCCAGATTTGCCCCCTGGCTTTCAGACAATACCTAGTAACTCGAGGTTAACTTGT
268 84 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGCGCAAGGTAGAAGACCCAAAGAAGAAACGGAAAGTGGGAAG
CGGCTCAATGGAAGTGTCCCCCTTCTTCAACGAACTGTTCAAGTACTACATATTTCTGTTTTTTGGTTTCAA
GGTGAACATCGTGAAATCACATTACCAGAGCATTAAGAAGCACAAGATAATATTCTATTCCGGTGGGATCAT
GGACGAGTATTACACTAACGCCTTCCCCATCAACAAATACTTTATCAACCGCATCATCTCTGAAAACTGCAT
CCGCTGCCTGTGCAAAATAACCAAGCTCGAGAAAAAAGAGAAGATCGAGGAGTTGCTTTACTCTATCAGCGC
CACCCTGGGGGGCATTTACATCGACGATTACAACCCAATGAAGAATAAGTTCAGCTTCTACATTTGGAAGGG
AATCCTGAATAAGAAGATTAAATCCTACGGGTCTGAATGGCTCATTAACAAGATGAAAAACATGGGCTTTAA
GGATCCGGAAAACAAGACGCTGTTGAACTATGTGAAAAAAAAGTACGAGAAAGACATAAAGTTCGACATCAT
AAAGAAAGAGAAGATAGAATGGAGTAACCTCGACTGGGAGATAAAGGAAAAGATAGTGCTGGGCGCCATAAA
AACTCACCCTACCATTCGCAAACTGATTGAATACAAGAATGAGAAATTCATTGACAAAATTGGAAAGAAAAT
TCTGACTTACTTTAGCATCACAATCACCAGCGACGAGAACGAGAATTACTTTCTGATCGTCAAGCCCAAGCA
TAAGATCATCAGCTCAGAGACAATTTACAACATGCTGAAGAACAACAAAATCGACTTTAAAACTCTTGAGAG
GAAGCTGCTGAACGGCAGCGCCCTGATAACCACCAGTAGGGCAGTCGGCAGACGGAAATACGTCAAAATCAA
AAAAATCATATCCCCCAAGGAGAAGGAGTATTGGCAACATACCCAGGACATCAATGAGCACTACGAAAAGGA
GGGCGTCCCGATCAGCGTCGGCGGTGACGACATCCACTGCTATATCTTCATCGGGGAAGACGATTACGCCTA
CCACACGAAGAACTCCTTGCTCTACGAGGGTGTGACGGAGGACGTGCAGAAAATACTCTTGGATATGGGTAA
GTTCCTGGAGGAGCTGGAGACGGCAAAATCTATCCTCAAGCAGGGCAACCTCATAGACTTCAGTCGCGAATT
CCTCAACATTAGCACGAAGGACGACTACACCCTTACTCTCCTGAGCACACTGTCCGATATCAAAGTGAAGCT
TAAGACCGAGTCTGGTATCATCACAGGCGACTACCAGAAACTTAGGGAGATCTTTGACTGGATCTTCGACAA
GAGCTTTAACCCCTTGAAGCCTAAGAATTGCTACCTTCCGCTGAGTATTCCCCCCATACTGAATGACAAGAA
AAAGATCGGCGTGTACATCTTCTATAGCAATATTAGCGACCCCGAGCTTAGGTTTATCGAAGGGATCTTTAA
GAAACTGGGCCTGATATGCGCCATCAATAAGAGTGTGCCAAAAATTGAGGTTAAACTCAAGAAGGAAGTGGA
CTTTGAGGACTACGCCAACAGCAGGATCATAATCACCCAGACCGTACTGAGCAATCTCGAGGATGGCGAGCA
GCCGTTCCTCATATGTATAAGTCCCTTGCTGCCGAATAACGAGTTCGATGAACTCAAAATGCATCTGTTCTC
TCACCCGCAGCTGATATTTCACCAATTCATGTATCCGTTCAACCTTCGAAAGTGCCTTGAGAAAGAATCATT
CAAGAAACCCTTCATCAACTCAATCCTGTCTCAGTTCTTTCACAAAATGGGCATGTACCTCTTTAGTCTGTC
TGACGAGCTGGGGAACTACGACTTCATTATTGGTTACGACATAAGTAGGGAAAAGGATGACATCGGGAAGAT
AAAAGGTATCGGCGGCTCCGCGATCATCTACAACAATTACGGCCATGTCAAGTCAATCATAACGTTCGACGA
CGTAGGGTCTAGCGAGATAGGCAGGTACGACCTCCTGTTCGCGCAGGTGCACAGCGAACTGATACCCCACCT
GAATCTGAACAATAAGCGGAAAATTAAGATTCTGCTTCTCAAAGACGGGCGGATTTTCAAAAAGGAACTCGA
AAAGCTCAGCCAAATCAGCAAGAAGTATAACTTCGAGATCACCTACATTGACGTTCGCAAGAGCACGCTGCT
CCGGTTCTGGGGTGTGCGGAGGGGCAAAGTGGTGCCCGAGTATAAGAATAGCTACGGGAAGTTCGGACGCGC
ATACTATATTAGTAGCCATTACTACAACCGCTTTTTCAAGCAACCAATCGCAATCGTGGAGAAGTACCACAT
AGACGAGGGCAATTACAAACGCGTGGAAATAGAGGAGAATGATATTAAGCAGCTGGTTCTGTTGACCAAGAT
TAACTACAGCCAACTGATGCCAGATAAGATGCGGCTGCCCGCACCCGTTCACTACGCACACAAGCACGTGAA
CGCCGTGCGACGGGGCTGGAAGATCAAGGACGTCTCTATACTGAGGAGCGGGTGTCTTCCTACGATCTAGTA
ACTCGAGGTTAACTTGT
269 81 GGTGTCGTGAGGATCCATGCCTAAGAAGAAACGGAAGGTGGAAGATCCAAAAAAGAAGCGAAAGGTTGGTAG
CGGCTCAATGGCCTATAGCCTTAACGCTTTCGAACTGGAAATTCCCGACATTGACGCCGACCTCTACAAAGT
TGACCCTCAACCCTCTGATGACCCATATCGAATCCTGGGGGGTTTGGAACGGTCCTTCGAGCAACAACTGGA
CGGCAAGGCCCAGAAATGGAAACAGGCGGAGGACGGAGATTGGTATATCGCCGTGATAGGCGCGTCAGAAAG
GAAAACTATCGAGTCCCCCTCCAGCGGTACGAGGGCAGGCTACACCACCACGCATACGCTGGATCCGAGTAG
CTTTTGGGACAGGATGGTGTTGCAAAGGGCAATTAGCGACTCTGTACGATGGTACATGACCAACTATCAGGA
CTTTTGGTATCATGAGGATGCGGATGCACTCTTTTATCCTTCTCCTAGAGGCAAAGTGGACGAGTACGACGT
CTACACCGGATTTAGTCATAGGGTCGAGTTTTATGACAGCCCACAACTTGTCGTGCGCAGCGTCACTAAGTT
CATCTCCAGTGAAAGCCTGGCGGACCGGATCAACCATCAGGGCACAGAAGAAGCAACGGAAAAATACGGTGG
TGAGAACTTTAGGCTGGACAGGCCGGAACCAACCAAATGTACTTTGCACGGCATCTCAACCGAGCGAACGGT
AAGTGACAAGACGATAGATTTTGGTGACGAGATGCTGTCCGTGTTGGAGTTTGCACAAAGAAAATATGGCAG
CGAGTGGGCGGACAAAATCGATCCCGACGAACCATTGGTGCAGATACGCTTCGGGAACAGCGACCCCTACGA
CACCGCTCCGAGCCTGCTGAATGCGAGCCCTGAGGAGCTGAATCGCAGGCTGACCAGCGAGGCAGCCCTCAG
CGCACAAGAAAGGCAGAAGGCCATACAGAACTTCATCGGCAGGATACACTACATCCAGGTTGAAGACGAGAA
GGTGAGCGTCAGCGATGACGGCGTACGGCCCACCGAGCAGGGCGACTTCGACTACCCCGATCTTGCGTTTGG
CAATGACGAGGTGCTCAGCACCGGCGTCCCGAACGCGGTAGATCCTAGCCAGGAGGTGCACCCGGGCAACTG
GCGATGGATAATCAGGGACTACCTGGAGGAATACGGCTTCTGGGAGTCACAACGAAAGCTGTCTGAGATCGT
GCTGGTGTACCCGAGAGGCGAAGAAAGACGGGCAGAGAACCTGTACCAGGACGTTAGGGAGAAGCTTTCAGA
GATAGGAGGCGTTCAGATCAGGAGCGATCCACATCGCGTGTGTTACACCGATCAGGTGGAGTTCGACGAATG
GGTGGCTGAATTCGGTGACTCAATCGACGGTGTTCTTGGATTGATTGAGGGAGATGGAGACGAATACTACGA
AATCATAGATGCATTTGGCGGAGCACCGACCCAGTACGTCAACACTAGCACCTACTCAGAGCACAGAGGGGC
GAGCGACGACGTGATCTTTAACACTGCTTGCGGACTGGCCGTGAAGTTGGGCGCATATCCTTTTGGCCTGGC
CAACGACCTGAACAGTGACGTGTACCTCGGCCTTAGCGTGGCAGGGGATAGAAGCACAACGGCCACCGCCGT
TGCCATAGACGGAAGAGATGGGAGGATTCTCTATCAAACAGAGGAACCCCTGGGCCAGGGTAGCAGCACAGT
AAGCGAGGGCTATCCCGCTAAGCGAATCATCCAGAGGAGCCTGAAGACCGCCTCAAGCGCCTTTGATCGACC
AATCGAGAGCTTCGACATTCACAGGAACGGAGACTTTGGCGACGCTGAGCTGGAAACCCTTAGCAGTGAATT
GCCTGCACTCCAGGACCAGGAATATGTGCATACCGATGTTTCATGGAGCGCCGTCGAGGTAATTGAAAACCA
CCCTTACAGGCTCTTTAGTGAACGGGGCAGCAGAGCTCCCGATACCGGAGCCTATGCTAAGCTGGACGACGA
GCATGTACTGGTTACTACCTTTGGAGAGCCCCAGATCCACCAAGGTACGCCAAAACCGGTCCTGTGCAAGAG
GAGAGCAACGAGCCAAGATCAAGACATCACCGCCATCGGAGAGGACGTGTTCAAACTCAGCTTCCTTAACTG
GGGTAGCCCAATGATGAAGATGAAGCCACCTGTTACCACTAAGATTCCGAAGGAACTCAACGAGATTTTCGA
GAAGTGCTCTAGGGTGAGATACCCCCCCTTCTAGTAACTCGAGGTTAACTTGT
270 83 GGTGTCGTGAGGATCCATGCCTAAGAAAAAAAGGAAGGTTGAAGACCCGAAGAAGAAACGCAAGGTCGGCAG
CGGAAGTATGAAGACGCAGGATGATATCGCGCACAAGCAACCCATTACCATCGAGGTCCAGATCCTGAAGGA
GCTCGACAAGCCAAGCCCAAAAATGGCCACCCGGTTCCTCGTGGCCGATAGGGACGGCAACAGGTTTAGCCT
GGCTATCTGGAAGAACAACGCACTCAGCGACTATGACTGGACGATTGGCCAGTGGTACAGGCTGGAAAACGC
CAGAGGAAATGTCTTTAACGGCAAACAGTCCCTCAACGGTAGCAGCAAAATGCGCGCCACTCCACTTGAGGC
CAGCGAGGAGGACGAAACCAGCACGGATGATGTGGGACGGGTCGACACAATCCTGGGTAATATGAGCCCGGA
CCAGGCTTACCTGAGCCTGTTTCCCATCAGTAGGTCTTTTGATACCCTGTCTGTGTACGAGTACAGCATTGA
GGCAGCCGAGGCATTCGAGGATGCGCCGGACACCGTGACCTACAGGTGCGCTGGCAGGCTTCGGAGAATCAC
GGGTGCGGGGGTCGCTTATGCTGGCTCAATGAGGATCGTGTCAACCCGCAAACTCCCGGACAAGCTCGCGGA
CCCCTTTAGCTTGAGTGAACCCACGGAGAGGGAACTGAACGCTACGGACGCCAGGGACAGGCATAGGATAGA
GCGGCTTCTGAAGAGCCTCGTGAAGGCCGCCATCGACGATAGCACCTACGACCCATACCAGATCAACCGAAT
CAGGGCCAGGACCCCGAGCATTACCGCTGGCGACGGGCTGTTCGAGGCGTGCTATGAATTTGCAGCAAGGGT
CGATGTGATGCCCTCCGGCGACGCCTTCGTGGGAATTGAGGTAAGGTACCACACGCGGAGCCAGGTCACTGC
AGACGTTTACGAAGACAAAACCGCGGAACTGGTGGGCACCATCGTGGAGCATGACCCAGAGAGGTACAACAT
TAGCGGTACGGGCCGAGTAGTGGGTTTCACTGACCACCACTTCACCGACGCCCTCGACGAATTGGGCGGTCT
TAGTTTGGCGGACTGGTACGCGCAGAAGGATCGCGTCCCAGAGGGGGTATTGGAGGCGCTGCGAGAGAAAAA
TCCTAGGTTGGTTGATATTCAGTACCAGGAAGACGAACCAGCCAGAATCCACGTCCCGGATTTGCTCAGGGT
AGCACCCCGCAAGGAAGTTGTCAAGGAGTTGGATCCCGCCTTCCACAGAAGGTGGGATCGAGAGGCCAAGAT
GTTGCCCGACAAAAGGTTCAGGCACGCCATAGAGTTTGTGGATCATCTCGGGTCCCTGCCGGATATAGACGC
CACGGTGGCACCCGAGCCTTTGGGGCCGTCACTGTCTTACATGAGCACAGCAGTCGACAGGGAGAAGAACCT
GCGCTTCAAAGATGGAAGGACCGCCACCACCCCGTCAAGCGGCATCCGGAGCGGCGTATACCAACAACCGAC
GAGCTTCGACATCGCCTATGTGTACCCCACCGAGTCTGAACAGGAGAGCAAGCAATTCATTTCTAACTTCGA
GAACAAACTGTCCCAGTGCCAGTGCGAACCAACTGCCGCTAGGCACGTTCCTTATGAACTCGGCGGCGAGCT
GAGTTACTTGGCTGTCATCAATGAACTTGAGAGCGTGGATGCGGTGCTCGCTGTGGTGCCTCCCCGAGACGA
TGACCGGATAACGGCCGGAGACATAACTGACCCCTATCCCGAATTCAAGAAGGGCCTCGGGAAGCAGAAAAT
ACCCAGTCAAATGATCGTGACCGAGAACTTGGGCACAAGATGGGTGATGAACAATACAGCCATGGGCCTGAT
CGCAGGGGCAGGAGGCGTTCCGTGGAGGGTGGATGAGATGCCGGGTGAGGCCGATTGCTTCATAGGACTGGA
TGTGACTCGCGACCCGGAAACCGGCCAACACCTTGGCGCTAGTGCCAATGTCGTTTATGCCGACGGAACCGT
TTTCGCCTCTAAAACGCAGACCCTGCAGAGTGGGGAAACGTTCGATGAGCAGAGCATAATCGACGTGATCAA
GGATGTATTCCAGGAGTTCGTTAGGCGCGAGGGGCGATCCCCTGAACACATTGTTATCCATAGGGATGGCCG
GCTGTTTGAGGACGCCGACGAAATCCAGGCCCCGTTCGCGGATAGCGGAGTGAGCATAGACATTCTGGACAT
CAGGAAATCTGGCGCTCCGAGGATTGCCCAATACGAGGACAACAGCTTCAAGATTGACGAGAAAGGCCGACT
TTTCATCAGTCAAGATGACACGCATGGATTCATCGCCACAACGGGAAAGCCGGAATTTGATGATAGCGACAA
CCTGGGCACTCCCAAGACTTTGAGGGTAGTGAGGCGGGCTGGTGACACACCGATGCTGACTCTGCTGAAGCA
GGTGTACTGGCTTAGCGAGGCACATGTTGGCAGTGTGAGCCGAAGCGTTCGCCTGCCTATCACAACTTACTA
TGCAGATCGCTGCGCCGAACATGCGCGGGAGGGGTACCTGCTCCATGGCGAGTTGATCGAGGGTGTGCCATA
TCTGTAGTAACTCGAGGTTAACTTGT
271 87 GGTGTCGTGAGGATCCATGCCCAAAAAGAAAAGGAAAGTGGAGGATCCGAAGAAAAAGAGGAAGGTAGGCTC
CGGGAGCATGAAGCCAGTGAACTTGGATGAAAACAGCCTCAACGACGTCCCGGTAGGCGACACCTATGCTGT
CCGCTTCACTCTTGATGCAGTCTTCGAGAACGAAGGGCAGTATCCCCGGAGGAATCTGAAATTCACAGACGG
AGGGGGGGATGACCGAACCATCACTATTTGGAAAAACTCTGCACCCGAGGAAATTTACGAGGCGGACTATGA
GCGCGGTGCGACGTATCTTATTACCGCCGTCGAGTATGACATCGACGAAGGTAATGACGGCGAGCGATACCA
GAATCTCACAGTCCAATCAGATGCTACCTTGCTGGAGATGAGCGGTCCCCCTAGTACCGAAGAGGCCTTGGA
AGACGGCCTCGCCGAAACCCCAGATACTAGCGCCGATTCAGGTGACCACGGGTTGACAACCTTTAGGACTAC
AGACGACCTGCCGGATTATGACGTCTATGAGTACGAGCTGGTGCCGAAGCAAGGATTCCGGCCGTCCGGAGA
AAATGCCCTCCGAGCCACATACAGGGCACGACGCAAGGTCCGCCAGCAGTTGGACGTAACACCCGTCGTGGT
CGGCGATGCGTTTAAGCTTGTGTCTCTGGTCAAGCTGGCCCACGAGCGGGTCGAGCTTCCGCGATTCAAGAT
CAACGAGGTTGACGAGAGGCCCATCGTCTACGCCGATGAGGATGACAGGGATGTGTTGGGGGAAATGCTCGG
TGAGATCCTCAAGGACGCGAAACGGGACCAGTACGACATCCATGGCATCGACAAAATACTGGAGCCAGAGCC
CGTCATAGAGAAAGAGGGCTTCAGGCTCCACGAACGGTACAACCTGACCGTGGAAGTTCTCCCTAGCAGGGC
CGCTTACCTGCACGTGGACTATCGACATCGGATATTGAGCGACAGGACCCTGGATCAACTCGATGAAGACGA
AATCCACCCTGGCCTGCGCGTGACCCCCTCATATAGGGACATGGGTCTGTACGTTATAGGCGTTGGGCCGGA
GACGGTGACCGATAAGCTGCATATCGAGGGCAACAAGAGCCTGGTCCAATACCATCGGGAAGAGCCGTGGGT
GGACCCGGCGAAGGTGCAAGAAATCAAAGACGCAGATAGGGAAGTGATCTGGACCGTGAGGCAACGGGGCGA
TGGCACCGAGATGGCATTCCCGCCGGAGCTGCTCGCGCTTCAAGGGCACCCCGAAAATTTGGCCCAGTTCGC
CAGCGACTTTGCTGAACAACAAAGGCTCAACACGCGCCTTTCCGCTGAGCAATGCATCACCAAGGCTAAAAG
GTTTGTGGAGCGACTCGGGCCCTTGCAATTCGACGGACACACTGTGGAATTCGAGACCAACCCGCTGTTGGG
CGATCGGAACATAGCCATAGATGGTCTGTTTCACCCGGAAGCAAACGTGCTGCAGTTTAGCGGAGGCCAGAC
CGGCACCCACCCCTCAGATGTGACACAGCTGGGCGTGTACGAAGCCCCGGACCCCTTCAGGGTGTGCCACAT
CAGGATGGAGAAGCGGGACAAAAGAATACAGAGGGGTTGGAGTACCTTGGAGACGAAGCTGGAGCAGATTGG
AGCGCCTCCCGACAGTGTCGAGGAGGTCACGTTCGACGCCACAATGAGCCCTGACCAGTTGGGTATGGAGAT
AGCGGCCGAGATACCGGACGACCATGATTACGACGCGGCCTTCTGCACATTGCCACCTAAAGACACCGGCTA
CTTTGACACCGCAGACCCCGAGCGAGTTTACGATGAACTTAAGAAAGTGTTGGCCACCAAAGACCTTAACTC
CCAATTCGCGTATGAAGCAACGCTGGACGAGCGCTTTACAATAATCAATATAGCACTGGGTCTTGTCGCCGC
AGCGGGAGGTATTCCGTTCACAATCGAGAGGGCGTTGCCAGGCGATAGCGAACTCCACCTGGGAATCGATGT
AACCCACCAATACGACGAGTCCGCGAATGGCAACCACATTCACCTCGCTGCTGCGACGACGGCTATCCACGC
TGATGGAGCTGTACTGGGCTACACCTCCAGCCGCCCTCAGTCTGGGGAAAAGATTCCCCCCAAGGAGCTGAA
AGAGATCATCAAGCAAGCGGTGATGGGCTTTCGCACACGCTACGATCGCTACCCAAATCATATAACCATCCA
CAGGGACGGGTTCGCAAACGAGGACCTGTCCGAGGTAGAAAAGTTTCTGACGGACCTCGACGTTGAATATGA
TGTTGTCGAGATCAGGAAGCAGGCCCCAGCGCGCGTCTTGAAATACAGTGGTGCCCACTTCGACACGCCTCA
AAAGGCGACCGCCGCAATCTACGAAGACATCCCGAAAGCGATTGTAGCGACGTTTGGTGAACCCGAGACTCT
CGCTAGCCGGGAGTCAACCGGGCTTCCCCAACCAATCACGGTGGAAAGGGTGCACGGAGAGACCCCCATCGA
GACACTTGCTGCGCAAACCTACCTGCTGAGCCAAGCCCACATAGGCGCCAGTAACGCTACAGCACGCTTGCC
CATAACCACCATGTATGCCGACTTGGCTAGTGCAGCGGCAGCCAGGCAACACCTTCCCCCGACCAACAAGCT
GAGGGATAAGATCGGATTCATCTAGTAACTCGAGGTTAACTTGT
272 86 GGTGTCGTGAGGATCCATGCCAAAGAAGAAGCGGAAAGTCGAGGACCCTAAAAAGAAACGAAAGGTTGGCAG
CGGTAGCATGAAGAACCTGAGATACAAAATCAACGCCTACAGAATCAAAAAAGACTATATTCCCAAGGAAGT
TTATAGATACAGGATCCGCTCCTTCATAGAGAACATTAACATATATAGGTTCGTCGGTTTTTACGGAGGCGT
GGCCCTCAATCAATCTGAGTTTATCCTTCCGTACCCGGTCGAAAATCTCGTCCTGGAATACGACGGAAAAGA
TGTAAAGCTTGAGCATATCGACACACTGAACCTGGAGGACATCGAGAATAAGGACAAGGAGAAAGCCGAGAA
GCTGGTGAGGGGATACCTGACCAGCATATACAAGTTGAAACCCATACTCTACAAGATCCTGCGGGACGTTCG
AGAGAGCAAGATCATTAACGATATCAGAGTGGATCCTATACCCGACTTTACAGTAAAAAGGCACAATAACGA
ATACTACCTTGTCATCGATTTTAACCACACCGCGACCGTGTTGAAAAATCTTTGGGACTTCGTGGGAAGGGA
CAAGCTGAAACTCGAGGATTATATCGGTAAGAAAATCATATTCAAGCCCAACCCGAAGAAGAGGTATACTAT
AAAGAGCATTGAAAAGCAGAACAAGAAGGACATTGATGACATTGTCGAGCACATCATCGAGTACTACAAGTG
GACGGAGGAGGAAATTAAGAGCACCTTCGGCGAAATCGACTATACTCAGCCCATCATCCATTGCGAGGGCAT
CCCCTACCCGTTCGCACCGCAATTTTGCAATATCGTATTTACCATGGAAGACTTGGATGAGAATACCCTCAA
GGACCTGCAGAGCTACTGGAGGTTGCCCAACGAGATCAAAGGCAACATTATCAATCAGATCGCTAAAAAACT
GCGATTTGTGGAGAACGAGCCAATCGAATTGGAATTCATTAAGTTCAATAACACCCCCCTTATCGTGAAGGA
CGAAAATGGCAAACCAACAAAGATATACACCACCAATCGCCTCTTCCGATGGAATTACGATAGTAAATCCAA
ACTGTACTTGCCCTACGACATCCCTGACATAATCAAGAACAAAACACTGACAACGTTTGTGCTGATCGACGA
GAATCTCAAAAACGTGAGTGGTAAGATCAAGAGAAAGGTCTACCAAATGTTCAAGAATTACAATAAGATCGC
CAGCAAGACTGAGCTCCCGAAATTTGACTTCGCCAATAAATGGAAATACTTCTCTAACAACAACATCAGGGA
CGTGATCCGAAAGATTAAGGATGAGTTCAACGAGGAGCTTGGCTTCGCGCTCATTATCGGCAACCGATACTA
TGAAAACGATTATTACGAGACCCTGAAGATGCAATTGTTCAACCTGAATATCATCTCCCAAAACATTCTCTG
GGAGAATTGGTCAAAAGACGATAATAACTTCATGACAAACAACCTGCTCATACAAATTATGGGCAAACTCGG
AATTAAGTACTTCGCACTGGACGCAAAAGTGAACTATGACTACATCATGGGGTTGGACAGCGGCCTGGGCGC
ATTCAAAAGCAACAGAGTGTCCGGGTGTACCGTGATCTATGACAGCGAAGGGAAGATCCGACGGATTCAACC
AATTGACGTGCCCAGCCCTGGGGAAAGGATCCCCATTCACCTGGTAGTGGAGTTCCTGGAGACCAAGACCGA
CATCAATATGGAAAACAAAAACATCCTGTTCCTTCGAGACGGCTTTGTGCAGAATAGTGAGAGGGAGGAGTT
GAAGAAACTGAGCAAAGAGCTGAATAGTAACATCGAAGTGATCTCAATCCGCAAGAATAACAAGTATAAAGT
CTTTACCAGCGACTACGGTATCGGCTCCATTTTTGGCAATGATGGCATATTCCTGCCACATAAAACTACATT
CGGAAGCAACCCGGTGAAGCTCAGCACCTGGCTGCGCTTTAACTCCGGGAATGAGGAAAAATTGAAGATAAA
TGAGTCTATAATGCAACTTTTGTACGACCTTACCAAAATGAACTACAGCGCTCTGTACGGGGAGGGTAGGAA
CCTTCGCATCCCGGCACCGATTCACTACGCCGACAAGTTTGTGAAGGCCCTTGGAAAGAACTGGAAAATAGA
CGAAGAGTTGCTGAAGCATGGCTTCCTCTACTTCATCTAGTAACTCGAGGTTAACTTGT
273 82 GGTGTCGTGAGGATCCATGCCTAAGAAAAAAAGAAAGGTAGAGGACCCGAAGAAGAAGCGCAAGGTCGGCTC
CGGAAGCATGAGTCAAGACTCTAGGAGCACCGAGGTGGAGAGGCAGGCCGAAATACAACCTGGTACCTACCT
GTTGAACGGCCGGGGGGAAATTCAGTTGGATGAGGTTGACGCATTCCAGTACGACCTCAAGGTGAGTGGAGG
CGTGGAGCAGTATTGGGATCGGGAACAATTCACCAGCTCTGCAGCCTACTACCTGGACCAGGAACACGGGAG
CCCTGTCGCTGAGATAGGCAAAATGAACGTGCTCAGCAAGACGGATTTGTCTAGATCAGTTAGAGTGTGGCA
GAGAAACGTGACTCCCATCAATAGGCAGAGCGTTACACTGACCGCAGCCCAACCCGAGGACCGAGAAAAGAT
CAAATCATTCGTGCAAAGCTGCTTCAAGAGGGCAGTGCCGACCGAAAAATACAGCTTTCGCTTTCTCAACAA
GATTGTCAGGGATGAGCCCGAGTTCACCACCGGCAGCGAAGGCTTTTCTGCACATCCGAAGCACGACGTTAA
GATACAGGTCACCGCTGATGGCAATGTGCTTGTGCACGTGGATAGCGGGTTCAGCATCAGGAGCAACAGCAC
CCTGGACGAAATCTACTCTGAACAGGATAACCCTTACGGTAAGCGCGTTGCCCACGACCCCGAGAGGTATGG
TACCCAGGGCCAAGGCACCCTTCGCGGTTGGAGCGACTATCGGTACACAGACCATATTAGCGATGCGGGTAG
CTCTGTGAACGAAATGCACAAAGGGGTGGCGGACGAAGAATGGCGGCAACGACTCGCAGAGGAGAATCCCCG
ACTTCTGAAAGTGGAGTATGGCAACAAAACTAGGAGGCAAGCCCCCCATTTCCTGAGGCTCTCACCGCGGAT
CGAGCAGGTGCAGGATCAGGATCGCGAGTTCTATAGCAGGTTTAACAGCCGGAGCGCGATGATGCCCGACGA
AAGATTTGAACTGTCTAAAGAGTTCCTGCAGAACGTGAGCCGCTTGCCGGTATTGGACATGGAACTCGAGCC
GGGTCCGGTGAACAGCAGTTACGAGTTGCTGGAAATGCGAGAGGAAAACAGGCTGGTTTTTGGAGGGAAGCA
GAGGGCTAGAGACCCGGGCAGCGGGCTTAGAGAGAATGGGGTGTATCAAAGTCCCAGTCAGTACCGGCTGGG
GGTGTTGACCCCCGAACGATGGGGAGAGAAGGCGAGCGAGCTGATCCCCCTGATTGTGTCCGGCCTGAACGA
TCTGAGCGCATCAGCAGGAGTTCGAGCATATGGATACGAATTGGGGGACGTCAGCAATTACACACCCGTGGT
TCAGGACCTCCACGAGGAGACGGACGCTGTGCTCGCCGTGGTCCCCAATAAGGGTGTGGCCGAGGATTTTGG
GATAGACGATCCATACAAGGAGCTGAAAAGAACCCTCCTGCGGAAAGGGATACCCACCCAAATGATGCAAAA
GTCCACGGTCGATGAAATCGTGGGTCAAAAGGCGGGAATCGGCAATGACAAGTTTCTGAACGCACTTAGTGC
AGTCGTGGCCAAAGTGGGCGGTACCCCATGGCAGATCGATAGCCTCCCCGGGAAAACCGACGCCTTCATGGG
CTTGGACGTAACTTACGACGAGAGTAGCGAGCAGCACGCAGGCGCCAGTGCAAGCGTAGTACTCGCGGATGG
GACGACTTTCGCAGCCGAGAGCACCACCCAGCAAGGTGGCGAGAAGTTCAGTGCACGGCATGTAGAACAGTT
CGTGAGGGACCTCGTCTTCGACTTTGCGGGGGAACAGGGCCGAGACATCGACAGACTGTGCATAATGAGAGA
TGGGAAGATCAGCGAGGATATTGACGCCGTAAGAGAGGGACTCAGTGGTATTGAGGCGGAGATCGACATAGT
TGGCATACGAAAATCCGGGCAACCTCGCATAGCTGAGTTTGACGGTACTCGGTTTCGGATCGCCGAAAAGGG
CGTGGGCTTTGTGGACGCCGACAGAAGCCAGTCTATCATCCATGCATTCGGCAAACCCGAAATCCACGACGA
CAATCCTGTGGGCACCCCACGAACCTTTCGACTGACCAAGGACTCTGGTCCCACAGATGTGGAGACCCTGAC
CCGACAGGCATACTGGTTGTCCGAGATCCATTTTGGAAGCCCCGTTAGGTCCCCTAGGCTCCCCGTGCCAAT
AGAGTACGCAGACATGGCTGCTGAGTATGTTCGGGAGGAGTACGTCTCACCAGGGACTGTAATAGAAGGGCC
AGCATACATCTAGTAACTCGAGGTTAACTTGT
274 8 GGTGTCGTGAGGATCCATGCCCAAGAAGAAAAGGAAGGTAGAGGATCCAAAGAAAAAGCGGAAGGTTGGAAG
TGGAAGCCTCCCCATCGTCCTGAACGCCTTCCCACTTAAAGTACCCGAACTGGAGCTGGAAGTTAGGCAAAT
ACCGTACGATAAAGAGACGCTTGACGGCCTCAGGGCTGCGCACAAGGCCACCCACGCTTTCCGCAGGCAGGG
CGACAACATACTGATTTTTTCCGGTGATGGCACATTTCCCGCGTCTGGGACGCCTCAAACTATTGCACTGAA
GGACAATTTCGGCGTGTTCTACAGCCTCGTGAAGGATGGTCTTATCCGCCACCTTGCGGGGCTCGGGAGGAA
TCCCAGCGGGTTCAACCCCATAGAGTTGGTGTCCGCAAAACCCGAAGACAACCTGCTGGTCCCCATACTCGG
CGATGCGTATCCTTTTAAGGTGTGCGCGAAATACAGCATTGACACCAGAACCGTGCTGGGGCACCCATGTCT
GGTGATCGATTGCACGACCAGGAGGGTGTTGAAGGAAAATGGCTTGTTCTTTTTGAACGCTGGGTTCGACCT
CGCGGGCAGGTACGTGGTGACGGAGCAAGATGACGGGTACAGGAAATTGCTCGGCAGCGTGAGCGGCTGTAA
GGGTGAAACGCTGTACGTGACTAGGCCCGATGGCCAAGTGGTGCAGGCCGAGGCTAAAAACGTGTACCTGGA
GGCATCCCGCACAAATTTCGACGACTATATTCTGCACACCCACAGGGCTCAGAAGGACGCGATCGTTGAACG
AATCAGACAGTCCGTTTCCGTGTTTAATGGGGGCGAAAATAAGAAAGCCCGAATCGACACGCTGAAGAAGTA
TATCCAGTCCAAAACCATTCCCTTGATCGACGGCACCAGGATTGAGATCCAAGATTCCCCTAACATACAGAA
AGACTGCGGCCAGATGCAAAAACCGGTATTCGTCTTTAACGACAACGGCGAGGCGGACTGGGCGGAGAAGGG
GCTGACCCAATCTGGGCCGTACACCAAGAGGACCTTCGACAGGAATGACCCCTCCATTTGCGTGATCTGCGC
CCAACATGACAAGGGACGCGTTGAGCAGTTCGTCAGGAAGTTGCTTAAGGGCATTCCAAACTCCAAATACTT
CAGCAACGGTCTCGAGGGGAAGTTTACCCTGGGCACTAGCAGGGTAGAAGTGTTCGCGACCGCTACTGACAG
CGTAGACGCCTACAAGAACGCTATTGAAGCCGCAATACGGAAGAAGGCCGACGACGGCGGCAGGTGGGACCT
GGCCCTGGTTCAAGTGAGGCAGAGCTTTAAGAAGTTGAAAGTGACCGAGAACCCCTACTACCTTGGCAAAAG
TCTGTTCTTCCTCCACCAGGTGCCCGTCCAGGACTTTACCATTGAGCTGTTGGCTCAGTCCGACTACTCCCT
CGGCTACTCTCTGAATAACATGGCCCTTGCATGCTACGCGAAGATGGGCGGTGTGCCCTGGCTGCTTAAATC
TTCACCCACCCTCAGCCATGAGCTTGTGATAGGCATCGGCTCCGCCAACATCGGCCAGGAGAGAGGAGCTGA
TAATCAGAGAATTATGGGCATCACCACTGTGTTCAGCGGAGACGGCAGCTATATCGTGAGCAATACATCTAA
GGCTGTTGTCCCCGAAGCTTACTGCGAGGCCCTTACCGCCGTACTTGGCGAAACCATCGAAAAGATTCAGAA
GAGGATGAACTGGCAGAAGGGCGATACCATCAGATTGATCTTCCACGCTCAGGTCAAGAAATTCAACAAGGA
GGAAATCGAAGCGGTCAGAGCCGTCATTGAGAAATATCGGGAATACCAGATCGAGTACACTTTTCTGAAGAT
AAGCGAAAACCACGGGCTTCACATGTTCGATAGTGCAACCGCAGGGGTGCAAAAGGGCCGACTTGCCCCTCC
GAGGGGGAAGACGTTCAAGCTGAGCAAACATGAGATGCTGGTTTATCTGATAGGGCAGAGGGAGCTGCGGCA
AGACACCGATGGTCATCCCAGGGGCGTCATCCTTGATGTTCACAAGGACAGTACATTCAAAGACATCACCTA
CCTTTCAGCCCAGCTCTACTCATTTGCCAGCCACAGCTGGCGCTCTTACTTTCCCAACCCTATGCCAGTAAC
CATTTCATACAGCGATCTGATCGCTCGAAACCTTGGTTGGCTGAACCAACTGCCCGGGTGGAACGACTCCGT
GATGATCGGAAAGATCGGGCAAAGCCAGTGGTTCCTGTAGTAACTCGAGGTTAACTTGT
275 39 GGTGTCGTGAGGATCCATGCCCAAAAAAAAGAGGAAGGTGGAGGACCCGAAGAAGAAGCGCAAAGTGGGTAG
CGGGTCCATGAAAGAGTTTAACGTCATTACCGAGTTCAAGAACGGCATAAACAGCAAATCTATTGAGATCTA
CATCTACAAAATGATGGTCCGAGATTTCGAGAAGCGACACAATGAAAATTACGACGTGGTGAAGGAGCTGAT
TAACCTTAACAACAACTCCACCATAGTGTTCTACGAGCAGTACATCGCCTCCTTTAAGGAGATTGAGAAATG
GGGGAACGAGCAATACATAAATGTGGAGAAGAGGGCTATCAACCTGGAGTCCAACGAGAAGAAAATTCTGGA
GAGGCTCCTGCTGAAGGAAATCAAAAATAACATAGACAATAACAAGTACAAGGTCGTCAAGGACAGCATATA
CATCAATAAGCCAGTGTACAACGAGAAGGGCATCAAAATTGACAGGTATTTCAATCTGGACATAAACGTTGA
GTCAAACGGAGACATTATCATCGGGTTTGACATCTCCCATAACTTCGAGTATATCAACACTCTGGAGTATGA
AATAAAGAACAATAATATCAAGATTGGGGACCGGGTAAAGGACTACTTCTACAACCTGACCTATGAGTACGT
GGGCATCGCCCCCTTTACTATCTCCGAGGAAAACGAGTACATGGGCTGCTCAATCGTCGACTATTATGAGAA
CAAGAACCAGAGCTATATTGTGAATAAACTGCCTAAAGACATGAAGGCCATCCTGGTAAAGAATAATAAGAA
CTCTATATTTCCCTACATCCCGAGCAGGCTTAAAAAGGTGTGCAGATTCGAAAACCTTCCCCAGAACGTGCT
GAGGGACTTTAACACGAGGGTGAAGCAGAAGACAAACGAAAAAATGCAGTTCATGGTTGACGAAGTGATCAA
CATCGTGAAGAATTCCGAGCATATCGACGTCAAAAAGAAAAACATGATGTGCGATAACATTGGGTACAAGAT
CGAGGACCTGCAACAGCCCGACCTGCTCTTCGGTAACGCCAGGGCCCAGAGGTACCCCCTCTATGGTCTCAA
AAACTTCGGGGTGTACGAAAACAAGCGGATAGAGATCAAATACTTCATAGACCCCATCCTCGCCAAGTCAAA
GATGAACTTGGAGAAAATCTCCAAATTTTGTGACGAGCTGGAACAGTTTAGCAGCAAGCTGGGCGTGGGGCT
CAACCGGGTTAAGCTGAACAACATAGTTAATTTCAAAGAAATCCGCATGGACAATGAGGACATTTTCAGCTA
CGAGATAAGAAAGATAGTGAGCAACTATAATGAAACTACCATCGTAATCCTGAGCGAGGAGAACCTGAATAA
GTACTACAACATCATTAAGAAAACATTCAGCGGCGGAAACGAGGTGCCCACCCAGTGCATCGGTTTCAATAC
GCTGAGCTACACGGAAAAAAACAAAGATTCTATCTTCCTGAACATTCTGCTGGGGGTTTACGCCAAGAGTGG
CATCCAGCCCTGGATCCTGAATGAGAAGTTGAACAGTGACTGCTTTATCGGCCTGGACGTGTCTAGGGAGAA
TAAGGTCAATAAAGCGGGAGTCATCCAGGTGGTCGGGAAAGACGGCAGGGTGCTCAAAACTAAGGTGATCAG
CAGCAGCCAAAGCGGAGAGAAGATCAAGTTGGAGACCCTCAGGGAGATCGTGTTTGAGGCAATCAACAGTTA
CGAGAATACGTACCGGTGCAAACCCAAACACATTACTTTCCACCGCGATGGAATCAACCGCGAGGAACTGGA
GAACTTGAAGAACACCATGACCAACCTCGGTGTTGAGTTCGACTACATCGAAATTACCAAAGGCATTAACAG
GAGGATCGCCACTATCAGCGAAGGTGAGGAATGGAAGACGATTATGGGGAGGTGCTACTATAAGGACAACAG
CGCGTACGTGTGTACCACCAAGCCTTACGAGGGAATCGGCATGGCCAAGCCCATCCGAATCAGGAGGGTGTT
CGGCACGCTCGACATAGAAAAGATTGTCGAAGACGCCTACAAACTGACCTTTATGCACGTTGGCGCAATTAA
CAAAATCAGGCTTCCCATTACTACGTACTACGCAGACCTGAGCTCCACTTACGGCAATCGGGATCTTATCCC
CACAAACATCGACACTAACTGTCTGTACTTTATATAGTAACTCGAGGTTAACTTGT
276 89 GGTGTCGTGAGGATCCATGCCCAAAAAGAAACGAAAGGTCGAAGACCCTAAGAAAAAGCGCAAGGTAGGTTC
AGGCTCTATGTCTGTGGACGCTATGATCAGGAGTATCGGGGTCGCACGGGACCGCCCGCTTCTCGTTTTCCT
CGGGGCAGGTGCCTCAATGAGCAGTGGTATGCCGTCCGCCACTCAATGTATCTGGGAGTGGAAACGAGAAAT
CTTCTTGACAAACAACCCCGACGTTGAGAAGACCCAGTTCTCCGAGCTGAGCCTTCCCAGCGTCAGATTGCG
CATCCAAGCATGGCTGGATCGGCAACGACGCTATCCCGCTCTTGATCATCCCGACGAGTATTCTACCTACAT
AGGTGAGTGCTTTGCACGCTCTGACGACCGCAGAATCTACTTCGAGAAGTGGGTCAAACGCTGTAGTCCGCA
CCTTGGATACCAACTGCTTGCCGAATTGGCACGGCAGGGGCTTGTGGCCAGCGTTTGGACTACTAATTTCGA
TGCCTTGGCGGCTCGCGCAGCTACGTCCATCAATCTCACTGCAATCGAGATTGGAATTGATTCACAGCAAAG
ACTGTACCGGGCGCCGGGCGAGGCGGAACTGGCGTGTGTGAGTCTGCATGGAGATTATCGGTATGATCCTTT
GAAAAACACCGCTCCAGAACTCATAAAACAAGAGAAGGAGCTCAGAGAGTCACTTGTCCAAGCGATGAGAAC
TCACACAGTCCTGGTTTGCGGCTATAGTGGTCGGGATGAGAGTGTCATGGCAGCGTTTTCCGATGCCTATGA
CGCAGCTCATTTTAAGGGTCATCACCCCCTCTTCTGGACACAGTACGGCGATTATCCCGCCAGTGAGCCCGT
AGCTGGACTTCTTGCTTCACCGCTGGATCAGGAACCTGCGAAGTTCCACGTGCCTGGGGCATCATTCGATGA
TCTTATGCGCAGGATAGCACTCCACGTGAGTGACGGTGAAGCGCGCGAGCGGGTGCGGAAGATTCTTGAGAA
CTTCAAGACGGCACCAGTTAACCAGAAGCTCCCCTTTGCCTTGCCTAGTCTTCCTGTGACGGGTCTCGTCAA
GTCAAACGCCATTCCGTTGATACCGCCTGGAGAGCTTATAGAATTTGATCTTGTCCGGTGGCCGCCGTCCGG
TGAAGTTTGGAGCACGCTCCGGGAAATAGGGGATAGACACGGATTCGTAGCTGCCCCTTTTCGCGGGAAGGT
GTATGCTCTGGCTACGATAGAGCAACTGACACAAGCCTTCGCGGACAATGTAAAGGATGGCGCGTTCAACAG
GGTGCCGCTGAATAATGATGACCTCCGCTACGAGGACGGAACCGCCAATCAGCTGATGCGACGCGCTACTGT
TCTGGCTTTGGCTGGGAAAGCTGGATGCGCGAACGATGGGGATGCCATTGTGTGGGACACGTCTCGCTCAAA
AACCGAAAGATTGGATAGGCAACTTTGGACTGTATACGATGCAGTACTTCTGCAGATTCGGCCGCTGGGAAC
TAAGCTCGCGCTCGTACTTAAGCCTACGCTGCGGGTTACGGATTCAACTGGCGAGGTAGCCCCGAAAGAAAT
TGAACGGGCAGTCAAGGTGCGCGTATTGGGATACCAGCATAACAAAGAGTTCAACCAGGCGACCGACTTTTG
GAGGAAAAGGCTCCTGCCCTCAAGAGATCTCCTTGTCAGATTTCCTGATCTGGATGGTGGAATGACTTTCAC
GATTTCAGGTCGGCCAATATTCGCCCGGCTCACCGACGAAAGGACTGAAACTGTCACACTGAACGATGCCCA
AGAGCGATCAGCATCTCAAGTGGGGTTGCAGCTTGCAGAGCCTAAACTGGTGTTTGCACGCACTGTAGGTAC
GGGTCCCGCAACGGACACCCTCCCGGTTAGAGGATTGCTGCAAAATAGACCTTTCGATGCTAATCTGACAGA
CTTGGGCATCGCGACGAACCTGAGGATCGCGGTTATTGCGCCCGCTCGGGACGCCAGAAGGGTACATGACTA
TCTTGGGCAGCTGCATCAGCCTATAGATCCTACAAAGTGGGATGCGGACTATCTGATGAGGTTTCCCGGCTT
CAGCTCCGCTTTTAAATGCCCTTTGGACATTCCGCAGCCGGGCCAGGCAGCTTTTGTAACACTTGACGAGCC
ACACGATGAGAGTCCTCAATCAGCGCGGACCCTTGCAGGCCGAATCACAGCGGCACTGTCTGCATTGAGGGC
GACGGAGAATCCCTCTGTTACAATAATATATATTCCGGCGCGCTGGCACGCGCTGCGAGCATTCGATCTCGA
ATCAGAGCAATTCAATCTTCATGACTTTGTTAAGGCCGCCGCAATTCCAGCGGGCTGTTCCACACAGTTTCT
GGAGGAGTCAACTCTTGCAAATGGCCAACAGTGCAGAGTGCGATGGTGGCTTAGCCTCGCTGTTTACGTAAA
GGCAATGCGCACCCCGTGGGCTTTGACGGGACTCGATAGGGACTCTGCCTTTGTAGGGCTGGGCTTCTCTGT
AAGACGAAAGATCGATGGCGAAGGTCACGTCGCGTTGGGTTGTTCTCATCTTTATAGCCCAAATGGTCATGG
TTTGCAGTTCCGCTTGAGTAAGATTGATAATCCGATAATGCTGCGAAAAAATCCTTTTATGTCCTTTGACGA
CGCTAGAAAGTTGGGCGAAGGCATCAGGGAATTGTTTTTTGACGCCCACCTCCGGCTGCCGAATCGCGTAGT
TGTTCATAAACAGACCCCGTTTCTTAAAGAGGAGCGGGAAGGGCTCCAAGCAGGTCTCGAGGGAGTCGCGTG
TGTGGAACTCTTGCAAATTTTTGTAGACGATACGTTGCGATATGTGGCTAGTCGACCAATGCCGAATGGAGA
TTTCGAAATCCATGGCTATCCTATCCGAAGGGGCACCACAGTAGTGGTCGACGACCAGACCGCATTGTTGTG
GGTACACGGCACATCAACCGCGCTCAACCCGCGGCAGAGCTATTTTCAGGGCAAACGCCGCATACCGGCCCC
CCTTGTGATGAGGCGGCACGCGGGGACGTCTGATCTGATGATGTTGGCGGACGAAATATTGGGACTGTCCAA
AATGAATTTTAACAGTTTTGACCTGTATGGCCAACTCCCGGCAACCATCGAAACGAGCCAAAGAGTCGCGAG
GATAGGCGCTCTGCTGGACCGCTATACGGAACGGTCATACGATTATCGACTCTTTATGTAGTAACTCGAGGT
TAACTTGT
277 29 GGTGTCGTGAGGATCCATGCCTAAGAAGAAGAGGAAGGTGGAGGACCCAAAAAAGAAACGAAAGGTGGGGTC
TGGCTCTATGCCACACACCTCCCTGCTGTTGAACTTTCTGCCCGTCTCTCTTAGCGGCGACACACGCATCCA
TGTCGGCTACCGGCCATATAACGAGGATGTGCTGCGGGAACTGAGGGAGGAGTTCGGCGAAAGCCACGTGTT
TAAAAGGGACTACCAGGAGGACACGATAAGCGAGATACCGGTCATCCCCGGAGCCGAGCCCCTTAGCGACAA
ATCTACTGGCGTGGATCTTGCCGAAGCGCGATGGCTGTGGAAACCACTTCTGAACGCTGCATTGCTTCGCCT
CTTCAGCGGAAGCAGAGAGATCACCTCTGATTATCCAGTCAGCGTGCTTGGTAACCCCAAGAACAACTTCAT
CAGCCATGCCAATCTCCCCGACTGGGTGAGAATCCTGCCCCTTCTGGAATTCGAGAGCCGAACCCTGTTCGG
TGGTAAATCCGGTCCGCAGTTTGGGCTTGTTTGCAACGCCCGAACTAGGCACCAGGTCCTGGCAGGCTGCGA
CCATCTCATTGAAAGAGGTATAAGTCCCATTGGCCGCTATGTTCAGATCGACCAGCCACAAAGAGACTCCAG
ACTTGCGCCACGCGGTCTGACTGTTGGTAAGGTGAGCTCTATCGATGGGGACACGTTGATCCTGGAGGATCA
CCGAAAGGGCTACGAGCGCGTGAAGGCAAGCGACGCTCGCCTTACCGGCAATCGGGCGGACTTCGACTGGTG
CGTGAACGCGCTGTTGCCTGGACAAGGTCAAGCAACGCTGAGCAGGGCGTGGGACGCCATGAGCGCCCTGAA
TCAGGGACCCGGCCGCTTGCAAATGATCAATCAGACAGCTGAATATCTGAGGACCGTGAACCTTGAGGCGGT
TCCTGGGGTAGCATTTGAGATCGGCGAGTGGCTGAGTTCTACCGATGCTCAGTTTCCTGTGACCGAGACCAT
CGACCGCCCTACCCTCGTGTTTCATCCCTCCGGCCGACCCAACGACACTTGGAACGAGAGGGGGATAAAGGA
CAATGGCCCGCACGACCAGAGGACATTCACCCCCAAACAGTTGAACATCGCCGTGATTTGCCAGGGCAGATT
TGAGGGACAGGTAGACAGATTCGTGGGCAAGCTGCTCGATGGCATCCCGGACTTTCAGTTGAGGAACGGCAG
GAAGCCCTACGACGACGGTTTCCTTAGCCGGTTTAGGCTGGAGAGGGCCAACGTGCAAACCTTTCAGGCTAA
CAGTGCGTCCCGCGAGGCTTACGAAGCAGCGTGTGAGGACGCTCTGAAACATGCCGCTGATAACGGCTTTGG
CTGGGATCTGGCTATCGTTCAAATCGAGGAGGATTTCAAGGCGCTGCCTGGGCCCCAAAATCCCTACTACGC
CACCAAGGCAATGCTCCTCCGGAACAACGTAGCCGTGCAGAACATCAGGATCGAAACAATGAGTGAGCCTGA
CAAAAGCTTGGTCTACACTATGAACCAGGTTTCTCTTGCTTGCTACGCAAAGCTGGGTGGTAGACCTTGGCT
CCTCGGTGCCCAACAGAGTGTCGCGCATGAGTTGGTGATTGGACTGGGCAGTCACACCGAGCAACAAAGCAG
GTTTGATCAGTCCGTGCGATACGTAGGCATCACCACCGTATTTTCCAGCGATGGAGGCTACCATCTGAGCGA
GCGAACCGGAGTAGTGCCCTTTGAAGATTACGCCAAGGAGCTGACAGACACCCTCACTAGGACCATAGAGAG
GGTGCGAAGGGAAGACAATTGGAAGAACACTGATAGAGTTCGCCTGGTGTTCCATGCTTTTAAGCAGATTAA
GGACATCGAGGCCGAGGCCATCAAACAGGCAGTGGAATCTCTTGATCTGGAGAACGTTGTGTTCGCATTCGT
CCATGTGGCCGAGCACCACCCTTATTTGATCTTCGACCAAAACCAAGAGGGATTGCCCCACTGGGAAAAGAA
CAGGAGCAAGCGCAAAGGCGTCTTGGGACCCAGCAGAGGCGTGCATATAAAGTTGGCGGACAGCGAATCCCT
TGTGGTATTTGCTGGTGCTAGCGAGTTGAAGCAGGCGGCACACGGTATGCCTCGGGCCTGTCTGCTGAAGCT
GCACAGAAACAGCACCTTCAGGGATATGACCTATCTGGCGAGACAAGCCTTCGATTTCACCGCCCACAGCTG
GAGGGTGATGACCCCTGAACCATTTCCGATCACAATAAAGTACAGCGACTTGATAGCAGAGCGATTGGCGGG
TCTCAAACAAATAGAGACCTGGGACGACGATGCCGTGAGGTTTAGAAATATTGGCAAAGCCCCCTGGTTTCT
GTAGTAACTCGAGGTTAACTTGT
278 52 GGTGTCGTGAGGATCCATGCCGAAGAAAAAGAGGAAGGTTGAAGACCCCAAAAAGAAACGCAAAGTGGGCAG
CGGAAGCATGTCCGGCCTTTTCCTGAACTTTTACCAGGTAGACATCCCCACCAAATCCGTACCGATCCACAG
CGTAGAGTATAGCCATTACAGTTCAAAGGAGGCCTTTATCGCGTTGAAAGAAAACTTCCCCTACTTTAGCTT
CTACCGGGATGACGACCGAATACTGATCTGGAAGAAAGACAAGGATGCCGAGCTCCCCGAGAAGAACTCATT
GATTGAAATTGATTTCACCGAGAAAGCGAAGGTCCTCAGCAAAATACTCGAGAGGGCCATCATTGACTTCAT
CGAGCCAAAGGGCTACAAGATATTCAAGAACAAGTACAGCAACAGCTGGGAAATAGTGAGCATGAAGGACAT
CCTGAATGGTGGGATCGAGGGACTCAGCATCAATCGAATCGTGCATTTTTCCCCCTGCTTCTTCTTCAAGGA
GAACAAACTCATGCTGGGTTTCAGCCTTAGCACAAGCCTCAAAAACGTGTTTACCTGGAATAAGGCGGACTT
CGAAAGGTACGGCTTTGACATCAAGGGCCTTAAAGGAGACGAAGAGCGGATTTTTGCCAACAAGCAATCCCT
TAAGAGGTTCCTGGAGACCAAGGGCGCAGTTGCAATGTATGACCAAATTATCGCAAAGGAAAACAAGAACGC
GAAAATGTTTAGCATCATCGACGGCTTCTATCGGTGGCTGGAGAGGAACAAGACTGAAATCCAGCTTCCATT
CGGACTGAAGATAAATTCAGTGTCTAAAAAGTACCTGCCGTTCGAGGATGAGCTGATCAAGAGCGAGATCAT
CCCTAAGCCCCAAAGGTATTTCTATAGCAATAGGAAGAACACCCAGAGCCTGCGGTACTATGACGAGATGGT
GAAGACTTATCAGCCCTACTCTCTGGAGCTCTACCAAAACAAACAGATCAACATCGGAATCATCTGCCCCAG
CGAGTACCAGGGAGAGACGGAGGGGTTCATAAAGAAGATCGAACTGAAGCTCAAGGAAGTATTCCATTTCAA
CAGCCTGATCTTTCACTTCAAGACCATTACGAACAAGGACCTCGCGTCCTATAAGGAGGTTTTGTACGACGA
TGAACTGCTGAAGTGCGACCTGATTTACGTCATCGTGAATGAGGCCCAGGAGAAACTCTCACCTAATAACTC
CCCTTACTACGTGTGCAAGGCCAAGTTTATAGGCAATGGCATACCTACGCAAGACATTCAGATTGAGACCAT
CCGGCAGAACTTGAATGCGTTCACAATGACGAACATCTCACTTAACAGCTACGCCAAACTGGGAGGCACCGC
GTGGACCATCGAGAAGGAAGACAAACTTAAGGACGAGCTGGTCATTGGCATCGGCTCCACCCTGTCAGAAAA
CGGCCAGTTCGTGCTCGGTATCGCACAAATCTTCCATAATGACGGGCGCTACATGGCGGGTGACTGCAGCCC
CCTTTCTACCTTCTCCAACTACGCGGAGAACCTGGAGGATCACCTGTACAAGACCCTGAAGCCCCTGGTGGA
GGAGATGAGCAAAAGCGGCACCTTCCGGCTGATTTTCCACTTGTTTAAAAGTGCCTCTGAGGAGTACGAGAT
ACGCGCGATCAACGGCCTGCAGAAGAGGCTGGCGAACTACAATTTCGAATTTGCACTCGTTCACCTGGCCTA
TGGACACAACTTCCGACTCTACTACAACGACGGCAACGGCGACATTAATCAGGGCACATATATACAACTGTC
AAAACACAGCGCCCTGCTCCACTTCGTTAGCAAGTCAGACTTGCCCCTGAAAATCGACCTGGACAAGCGGTC
TACTTTCACCAGCCTGTTTTACATCGCCAAGCAGGTGTACTGGTTCAGCCATCTGAGTCATCGCAGCTATAT
GCCCAGTAAGAGGACCGTGACCATCATGTATCCGTCAATCATGGCGAAGATGACCGAGGAGCTTAAGAAGGT
GGAAGGATGGGACTACGAGCGCCTGAAAGCAGTAAGCGATAAGCTGTGGTTCATCTAGTAACTCGAGGTTAA
CTTGT
279 60 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGAGAAAGGTCGAGGACCCGAAGAAGAAGCGAAAGGTAGGAAG
CGGTAGCATGAAAAGCAACTTCTTCCCCATCCAGTTCAACTTCGACGACTTCCATATCCAGAGGCTTCCCTA
CCAGAAGGAGGTGCTGGACAAGCTTCGGCAACAACACAATGCGACCCATAGCTTTTTCCGCAGAGACGATTT
TATCTATATTAGCCCAGGGGTAGAGGCCGCAGCGAACCTGGGAGACGTAGTACGCCTCTCTATTACCAAGCA
CCCCGAGGTCGTTGCTTCTCTTGTTAGGCACATATTCTTTAGGACAATCAAGGATAAGGTCCCCGGTCTGCT
GCCAAGCTTTCACCCATTCACCTTTCCCGCCAAACAGGACAAATACGATCTGGCCCTGAACATGCTCCCCGA
GCGCCTGCAGAATGTTATCACCTACAAGAGGATAACCGAGGTACAGCTTCGATTCAACGAGACCGAAGAGCA
ACCCCAGTTCGTCGCCGTAGTTAACCACAGGTACCAGTGGACTATCGACCGAACTTGCGAGCAATTGGTAAA
CGAGGGTCTGGACATCCTTGGCCTGGAGGTGAACTCTAGTACGAGCCCTGATTATTCAGACGGAGTTGTGGC
ACCAGAGCTGACACTGTTGGGCAGGGTGATGGCCGTGAACGGGGATCACGCCACAGTAGGGACCAACCAGGG
TCCGACAGAGTATGCCCTGTTCGAATTGACCTTGTTCAAGTCCAAGGAGAACATAGTGAACTACCTTGGATC
TTTGGTGGGCGAGGGTAAAGCCGAACAAATAGTCAACCATATCAAACAAGATGAAAGCAGAAGGCTGCAACC
GGACGTTGTGATGAGGGAGATCGAGGAAATGGGAGTGTGGCTGTCTAGGCTGGCCTACAGAAACTTTGACTC
CTTTTGCTTCACCATCGGAACGAACAACGCTGTCAGCGGCCAAGCAGGTATCAGACTGGAGGAGCCAAAGCT
GATATTTGACGTCTCAGGTACGAACATACACGCTACCCCCACAACCGGGCTCAACACCTTCGGCCCCTATAG
TAGAAGCACGAGTTTCGACGTTAACTCTCCGAAGATTCTGGTTGTGTTTCACCAGCGGAACGCAGGCCACTT
CGCAGAGTTTCTCGCACAGCTGAAGGGCGGCATCGCTCAGCACGCATACTTTGCTAACGGGATGGTCAGGAA
GTATGGTCTCACGGCAATGGAGTACCGGATTGCCGAGATCACTGACTACACCGTGCCCCAATATCTTACCGC
CATCAATAAGCTGCTTAGGGCGGAGAACGGAAGCTTTGACATCGCCATCGTGGAGACCTGTGAGGATTTCCG
GAGGCTGCCTCCCATGGATAATCCGTATTTTCAGGTTAAGAGTTTGTTGTACAGCCATGGAATCAGCACCCA
ATTCATCAGAGCGGAAACCGCTCAGAAACCGATTTATTCAATAGATAGCATCGCGCTCCAAATGTACGCCAA
ATTGGGCGGAACACCATGGACGGTGCCAATAGGGCCGAGCGTAGATCACGAATTGGTGATAGGCATCGGTAG
CTCCATATTGCGCAGCAACCAGTATGCAGGTGCAACCCAAGCTCGAATAGTGGGGATTTCTACCTTCTTCAG
CGCCGACGGGAAGTACATAAGCAATAGAAAGACCCAGGACGTGCCTTACGATCAGTACTTCGATGAGCTCTT
GCATAACCTTAAAGTCTCCATCGACGAGATTTCCAATAACTACAGCTGGAGCTCAGGCGACCGCATCAGGAT
CATATTCCACATCTTCAAGCCCATAAAACACATCGAGGCAGACGTCGTCGCAAGCCTGATGGAACAGTACCA
GGAGTTCGATATAAAGTTCGCTTTTGTGACCTTTAGCGAGTTCCACCCGTATGTGCTGTTTAATGAAAATGA
AAGGGGGGAATTTGATGCGTATAGGAAGGTTTACAAGGGCACCCATGTACCGTGGCGCGGTTACAATGTTCT
GCTGGATCCTCGGTCATGCCTGGTCCAGATGCTGGGACCCCATGAGATGAAGACCAGCCGGCACGGCGCTTC
TAGGCCCGTCCTTGTGAGAATCCACCGCAGTTCTACGTTTGTAGACCTCGCGTACGTCGTGCAACAGGCCTT
TAAGTTTACTAGGCTCTCATTCCGCACGTTCTACCCTGTGCATAGCCCTGTGACGCTGCTCTACAGTAATAT
GTTGGCCCGACAGCTCAAGGACCTGAGGGGCATTCCGGGTTGGAACTACGATGTAGCTAGCAGGCAGTTGAG
GCACAAGAAATGGTTCCTGTAGTAACTCGAGGTTAACTTGT
280 40 GGTGTCGTGAGGATCCATGCCTAAGAAAAAAAGGAAAGTGGAGGACCCAAAGAAGAAGCGGAAGGTGGGCAG
CGGTAGCATGCAAGGCACTATATCCATAAACGAGGTGAGGATCCAGCTTAATACTATTAAGAATCTTTCAGT
GTTCAAGTGCAGCCTCAGCGGAATTAGCACCCGCCATAAGAACCAGATCGAGTTCATCCTTCGCAGCGAGCA
AAACCGAGTTAGCATCTTTGAGGGTGAAGTGATCTTTGCGCTTCCCGTCGAACAGCAGAACCTCGAAAGAGA
TAAGCAGGCTCTGTTCAGCTTCCTGGTCAAACAACAAAGGGATCTCAATCTGAAACAGCTGAGCCTGGTGCC
CCTGAGGGAGGTGCCCGAGCGCGTTATCGAGCGACTGACTTTCGCAATGGTTAGCTATCAGGCCATGAAGCA
GGGCATCTTCTCTATCTATGGTCATACATTTTTTCGCCCCACCCTTATGACGGATAGGCTTGCGCACAAGGC
GGTGGAAGTCACGACGTGCATCGAGGATGGCTTCCTCAAGTTTTATCTGGACCCGACGTACATTGCACTGAC
ATGCATAACGGACACAGCACGCGAAAATAGGGAGAACCTGGAACTGGTCGGGCTCTGCTCTTTCCGCAACAA
AAACCTTTGTAGCCTTGTCAGGCCGGACGGCTCATGCAACTGCCTCATACCTGGTAAGTTGGGGTATTACGT
CCAGGAGATGGGGATTAAGGACGTTGAGGATGATAGCAAGGACTTTCTGGCCAAACGGTTCAATAGCTGTCC
CCGGTTTAGTGAGCACACGCGCTTTATACAAGTGAAGGCGAGTAAAAGAGGCACGAAGTACTCCCTGTTCCC
TTCTTACGTAGTTTTTAGCAGGTTGTCCCGAATGGACCTGTCCGCTAAGCCAGATGTGCGGTCCAGTTATCG
GAAGGCCACATTGATGGACTCTCACGAAAGGCTTAACTTGACCAACGACTGGATAAGACAAATTTTCATGAT
CGGGCAGAAGGGCCTTCAAAATTGGGGTGTTATAAAGGTCAACCAGACCGAGATTCCCGTTGAAATTGTACT
CACAATTGCCCACGCCATCGCGCCCAAGACTTCTCAAGGCATCTATAAGGCTATATTCCTCCCGGACCAGCA
AATTACGAATGACAGCAATAACCCAACGCCTCAAACGCTGAGCGGGGGTTGGCTCTTCACGAATAGGGGTGC
GTTCGACAGGAGGGATCCTAATAGGCCTTTTAAAGTAATCAGCCCCTACATCATCGTGCCCAACAATGAGCA
AAGCATCAGCTCTTGCCGCCAGCTGATCAACTACTTCAGCAACGGCAGGTACAAGGCCCGGTGCAAGGGTGA
CAGAGACTTTATTGGTATTTCATTGCCCGAAAACAAGGGCAAGTACAACACATCATTTGTCAATGCTTTCGA
AGAGGAGGACGGCCTGTATTTCGTTGAAGAGACGATACAGGGCTACCAGAAGGCGCTGCAAGACATTGTTAG
AGACTGGAATATCACGTCCAAGCGGGACATCAATAAACACGCTATAGTGATCATACCGGGCGAGAACGATAT
TGACGACAATCCTTTCTATTATCAACTGAAAAAGGCGTTCGTAGAGGAAGGGATTCCCAGCACCTTCATCAC
GTACGAGACTATGAACAAAATCAACGACCCCGACATCGCGTTCGGGCCAATCATGGACAGCCTGTGGTTGAA
CATTTACAGCAAAATGGGGGGCAAACCGTGGCGCCTCGCTAATAGCCTCGGCAACGTGCACTGCTTTATCGG
TATTGGGTTTGGAATTAACCCCGAGACCACCGGAAACCACATATTCGCAGGGATCGCCCACATCTTCGACAA
CTACGGGAGTTGGATAGACGTAGCGAGTGATTCCGCCAACCTCTCCCAAAACGATCTGAACTCATTCGAGGG
CACGGAAAAGTACACACAGGGGAGTGCTAGCTTTAAGATCAGTCAGAGCGTGTCCCAGTCCATTGTGTATAA
CGCATTGAAGCTGTACCAACAGAAGCAAACTAAGACCCACGAAAACGCCACAAACATCGTCCTGCACAAACT
GGGCCAGATCTACGAGTGTGAGGTCATCGGGTTCCTCGAAGGAATTCGCCAAGTGCTCGGGAGTCTGGGCGA
CTGCAAGCTGGGATTGCTGCAAATTGAGCAGGAGCACCACCTGCGCCTCTATGGCGCAGCAGCCCAAACCGG
CAAGGAGAACAACACGATCTTTCGCGGTTCAGCACTTCAACTCAACCCGGAGAAGCTGGTTATCGCGTCCAC
TGGCCGCTCTTACCGGCAGACGAGCTCCGGGCTGTTTATGAATTATCCGGGCATCGGCACCCCCCAGCCGCT
CCTGTTGACTTCTATCGTACCGAATCAGCAGATCCTGCAGAAGTACGGCTGTAACGCAAACCAATTCTACTC
AAGCGAGGACCTGGCGAAACATGCAATGGCCCTGACGCAACTTCACTGGGGGTCACTGAAGGATAATGTAAG
ATTGCCGATTACCACGCTTTACGCGCAAAAGGTCGCCGACTTGATTAGCAAGACCAACATGCGGATCAATCC
AGGCTTGGGCTACTTCCGACCCTGGTTTCTTTAGTAACTCGAGGTTAACTTGT
281 58 GGTGTCGTGAGGATCCATGCCCAAAAAGAAACGGAAGGTGGAGGACCCTAAGAAAAAACGAAAGGTCGGAAG
TGGCAGCGTTCCAGTGTACCTTAATCGGTTCCTGCTGGACCACCTCACATCACCCTTGTCCTTGCCGGCGTT
TCGGGTCGAACTGGACCCTCCCCCTTCCAAAGATGAAGTGCACCCGCTCCTGGCTCTCGTCGGTCGGGAAGC
GGGAGGGCTCGTGAGGTTCCAGAACAGGCTGATCGGCTGGGAGGCTCCACGGGCCCTCGAAGGTCAGGTTAG
GCGAGGCAAGCAGTCATATAGACTGGTGCCCCTTGGCCGGCAGGCACTCAATCTTAGAAAACCCGAAGAAAG
GCAGGCGCTCGAGAATTTGTATAGGATCCGACTGGAAAACATCTTGAAAGCCCTCGCCAAACGACATAGGGC
TAGAGTCGAACGCAGGGGCAACGGCCTTTTTCTGTGGAGGCCAGAGAATCCCCGAGAGGAGAAGGAGGGGTG
GCACCTTTACCGGGGAAGCCTGTACCGCATACATCTCTATCCTGACGGCGAAGTGATACTTGAAGTCGACGT
GCAGCATCGATTTCAACCCACTCTCCATCTCGAGGAGTGGCTGCAACGAGGCTATCCACTCCCTAGGCGCGT
GACTAACGCCTACGAGGACGAGAAAGAATGGGCACTCCTGGGCATCGAAGAGGGGAAGGATCCCCGCTCTTT
TCTCTTGGATGGGGGCGAGTCATTGCTTGACTACCATCGCAAGAAGGGACGATTGGCAGAGGGGCAGGACCC
CGGTCGAGTGGTCTGGGTTGCTAGAGGTAAAGAACGCGAGCGGATCCCACATCTGAGCGTCTTGTTGAAGCC
AGTCATCACCATGGAGCTGCTGGCGGAAGTCGCTGAGGTCACGCAGGAGGCCTTGCCTGCGCTTCAGCTCGA
ACCCGAGGAACGGCTGAAGGACATTAGGCGCTTCGCTGAACCTGTACTGCAAGCGTTCGGCAAACGCGAAAC
TGCAAAACCCCTTGAAGGCAGAGCCCAGCGATTGCCGCGACCCAGTTTGTTGGCACGGGGAAAAAAGCGAGT
GGGCAAAGTAGCGGACGTACTCGAAAAGGGAGCATTGTCACCGGGCGAGACACGGTTGGCCCTGCTCGCATG
GGAGGGAGACGGGAAGGCCAAAGGCGGTCTCGCGTACTTGGAGGAGAGGCTTCAGGGCGTCGGGTCTGCATC
CGGCATCAAACTTGAACTTAAACGGCGATTTCTGCCCCGAGGCGATAACCTCGAAATGGCACAGGTGTTTGA
GGAGCTCTCCCAGGAAGGAGTAGGTGCCGGTCTGCTTCTGACTCCGCGCCTCACAGAAGGGGAAAGACGCGA
ACTGAAAAATACTGCGGCGAGCCATGGGCTCGCTCTCCAACTCCTTAACCCGTTTGACCCTGGCGACATCTA
CAGGGTGAATAACGCTCTGCTTGGATTTCTCGCGAAGGCCGGGTGGCTGTTCCTGAGACTGGAGGGAACTTA
TCCGGCCGACCTGGTGGTGGCCTATGACGCAGGCGGGGAGAGTCTCCGATTCGGCGGAGCCTGCTTCGCCCA
CCTGACTGATGGCACGCATCTGGGGTTCAGTCTGCCAGCCGCTCAGGGTGGTGAACGGATGGCCGAGGAGGT
CGCGTGGGAGTTGCTGCGACCCCTGCTGTTGAGATACCGGAAAGCGAAGGGCCAGACACCAGGGAGGATCTT
TCTGCTCCGCGACGGTAAGATTCAAAAGGAAGAGTTCCGAAAAGTGGAAGAGGAACTGAGAAAGCGCAATAT
TCCCTACGCGCTGTTTAGCGTCCGGAAGACGGGGGCTCCCCGACTGTTCAGCAAAAATGGGCCGCTCGGTGA
CGGTCTTTTTTTGCGACTGCCAGAGGAGGAGGGCGGGTTTCTGTTGCTTAGCGCCGAGGGTGGGAAGGGCAC
CCCACGGCCGGTTAAGTATGTGTTGGAGGCGGGAGAAGTGGACCTCAACCTGGAGGAAGCTGCCAGGCAATT
GTATCACCTGAGTCGCATCTACCCGGGCTCCGGTTACCGATTCCCCAGGCTGCCCGCACCGTTGCATATGGT
TGATAGGATGGTGAGGGAGGTTGCACGGCTCGGCGGCAGCCATAACTTGAGACTCAAAGAAGAACAACTGTT
TTTCCTGTAGTAACTCGAGGTTAACTTGT
282 41 GGTGTCGTGAGGATCCATGCCGAAGAAAAAGCGAAAGGTGGAAGACCCAAAGAAGAAACGCAAGGTGGGCTC
CGGCAGCATGAATAACCTGACACTGGAGGCCTTTCGGGGCATTGGCACCATCAAGCCACTGTTGTTCTATCG
GTACAAGCTGATCGGCAAAGGGAAAATAGAGAATACCTATAAGACGATACGCAACGCACAGAATCGGATGTC
TTTCAACAATAAGTTTAAGGCCACCTTCAGTAAGGATGAAATCATATACACCCTGGAGAAGTTCGAGATTAT
CCCGACGCTGGATGATGTGACGATCATCTTCGACGGGGAAGAAGTGCTTCCTATAAAGGACAACAACAAGAT
TTACAGCGAGGTAATAGAATTTTACATTAACAACAATCTCCGGAACGTTAAGTTCAACTATAAGTACCCGAA
GTACAGGGCTGCCAATACAAGGGAGATCACGGGCAACGTGATCCTCGACAAAGATATGAACGAAAAGTACAA
GAAGAGCAACAAAGGCTTCGAACTCAAACGGAAGTTCATAATCAGCCCCAAGGTCGACGATGAGGGTAAGGT
CACATTGTTCCTGGACCTGAACGCGTCATTTGACTACGACAAGAACATCTACCAGATGATAAAGGCCGGAAT
AGATGTGGTAGGAGAGGAGGTCATCAACATCTGGAGCAATAAGAAGCAGCGCGGTAAGATCAAGGAAATCAG
CGACATTAAGATAAACGAACCCTGCAACTTCGGCCAGAGCCTGATAGATTACTATATAAGCAGCAATCAGGC
GTCACGGGTGAATGGATTTACGGAGGAAGAGAAGAACACAAACGTCATCATCGTGGAAAGCGGCAAAAGCCG
CCTGTCATACATACCGCACGCGCTCAAGCCTATCATAACGCGAGAGTACATCGCCAAGAACGACGAAGTCTT
TAGCAAGGAGATAGAAGGGCTCATCAAAATCAATATGAATTACAGGTACGAGATTCTCAAGAGGTTCGTCTC
CGACATCGGCACTATTAAAGAACTGAACAACCTGCGCTTCGAGAAAATCTATATGGACAATATAGAAAGCCT
GGGTTACGAGCAGGGTCAACTCAAGGACCCCGTGCTCATCGGCGGCAAGGGTATACTTAAAGACAAAATACA
TGTCTTCAAGAGCGGCTTCTACAAATCCCCCAATGACGAAATTAAGTTTGGCGTGATATACCCGAGAGGCTA
CATAAAAGATACCCAGAGCGTTATCCGAGCCATCTACGACTTTTGCACCGAGGGCAAGTACCAGGGAAAGGA
TAACATATTCATCAATAACAAGCTCATGAACATCAAGTTCTCCAATAAGGAGTGCGTCTTTGAAGAGTACGA
GCTCAATGACATAACCGAGTATAAGCGGGCTGCAAATAAGCTCAAAAAGAATGAGAACATAAAGTTCGTGAT
CGCAATCATCCCCACTATCAATGAAAGTGACATTGAGAACCCCTACAACCCCTTCAAAAGGGTCTGTGCCGA
GATCAACCTCCCCAGCCAAATGATCAGTCTCAAAACTGCAAAGCGGTTCAGCACCAGCAGGGGCCAATCTGA
GTTGTATTTCCTGCATAACATCAGCCTCGGCATTTTGGGCAAAATAGGCGGCGTACCCTGGGTAATTAAGGA
CATGCCAGGCGAGGTCGATTGTTTTGTGGGCCTGGACGTGGGCACAAAAGAGAAAGGAATCCACTACCCCGC
ATGCAGCGTGCTGTTCGACAAGTATGGCAAACTCATTAACTACTACAAGCCGACGATCCCGCAGAGTGGAGA
GATCATTAAAACAGACGTGCTGCAGGAGATCTTTGACAAGGTTCTGCTGAGCTACGAGGAGGAGAACGGCCA
GTATCCCCGCAACATCGTGATACACAGGGACGGCTTCAGCCGGGAGGACCTGGAGTGGTATAAGAACTACTT
CCTGAAAAAAAACATCGAATTCAGCATAGTAGAGGTCCGCAAGAACTTTGCCACGCGACTTGTAAACAACTT
CAACGATGAAGTGTCCAACCCAAGCAAAGGTTCATTCATTTTGAGGGACAACGAAGCGATTGTCGTCACGAC
GGATATTAACGACAACATGGGAGCGCCCAAACCGATCAAAGTTGAGAAAACGTATGGCGATATTGACATGCT
CACAATTATCAACCAAATTTACGCACTGACACAGATTCACGTGGGGTCCGCGAAATCCCTTAGACTGCCTAT
AACCACGGGCTACGCCGATAAGATCTGCAAGGCTATCGATTACATCCCGAGCGGCCAAGTCGATAACAGGCT
GTTCTTTCTGTAGTAACTCGAGGTTAACTTGT
283 1 GGTGTCGTGAGGATCCATGCCTAAAAAGAAAAGGAAGGTAGAGGACCCCAAGAAAAAGCGCAAAGTAGGGAG
CGGTAGCATGAACTATACCGCTGCTAACACAGCGAACTTCCCGATATTTCTGAGCGAAATAAGCTTTCTCAC
AACCAATAACATTTGCTTGAACTGTTTCAAGCTTAACTACCAGGTAACGAGGAAGATCGGTAACCGATTTTC
ATGGCAGTTCAGCAGGAAATTCCCCGACGTTGTAGTGATATTCGAAGACAACTGCTTCTGGGTCCTGGCAAA
GGACGAGAAGTTCTTCCCCTCACCACAACAGTGGAAGGAAGCACTTAGCGATATCCAGGAGGTTCTTAGAGA
GGACATCGGGGACCACTACTACAGCATCTATTGGCTTAAAGACTTTCAAATAAAGGCCCTGGTGACCGCCCA
ACTGGCGGTGAGGATACTCAAGATTTTCGGCAAATTTAGCTACCCAATCGTCTTTCCCAAGGATAGCCAGAT
ATCAGAAAATCAAGTGCAGGTCAGGCGCGAAGTTGACTTTTGGGCCGAGATCATCAATGACACCAACCCCGC
AATCTGTCTGACCGTGGATAGTAGCATTGTGTACAGTGGCGACCTTGAACAGTTTTACGAAAACCACCCCTA
CAGGCAAGACGCCGCTAAGCTGCTGGTGGGACTGAAGGTGAAGACCATCGAAACCAATGGCACCGCGAAGAT
CATACGGATCGCCGGTACCATAGGCGAGCGCAGAGAAGACTTGCTGAAGAAGGCCACAGGCTCAATGTCACG
ACGGAAACTGGAGGAAGCCCATCTCGAACAACCCGTCGTCGCAGTCCAGTTCGGAAAGAACCCCCAGGAGTA
CATATACCCGCTTGCGGCCCTTAAACCTAGCGTGACCGACGAAGATGAGAGCCTCTTCCAGGTCAACCACGG
AGACTTGTTGAAGGAGACCAAGATCCTGTATGCGGAGAGGCAGGAGCTTCTGAAGCTGTACAAGCAGGAGGC
CCAGAAAACCCTGAACAACTTTGGGTTCCAGTTGAGGGAGAGGTCCATCAATTCTCAGGAATATCCTGAGGT
GTTTTGGACTCCCAGCATCAGCCTGGAGCAAACCCCAATCTTGTTTGGCAAGGGGGAGCGAGGTGAAAAAAG
AGAGATTTTGAAGGGCCTGAGCAAAGGCGGAGTGTACAAAAGGCACAGGGAATACGTGGACACAGCTCGCAA
AATTCGCCTGGCCATACTTAAGCCCGCTAACCTCCGCGTGGGCGACTTTCGGGAGCAACTTGAGAAGCGATT
GAAGCTTTATAAGTTTGAGACAATTCTGCCACCGGAGAACCAAATTAACTTCAGTGTCGAAGGCGAAGGTTC
CGAAAAGAGGGCCCGATTGGAAGAAGCGGTCGACAGACTCATAAGGGGGGAGATCCCCGTAGACATTGCACT
GGTGTTCCTCCCGCAGAGCGATAGGAATGCAGACAACACCGAGGAGGGAAGCCTTTACAGTTGGATCAAGAG
AAAATTCCTCGATAGGGGCGTGATTACACAGATGATTTATGAGAAAACGCTTAACAATAAGTCACAGTACAA
CAACATCCTGAACCAGGTGGTGCCGGGGATTCTTGCGAAGCTGGGAAACCTGCCATACGTTCTTGCAGAGCC
GCTTGAGATAGCCGACTACTTCATAGGCCTGGATGTGGGGCGGATGCCAAAGAAGAATCTTCCGGGGAGCCT
CAACGTGTGCGCGTCTGTCAGGCTCTATGGCAAGCAAGGCGAGTTCGTGCGCTGCCGCGTCGAGGACAGCTT
GACCGAGGGCGAAGAGATTCCCCAGCGGATCCTGGAAAATTGCCTGCCCCAAGCAGAACTTAAAAACCAAAC
TGTCCTTATCTACAGAGATGGTAAATTCCAGGGAAAGGAGGTGGATAACCTTTTGGCTAGGGCTCGCGCAAT
CAATGCCAAGTTCATACTGGTTGAGTGCTACAAGACCGGTATCCCCCGACTGTATAACTTCGAGCAAAAACA
GATCAACGCACCCTCCAAGGGGCTGGCACTCGCGTTGAGCAACCGAGAGGTGATCTTGATTACGAGCCAAGT
GAGCGAGAAGATAGGCGTTCCTCGGCCACTTAGACTCAAAGTGAATGAGCTGGGTGAACAGGTGAACCTGAA
GCAGCTGGTCGATACCACTCTTAAACTCACGCTGCTCCACTATGGGTCTCTGAAAGACCCACGGCTGCCTAT
TCCCCTGTACGGTGCCGACATCATAGCCTATCGGCGGCTGCAAGGAATCTACCCATCCCTTCTCGAGGATGA
TTGTCAGTTCTGGCTGTAGTAACTCGAGGTTAACTTGT
284 65 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGAGGAAGGTAGAAGATCCAAAGAAAAAGCGGAAGGTCGGGAG
(Helicase) CGGGTCCATCACCAGCTACCCTTACGCTAGGAACAAGGCCGACATGATTCGCAAGGTTAATTGGAATCTGAT
CGTGTTCGACGAAGCCCACAGGATGAGGAATGTCTATAAGAAGTCCAATAAGATCGCCCGAACCCTGCGCGA
GGCCACTGCCGGCTATCCCAAGATCCTGCTCACTGCAACCCCCCTCCAAAACTCCCTCATGGAGCTCTACGG
ATTGATATCTTTTATTGACCCCCACATCTTCGGGGATGAGACAACTTTCCGCAGACAGTTTAGTCGCGGCAC
CAAGGAAATGAGCGAGATGGACTTTATCGACCTGAAACAACGAATTAAACCCGTGTGTCACCGCACCCTGAG
GCGCCAAGTCACAGAGTACGTTAACTACACTCAGCGCATTCCGATCACCCAGGAGTTCATGCCCACCAACGA
AGAATGGGAGCTGTACGAGAAGGTCAGCGCCTATTTGCAACGAGAACATCTCTTCGCGCTCCCCGCGTCACA
ACGAGCACTTATGACCTTGGTAGTGCGCAAACTGCTCGCCAGCTCTTCATTTGCTATTAGCGATACCCTGCT
GAGCCTCATCAAGAGGTTGGAACAACTGCTGGAACAGCTGGACTCCGGCAAGACGGAGATTACCGTAGAACA
CAGCGATGTCTACGCGGACGTGGACGAGTTTGATGATACAGTGGAGGAGTGGGAGGAGGACGACCAGCCTTC
TTACATAGATAAACTGAGCCCAGACGAGATGAAACGGTTGATTCAGGAGGAAAAGGAAGAACTGGAGCAGTA
CTACAGCCTTGCAAAAAGCATTAAAGAGAACTCAAAGGCTGAGGCCCTCCTCATAGCGCTTGAAAAAGGGTT
TGAAAAGCTCAGGATGCTGGGGGCTAATGAGAAGGCCGTGATCTTCACAGAATCCCGACGCACACAGATGTA
TCTGAGAGAATTCCTGGAGAGAAACGGCTACGCCGGGAAGATAGTGCTGTTCAACGGTGAAAACCAAGACGA
ACAAGCGAAGCAGATCTATGAGCAGTGGTTGGAGAAGCACCGACACGACGACAAGATTACGGGCTCTAAGAC
GGCGGACATGCGAGCCGCGCTCGTGGAGTACTTTAAGGAGCAGGCTAGTATAATGATAGCGACCGAGAGCGC
CAGCGAAGGCATCAATCTGCAATTTTGCAGCTTGGTTGTGAACTATGACTTGCCATGGAATCCGCAAAGGAT
AGAGCAACGGATCGGGAGGTGTCATCGCTATGGTCAAAAGCACGACGTGGTGGTAATAAACTTTCTCAATTG
TAAAAACGAAGCGGACAAGAAAGTAGATGAGATATTGTCCGAGAAGTTTCGGCTGTTTGAGGGCGTATTTGG
CAGCAGTGATGAAGTCCTGGGGTCCCTCGAAAGCGGCGTGGATTTCGAGAAGAGAATCCAACAAATCTACCA
GACCTGCCGAACCGCGGAAGAAATTGAGCAAGCGTTCAAGAACCTGCAAGCTGAGCTCGACGAGCAAATTCA
ACTGAAGATGAAGGAGACCCGAATGCATCTTTTGGAAAACTTCGATGACGAGGTGAGGGAAAAGTTGCGAGA
CCATTATCACCAAACCTCCCTGCATCTGAATAGGATGGAAAGGTATTTGTGGAACCTCAGCAAGTACGAGGG
GGCACGCGAAGCCATCTTTGACGACGAGACGCTGTCCTTCGTGAAGGACTACGAGACCTATCAGATGATCAG
CCAGGCGAAGAAACAAAACAGTCCAAACGTGCATCACTTTCGATTCTCCCACCCGCTTGCGCAGAAGTGGAT
CGAACAGGCCAAGAGCAGGGAATTGTTGCCAAAGGAGATAACGTTCAGGTACAGCGACTACAAGGGCAAAGT
CTCCATCTTGGAAAGACTCATCGGCAAGGAGGGTTGGTTGAGTCTGGACCTGCTTCACGTCCAGAGCCTTGA
GAGCGAACAACACCTCATCTTTAGCGCCATCGACACCGAGGGCGGTCAACTGGACCAGGAGATGTGCGAGAA
AATGTTCGAGCTGCCCGCTGTGGAGGGCGAGGAAGTAGAGATATCCGACTCCATCCGAAACACATTGAGACG
AATCTCAGAGGGCCAGCAAGAGGCAATACTGAATGAGATTATGGAACGGGCGTCCGCCTACCTCGACTCAGA
ACTCGAGAAACTGGAAAAATGGTCACAGGACCTCAAGAATAAGCTGGAGAAAGACATTGATGAAATGACGGT
GGAGATCGAGCATCTTAAACGGGAAGCTAAATTGACACGCAACCTGGCAGAAAAACTCGAAAAAAACAAACA
GATCAAGGAGCTTGAGAAGAAGCGCAACGAAATGCGCCGGAATCTCTATGACCAACAGGACGAAATCGATGA
ACAAAAGGACCGCCTCTTCGAGGAGGTAGAGAAAAAACTTGAACAACGGACTGCGACGGAGCACCTCTTCAC
TATCAAATGGCGGATCGTGTAGTAACTCGAGGTTAACTTGT
285 44 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGCGAAAAGTAGAGGATCCAAAGAAGAAACGGAAGGTCGGCAG
CGGAAGTGTGAACCATTACTATTTTTCCGAATGCAAGGCGGACGAGAAAGCCAGCGACATAGCCATCCACCT
TTACACCGTGCCCCTGTCCAACCCCCATGAGAAATACAGCTATGCGCACAGCATCGCCTATGAATTGAGAAA
ACTCAACTCATACATAACCGTGGCCGCGCACGGTCAGTACATCGCGTCTTTCGAGGAGATATGCCACTGGGG
CGACCACAGGTACATACAGCACGAACATAGACCAATCCAGTGCAGCCTCCCGATGGAGAGGACCATACTGGA
AAGACTCCTCAAGAAAGAGCTCGAGAATAGGTGCAAAAGCAGCTATAAGATGGACAACGACCTTTTCCGGTT
GGCTAACGAGCAAAGCATGCACGTGGGCGAGATCAGCATACACCCAGCGATCTACATCTCATTCAGCGTGGA
GGAAAATGGTGACATATTTGTTGGCTTCGACTACCAGCACCGGTTCGAGTACCGCAAAACACTCCAAGACGT
CATCAACAACGATCCCTCCCTGCTTAAGGAAGGCATGGAAGTGGTGGACCCCTTCAATAGAAGGGCCTACTA
TTACACTTTTGTGGGCATGGCCGATTATACCGCCGGACAGAAAAGCCCCTTCCTGCAGCAGTCTGTGATCGA
CTATTATCTCGAAAAGAATGAGCTGTGGAAGCTCAAGGGTGTGCACGAAAAAACCCCCGTGGTGCACGTCAA
GAGCCGAGACGGTCACTTGCTCCCGTATCTGCCGCACCTGCTCAAATTGACATGTTCATACGAACAGCTCTT
GCCCAGCATGACCAAGGAAGTCAATCGCCTGATTAAGCTGAGCCCCAACGAGAAGATGAGTAAGTTGTATAC
GGAGATGTTTCGATTGCTCCGGCAGCAACAGGTGCTGACCTTCAAGAAGGAAAACGTGCGAGCCGTCAACCT
CGGCTACGATGTGAATGAACTTGACAGCCCGATCATGGAGTTCGGACAAGGCTACAAGACAAACGAGATCTA
TCGAGGCCTGAAGCAGAGCGGAGTATACGAGCCCAGCTCAGTGGCCGTGAGCTTTTTTGTTGACCCCGAGCT
TTACTACGACCCCCAGAAGCGGAAAGAAGTAGGTTGCTTCGTCAAAAAACTGGAGAGCATGAGCGAGGCCCT
GGGAGTAAAACTGAACATAAGCGACCAGCCCCGACAACTTTATGGCCAGCTCCCCAAGGACTTTTTCAAGCA
GGACAACCTCTCATATCATTTGAAATCTATCACCGACCAGTTCAGGGGAACGGTGGTGGTTGTTATCGGCAC
TGAAGAGAACATCGACCGGGCATACGTTACAATCAAAAAGGAATTCGGCGGCAAGGAGGATCTGATGACCCA
GTTTGTCGGCTTCACCTCCTCCCTCGTCACGGAGAACAACATTTTTCACTACTACAACATCCTGCTCGGCAT
CTATGCGAAAGCTGGTGTTCAGCCCTGGATACTCGCCAGCCCAATGCACTCAGACTGTTTCATTGGACTCGA
CGTAAGCCACGAGCACGGTAAGCACGCATCAGGGATAATACAAGTGATTGGACGGGACGGCAAGATTATCAA
ACAAAAGAGCGTTGCGACAGCAGAGGCCGGAGAGACTATTGCCAATAGCACGATGGAAGAAATCGTCAACGA
AAGCATTTATTCCTACGAGCAGATCTACGGGGCCAAACCGCGCCACATAACATTCCATAGAGACGGGATCTG
TCGCGAGGACCTCGATTTTCTGCAAGCGTATTTGCGGAGTTTCCAAATCCCATTCGACTTCGTAGAAATCAT
AAAGAAGCCGCGACGCAGAATGGCGATATACTCTAATAAGAAGTGGGTCACGAAACAGGGAATATACTACAG
TAAGGGCAACACCGCTTATCTGTGTGCCACGGACCCCAGAGAATCCGTGGGTATGGCGCAACTTGTCAAGAT
CGTACAGAAGACTAACGGATTGAGCGTTCACGAGATAGTGAGCGACGTGTATAAGCTGTCCTTCATGCACAT
ACACAGTATGCTCAAGACCAGGTTGCCTATCACGATACACTATAGCGACCTCAGCTCAACGTTCCACAACCG
GGGCTTGATCCATCCCCGGTCCCAACATGAGAGAGCACTCCCGTTCGTGTAGTAACTCGAGGTTAACTTGT
286 67 GGTGTCGTGAGGATCCATGCCCAAGAAGAAGAGAAAAGTGGAAGATCCCAAAAAGAAGCGAAAGGTGGGTAG
(Helicase) TGGGAGCATGAATTTCCAGCTGTGCGACCAACGCAAAGCCATTATCGCCGAACCAGGCCATCTGTTGGTCCT
CGGTGGGCCAGGAAGCGGGAAAACTACCGTCGCCCTCTTCAAGGCCAAGCAGAGATTTAGCACTCTGAAACC
TAGCCAAGAAATCCTGTTCCTGTCATTCAGTAGAGCTGCCATCAGGCAGGTCCTGCTGCGGTGCAAGGAGAT
TCTGAAGCCCGCAGAGAGACGCGCTGTCGCCGTTCAAACCTATCATAGCTTCTGCATGGACATGCTGAGGGC
GCACGGTAGACTGCTCCTGGGCCACCCCGTGCGATTCATGTATCCCGGCGACGAGAGGCTTCAAAAGGCCGC
ATTCGAGGGGGACTGGGAGGCGGAAAGACAAAGGCAAGCCAAAGAGATGGGCATCTTTTGCTTCGACCTTTT
CGCGCAAGGCGCAGCTGAGTTGCTCGAGAGGTGTGCCGCACTTAGGAAGCTTATAGGGGACAGCTTCCCCAT
GATAATAGTGGACGAGTTCCAAGACACCGACGACAACCAATGGCGGATCGTGGCGCAACTTGCCAAGGTAGC
GGACATCTTCTGCCTTGCCGACCCCGACCAGAGGATCTTTGACTACCGAGACGACATCGACCCCCTTCGGAT
CGAGGGTTTGCGGACCACTCTTGCCCCCAGGGAGTTCGATCTTGGCGGTGAGAATCACCGCTCCCCGAACGC
AGGGATATTGAACTTCGCCAACGCTGTGCTGCATAACCAGAGCCCCCTGCCCGATACCAGCGACATCATGCA
ACTGCGGTACTGGCCTAGAGCGTTCGCGAGCACCGTGCATGCCTGCGTAGTGTTTACCTTCAGCGAACTCAG
GAAACTGGGCGTGGAGAACCCCAGCGTGGCAGTGCTGAGCCGATCCAACGGGCTTATCAGCGATGTGAGCGC
CATACTGGCTGAGAAGCACGCGTACAACGGGAGGGAACTGCCAATCGTGGAACACGACGTGGTTTGGGACGC
GGAGCTGTCTGCGGCAGCAGCCGTCGTCGTTGCGTCCACCCTGGAGTGGCCAACAGCCGCTGCAGAGGTTGC
TGTTGCCAGGACACTTGCGCTCATAGCAGCCTATTACAAGCTGAAGAACGCCGAGGAACCCACCAAGAGCGC
GGCTGAGGCTGCCCAAAAGTACGAGGCGGCTGCAAGCAAGGTGGCCAGTGAGGAGACCCCAAGGATCAAAGC
CGCGAAAGAATTGCTGGCCGCTCACCAAAGTGGCATCCAGATGGTGGGCGACCCGGTGGCCGATTGGAAGTC
TGCGAGGAGGGTATTGCAAGAGATAAGCGCCCTGGGTGAGTTGTACAGGGAGGTCCGGCTCGTGAGGTTGTT
CCGGGCAACCGACGCCTTGGCTTCCGGCCTGAGCAATAGGTGGTTGGCTACTGGAAGCTACGAGGGCGTGTC
CGACCTGGTGAAGGGCATCCTTGAGCAGGAGAAACTGATTGCCGTGGAAAGGGACCCAAGAGGCTGTATACT
GATGAACATCCATAAAAGCAAAGGTAAGGAATTCGACGGCGTGGTACTCATTGAGGGGGCATTTAAGTCCCA
TTTCTTCGATGAGCGGAAGGAAGTCAGCCCCTATGAGAGGTCCAGACGGCTCCTGAGAGTCGGTCTGACCCG
CGCTAGGCATAGGGTGACAATCCTTAGACCTCAGGGAGCGAGGCCCCTTGTGGATCCCATCTAGTAACTCGA
GGTTAACTTGT
287 34 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGAGGAAAGTTGAGGATCCCAAGAAAAAACGAAAAGTGGGTAG
CGGTAGCGTTCCAGGCGGTAGGGGACCGCTGCTCGTGCTTAACTTCCTTCCCGCTCGCTTCGACGGCCGAGT
TGATGCGGGCACCCTCCCCTTCGAGACCCCTGATAAATTGAGGGCCATTAGGGAGGAACTGAGAACTTCCCA
TGTAGTTGTAACGCGAGGAAAAGAGGTCGTATGCGTGCCCTTCGTTAGTGGCGCGAAATTGATCGGCAAACG
AACCACTATCACCGCAGCGGGACCCGACCTCGTCGTACAAACGAGTCTTCTCGAATCCAGCCTGAGGCGGAC
CTTGACCGAAAAATGGAAGTACGAATTGCGCAGGGAAAACCCGCTCACCTTTGTGTCAAGGACGCCAGGAAG
GGACCTGCTGGAGAAGGCCCTTGGTCGGGAGTTGCCGGGACTCCATGTGTTCCCCGCTTACAGCCTGGACGT
GCGCAGATACGGTCCTGGGGGGTTCAGCGGGGTTGTTGTAGGATTGAAGACCCGCTATGAGATCGACCTGCC
TGTCGGAGTGCTGCTCAGGAGGGGCGTTCAAGTAAACGGCCTTTATGTCCTGGCTGAAAGCCCCCTCGCGCC
TACGTGGCCCTTCCAAGATCCCCACACCAGAAGGCGGCTCGTGGGACAAGTTGTCGCGGTGGATGGCGACAA
ATTGCGAGTGAGGTGTAGGGACGGGGAGCTGGAACTTGATGCCGCCGAAGCATGGATTGAGCCCAACACTGC
CAACTTCTACGCCGTCCTGCGGAAGGCGTGCGGACGCTCTTACGAACGAGACTTTCACGCCCTGGAAGCCCA
AGTCGTGTCCCTGACTAACGCCCAGCAGCGAATCGCCGATACCAACAGGATCGCCGCCAACCTGATAGGCCT
TGGTAAATTCGACATCAGTAACGGCTTGACTGCCGAGCTGGGGAAACCACTCAGACTGACTTCCACTCAACA
TCCACACGTTCGGACTCTGGCCGAGCCCACATTTGTGTTTGACCAGAGCGGAGACAAAACCGCGCCTTTTCC
CGAGACCGGGCTGACCAAGTGGGGCCCATTGGACGCTGAGAGCTTTACACCCAAGGCACCACACATCGCCGT
GGTGGTTCCGCGGCAGTTTCAGGGTCGCGTCGAAACGCTGGTTGAGCGGTTCAGGAACGGCGTGAGGGGCAG
CAACGCCTATGCCGAGGGCTTTGTCCGAAAGTTTAGGCTCACCGACTGTACCTTCAGCTTCACCGTTTTTGA
CGGTGACGCTACTGACGCAGCCGCATATAGGCAAGCGTGCCTTACCGCCCTGAGTAATGACGAGCAAATTAA
CCTCGCCTTCGTCTTCACATCAGCCGTGCAGGAGCATCAAACGGGGGACGACAGTCCCTATCTTGTCAGCAA
ATCCACCTTCATGAGCCAGGGTATCCCCGTGCAAGAGTATCAAGTGGAGAACATCATCGGGGATTCAAACTT
GGCTTATCCCCTGTCCACGATGGCGCTGGCGTGCTACGCCAAACTGGGTGGCACCCCTTACGCCATAAGCGA
TCGAGGACGACCTATGGCACGAGAACTGATCTTCGGCATCGGGTCTGCCCAGGTAAGCGACGGAAGGATGGG
CGAAACAGAGCGATTTGTGGGCATTACCACCGTGTTCAATTACGACGGTAGGTACTTGGTTAGCAACGTTAG
CCGCGAGACACCCTACGAAAGGTACCCGCAAGCCCTGCTTGACGCATTGCGGACTTGCATTGCCGACGTGAA
GGTTAGGCAGGGATGGAGGTCCGACGACTTTGTGCGGCTTGTCTTCCATATCTTCAAACCTCTGAAGGACAA
GGAAGCACGCGCCGTAAAAGAGCTGGTGACGGAGCTGACGTCTGAATATGCCAGCGTGGAGTTCGCTTTTGT
GACAGTGGTGGACGATCACCCGTGGCTGGTGCTCGATGAAAACAGCGATGGGGTTAAGGTTGGGCGAGGGAC
TAAGGGCAAGCACGTAGCTCGGAGGGGTTTTGCCCTGCCGATTTCCAAAAGGGAGCTTCTTGTGACGGTTAA
AGGTCCCCGGGAAATGAAATCCGATAAGCAAGGGGCTCCCAAGCCCCTCTTGCTCAAGCTCCATCGCGAAAG
CACCTTTACAGACATCGACTACCTGGCTTCCCAGGTCTTTCAATTCACCGCCATGAGCTGGCGCAGGCCATA
CCCTACCAGCAAACCCGTGACTATAAGCTACAGTGACCTGATTGCGGGACTTCTCGGAAAGCTGCGACACGT
GACGAACTGGAATAGCGACATGATCTACATGAAGTTGCGCTTCAGCAGATGGTTCCTGTAGTAACTCGAGGT
TAACTTGT
288 30 GGTGTCGTGAGGATCCATGCCGAAGAAGAAGCGAAAGGTCGAGGACCCGAAAAAGAAAAGGAAAGTGGGGAG
CGGCAGCATGCAGCAGGAGATCCAGCTTAACATCATCCCCTTCACCGCCCCTGTGGAAGAGGCAGAGTTCGC
TTTTTACACCGCCAAGCAAGACGGCTACTGCCCCATCCATAAGGATGACCTGAACGGGGCCATCGAAGGCCT
CGTGGATGAATCAGACCTGCACTACGGCAACTGGCTGTACACTGACTTCGCTCCCGCCAAAGAGAACGCCAT
CATAATTAGCGTCAATCTCAATGACTGTAAGTACTTCGCCCAGCACTACTACAGGCACCTTATCAGGACCCA
CTTCAAGGGAGTGGCCGACATCATGAGGAAGAATTTCACCAACGAAATCGAGGTCTGGTTCCACAATACCAA
AGCCAGCTCTACCAAGTTTAAGGTCTATAACCAGTTTACCCTCAAGGTACAGCACAACAGGGTGACGGACGG
ACCGGAACTTGTCGTGTCCTTCGACGGGACGACGAAGGTGCTGAACAAGTCTATCGCCGAGATACACAACTT
CAAAACGGAGCTTTACAACTGGATAAACTGCAACGGCGAGCTTAATCGCTGGAAATACCTGACCGACGATCA
GAAGCTGAATCACGAAAAGAACTACCCGGTAGTGTCAAACACACTTAAACCGCATTTCGACATTGCCTTTGA
CGTTCCCGATTTTAAGAACCGGTATCCCAAATACTTCACTCTTCTGAATGACTTCTACAACAACTATCTGAA
TACAGACGCCTTTACTGCGATCTTGCCGCTTTCCGCTGACGGATTCTTCAAGCCAAATGGCCTGTCAGTGCA
GAGGATCAACGGCACTAGCAATGAGCTGCAATTCGGCAATGGCGTCGGCGTGGAGCCCAAAAGGGATCTCAA
GCGCCTGAAGCCGTATAAACCCGTGCCCAAACCCAGCAACGTAAAGTTTTTCTTCATCTATCACAAGCCAGA
TAGGGAGCATGCGGTCAAAAACATCTGGCAGTATTTCAAAGACGGATACAACGGCCAATACCCCTTCCCCAA
GATGGAGGAATACATATCTCAGCCCTTCGAGCTTGAGGAGAATGGATCTATCTCATTCGACAATATCGACGA
CGCGGTAAGCGTTGTCCAAAAAGCCATCAAGAACAAGGATCGGCTGCCCGACACTAAATACTTTGCGGTATA
CATCTCCCCCGTACCAAAATGGGAGAAGGACCCTAAACGGAATAGTATCTACCATCGGATGAAAGAGATACT
CCTGTACGAGGGGATCACCAGCCAGGTGATCTGGAAGGAGAACATTAGCAAACCGGCTTTCAACCTCTTCTT
GCCTAACATCGAAACCGCCATACTGGCCAAGCTGGGAGGCGTCCCCTGGAGGCTCAAGAGGGACACCACGAA
CGAGTTGATCGTTGGCGTGGGTGCTTTCTACTCAATCACGCGGAAGTCCAAGTACGTGGGCTCTGCATTTTG
CTTCAATAACGAGGGCATCTTTAAGGGGTTCGACTGTTTCGGTGCCAATGACACCGACAGCATCGCGGGCTC
TATCAGGGAGGCCGTGGGAAAGTTCATCGCGTCTAATTACAAGGCCACAAGGCTGATCATTCACTTCTATAA
GGACCTGTCAAAGAAGGAGCTCAAACCAATCATCGATACACTTCACGCCCTGGGCTTGCCCATCCCAGTGAT
AGTCGTGACCATCAATAAAACCGAGAGCAAGGAACTCCTGGCATTTGATACCAGCTCACAAAAGCTCATGCC
CTACTCTGGCACCATCGTGAAGGTGGGAGCCAAGGAGTACCTGCTGTTCAACAACACGCGATACGAGGAAGC
ATCCGCCCCAACGGATCGCGAGCACCACTTCCCGGTGAAAATCAGCTTTTTCTCAGACAAGGCGGAGCTGTT
GGACGATCCCGCACTGATCAACCAACTGATCGACCAGGTGTACCAGTTCAGCCGCATGTATTGGAAAAGCGT
GAGCCAACAGAACTTGCCCGTAACCATTAAGTATCCCGAGATGGTGGCGGAGATTTTCCCATACTTTACCCA
CGATAAATTGCCCGATCATGGAAAGGAGAGCCTGTGGTTCCTGTAGTAACTCGAGGTTAACTTGT
289 47 GGTGTCGTGAGGATCCATGCCTAAGAAAAAGAGGAAAGTGGAGGATCCGAAGAAGAAACGAAAGGTCGGCAG
CGGCAGCATGTATCTTAACCTCTACGAAATCAAGATCCCCTACAGGGTTAAACGATTGTACTACTTCAATAA
GGAGAACGACCCCAAAGAGTTCGCCCGGAATCTGAGCCGAGTGAACAACATACGGTTCAACGACAGTAAGGA
CTTGGTGTGGCTCGAAATCCCCGACATCGACTTCAAGATTACACCCCAGCAGGCGGAAAAGTACAAAATAGA
AAAGAATGAGATAATTGGGGAGAAGGAAGACAGCGATCTGTTCGTCAAAACCATTTACAGGTACATCAAAAA
AAAGTTCATCGACAATAACTTCTACTATAAACGGGGAAATAACTACATTTCAATCAATGATAAGTTCCCGCT
CGATTCTAATACAAACGTTAATGCGCACTTGACATATAAGATTAAACTGTACAAGATAAACGAACGGTATTA
CATTAGCGTGCTTCCAAAATTCACCTTCCTCAGTGACAAGCCAGCCCTTGAGAGCCCCATCAAGAGCACCTA
CCTGTTCAACATTAAAAGCGGCAAGACGTTTCCCTATATTAGCGGGCTCAACGGAGTCCTGAAAATTGACCT
GGGCGAGAACGGCATAAAGGAGGTCCTTTTTCCGGAGAACTACTATTTCAACTTTACCTCCAAGGAGGCCGA
GAAGTTTGGGTTTTCTAAGGAAATCCATAACATCTACAAGGAAAAAATCTTCAGCGGCTACAAGAAAATCAA
ACAGAGCTTGTATTTCCTCGAAGACATCATCAATATAAACAATTACAACCTTACCATGGACAAAAAGATCTA
TGTGAACATAGAATACGAGTTCAAAAAGGGCATCAGCAGAAACATAAAAGACGTGTTCAAATACAGCTTTTA
CAAAAATGACCAGAAGATCAAAATTGCGTTCTTTTTTAGCAGCAAGAAGCAAATCTATGAGATTCAACGCAG
CTTGAAGATGCTGTTCCAGAACAAGAATAGCATATTCTACCAGACCATCTACGAGATGGGGTTCAGCAAGGT
GATTTTTCTCCGCGAGCCGAAGACTAACAGCAGCGCATTTATGTATAACCCCGAGACCTTCGAGATTAGCAA
CAAAGATTTCTTTGAAAACCTGGAGGGGAACATTATGGCAATCATTATACTCGACAAGTTTCTGGGCAATAT
CGACAGTCTTATCCAAAAATTCCCTGAGAACCTCATCCTTCAACCCATACTCAAAGAGAAACTGGAAAAGAT
TCAGCCGTATATCATTAAGTCCTACGTCTATAAAATGGGAAACTTTATTCCAGAGTGCCAACCATACGTCAT
AAGGAACCTGAAGGACAAGAACAAAACCCTCTACATCGGCATCGACCTGTCCCACGACAACTATCTCAAGAA
GTCTAACCTCGCCATCAGCGCCGTAAACAACTTCGGTGACATTATCTACCTGAACAAGTATAAGAACCTTGA
GTTGAACGAGAAGATGAACCTCGATATAGTCGAGAAAGAGTACATACAGATCCTCAACGAGTACTACGAGCG
CAATAAGAATTACCCCGAAAACATCATTGTTTTGCGAGACGGACGCTATCTCGAGGACATAGAGATCATAAA
GAACATACTGAACATTGAGAACATCAAGTACAGCCTCATCGAAGTTAACAAGTCCGTGAATATCAACTCCTG
CGAAGACCTTAAAGAGTGGATTATCAAGCTTAGCGACAACAATTTCATATACTATCCCAAAACGTACTTTAA
CCAGAAAGGTGTAGAGATAAAGATAATAGAGAACAATACCGACTACAATAATGAGAAAATACTGGAGCAGGT
GTACTCACTGACGAGAGTGGTGCATCCCACCCCCTACGTAAACTACCGCTTGCCCTACCCCCTGCAAGTCGT
CAACAAGGTCGCCCTTACCGAGTTGGAATGGAAGCTTTATATCCCTTACATGAAATAGTAACTCGAGGTTAA
CTTGT
290 5 GGTGTCGTGAGGATCCATGCCAAAGAAGAAGCGAAAAGTGGAGGACCCTAAGAAAAAAAGAAAGGTGGGCTC
AGGGAGCATGGAGGCGTACATAACGGAGATGGTGTCCAGGGAGAGGGCCAACGAGCTGGAGGTTTACGTGTA
CGTGTTTCCACGGAAGCAATCCGACAACAACTACGAGGGTGTGTATCACATAATGAGGGCGTGGCAACGGGC
TAATGACCTGCCTCTGGCGTATAATCAACATACGATCATGGCATTTTCCCCCGTGAGGCATATGTGTGGCTA
CACGCCGATGGAGACGCAGAAACGCCATATTAACATTGACTCCCCATTCGAGAGAGCCCTGCTGGAGCGACT
GATAAAGAACAGCCTGATTTTTACAGCCGAGCGCCATTTGCATGCCAAGCGGGTAGGCCATGCGCTTCGGCT
GAACCAGGTGCAGCAAATCCGGCAGGTGATCATCTATGAGGCCATCGAGCTCTATGTAAATATCATTGAGAA
TAGAATAAGCATCGGCTTTCACCTCACCCACCAGTTCGAGTACGTATACACTCTCCAGAGCATGATAGAACA
GGGAAAAACAATCAGACCTGGAATGCGCGTCGTGCATTCTAACGGAAGGCAGCATTATACCTACACCGTGGA
GAACGTAGCAACATATGGGGTGACCGACAGATGCCCGCTGCTGCAGACCAGCATTTACCAATACTACGTCGA
AAAAGGCGCGCAGCACATTTTGCGCACCTTCACCCGATCCACCAGGGTGATCCACGTAAGAACGAAAGAGCA
GAGGTTGAGCTACGCGGCGACACTCCTGAAACCGCTGTGTACTTTTGAGACCATGCAACCCCAGGACGTGCT
CAATGTCAGCAAGTGCATCAAACTTAGCGCGAGCAAACGAATGAAATGTACTTACAGGTGGATTCAGCAACT
CCGGGCACAGTACCGACACCTGACCTTTGCGCCGAACCCCTTCACGATCGCCCAGAATGGCTATAAACTTGA
TCAGCTCAGCACCCCCAAGGTGCACTTCCACAGAGACTACGCCACCGTCGTGAGCGGAATGAAGACCGGCAA
GCTTTACAAAGGCGGTAATATCAAGATCAGCGTGCTCTTCGACGAGGACTTTTACTTGAAACACCACATCAC
CAAGAAGGACATATATCAATTCATTGCAGTCCTGCAGAAAATCGCCATCGCACAAGGCGTGAACATGACCAT
AAGCACGAGCACCAAGTCCATTACGGGCAAGTTCACGGACGACTTTTTCCACCACTTCACCGAGGAGGTCGA
AGCACTGCAGCCCATCTTCGCGCAAACCACAGTTCTGGCATTCATTACCAGTACCCACCTGAGCAACAAGAA
AACCAGGAGTTACCAGCTGCTGAAACAGTACTTCGGCGGCAAGTGGGACATTGCCTCTCAAGTCATCACGGA
GAAGACGATTGAGGCGTTCCAAAAAATCTTGCACAAGCACGGCCTGAAGAATTTCTACCCCAATGACGAACA
GCACTGTCTCCGCGTGATCGATGTCCTCAAGAATGAGAGCTTCTACTACACGGTCATGAACATCCTCTTGGG
AGTATATGTGAAAAGCGGCATCCAGCCCTGGATCCTTGCTAATACAACCCACTCAGACTGCTTCATCGGCAT
CGACGTTAGCCACGAGAACGGAAACTCTGCGGCTGGGATGATGAATGTTATCGGCAGCCAGGGCCACCTTAT
CCAACAGGCGCCCCTGAACGGCATATTGGCGGGAGAAAAGATTGACGACACCCTGCTCGCAAACTTGCTTAA
ACAAATGATTAAGGCATACCACACCCAGTTCCAGCGCTTTCCCAAGCATATAACAATCCACAGGGACGGCTT
TTGGAGAGAACACACTGCACTGGTCGAGAAGATCATGAGCCACTATGAGATTACCTACGACATCGTCGAGAT
CATCAAAAAGCCTAATAGGAGGATGGCTTTCTTCAACAGCGTGGACAACACCTTTAGCACCAGGCAGGGGAC
AGTGTACCAACGGGGCAACGAAGCCTTTCTGTGCGCCACTAACCCTCAGCAGAAAGTGGGCATGGCACAACC
AATCAAAATACATCAGGTGACCAAGACCCTGCCCTTCTCACACATCATAGAAGATGTCTACAACCTCAGCTT
CCTTCATATTCACGCTATGAATAAGATGCGACTGCCGGCCACCATACATTATGCCGACCTGTCTGCCACCGC
TTACCAGAGGGGCCAAGTGATGCCCAGGAGCGGTAACCAGACAAATCTGCCTTTCGTGTAGTAACTCGAGGT
TAACTTGT
291 45 GGTGTCGTGAGGATCCATGCCTAAAAAGAAGAGGAAAGTAGAAGATCCAAAGAAAAAGCGAAAGGTGGGAAG
CGGCAGCATGACCGGCGAGACTAAAGTGTTGGTCGGGAGGCAACCCTTCGACGTGGATCGGCTGAATGAACT
CAGAGACGAATTCCGGGAGACGCACGTGTTCAGAAGGGATGGCATCGACGATGTCATTGTTGATGTTCCGGT
CGTGGCCGGACAGAAGCCCATCGGCAACGTCCAGGAGGAAATAGACCTGGCTAGGTACCAAAAGGTGTGGCC
CTCCCTCCTCAGTGCTGCTCTTGTCCGGGCGTTTAGCGGCGTAAGGGACATCCTGAGCGATAGGCCCGTGAG
CGTGGTGGGGAGCACACTGCGGGGTCTGGTTCAACATCCGGAACTCCCCGAATGGATGCAGAAACGCACACT
CCTTAGGTTCGACACCCGGACCATCTATGCTGGTGATAAAAGAACCTTTGGCTTGGTGTGCGAGGCCAGATT
GAAAAACCTTATCCAAGGTAGTTGCGCGGAGCTGCTGGCACTTGGAGTTTCCCCACTGGGTCGATATGTCCA
AGTCGAGGAGCCACATTACGATCCCAGGCTTATGAAAAAACGGCGCCTTGTGGGCAGGGTATCAGCGATCTC
CGGCGATAATCTGGTGCTGGAGGACCATGCCGAGGGCTTTCCGACCGTGAGTGCAAAGCTGGCATTTCTGGA
GGCGCGAAGGGAGATTTTTGACGACTGTGTGCGGAGGATTTTGAACTCTGATGCGGCCTCCGTGCTGAACAA
GGCCGAAGCTACTGCTGCCTCATTTCACTCAGGGCCAGGTAGGAAAGAGCAAATAGAGGAGGCTCTCAAGTA
TCTCAGGGAGAAGGTGAGCCTCGAAGCTGTACCCGGAGCGAAATTCGTGATCGGGCCGATGCTGAGTAGCGG
CAACAAGGGCTTCCCCATCACGGAGATGATCCCGAAACCCATTCTCGTGTTCGATCCGAGCGGTACACGGAA
GGATGAGTGGAACGAAAGGGGCATTAAGAAGAACGGGCCCTACGACCAGAGGACGTTTTCACCTAAGCAGTT
GAAGGTGGCGGTCATTTGCCAGGCGAAGCACGAGGGGCAGGTGGATGGATTCATCGCGAAGTTCTTGGAAGG
TATGCCAGACGTTATGACGGGCAAGAACCGAGTTGCTAGATATGGTGACGGTTTTCTGCGGCGATTCGCCCT
TGAGAAACCTTCTGTGACCTTCTTCACAGCGCCCTCAGCCAAGGCGAGCGATTACCTGGTGGCCAGCCGGGC
TGCGCTGACCAAGGCAACGGACGAGGGTTTCAAATGGGACCTCGCGCTTGTGCAAGTGGAGGAGGAGTTTAA
GGGATTCGACGACGAGAGCAACCCCTACTATGCCACTAAATCCGTCTTCCTGAAGCGAGACGTGCCGGTCCA
AAGTGTACGACTCGAAACCATGGCTCAGGCCGACAGCCAGCTGATTTTCTCTATGAACCACATGAGCCTGGC
GACATACGCCAAGCTCGGTGGTACCCCCTGGCTTTTGGCGTCACAGCAGACGGTAGCGCATGAACTGGTTAT
CGGTCTTGGCAGCCACAGCGTGGCCAACAGCAGGATCGGTAGCCAGCAACGATTCGTCGGGATTACGACGGT
GTTCTCCTCCGACGGGAGCTATCTGCTCTCAGACCGCACGGCGGTTGTCCCCTATGAGGAGTATGCGACTGC
GCTTTACGATACGCTCAAACGGAGCATCACTACGGTGAGGAAACAAGACAACTGGAGGTCTACGGATAAAGT
CCGCCTGGTGTTCCACATGTTCAAGCCCCCCAAGGACACCGAGGCCGAGGCTATAAAACGGACAGTGGACGA
TCTGGAGCTGGAGAACGTGACTTTCGCCTTCGTGCACATCGCCCCATCTCATCCCTACCTCATCTTCGACAA
TACACAAAAGGGAATTGGTTTCCGAGACCCCAAGAAGGGGATACTCGGACCCGAGAGAGGTCTGCACTTGAA
GCTGGGGGACTACGAGTCCTTGATCGTATTCAGCGGCGCAAGCGAGCTGAAACAGGCAAGTGACGGGATGCC
CAGGCCATGCCTGCTCAAGTTGCACCGGCTTAGCACGTTCACTGACATGACGTATCTGGCGCGACAGGCATT
CGAGTTTTCAGGTCATTCATGGCGAATGCTCTCCCCAGAACCGTTCCCTATAACTATTAGGTACTCCGACCT
GATCGCCGAAAGGCTCGCAGGTCTCAACGCCGTCCCGGGTTGGGACGCGGAGGCTGTCAGATTCGGCCAAAT
CGGCCGCACGCTCTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
292 42 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGAGAAAGGTCGAGGACCCGAAGAAGAAAAGGAAAGTGGGCAG
CGGCAGCCTGAAAATCAAAATTCTCAAGGAGCCGATGCTGGAGTTTGGCAACGGCGCTCACATATGCCCCAG
GACCGGTATCGAAACCCTGGGAGTGTACGATAAGAGAGATGAACTGAGGAGGAGCGAGCTGCGAATAGGCAT
TGTGGGTCGGGGCGAGGGCGTGGACCTTCTGGATGAGTGGCTCGACAAGTGCAAGCGCGGCATCGTGGGTAA
AGAGGAGACCAAGTTCCCCAACTTGTTCAGGGGCTTTGGGGGCGTCGATGAGTACCACGGTTTCTACACCAA
GATTCTGAGCAGCCCCCAGTATACCCGGACTTTGCAGAAAAGCGAGATTAACAACATCAGCAAGATCACCGC
CCGAGAGGACAGGGTAGTGAAGTGCGTGGAGCTGTACTACGAGCAGATCCGATTCCTGTCAGAGAACAGGAG
CATTGACGTGATCGTGTGCGTCGTTCCCAATGATATTTTCGACAGCCTTACTAAGGCCACCGGAGACAAAGA
CACCGAGTCCCTGGAGGCCTACCTCGAGCACAACTTTAGACGGTTGCTCAAGGCCCGCTGTATGCACCTTGG
GATACCCTTGCAGCTTGTGAGGGAGAAGACCATCCTGAGCGTGAAGCCTAGCATAGACCAGCAGGACCTTGC
CACAAAGGCTTGGAACTTCTGTACGGCCCTCTATTACAAGGGGAATAGGACTGTACCATGGCGCCTGGTGGA
GGATAAATTCAAGCCTAAGACCTGCTACATCGGCATTGGGTTCTATAAGAGTAGAGACGGCGAAACGGTGAG
CACATCACTTGCACAGGTATTCGACGAGTTCGGCCACGGGGTCATCCTTCGGGGAGCACCAGTTAGCCTGGA
CAAACGAGACAAGAGGCCCTACATGGACGAGTCTCAGGCTTACGAACTGCTGGACAGTGCCCTGGCGGAGTA
CGAGAAGGCCCTGATGCAAAAGCCCGCTCGAGTGGTGATCCACAAGAGCAGCAGGTTCCGGCCCACCGAGGT
GAGCGGCTTCAGCAGAGTGCTGAACGCGAAAGGAATCAGAACGAAGGACCTCGTGAGCATCACATCAACCGA
CATCCGCCTGTTCAGCGACAAAAACTATCCCCCCACCCGCGGTACCTTGTTGTCCCTGTCTGAAACACAAGG
AGTACTGTATACCAAGGGAATCGTAGATTTTTACAAGACCTATCCGGGCATGTATATCCCTTCACCCCTGAG
GGTTGAGGCGTTCGAGTCCGACAGCTCTCTTGAAGACTTGTGTAAGGAAATCCTGGGCCTGACCAAAATGAA
TTGGAACAACACACAACTGGACGGCCGACTGCCCATTACCCTGGAATGCGCCAATAAGGTGGGCGATATCAT
GAAGTATGTGGACGCATCCGAAAAGCCACAGGTTGGTGTGGCGCTGTTTATCTTCATGTTGGAGCAACTCGT
ACCCGGCTGGAAGCTGCCTAAGGTGAGTACATGGGTAGCACGGGTAATTTTCCTGAATATTGTACAGGTGTC
TATCGCTCTGCTTGCCGGGATTACTTGGAATAAATGGATGATGGGCCACAGTTTGTTGCATACCAGCGATGC
CCTGCCCCCCTTGCTCGCAGGATTCGCCGCCTACTTCGTTAACACCTTCGTGACCTACTGGTGGCACAGGGC
CAGGCACGCCAACGACACCCTTTGGCGACTTTTTCACCAACTGCACCATGCGCCCCAGAGGATCGAGGTGTT
TACTAGCTTCTACAAACACCCAACGGAAATGGTATTCAACTCTCTTCTTGGCAGTTTCGTGGCCTACGTCGT
TATGGGGATCTCCATCGAAGCTGGCGCGTATTACATCATGTTTGCGGCTCTTGGCGAGATGTTCTACCACAG
CAACTTGCGAACACCGCATGTTCTCGGTTATCTCTTTCAACGCCCTGAGATGCACCGGATCCACCACCAGAG
GGACCGACACGAGTGCAACTACAGCGATTTCCCCATCTGGGACATGCTCTTCGGCACCTACGAAAATCCCAG
GAGAATAGACGAACCACAGGGGTTTGCCGGCGACAAGGAACAGCAATTCGTTGATATGCTTTTGTTTAGGGA
CGTGCATTCCCTCCCCGGGAAGACACAACCAGCTCCCGTACTCGTCAAACCCGACGTGAGGTAGTAACTCGA
GGTTAACTTGT
293 78 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGCGGAAAGTCGAGGATCCAAAGAAGAAGCGCAAGGTGGGTTC
(Helicase) CGGGAGCAAAGGGCGGCACCAGGCGAAACACTACGCGGACGGCCTGGAAAAAATGCACGGGCAAAGGCCTGT
GATTTTCTACACCAACGGCCACGATATATGGATATGGGATGACCATCCGGCTCAGCACTACCCGCCCAGACG
GTTGTACGGATTCTACGCGAAGTCCAGCCTGCAGTATTTGATAAGGCAGCGCAGTGAACGCAAGGCGCTGAA
TACGGTGAGCTCTAAAACCGATATACTCGGAGAAAGACTCTACCAGCACGAGGCACTGAAGCGGATCTGCGA
ACGCTTCGAGACCAAGCAGAGGAAGGCACTCGCAGTCCAAGCGACCGGCACGGGGAAAACCCGCTTGTCCAT
CGCACTTACTGACTCTTGCATGAAGGCCGGGTGGGTGAAAAGGGTGCTTTTCCTGTGCGACCGAAGGGAACT
TAGAAAACAAGCTAAGAACGCCTTTAGCGAATTCCTCAGCGCGCCTATTAGCGTACTGACAACGAAAAGTGC
GCAGGATACCCACAATAGAATCTTCGTGGCAACCTACCCCGCGATGATGAAGGTGTACGAGCAACTGGATAC
GGGATTCTTCGACCTGATCATAGCCGACGAGAGTCACCGAAGTATTTACAACATCTACGGCGACCTCTTTCG
CTATTTTGACGCCCTTCAAGTGGGCCTGACCGCAACCCCCGTGGAGATGGTATCTCGGAGCACCTGCCAGCT
CTTCGGGTGTGACTTTAAGCAACCAACTTCTAATTACACACTCGAAACGGCTGTGGAGGAGGGTTATTTGGT
GCCCTACCAAGTCGTGAAACATACCACAAAGTTTCTGCGCGATGGGATCAAGGGCCACGCGCTTAGCGCGGA
GGAACTGGCGGAGCTGGAGGACAAGGGCATCGATCCTAACACTCTTGATTTCGACGCCGAGCAGATCGACCG
AGCGATCTACAATAAAGACACCAATCGGAAAATCCTGCAGAACCTCATGGAGAACGGTATCCGGCAGGCCGA
TGGCCAGACCCTCGGTAAGACGCTGGTATTTGCTAGGAACCACAAGCACGCCAAACTCCTCGAACAGTTGTT
CGACGAGCTGTACCCCCAGTACGGCGGTAAGTTCTGTCAGGTTATAGACAACTACGACCCCAGGGCGGAAGA
GTTGATAGACGATTTTAAGGGCGAGGGCAGCAACGAACAGCTCACTATAGCAATCTCAGTCGACATGCTCGA
CACCGGGATTGACGTCCCGGAGATCGTAAACCTCGTATTCGCACGGCCGGTTAAAAGCCCCGTGAAATTTTG
GCAAATGGTTGGTCGGGGAACGCGACTCTGTAAGAATTTGTTTGGACCCGGCAAGCACAAGACGCACTTCCT
TATTTTCGACCACTGGGGAGTCGTGGAGTATCACGGCATGAAACAACGCGAGGTAACTGTGTCCCAGAGCAA
GTCCCTGATGCAGCAATTGTTTGAAAATAGATTGGAGCTCGCCAAGACCGCGTTGCACCACGCCGAAGCCGA
CTTTTTTGAGACGATGGCGGGGTGGCTGCACAAAACGATAAATAGCCTGGACGATCGAACGATTGCCGTTTG
TGATAAGTGGAAAACTAAGCAGCAAATGTCCGACCTGGAGACGCTTAGACAGTTCGGTGCAAACACCGTCAC
GCTGCTTGAGTCAGAAATCGCCCCGTTGATGCAATGGCTGGATGTCAGAGGGCATAGTGACGCATATCAGTG
GGACCTCCTGGTCTCACAGATCCAACAACAAAAATTGAAGCAGGCGGCAGCCTTCGATGATCTCGCTGGGAG
GGCAATCAATCAACTGTGGCAGTTGCAGATGAATTTGAATCAAGTTAAGGCAAAGTCCGAGTGGATTAAGCA
GTGCCGAGAGACGGAGTGGTGGCAGAAGGCGTCCCTGGATGAACTGGAACAAATGCGACAAGAACTGCGGGG
CATTATGCAGTACAGGAACAAGGGTGACATTCCGAAGACAGAGGCGCCCATCATAGACATAACGGACTCAGA
GGAGGTGCGCGAGAAACAATCCTCCTACCTGAACTCAGTTGACATGGTCGCGTATCGGGTCAAGGTTGAACA
GGCGCTCCAGGAGCTCTTTGAGAGAAACCCCATCCTTCAGAAGATCCGGAACGGGGAGGCCGTGTCTGAGCG
CGAGCTTGAGAACTTGAACGCTCTCGTGCATACACAACACCCGGATATCGATCTCAACACACTTAAAAAGTT
CTATGGGACCGCGGCTCCGATGGATCAAATCCTTCGGACAATAGTAGGCATGGACGGGAACACGGTTAATCA
GCGCTTTGCGGCGTTCATACAACAGTACCCCTCACTGAGTGCGCGCCAAGTTCAATTCCTGTCCCTGCTGAA
ACGACAAATTGCTCAGAGTGGGGCCATAGAGATTGACAACTTGTACGAAATGCCATTCGCAGCTATCGGCGA
ACCCGACAGCGTATTTAGTAACGCGGAACAGATTGATGACCTTCTGGCGATTGTGGAGAGCTTCGGGAAGCA
GCCCCAGCAGCAGTCTACGAGACAGGCCAATGAGACATAGTAACTCGAGGTTAACTTGT
294 64 GGTGTCGTGAGGATCCATGCCTAAGAAAAAACGCAAAGTAGAAGATCCTAAAAAGAAGAGAAAGGTCGGCTC
(Helicase) CGGGAGCATGGATTACATACTTGAATTCGACGAGTTTATTCGAAGCATCAAGCAGAATATTGATACAAAGTA
TTCATTCCTGTTGGGGGCTGGCGCTTCAGTCGAATCAGGTATTCCGTGTGCCAGCGAATGCATCTGGGAGTG
GAAGAGGGATATCTTCATCAGCCAAAATCCGACCCTGGCTGAGATGCACAACAACATCAAGAGCCAGAACAT
TAAGCGCAGCATCCAGAACTGGCTCGATAACCAGGGCACCTACCCAAAGGAGGGCGAGGACATCGAGTATTC
CTACTATATTGAGAAGGCTTTCCGGATTCCCGACGACCGGAGGAAGTATTTCGAACGAAACATCACCGGCAA
GACTCCGTCACTGGGCTACCATATCCTGTGTCTGCTGGCGGAACGCGAGATAATCAAGTCCGTTTGGACAAC
AAACTTCGACGGCTTGATCATTAAAGCCGCCCATAAGTACCAGTTGGTGCCCATCGAGGTCACCCTCGAGAG
CCAAGATAGAATCTATCGGACGGATGCCAACAAGGAGTTGCTTTGCATAGCCTTGCATGGGGACTACAAGTA
CGGTCCGCTGAAGAATAGTAAAGAGGAGCTGGACAGCCAGTCTGACATCTTCGTGAATGCCCTTTCCTTCGA
GGCGTCTAAGCGCTATTTTGTGGTGATGGGATACAGTGGGCGCGACAAAAGCCTCATGCAGGCTATTGAGCG
AAGCTTTTGCAGAAGCGGCGCTGGCCGCCTTTACTGGTGTGGATACGGCCGGAACATCGCGCCTGAGGTACG
CGTGCTGATCGAGAAGTTGAACTTGTATGGACGCGAAGCGTTCTATATTCCCACGGACGGGTTTGACAAGAC
GATGTTGAACATAGCCCATATGTGTTTCGAGGATAAGGAATTGCAGGAAGAAGTGGAGAAACTCAAAGCGGA
TCTCGGTGCGGGGTATGAGTGTCGCACCACCACGTTCAGCCCCTACAAGGAAGGGGTGAATAAGATCGTGGA
CACAAATGTTTACCCGATCAAATTCCCCGACAAGTGCTATCAGTTCGAGGTGAAGAACAGCAGCGTAATGAA
CCTCTGGGATTACTGCAAGCAGCTGATAGACTATAACATTGTGGCCGTCCCCTATAACGGAATGATCTACGC
CTGGGGAAACCGCAACAGCATCAGCAACATGTGCGGACCAAATGTGAACGGGACGATCGAACTCGTTCCTCT
CACTAGGAAAATCTTTTTCGACAACGGCACTCTCAAGTCAATGCTCCTTAAAACTTTGCTCATCGTGATTGG
AAAGCACTCCAATTGCAAGTATAACCGAAACAAAATCTGGCGAGAGTCCAAGAAAATCAACTACACTATTAA
CGGCAAAAACATTGAAGCGTACCAAGGCATTAGGTTTAGCTTGTTCATGGACTGGAAATACAGCTACCTCAC
CCTGACCCCCGCTTTCTACTACAAAGACAGGAACAACGTTAGCAAGGAGGAGAACAAAGAGTTCAGCGACCG
GTTTATGGAGCAAATATGTAAGATGCAAGCCAATAAGAATTACGCCGCGTACATAAAACACTGGATTAACAT
TATCTTTCCTGATGGCAAGTCCATCATTTCCATGTACCCGTGTAACAGCGAGAGCGGATTCGAGTTCACCAT
TGTTAATAAGTCACTGCTGGTCGGACTGCGGAGTAGGCAAGCACTGCATAATCCTGACGATGACATGAAGAA
ACGGATTTGCATCGGTGGAGCTGAGTTGGCGGACACCGAGCTCAAGTTCTACAATCCGGCTCAGAATGCAAT
GCACACCGACTTCCACCCCATGAGGGGCCTTATCAACAATAAGCCCTACGACTTCTACATGAATAACAGGCT
GTTTAAATCTTACATCTCCCTGGGCGTGATCTCTCCTGTGGGTTCAGAGAAAAAGCTGGAGGACTTCCTGGA
CCGACTCAACAAAAAGCACAAAGTGAACTACAACGTCGACTATGTCATAGATTATCCTGGGTTTCAGTCCGT
CTACGGGGTTGGCCTTTCTGTCCCTCTGATCGCAGAATGGGCGTTGTTGGATGATAAAATGCTGAATAAAGC
CAACCTGTATCAGAGCTGCCTTAACTTCGGGGATCAGATCAAGAAGAAGATTGAGTACCTGAAGAGCCGCGA
CAGCGTGGACGTGATCATCATATACATTCCGAAAGAGTACGAGCTGTTCACCTTCTTCAACGACGGAAATAT
CCATTATGACCTGCACGACTACGTGAAAGCATTCAGCGTGCAGAGGCACATTAGCACCCAGTTCATACGGGA
GAAAACAATTGACTCTGAGCTTGACTGCCAGATCGCGTGGGCCCTCAGCCTCGCTATCTACGTTAAAGCAGG
CCGCACTCCGTGGATTCTCAGTGGCTTGAGGACTGATACCGCCTTCGCCGGCATCGGCTATAGTGTGGACCA
TATAAAGACCGACAACCAGACCCTTATCGGCTGTAGCCATATTTACGGGGCAGATGGCCAAGGTCTCCGGTA
CAAGCTCTCCAAGATTAAGGATGTGACCTTCGACAGCAAGAACAATCCCTACCTGTCCGAAAACGAGGCCTA
CCAACTCGGCCTGAATATCAAGGAACTTTTCTTTGATAGCTTCAAGACGTTGCCCCAACGAGTGGTCATACA
CAAAAGGTTTCCGTTCCAGAAGCAGGAGATCGATGGCCTGACTAAGTGTCTTGGGTCCGCGGGAGTGAAAGA
CATAGACCTCATCGAAATCACCTTGGAGGATCGATTTAGGTGCTTTGAATACGACAGGCGACTCCAGATTGA
CGGCTACCCCGTGAGGAGGGGCGTGTGCTTCGCCATCAACGAGAACACCGCCTATCTGTACACCCACGGTAT
TGCACCAAGCGTCAAGAATGCCAATCTCCGCTACATACAGGGCGGTAAGAGCATCCCTGCCCCCCTGAAAAT
CGTTAAGCACTACGGGAACGGCGACCTGGCCCAAATTGCGACAGAGATCTTGGGCCTGTCAAAGATGAATTG
GAACAGTTTTGGTCTGTATAGCAAGCTTCCGTGCACTATCCAATCTAGCAACGCTATCGCTCGCGTAGGGTG
GCTGCTCTCCCAGTATGAGGGCGTAGTTTACGACTATAGGAATTTCATGTAGTAACTCGAGGTTAACTTGT
295 70 GGTGTCGTGAGGATCCATGCCAAAGAAGAAACGAAAAGTGGAAGACCCCAAAAAAAAGCGGAAGGTGGGCAG
CGGCAGCATGAACAATCTGATGCTGGAGGCGTTTAAGGGCATTGGCACCATCAAGCCCCTGGTGTTCTATAG
GTACAAGCTCATCGGCAAGGGGAAGATTGAGAATACCTACAAGACGATCAGCAACGCCAAGAATAAGATGAG
TTTCAATAACAAGTTCAAAGCGACGTTCAGTAAGGGAGAGACCATCTACACCCTTGAGAAATTCGAGGTCAT
GCCCAATCTTAACGATGTGACCATTGAGTTCGACGGAGAAGAGGTTCTCCCGATAAAAGACAATAATGAAAT
TTACTCCGAAGTCGTGCAATTTTACATCAACAATAACCTTCGAAAGATCAAACTGGATAACAAATATCAGAA
GTATCGAGCAACGAATACCAGAGAGATAACTGGCAACGTCATACTCGACAAAGACTTCAAGGAGAAGTACAA
GAAGTCTAAGTCAGGGTTCCAGCTCAAGCGCAAATTCATAATTTCCCCCAAGGTGAACGACGAGGGTAAGGT
AACCCTGTTCCTTGACCTGAACAGCAGCTTCGACTATGACAAAAACATTTACCAGATGATCAAGGCCGGGAT
GGACGTGGTGGGGCAGGAAGTGATTAATACGTGGAATAATAAGAAGCAGAAGGGCAAGATTAAGAAGATTTC
TGAGCTGACGATCTCAGAGCCTTGTAACTTCGGCCAGTCCCTTATCGATTACTACGTTTCCCTCAACCAAGC
TGTGAGGGTGAAGAACTTTACGGAAGAGGAAAAGAACACAAACGTTATCGTCGTCCAGGTGGGAAAGGGCGA
GGTTGAGTATATTCCGCACGCGCTCAAACCCATCATTACTAGGGAGTACATAAAGAAATACGATGAGGCCTT
CAGCAAAGAGGTAGAAAACCTGATCAAAATCAACATGTCATACAGGTACGAAATACTGAAAAAGTTCATCGA
CGACATCGGCTCTATAACCGAACTGAACAACCTTAAGTTTGAGAACACGTACATAGATAACATCGAGTCACT
GGGCTACCAACAGGGAAAGCTGAACGATCCCGTGCTGATAGGCGGCAAAGGCATCCTGAAGGATAAGATACA
TGTGTTCAAATCCGGCTTTTACAAAAGCCCCATTGACGAAGTCAAGTTCGGCGTGATTTACCCGAAAGGCCA
CACCAATGATAGCAAGTCCACCATCCGGGCGATTTATGATTTTTGTACCGACGGGAAATACCAAGGCAAGGA
CAACATCTTCATTAACAACAAACTGATGAATATCAAATTTAGCAACCAGGACTGCGTGTTTGAGGAGTACGA
GCTCAATGACATAACGGAGTATAAGCGAGCCGCGAATAAGTTGAAAAACAACGAGAACATCAAGTTTGTAAT
CGCCATCATCCCCGCGATTGATGAGAGTGATATAGAAAATCCCTACAACCCTTTTAAGCGGGTCTGCGCCGA
GTTGAATCTGCCCAGCCAGATGGTAAGCCTGAAGACCGCGAAAAGATTCGGCACCAGCAAGGGTAATAACGA
GTTGTATTTTCTGCATAACATTAGCCTGGGTATCTTGGGTAAGATAGGGGGGGTCCCTTGGGTCATTAAGGA
CATGCCTGGGGAAGTTGACTGCTTCGTGGGCCTGGATGTGGGCACCAAAGAGAAAGGGATCCACTACCCCGC
ATGCAGCGTCCTTTTCGACAAGTACGGCAAGCTGATTAACTATTACAAGCCCACAATCCCGCAGAGCGGCGA
GATCATCAAGACAGACGTGCTGCAGGAGATCTTCGATAAAGTGCTGCTGAGCTACGAGGAGGAGAACGGGCA
GTATCCTCGAAACATCGTGATTCACAGGGACGGGTTCAGCAGGGAGGACCTGGAGTGGTATAAGAACTACTT
CATCAAAAAGAATATAAACTTCACGATTGTAGAAATCAAGAAAAACTTCGCCACCCGCGTCGCGAACAACAT
AAACAATGAAGTGTCCAACCCATTTAAAGGGAGCTTCATACTGCGCGAGAACGAGGCCATCGTTGTAACCAC
CGACATCAAAGATAATATCGGCGCTCCGAAACCAATCAAAGTCGAGAAGACATACGGCGATATTGACATGAT
GACCATAATCAACCAGATCTACGCCCTCACGCAAATCCACGTCGGAAGCGCGAAATCTATGAGGCTGCCGAT
CACGACCGGCTATGCCGACAAAATATGTAAATCCATCGAATACATCCCGAGCGGTAGGGTGGACAACCGGCT
CTTCTTCCTGTAGTAACTCGAGGTTAACTTGT
296 61 GGTGTCGTGAGGATCCATGCCGAAGAAGAAGCGAAAGGTCGAGGATCCCAAAAAGAAACGGAAGGTTGGCTC
CGGGTCTATGGGCAGGCAACTCCAACTGAACTTTACCCCGCTCAGGGTTAGGGGCGACGCCATCAGACTTCA
GGCGCTGCCTTTCGAGGACGCTCAACAATTTAGGAATCTGCGCGATGAGCATCGAGCACACTACGCTGTGAC
GAGAAGGAGCGACCACATCGTGGCCCTCCCACTTACACTGAATGCCTCCCCAATCGGCGAGGAGAAGATCGT
GAGCGTTGTGGAGCATGCGAGTTTGATTCGGCCCCTGCTTGAACAGAGGTTGGTGACCCTTCTGTCCAGTAA
CCGGAGGCCGGTGGCCCGGTATAATCCGATCACCACCATTGGAAGAACCTTGCCAACGGGCTTCATAGAAGC
CGACCGACACCTCCATTTGCAGTCCCGCGTGCTTATTGCTATCCGCTCCCTCAAGCTGCCGGACGCCGAGCC
CTTGGGATTGCTCTGGGACATCGAAATCCAGAAAACATGCGCGACTAGCCTTGCCGTCCTGCACGCACAAGG
GGTACGGCTGGACGGTCTCACAGTGGAACGGCTTGTCCCGGTGGAGGACGTGCGAATGTTGCCTTATAGGCG
ACTGGTGGGCAGAGTAGGCGCGCTGACCGATGGCCACGCCCGATTGAGCGAGCGGTTCCAGAACGTCGAAGA
ATTGCTGCCCCTGGACGAGCTTTACCTGGAGGCCAGTCCGGAGAACCTGAGGCACCTTCTGCAGCATTTCAT
GCGCAACACAAGCGGGCGAGTGCAAGGGAAGATAGACGAGATCGTCTTCGAGAACTCACGGGGACGCGCTCG
GATGGAGCACATTGCCCGGATCTCCGACTGGCTTAGAGGCCTGGGCGAGATTGAACTGCAGGAGGGTTTGTC
TGTAGGCATCGGAAACCTGCTCTCTGAAAAGGACGCCCAGAACTTTCCCAGGTTCACTGAGGGAACGACCCC
AACCTACGTGTTTGACGCTGGGACGTTGAAGAGCGAGTCAAGGGCCGCAGTGGGCCTCAGTAAATTCGGGCC
CTACAGCCGGCATGTATTTACACCGACTCGACCCAACGTTTGCGTCATCTGCGACCGCGCAAGAAGAGGACA
GTTTGAGCTGTTCCTGCGGAAATTCCGGGATGGCCTGACTGTTGATGGGAAGTCCCTGCCGTTTGGTCGCGG
GTTTCTGGGAATATATGGCCTTCAGGATATCAACCTGACCTTCGTCGAGGCGGATGCATTCACCGCGGACGC
GTACCATGCTGCCGCAAGCAAGGCAGTACGGATGGGAGCCGAGGGCGCACCGTGGCACCTGGCACTCGTGCA
AACAGAACGCGACAGTCGGCAACTGGCTCCCCCCAAGAATCCGTATTTGGTAGCGAAGGCGGCGTTTCTGTC
TAATCAAATTCCTACCCAGTTTGTGGCGTTCGAGACATTTTCTATGGCGCCTCTGAACCTCGCGTACACACT
GAGCAACCTGGCGTTGGCGGTTTATGCCAAGTTGGGCGGCATCCCATGGCTGATCAAGAGTGATAAAGGTAT
AGCCCACGAGGTCGTCATCGGGTTGGGTAGTGCCGCGATCGGGGAGTCCCGATTCAGCCGGAAGGAGAGGAT
TGTCGGCATCACAAGTGTTTTTCGGGGTGACGGCGGGTACCTCTTGTCTAACCTGTCCAATGCCGTGCCCAT
GAGCAAGTACGGCGAAGCATTGACCGAATCTCTCCAGGCGACCCTGCAGAGGGTTCGCAATGAGATGAACTG
GATCAGGGGGGACAGCGTTCGGGTCATAGTTCACGCTTTCAAGCCAATGAGGAACACGGAGGTGGAGAGCGT
TAAGGCTGCGCTGAAAGAATTCAGCGAGTTCGACCTGCAATTTGCTTTCCTTCACGTTAAGCAAGACCACCC
GTACCTCCTTTTTGACGACGACAGCATCGGTACAAAAGGGCGAGGCGAGAAAACCCCCGTGCGAGGCTTGTT
CGCGGAGGTCGGACACAACGAGACACTGCTGACCCTGACCGGACCACAGCAGCTGAAGAGACCCACCGACGG
GCTGCCGAAACCGCTTCTGCTCAGCCTCCATAGGGACTCTACTTTCACAGATATAATCTACCTCACGAAGCA
GGTGTACTGGTTTAGCAATCACTCATGGCGGTCTTTCCTGCCAGCAGCGATGCCGGTGACGATATACTACAG
CGACCTGGTGGCTGGTTTGCTCGGAAGACTGGATAGGCTGGGGTCTCGCTGGTCACCGAGTGTAATGCTGGG
CAAGATCGGAACCACAAGATGGTTCCTGTAGTAACTCGAGGTTAACTTGT
297 12 GGTGTCGTGAGGATCCATGCCTAAGAAAAAACGGAAAGTGGAGGATCCCAAAAAGAAGCGGAAGGTCGGCAG
CGGCTCAATGGCCTATCCAATCGCTGACGACCGGCGAAAGTACTTCCACAGTCTTTTCGAGAACAAGGAGCC
GTACATCGGATACAAGGCTCTGTGTCTGCTGGCCAAGAACGACATCATCAAGAGCGTGTGGACGACCAACTT
TGACGGGTTGACTGTGCGGACCGCATTCCAAAGTAACTTGACCCCCATAGAAATAACCCTCGACAACGCAGA
CAGACTGTTTAGGAACCAAAGCAAGAGAGAGCTGCTGAGCATATCACTTCATGGCGACTATAAGTATAGCAC
GCTGAAAAATACCGAGAAGGAGTTGGACTCACAGGACGGCACCTTCAGCGAGCATCTGGGTAACTATCACGT
CGACAAGAACCTGATTGTGATAGGTTATTCAGGGCGCGACAAAAGTCTGATGAAATCCCTGAACGATGCATT
CACCAAGAGGGGCACCGGCAGGCTGTATTGGTGCGGCTACGGTGACAAGATCAACACTGAGGTGGAAGAACT
TATACGCAACGTACGAACCGCTGGAAGGGAAGCCTTCTACATATCCACCGATGGTTTTGATAAGACGCTGAT
CGACCTTTCTAAAAGCGCTCTGGAGGACAACAGCATGAGCCTCGAAAGCCTTAATTCCATCCTGAAACTGGC
AAACAACGAGGAGCTCTCAAAGATCGAATTTAGCCAGAGCATCACCAGGACCGACAAATACCTGAAGAGTAA
TCTGCACGCAATTGTGTTCCCCAAGGAGATATTCCAGTTTGAAGTCGAGTTTGGCGACAACAAGCCCTGGTC
ATTCCTTAAAGACAAAACTAACAACACCGACATATGCGCCATCCCCTTCAAGAGGAAGGTTTACGCCCTGGG
CACGCTCAGCGGTATATCTAGCGTGTTCAAAAACGTGCTCAAAAGCGAGATTAGGAGGGTACCAATCTCCAA
GTTCGACATCGACAATGTGAGCAGCTTTAGGTCTCTCATGATCCAAACGGTGATCAAGCACTTTCTGTCATA
CGGAATCTTCGACAGCAACCTCAAGGACAAACTGTGGCTTAGAAATTCCGACAATTCCTTCGGGGACAAGAA
AATACACAAGGCGATTTACCTCAGCTTCTACTTCGATAAGAGCAGCAAATTCGGCTACATTAGCTTCAGCCC
CAGCATACACATAACCTCCGATAACGAGATCAGCAAGGAGGTGAAACAAAGGATTAGCAAAGAGATCTTGGA
AAAGCTCCGAAACGATAAGTTTGACGAAATACTGGAGTACTGGAACACCATACTGTTCAATTACAAAAATCT
TAAGTTCGAGTACCCCCTTAACAGCGGGACCGGATTCGAGTTCCAAATAAGCCGAAACACTGCGTTTGCCGA
AATCATGGTGCTGGACCCGAACTATCGAGTCTATAAACCAAGCGATTACAACAACAAGCTGACCCAGTTCAG
AGGTGTGCAGTATCTGGAGCCGCAACTGATCTTTCAGAACTCACTGAGTAACTCCCACACCAAGGACTACCA
CCCCATGAGGGCGTTGACCAATAACAGGCCATACGACAACAACTTGAATGGCATCATCTATTCAAACGAGGT
CAATTTGGCCGTGATTTGCGGGGAAAACTACTCCAAAAACCTCTACGACTTCCTGAACCAGCTTAACCTTAA
ACACCCCACAGACAACATCAACCCCGATTTCCTTATAGAATATCCTGGCTTCGCGAGCGCCTACAACCTCCC
CATCAACATCCCATACTATGAGGACGCGGACAAGTGGATTAACATAGATTTGGAGAAGAGCAACAAGTCCGA
CAGCGAGAACGCCATCATCGTTGCACGCCTCATCACAAGCAAAATCGAGCAGATCATAAACATACAGTCTCA
GCACACCATCGTCATCTTCATCCCCAAAGAGTGGCAGGCCTTCGAGAGCTTCCAGGAAAATGGCGAGGACTT
CGACCTCCACGACTACATCAAGGCGTTTAGTGCATCCAAGGGCGTGAGCACCCAGCTCATCAGGGAGGAGAC
ACTGTCAGACAGGTTGAAATGCCAGGTCTACTGGTGGCTGTCTCTGAGTTTTTATGTAAAGTCTCTGCGCAC
GCCATGGGTCTTGAATAATCAGGAGAAAAACACCGCCTACGCCGGCATAGGCTACAGCATTAAGAAGAACAG
CAATGACACCGAGGTGGTGATCGGTTGCAGCCACATTTACGATTCTAATGGCCAGGGCCTGAAGTACAAGTT
GAGTAAAGTAGATAATTACATCCTGGATAAGCAGAGCAATCCCTTCATGAGCTATAATGACGCGTTTCAGTT
CGGCGTGTCAATTAGGGAACTGTTCTACAATAGCCTGGACAGGCTCCCCGAGAGGGTGGTTATCCATAAGCG
GACCAAGTTTACGAACGACGAGATAAAAGGTATTACTGCCAGCCTCAACATGGCGGGGATTACCAAGATAGA
TCTCATTGAAATCAACTACGAGACGGAGGCTAGGTTTCTCTCCATGAACGTATTCAACGGCCTTCTGGGCAT
AGACAAATTCCCTATCAGTAGGGGTACCTGCATTATTACGAATAAGTACGAAGCCCTCCTTTGGACCCACGG
CATCGTGCCCTCCGTGAAGAATCCCATTCACAAGTATTACCTGGGCGGCAGGAGCATCCCAGCCCCGATCAA
AATTACTAGGCATTACGGCGAGAGCGATCTGAATACTATTGCCATCGAGATCCTCGGCCTCACCAAAATGAA
TTGGAATAGCTTTGACCTTTACAGCAAGCTCCCTGCGACGATTAACTCCTCAAATCAGATAGCCCGGATCGG
TAAGTTGCTGGCGCGCTTTGAGGGCAAGACCTATGATTATAGGCTCTTTATTTAGTAACTCGAGGTTAACTT
GT
298 54 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGAGAAAGGTGGAGGACCCAAAGAAGAAACGGAAAGTTGGCTC
TGGGTCAATGAACCTGACCGTAAACCTCGCCCCCATCAGCGTGCAGGGCGACTGCTCAGTCCTGATTGGCAG
ACAGCGCTACGACGAGCAGAGGCTGGCTGAACTTAGGTCAGACTTTCGGGGCACCCACGTGTTTCGGCGAGA
CGGTCCAGATAGCATGATTGACATCCCCGTGGTCCCCGACGCGGCACCTCTGGGCAACCTGAGGGAGACGAT
CGACCTTAGGCGGTACCAGCGGCTGTGGCCCATGCTTCTGCAGGAGTCCCTCATCCAGCTGCTTGGTAAGCG
CCCCATCCAGTCCAGCAAGCCCTTGAAGTTCCTGGGAGCTAGGTCTCCTCTGATCGAGCACCCGGATCTCCC
TGAGTGGTTGAGGCGGGTGAGCGTTACCGAGATCCACACCCGACACATCACCGTGGACGGCAAGCAAATCTA
CGGTATCGTGTGCGATGTGAGGGCCAAGTCTTTTATCCTCGCCACCTGCAGCGAACTTCTGAAATTCGGCGT
GACCATCCTTGGTAGATACGTCCAAATAGAACAGCCCGCGATAGACGAGAGAACCATGCCTAAAAGGAAGCT
CATCGGCAGGGTAAGGTCCATCCAAGGGGATGATCTGCTTCTTGACGACTGTGAGGCCGGCTTCGAAAAAGT
CGCTGCGAATGAGGCATTTCTCGAGCCGCGGAAGGAAAATTTCGAGGACTGCGTGAGGCAGGTGCTGAAGCG
GGACGCCGAGAGGGTGTTGGAGAGGTCAGCTCGCGCCAGCCAAAACCTGGCCGCAGGCCCTGGGAAACTGGA
ACACATCGACGGAATCATCAGGTATCTTAGGGAGAAGAAGCCCGCAGCGGTGCCCGGCTGCCATTTCGTGAT
CGATGCCATGCTCAACACAAACGGCCACATTTTTCCACCCGGGGAAACAATGGACAAACCCTTCCTCTTGTT
CGACCCTAGCGGTTCACGGAGAGAAGACTGGCCCGAGAAGGGCCTTAAAGATCACGGCCCCTATGATGAGCA
GGTGTTTTCCCCCAAGTCCCTGAAGATCGCTGTTGTGTGCCAAAGCCGGTTGGAGGGCAGAGTGGACGAGTT
TCTGGCGAAGTTTCTCAATGGGATGCCGAAGGTCTTTCAACCCGGCAAGAGCTTCGCCCGCTACGGCGACGG
ATTCGTGAAACGATTCAGACTGAACAAGCCCGAGGTGCACTTCTTTCTTGCAGATGGCAACTCCGACGAGGC
ATACGCCGTGGCCAGCCGCGAGGCACTCGATAAAGCGAGGGATAGCGGGTTCGAGTGGGACCTGGCGATTGT
GCAAATTGAGGAGGAGTTCAAGTCACTGGCCGACGGCTCCAATCCCTACTACACCACTAAGAGCATCTTCTT
GCGGAGGGACGTTCCGGTGCAGAGCGTCAGGCTGGAGACCATGAGCCTGTCAGATAATGACCTGGTGTTCCC
CATGAACCACCTGAGCCTCGCTACCTACGCCAAGCTGGGGGGCACGCCCTGGCTCCTGGCTAGCTCACAAAC
CGTGGCGCACGAACTGGTGATCGGACTGGGTAGCAGCACCAGCTCCGAATCAAGGCTGGGCAGCCAGATGAG
ACATGTGGGAATCACCACCGTGTTCAGCAGTGACGGCAGCTACCTGCTTTCTGATAGAACCGCCGCAGTGCC
CTTCGAGCAGTACCCACAAGAGTTGAGGAAAACGTTGCGAAAAACAATCGAGGCCGTCAGGGCCGAGGACAA
TTGGCGGAGTAGCGACAAGGTGAGGTTGGTATTCCATTCATTCAAGCCGTTCAAGGACAGCGAGGTAGAAGC
CATAGAGGCGCTGACCACCGACCTGGGCCTGGGCGACGTGAAGGCCGCCTTTCTGCACATTGCGCCCGACCA
CCCGTTCCTTATCTTCGACCACGACCAAATGGGCATCGCCGCACGAGGGGGCAAAAAAGGCGTGTTGGGCCC
TGCTAGGCAGTTGCACATCCGGCTTAGCGACGCTGAGAGCCTTGTGGTCTTCGCAGGGGCCAGCGAGCTTAA
ACAGGTGACGGATGGTATGCCGCGACCCGCGCTGCTCAAGCTGCACCCCAAAAGCACCTTCAAAGATATGAC
CTACCTGGCAAGGCAGGCCTTTGCCTTTAGTGCCCATAGCTGGCGGATGCTGTCCCCCGAACCTTTCCCAAT
TACTATCCGCTACAGCGACCTGATCGCCGACCGCCTGGCGGGACTCGCGTCTGTTAAGGGCTGGGACCCCGA
TGCCGTGACGTTCGGCGCTATCGGTCACAAGCCTTGGTTCTTGTAGTAACTCGAGGTTAACTTGT
299 23 GGTGTCGTGAGGATCCATGCCAAAGAAGAAACGAAAAGTGGAAGATCCCAAGAAAAAAAGGAAAGTTGGTAG
CGGCAGTATGATAATGAGCCTGGAGAGCAATATCTTCACTTTTAGCAACCTCGGGACACTTACCACGCAGTA
CCGACTGTATGAGATCAGAGGCCTGCAGAAAAGGCACCAAGAGTACTACCAGAACAGGCAAATCCTGATCCA
CCGACTCTCCTACCTTCTGAAAAATGCCGTAACTATCATAGAGCGCGACGAGAAACTGTACCTTGTTGTAGC
TGCCGATGCCCCGGAACCACCCAATAGTTATCCCATCGTTAGGGGCGTCATCTACTTCAAGCCCACCGGCCA
GATTCTGACCCTGGACTACAGCCTCCGAACACCCCAGAACGAAGAGATCTGCCAGAGGTTCCTCCATTTCAT
GGTACAAAGTGCCCTGTTTCAAAACGCGAATTTGTGGCAACCCAGCGCCGGAAAGGCTTTCTTCGAGAAAAA
GCCCTCATTCGAGTTCGGATCAATTCTGTTGTTTCAGGGATTTAGCGTTAGGCCCATATTCACCAAGGACAA
GATCGGCCTGTGTGTAGACATCCACCATAAATTCGTCAGCAAAGAACCCCTCCCTAGCTACCTGAACTTCAA
CGAGTTCCAAAAATACAGAGGCGTGTCATGCATCTACCATTTCGGCCACCAGTGGTACGAGATCCAACTCTC
TGAACTCTCCGAGCTTAACGCGACGGAGGCAATGGTACCCATCGAGAATAAGTTCGTGACCCTTATTAACTA
CATCACCCAGCAAGCCAGGAAGCCCATCCCGGAAGAGCTGGCAAACGTGTCACAGGACGCAGCCGTCGTGCA
CTACTTTAACAATCAGAACCAGGACAGGATGGCGGTGACGAGTCTGTGCTATCAGGTTTACGACAACTCTTA
TCCAGAAATCCGAAAGTACCACCAGCACACCATTCTGAAGCCACACATCCGCCGCAGCGCGATCCACGGAAT
AGTGCAGAAGTATCTCGCGGAGCTCAGGTTCGGCGACATAACCCTGAAGGTATCAACTATCCCCGAGCTGGT
GCCCCAGGAGATGTTCAACCTGCCCGACTATTGCTTCGGCAACGATTACAAACTGAGCGTGAAAGGAAGCGA
GGGCACAGCCCAGATTAGCCTCGACCAGGTCGGGAAGCAGCGCCTTGAGCTGCTGAGTAAGGCTGAAGCTGG
TATCTACGTGCAGGAAAAGTTCGACCGCCAATACATTCTCCTGCCCCAAACCGTGGGGGACAGCTTCGGGAG
CCGGTTCATCGACGACCTCAAGAAGACCGTGGACAAGCTGTACCCCGCTGGAGGAGGGTACGACCCGAAGAT
CATTTACTACCCCGACCGAGGTCTCCGGACCTACATCGAGCAGGGTAGGGCTATACTGAAAACAGTTGAAGA
GAACGAGCTGCAGCCCGGCTACGGTATCGTAATGCTTCATGACAGTCCGGATCGACTGCTCAGACAACACGA
CAAACTCGCAGCTCTGGTCATTAGGGAGCTGAAGGACTACGATCTGTACGTGGCCGTCATCCACAGCAAGAC
CGGGAGGGAGTGCTATGAGTTGAGATATAACAACCAGGGCGAGCCCTTCTATGCAGTAATACATGAAAAACG
GGGGAAGCTCTACGGCTACATGAGAGGGGTGGCGCTCAATAAGGTGCTTCTCACCAACGAGAGGTGGCCCTT
TGTGCTTTCTACCCCCCTGAATGCGGACGTGGTGATCGGAATCGACGTCAAGCACCACACCGCCGGTTACAT
AGTCGTCAACAAGAACGGGAGCAGGATCTGGACTCTGCCCACGATCACGAGCAAGCAGAAGGAGAGGCTGCC
CAGTATCCAAATAAAGGCGAGCTTGATCGAGATCATCACTAAGGAGGCCGAGCAAACAGTAGATCAGCTGCA
CAACATAGTGATACATAGGGACGGACGAATACACGAAAGCGAGATCGAGGGCGCCAAGCAGGCGATGGCCGA
GTTGATTAGCAGGTGTACGCTGCCTGTGAACGCCACACTCACGATCCTGGAAGTGGCGAAGAGCAGCCCCGT
TAGCTTTAGGCTGTTTGATGTCTCCAATACCAATTCTAAGGACCCGTTTGTGCAAAACCCACAAGTCGGGTG
CTACTACATTGCCAACAGCACTGACGCCTACCTGTGTAGCACGGGGAGGGCGTTTCTCAAGTTTGGCACCGT
GAACCCCCTGCACATAAGGTATGTGGAAGGTACGCTCCCCCTTAAACTGTGTTTGGAAGACGTGTACTATCT
GACAGCCCTGCCTTGGACGAAACCCGACGGGTGCATCAGGTACCCCATTACCGTAAAGATCAACGACAGGAG
GCTTGGGGAGGACGCCAGTGAGTACGACGAAGACGCCCTGCGCTTCGAGCTGTTCGAGTCTCTCGAGTCCGA
GGATGACTTTGACGAGATGACCGACAGCGACTTTAATCAGGAGGAGACAATGGTGTAGTAACTCGAGGTTAA
CTTGT
300 16 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGCGGAAAGTCGAAGACCCCAAGAAGAAGAGAAAGGTGGGCTC
CGGCAGCGTGGGCGACAAGACCTTCAGCTTCAAGGTGTATAGGAAACTGAAACAGCAGAACGACACCAAGGA
AGACGAGATATACCTTTACAATTTGCCCCAAGGCGAGACCCTGAATGATTACAAGCCATATTGGATCAGTTT
TACCCCGAAGGACGGATTCGAAGAATACATCGCTAATTCTTACTTGAGCATCGGCCTGTCAAAAAAGTACCT
GTTCAATAGATTCGTGGAGACGCTCAGCAACTCAAAACTGCACTTCACCTACAAGGTCAAAAGGAAATTCAC
CGACTGGTACGTCGATTTCGTAATCGCGCAGTACAGCCAGGGAGACAGGATCATCTACATGAGCCCCTACTT
CCTGGAAGAGCAAAACACCTACGGCTTCATCATCGACTTCAAGTTCAGCAAGAAGGATGGTATCCCCTTCGA
TTAGGAGGTGCAAAAGCTGTCCCTTTCACTGGATAGCAACGGCCGCAGCAACAAAAACTATTACTCTGACAA
ATTTAGGCTGGTGAACAATTTCATTAAGGAGATTTACACCTCCATAAAGAACATCGGGACCAGTAATAATCC
TATCACCATTTCCAGCAACCTCATAGAGACCACCGTGTTCCACCTGAACAAGAAAGAGTACATCTTTAGCAA
TAACAACGTAAGCTCTAGCCAGTTCCAGGGCGTGAGGAATTTCGGTGTCTATAAGAATATCCCCCAGGACGT
GATCTTCGCGTTCATATTCGAGGATAGGTTCAGGAGCTTCGCCAACGAGCTGTATCTGAGCCTTACCGGAAA
ATTGAACCCCGGGACCTTTCCCGGACTGGAGCAGATGTTCGGCATCAGCATCAACACCAAAAACGTGAGACA
GATCAAGTTGGAGAACTACTCTCTGGATTCAATGCTTAGGGTGGTGAATGACGTGAAGAGCTTGCAGGAGAA
CAATCCCGATAAGAAGATCGTGGGAATCTACGTGGAAGACTGCACCATCGACAGCGAGGACATCCCTGCGTC
CAACAACTACTACTTTCTGAAGTATCACTTTATCAAAAATGACCTGCCACTGCAGGTTGTGAATTATCGGAA
GCTGGGCGAAAGGAATTCTCTGAAATGGAGTACCTCCAACCTGGCCCTGGCCATGTTCGCAAAGATGGGCGG
CATCCCCTGGGTCGTAAAACCGTCTAATAAGAACTGCTTGATTCTTGGCATCGGATCTAGTCATAAGATAAA
CCGGGAGACCGGCGATATACTTAAATACTTTGCATACACCATATGTCTCGACTCCAGTGGCCTGTACAAGGC
CCTTGAGGTGCTGGCCGACGAGGAGAGCGAGGTGAGCTACCTTGAGAAGCTTACTGCCAATCTGGTCGCCAT
ACTGAAGGAACAAAAGACCAATTACGGCACCTGTGTGCTGCACCTGCCCTTCAAGATTAAGAAAAAAGAGGT
AGCCGCCATTAGTGATGCCATAAAACAAATCAACGACATCGAGCTGGTGGTGGTAAAGATCAATGTGGATAA
CAAGTATTTCGGATACTCCTTCCACAACACATTGGTGCCCTACGAGAGCAGCTTCGTGAAGCTTTCTAAGGA
TGAGTATCTGGTGTGGTTCGAGGGCCTGCTGTACGGCAAAGAGATCGTAGATAAGAGGTTGAGCAACCCCGT
GCACATCCAATTCTTGAACATCACCAACAGGAAGAACTTCGATGAGCAGGCGTTTCTGCAGGACATTCTGAA
TTTGAGCGGAGCCAACTGGAGGGGCTTCAACGCCAAAAGCATCCCTATCTCAATTTACTATTCTCAAATCAT
CGCGAGGTACACCGAGGCCTTCGAAAACATCGACGGTTACAAGGAGGGTACTATCTCTAACGACAAACCCTG
GTTCCTGTAGTAACTCGAGGTTAACTTGT
301 53 GGTGTCGTGAGGATCCATGCCGAAGAAAAAAAGGAAGGTGGAGGACCCAAAGAAGAAACGGAAAGTTGGCAG
CGGCTCCATGAGCGTGGCGATCGTGAGCCCCCAAATGTACAAGAGTCTGAGCGAGGTGTTTCCTCTGACCGC
CTCCCAACTGAACTTTATGTGCTTTAGGCTGACTCCCGAAATCGAAAAGAAGGATGGTAATAGGCTCAGCTA
CCATTTCAGTCTGAAGCTGCCGGAAACTGTTGTGATCTGGCACCAGCCCTACTTCTGGGTGTTGGCGAGTAG
TAACAGGCAAATCCCCAATAAGGACGAGTTGCAAGAAACTCTGATAAGGATCCAAAACGAGGTGGATGACTT
CAAAGAACGACTCTTCGGTTTCCAGAGCGTTCGCCACCCCCAACTCACCCCCTTTATCATCAGCCTCTTCGC
CGTGCAGGTCCTCAAAAAAACAAAGTTCGACTACCCCATTGCATTCAGCAACAACGGTGTAATCGTCAGGAG
GGAGCCCGACTTTTGGACGGAGAGCATAGAGCTTCAAGACAGCCTGCATCCTGCCCTCACGCTGACCGTAAG
TTCATCAATAGTGTTCCGCGACAACCTCGCGGAGTTCTATGAAAAACATCATCAAAGGGAGAAGCCCGAGCA
GTTTCTGATCGGCCTGAAGGTGCAGGAAATAGAGAGGGGCAACAATGCGATCATCGTGGGACTCGTCGGCAC
CATCGGCGAGCACCGGGACCAGCTGCTTGAAAAAGCAACCGGGAGCACTAGCAAGCAGGCGCTGCGAGAGGC
ACCGGACAACCAGCCGGTGGTTGCGATACAGTTCGGCAAGGATACGAAGCAGTTCTACTACGCAATGGCCGC
GTTGCGGCCGTGCGTAACCTCAGAGACGGCAAACCAGTTCGAGGTAGAGTACGGTAAGCTCCTGAAAGCTAC
AAAGATAAGCCACCAGGAGCGAACCAACCTGCTGGCCTCATACAAGAAGACGGCCCAGGAGTCATTGGCCGC
TTATGGCATCCGCCTGGAGCTGAGTGTGAATAGCAGGGATTACCCCAGCTTCTTCTGGCAACCCCCCGTGAA
GATCGAAGATACCAAACTTCTGTTTGGCAACGGCATAACCGGCAAGCGGACTGAGGTGCTCAAGGGGCTTTC
TATAGGGGGCGTGTACCGACGCCACGGGAAATTCCAGGACAAGTCAAAAGTGATCCAGATCGCGGCTCTTAA
GCTTTGCGACGTGACCGTTAGCTTGTTCCTGAAGCAACTTACTCAAAGGCTGGCAAAATACGGCTTCCGAAG
CGAGATAATCACCAAGAAGCCTCTGTCAATCAAGAACCTTGCCACCGCCGAAGCCAGGGCTGCTGTTGAGAA
AGCGGTCAATGAGCTCGTGGAAATACCCCACGACATCGTGCTTGCCTTCCTGCCTGAGTCCGACAGGCACAC
CGACGACACGGATGAGGGTTCCTTCTATCACCAGATCTACTCCCTTCTCCTCAGAAGACAAATAGCCTCACA
AATTATCTACGAGGACACCCTGTCCAACTCTGGGAACTACCAGTACATCCTGAACCAGGTCATTCCGGGGAT
CTTGGCGAAACTCGGGAATCTGCCCTTCATTTTGGCGGAAAGCCTCGATATAGCGGACCACTTCATCGGACT
TGACATCAGCAGAATCTCTAAGAAAACGCAGGTCGGGACACGAAACGCGTGCGCCAGCGTGCGACTTTACGG
ACGCCAGGGTGAATTTATCCGCTACCGGCTTGAAGACGACCTGATCGACGGCGAGGCGATTCCACCCAAGCT
GCTGGAAAGGTTGCTGCCTGCGACCGAGCTTGCGAATAAAACCATACTGATCTACAGGGACGGGAGCTTCGT
GGGCAAAGAGGCCGACTATCTTGTGGAGCGAGCCAAGGCGATAGACGCGAAGTTTATCCTCGTCGAGTGTAA
GAAATCCGGCGTGCCGCGCTTGTATAACTTGGAGCAAAAGACCGTGATCGCGCCGAGTCAGGGACTGGCTCT
TCGACTGAGCAGTAGGGAAGCAATACTCGTGACCACCAAGGTGCCCGATAAAGTGGGCCTGGCTAGACCCAT
CCGGCTCACAATCCACGAAAAGGGCCATCAAGTAAGCATCGAATCCGTGCTGGACACTACACTCAAGCTTAC
TCTTCTTCACCATGGCGCGCTGAAAGAACCGCGACTGCCCATGCCCCTGTATGGGAGCGACAGGATGGCATA
CCTCCGGCTGCAGGGGATACGGCCTAGCGTTATGGAGGGCGACCGCCAATTCTGGCTGTAGTAACTCGAGGT
TAACTTGT
302 88 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGAGGAAGGTAGAGGACCCTAAAAAAAAAAGAAAGGTAGGTTC
CGGATCCATGGAAGAAAATCTGTATCTTGAATACGACGCTTTCTTGAGGAGTGTGAAGCGCAACGTGGACGT
CCCTCATAGTTTCTTGCTTGGAGCCGGAGCTTCCATCTCCTCCGGAATTCAGTCTGCATACGACTGTATATG
GGAGTGGAAGAGAGATATCTACATCACGAAGAATATAAACGCCGCCGAGTACTATAAAAATCATAAAAACGA
AACGGTTCGCAAATCAATACAGAAGTGGCTGGACAACCATGGCAACTACCCCATCCTGGATGCAGCAGAAGA
GTACACATTTTACGCCGAGAAAGCTCATCCAATCGCTGACGATAGGAGAAAGTACTTCTTTAGTCTGATTGA
GAATAAAGAACCATATATCGGTTACAAATTGCTGTGCTTTCTCGCTTCACAGGGGATTGTAAAGAGTGTATG
GACGACCAATTTTGACGGGCTGATTGTACGAGCTGCTCACCAGAATAATTTGACGCCTATAGAAATCACCTT
GGATAACGCGGAGCGCATATTCCGAAATCAGAGTACTAAGGAGCTTCTCTGCATAGCTCTGCACGGTGACTA
CAAATATAGCACCTTGAAGAATACTGATACCGAACTGGATAACCAACACGAAATTTTTCAGGAGCACCTCGG
AAATTATCACGTAGATAAAAATTTTATAGTAGCTGGTTATAGTGGACGCGACAAGTCTCTGATGGATGCACT
CAAGGCCGCTTATTCCAAGAAAGGATCTGGTAGGTTGTATTGGTGTGGCTATGGTGAGAAGATAAATTCTGA
AGTGAAAGATCTTCTTAAGTATATTAGAGCGAGTGGGAGGGAAGCATACTATATAGCTACGGATGGGTTTGA
CAAAATGCTCATACACTTGTCAAAGGCAATATTTGAGGATAGCCAAGAGCTGAGTGAAAAAATCCAGAAAAT
ACTCGAAAGCACGAATCAAACCGAGACCTTCAACACAGAATTCAAGTTGGAGTTTAAAAAAACCGACAAATA
TATCAAATCAAATCTGCACCCTATTGTTTTTCCTAAGGAAGTATTTCAGTTGCAGATCGAGTATGGCAATGA
AAAACCGTGGTCCTTCCTGAAAACACTGACAACTCAAACGAACATTAGCGCCGTACCGTTCAAAGGCAATGT
CTACGCACTTGGTACGCTTAGCGAGATCAATTCCATCTTCAAGCCGTATCTTAAAAGCGAGGTCAAGAGGGA
AGCGATCAGCCGATTCGACATCGAAAACGTCACCGCATTCAAAAACCTCATGTTGACAGCCATATCCAAATA
TTTTTGCTACACGAAAGAAGTGAACTCTAACTACAAAGATAAGATTTGGTTGAAAAACATCCTGTCCAAGGT
GGGGGATATCACTGTTCACAAAGCAATTTTCATATCCCTGTACTTTGACAAGAATTCCCATTTTGGTTATAT
GGCGTTCGCTCCTACCGTTTATTTGGATTCCGACTGCGAAATTGAGAAGAGTCAAAAGCAATCCATCAGTAA
GAATTTGCTTGAGAAGTTGTATAATAACAAATATAACGAAGAGCTCGAACTGTGGAATGGTATCTTGTTTAA
TCATAAGAAAGTGAAATTTGAATATCCTCCCTTGTCTGGTACGGGGTTCGAATTTCAGATATCAAGCAACAC
TGCCTTCGGGGAGATAGACGTGATTGATAACAAGTACCGCTCTTACGTCCCCCAGAATTATGATAATAAGCA
GACTCAGTTCCGGGGAATCCAGTTTTTGGAGCCGCAGCTGATATTTAAGAACATCGCAACGAACTCTGACTT
CAAGGATTATCATCCCATGCGAGGACTGATTAACAACCGACCATATGATGTAAATCTCAACGGGATTATCCA
CTCCAATGAAATTAACCTCTCAATCATCTGTAGCCAAAAGTATGGAGAAAGGTTGTTCGCATTCTTGACACA
GCTCAATAGTAAGCACAGTACAGAAAATATCAACACTGACTACCTGATAGATTACCCCGGCTTCCTGTCCGC
CTTTAATCTGCCCATCAACATCCCAGCCACCAACGATGACGCTAGCTGGATGGACATCAACTTCGTAGCAGA
TAACTCTAAAGAAACACACGAGAACGCTATACGACTCGCGAGGGCAATTACCAATAAGATCGAGAAGATTTC
TGCTATACAAAGCGCCAGCACTATAGTAATCTTTATACCTTTCGAGTGGCAGCCCTTCGAAACATATATTAA
CGAAATAGAGACGTTTGATTTGCACGACTACATTAAAGCGTTTAGCGCCAGCAAGGGGATATCAACGCAACT
TATTCGGGAGGACACCCTTGACGATAAGCTCAAGTGCCAAATATACTGGTGGTTGTCTCTTTCTTTTTACGT
GAAGAGCCTCAGGACCCCATGGATATTGAACAACCAGGAGCGGAAAACAGCTTATGCCGGAATTGGGTACTC
CATAAGCAAGGTAAAGAACAAGTCAGAGATCGTGATCGGATGTTCACATATATATGATTCAAATGGCCAAGG
CCTTAAGTATCGCCTCTCAAAAATTGATAACTACTTTCTCGATAAGCAAAATAATCCGTACCTGTCTTATAA
GGACGCTTTTCAATTTGGGGTTAGTATCAGAGAGCTCTTCTATCAGTCACTCGATTCTCTGCCAGAAAGGGT
CGTCATCCATAAAAGGACAAAATTCACCGAGGATGAGATCAATGGGATAAAGGCTTCACTCAACCAGGCTGG
TATTAAGAAGATTGATCTTATAGAGATCAACTACGATATAGATGCAAAATTCGTTGCCATGAACGTGTTCGA
TAACAAATTGCAGGTCGATAAATTCCCGATATCCAGAGGAACATGCATTGTGACAAATAAACGGACGGCGTT
GTTGTGGACGCATGGTATAGTACCTTCAGTTAAGCAGCCCAATTATAAGTTCTACCTGGGCGGGCGCTCTAT
CCCTGCGCCCATAAAGATTACCAAGCATCACGGAGAAAGCAACATTGATGTGATAGCTAGTGAGATCCTCGG
ACTCACAAAAATGAATTGGAATAGCCTGGATCTCTACAGTAAACTTCCCTCTACGATAGATTCTTCTAACCA
GATTGCTAAGATAGGAAAACTTCTGTCTCGCTTTGAGGGCCGCTCATATGACTACAGGCTGTTTATTTAGTA
ACTCGAGGTTAACTTGT
303 17 GGTGTCGTGAGGATCCATGCCGAAGAAAAAGCGAAAAGTGGAAGACCCCAAAAAGAAGCGGAAGGTGGGCAG
CGGCAGCATGGACAATTTGGCTCTCTCTGCGCTTCAGCTGGACAGTAGATTGGATCACTGTATGGTATATCA
ATACAGGATCGTGTACCATAAGTTCGACGAAACAGAGGCGGGTGAAAAACTGGCAAGAAAGGCCGCCTACGA
ACTGTGGAAGGTAAACAACTTCGGACTGCTCACCAACCTGGGTGCCAGTAGCATCCTGTCCCTTAAGAGCCT
GAGTCAGCTGTCTATCGATTCACCGCTGTTGCAGGCAAGTTTGAAAGCTGACGGCCAGTTGGAGCTGGATTG
CGGTAACGAACAGCATCAGGAGGCGCTGCAGAGACTCGTGAACCAGGACATAAACAAAGCGGCTTGGAACCT
CAAACAAGCGAGCGAGGGGAAGCTTGATTGCCGAAAATCACCAGGCGGGCACGCCGAAATCTTCGAGCCAAG
TCACAGTAGTCGGATCAAGGCCCACAGTACCTATTTGGATGCCTTCTGCACCGTAAGGCTGATTCCCGAAGT
GCTGTCAGACGGGACAGTGCTGATAGGGTTGCATCTTAAGCACAGCCTGACCGCGAAGGCGGACATCTCTCT
TCAGTGGGTCATTGATCATAGGCCCGATTGGCTGATATCCATAGAGAAGGTGCGCCACAGGTATTACGAGCC
CGGCAAAGCACCCCTCGTTGCGGAGTTCGTGAAAGTCGATGATTCCATCAACGGATCATCCCTTCTCCCACA
CTTGGGCAAATCCCTTGTCGCTTACCACCAGGAGAAAGGGCTGCTTTCAGCCGGACAGCTCGCAGAGGCAGC
CACCAGCTCACTCATCAAAGTGCGCTACGGACAGAAGGAGGCAGACCACGTTGCTAGCTTGGTGGAACCCAT
GTTTGATTTCGATACTCTGTCAAAGATTGACAGCCCCTTCCTGAATAGGCTCGCCAAAGACCTGAAGTGGAG
CTTGGACGATAGAATAAAGACAAGCGCGGAGATGGTCAAGAGGCTCTACCTGCCCGGGTTTAATCGAAAGTT
GGTACAAGTTGACTACCAGAATCTGAGCAGGAAGAGGTTCAACCACAACCTTATGCTCCAGTTCGCGGATGG
GGCAAGGAGCGGCCATGAACAAGACGTCCTGAAATACAAGGCTTTCGCCGACATGACCAGGGCTAGGGTAAT
CCCACTCGTGGTAGGAGAGAGGAACAACACCGAAAGCAATAGACAATTGCTCCGGAACGCCTATAACGCACT
GAGGCAACTTACCAAGGCCGAATTGCCCCCCTTCACGTCATTTCCCCCCAGCATCGGAAACGCCGACGAGTT
GGACGCACGGCTGCACAAGAAATGTCCCGACAACGCCATCCTGCTTATCGGGCTCACAGAGAAGAGTGACAA
AGCCGCGATCAGGGACACGGCGTTCAACTACGGCCTGGCCACCCAGTTCATGAGGCTCGATCACAAGCCCAA
GGTTTACGACAGCTTCTACTTCAATAACGTCGCAGCGGGCCTGTTCTCCAAGGGAGGAGGGCAACTGTGCGC
CGTGAACGACATGCCCGGTGAGACTGAACTGTTTATCGGTCTGGACATGGGCGGCGTGAATGTAAGGGCGCC
AGGTTTCGCATTCCTGTTTCTCAACTCTGGCGCGCAACTGGGCTGGCAGCTGGCTGACAAGCAGCAGGGCGA
GAAAATGCAGGACGACGCTCTCAGCAATCTGCTGGAGAAGTCTCTCAAAACCTACCTGAGGAGCACCGACGG
GCTTTTGCCAAGGAGGATAACTCTGCACAGGGACGGCAGGTTTTACGAGAGCATCAATGTGATAGAACAGTT
TGAGCAGAAGCACGGGGTCAAGCTCGATGTTCTGGAAGTCTTGAAAAGCGGAGCCCCGGTGCTGTACCGGAG
AGAACGCAGTGCGGACGGTAAGAAAGTTTTCAGCAACCCAGGGGTTGGCGATGCCGTCTTCCTTAGCGACAG
GGAGGTCATTCTTAGCACTTACAGCGGCGAGGAACTTGGGAAGTCATGGGGTAACAAGGTGAGTGTGAGGCC
ACTTCGACTCCGAAAGAGATACGGCGAGACCGCATTGAGCGTGTTGGCCCATCAGGTGTTGGTCCTGTCTAG
GATCCATGGGGCCAGCCTCTACCGACACCCCCGACTTCCGGTGACCACCCACCACGCGGACAGGTTCGCAAC
CTTGCGGCAAGATGCGTGCATAGACGCACTTAGTAAGATGGATAGACTGTGTCCGGTGTATCTGTAGTAACT
CGAGGTTAACTTGT
304 37 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGCGAAAAGTGGAAGATCCGAAAAAGAAGAGGAAAGTGGGCAG
CGGGTCTATGAATAACGTGATGCAGGAGTTTCCCGTCGCAAGCTTCCCCACATTCTTGTCCGAGATCAGTCT
GCTTGACATCACACCGAAGAACTTTATCTGCTTTAGGCTCACCCCCGAAATCGAGCGCAAGACCGGTAACAG
TTTTAGCTGGCGCTTCAGCCAAAAATTCCCTGACGCCGTCGTGATTTGGCATAACAAGTTTTTCTGGGTACT
CGCTAAGCCCAATAGACCAATGCCCAGCCAGGAGCAGTGGAGAGAAAAGTTGCTGGAAATCTGCGAGGAACT
TAAGAAGGACATAGGCGACAGAACCTACGCCATTCAGTGGGTTAGCCAGCCCCAAATAACCCCTGAGATCCT
GTCTCAACTCGCCGTCAGAGTGTTGAAGATCAACTGTAGGTTTAGCTCTCCCAGCGTAATTTCTGTCAATCA
AGTTGAAGTGAAGAGGGAGATCGACTTTTGGGCCGAAACAATTGAGATTCAGACCCAGATCCAACCCGCTTT
GACCATCACCGTGCACAGTTCATTCTTCTATCAACGACACCTGGAAGAGTTCTACAATAATCACCCTTACAG
GCAGAACCCCGAGCAACTGCTCATCGGCCTCAAGGTGAGGGACATTGAAAGGAATAGCTTCGCGACGATTAC
TGACATTGTGGGCACCATAGCGGACCACCGCCAGAAGCTGCTCGAGGATGCCACTGGAGCTATTAGTAAGCA
AGCCCTTATAGAGGCCCCAGAAGAGCAGCCCGTGGTCGCCGTACAGTTCGGTAAGAACCAACAACCCTTCTA
CTACGCAATGGCCGCGTTGCGGCCTTGTATCACCGCCGAGACCGCTAGGAAGTTTGACGTGGACTACGGCAA
ACTGCTGTCCGCCACCAAGATACCCTACTTGGAGCGGAAGGAGCTGTTGGCTCTCTACAAAAAGGAGGCGGG
TCAATCTCTGGCGACTTATGGTTTCCAATTGAAAATCAGCATCAACAGCAGGAGGCATCCGGAGCTTTTTTT
CAGCCCAAGCGTGAAACTGAGCGAGACCAAACTCGTATTCGGGAAAAACCAAATAGGGGTGCAGGGGCAAAT
TCTTAGCGGATTGAGCAAGGGTGGGGTGTACAGAAGGCATGAGGACTTCAGCGACCTCTCAAGACCTATACG
CATCGCTGCGCTTAAATTGTGCGACTACCCTGCGAATTCATTTCTGCAAGAGACCCGGCAACGCCTCAAACG
GTACGGTTTTGAGACTCTGCTGCCCGTCGAGAATAAGAAAACCCTGCTGGTAGACGATCTGAGCGGGGTCGA
AGCACGCGCGAAAGCCGAGGAAGCCGTTGACGAACTGATGGTGAACCACCCCGACATCGTGCTCACTTTCTT
GCCGACCAGTGATAGGCACAGCGACAACACGGAAGGCGGCTCATTGTATAGTTGGATTTATTCCCGACTGCT
GCGGCGAGGGATTGCTTCACAGGTTATCTACGAGGACACGCTTAAGAGTGTGGAGGCGAAATATCTCCTTAA
CCAGGTGATCCCCGGAATATTGGCAAAACTCGGCAACCTGCCGTTCGTACTTGCGGAGCCCCTGGGAATCGC
TGACTACTTCATAGGCCTGGACATCTCCAGGTCAGCAAAGAAACGGGGGTCTGGAACCATGAATGCCTGTGC
CAGCGTTAGGCTGTATGGTAGGAAGGGCGAATTTATCAGGTACAGGCTTGAGGACGCACTGATCGAAGGGGA
GGAAATACCTCAGCGCATTCTGGAGAGTTTTCTGCCAGCCGCTCAACTGAAGGGCAAGGTAGTGCTCATTTA
CAGGGACGGCCGATTCTGTGGTGACGAGGTCCAGCACTTGAAAGAGAGAGCAAAGGCTATAGGAAGCGAGTT
CATCCTGGTTGAATGCTACAAGAGTGGGATTCCACGACTGTATAACTGGGAAGAAGAAGTCATAAAGGCACC
AACTCTGGGACTGGCCCTTAGGTTGAGTGCGAGAGAAGTGATTCTGGTGACAACCGAGCTGAACAGCGCAAA
AATCGGTCTTCCTTTGCCTCTGCGACTCAGAATTCACGAAGCCGGTCACCAAGTATCTCTCGAGTCTTTGGT
AGAAGCCACACTGAAGTTGACCCTCCTCCACCACGGCAGCCTGAACGAACCGCGGCTGCCTATACCACTGTT
TGGTTCCGATCGAATGGCCTACCGGAGACTCCAGGGCATATATCCCGGATTGTTGGAGGGGGATCGGCAGTT
CTGGCTTTAGTAACTCGAGGTTAACTTGT
305 38 GGTGTCGTGAGGATCCATGCCTAAGAAAAAGAGAAAGGTAGAAGACCCAAAGAAGAAGCGGAAGGTGGGCTC
CGGTTCAATGAACCTGACTCTGTTCAACGAGATCCTCCCCATCAACATCAGCCAACTGCCCAACCAGTACTT
CTACAAGCTGTGCACTGCCGGCGACGTGGACCTGGATTCTCTGGGCAGGAGCATCAAGTACCGGATCCAGAA
ATACTTCAGAGGAATCTGGGTGTGGAGTACCAACGACCAACTCCTCATTTCAGACAAGCTCATCGAGTACCC
CGAACTGCAAAAGTTCACCCAGTATCTGTGGACCGACCAGTCTAACCTCACATTCAACCAGCTCGAGGGGAT
AGAAATCGAGAACATTAGGTGTTGCACCCCCCAAGGCATCGCTGATTTCTGTAGCCAAGGTCTCATCAAAAA
GTACGACCAGCAGATCAAGAAGATACTCGAACAGTCCAAGACAGCACGGAGAGACTATCATATCAAACTGAT
CCACAAGTTCGGCTCCTGGGTGGTGAACAATCAGCCCTGCATAAGCCTGAGCCTGAAACAGGAGATCGATTT
TAACGGAACTCTCCAGGACTACCTGACCAAGTTCCCCAACTCTAACATCATCGGCCTGCATGTGCTCGACAT
CACTAAGCCTTTCAACACCGCACAGGAGGTCATCAAGATTCTCGGTATCTTGGGTGAGGGAAATCGGCGGCA
GCGCCTCCTGACTTGGGTCAAGGAGCCAACCATGAAAAAACTCGTGGAAGAGGCCCCAGATAGTGAGCTCGT
AGTTGAGATCGGGAACAAGAAAAAATCCTATCATTACATCATTTCTGCCCTGCGCATCAGAGTCCTCAACCA
AGATTACCTGAGGCTGGGGATTAGCGAGAAGCTGCAAATAGTCAGTGAAGAGAGGTTGAAGTACATCGAGCC
ACTTTTCCGCATACTGCAATCAGAGGGCTTCCTGGACAAGGTGTATACTAGCCAGCGCAACCCCGAGCTGTT
TAGGTCATGCAGCGAGGAATGGGGTTACAATCCCCTGCTGAAGTTCAAGAATAACGCCACTGTTGCGGCGGA
ATCCGTGCAGTCCACGGTCCAGGTGGTGCAGAAACACGGCGAATTCAGGAAAGCCGACAAAAGCGAAATTAG
GATCGCCATACTCAACACACTGAAGAGTGAAAACAGCACCAAATTGATTGAGATTTTCCGAAACAACTTTAA
GCGAAGCTTTAACCAGAATTTGGAGGGAATCGGTAATCAGCTTAAGTATAAACTCAAGTTGGTGGGCCAGCC
CATTGCACTGGATCTCAGTAAGAACTCCCTCAGCCTGCTGGACAGCAAAATAGGAGAATTGTCTAAAAAGAA
GCCGGACATTGTGATCTGTGTGATCCCTAACTTCCTTAGCAAGGGCGAAGACGGGCGGACACTTTACGACGA
TTTGAAGCAGACGTTCCTCAAATACAATCTCCAATCACAAATGTTGCAGGAGAAGACTCTCACGACGTCATT
TGCCACAAAGAACATCGTGTTGGGCGTGCTGGCGAAAATTGGAAGCGTTCCCTATATTCTGCAAGAACCGCT
GACGTACACGGACTTTGTCGTAGGTTTGGACGTGAGCAGGCGACGCAAAAAAAACCTGCAAGGAACCAACAG
CGTAGCCGCCATGACCCGAATCTACAGCAATCAAGGCGAACTGGTCCACTATAGCATCCGAGACGCAACCAT
CGACGGCGAGATCATTCCCAAGAGGATGCTCTACGACCTCTTTCCACTTCACGAATATCAGGGCAAACGCGT
GGTGATTCACCGGGACGGAAACTTCCCCGAGGAAGAGCGCCAGGCACTCGAGGAAATTGCCGAAAAGATTGA
CGCGAAGTTCTACTTCGTAAGCATTATCAAATCTGGCAATCCCAGGATCTACGGTAGGACCAAAAACGAAGA
GGGCATCGGCAGTTATCGCAAGGCACCTAAGGGTAGCATTTTCCTCCTCAGCGAGACGGAGGCCTTGCTTAT
CAGCAGCGACTTTCCGGACCGCTTCAGGGCCACGCCACAGCCTCTCAGAATTAAGACGTTTGGCAACTTTCC
CCTTCAAAGCGCCGTCCATAGCGTTCTGTCACTCACCTACCTGCACTACGGTTCCGAGCGCCCACCGAGGCT
GCCGGTGTCTACCTACTACGCAGATAGCATTAGCACTATGGTATCCAAGGGCATTAAGCCCAAGGACGTTGA
CGGCAATATACCCTTTTGGCTGTAGTAACTCGAGGTTAACTTGT
306 25 GGTGTCGTGAGGATCCATGCCGAAAAAGAAGCGGAAGGTTGAAGATCCAAAGAAGAAGAGGAAGGTGGGGTC
TGGGTCAATGCTCCTTAATCATCTCCCAATCGAGTTCTCCAGCGCACAGTTCGCTGGACACGAAATTGCTTA
TGTCGACGGCGAGCAGTTGAGGTCCATACGACAGAGACTCACGCGCACGCACTTCGTGTTGAGGGATGGGGA
CAATGTTCTGCTCTTCCCGTACGAACATGGAACCGCGACCGAGGGAACCAGGCGAACATTCGACACGGGCGT
TAATTTCAGCGTAGCCAACGCCCTGGCGCGCAACGGCATGCTTCTGCGATTCTTCCAGCACTCTAGAAGTAT
TTCCGGCGTCCGACCGGTGAAATTTGTGAAAGACAACCAGAACCTGCTCACGGGTGACGTAGGCCGGTTGTT
TGCTATATGTCCGGAGTACAGTTTCGACATCCGACCCCTGGCACCTCAAGACGGCAGCCTTGTGAACGGGGT
ACTGGTAAACTTCTCAGCCCGATTTTTGGTGAAGCCCTCCCTCGACGAATTGATTGCGCAGGGGCTCGACCC
ACGGGGCCTGTATGTTGTTAAAGAGGCAGAAAGAGAATCACCCTACATCCTGCCGATGTTTAATCGGAGATT
GGTAGGGCGGATCCAGGACGTGGTCGGAGGTATCGCCAAGCTGGTGGACGAGCGCGAACAGGACCTCCCTGT
ACATGAACTTCATGTCGAGGCCAACCTGGTCAACTTCGAGAAAGTAGGCAGAGCACTGCTTGGCCGGGATTA
CGAGCGAGTGAGTCGACAAGTGCTTCCCACCCTCCATAAGGTGAGCGGCGCAGAGAAACAGCTCGATCGCTT
GGTCCAGCTGCTGACGAGCTTCAAAGACCTCCAGGGTGACATCCCGTGTTGCGACGGCCTGACCGTTAGACT
GGCAGGCATACTTACAGATGTGCCCTTCGGCAGTGAGGTGGGCCAATTCCGCAAATTGTCCGCGCCACAGTG
CAGCCTCCGCCCAGGGGGAACTATTACGGTGCCGTGGCCCGTGGACGGCAAACTCAATGCCAACGGCCCCTT
TGATGCAGACGCCTTCAGCAGGAAGGAACCAACAATCGGCGTTCTGTTTCCGGAGCAGCACAAGGGTAGTGT
AGAAGAGCTGGCCGCTAAACTCAGAGACGGCGCACCGAGCGATGGAAAGTACCCAAGTCCATTTCCCCAAGG
AATGCCCCGGAAGTATAGACTTAGGAAGATGACATATGAGCTGACGCCCACGAAAGTTTCAGGGGACAGGGC
CGCAGCCTACAAGAATGCCGCGCTTGCAGCCGCCCAACAAGAGCTTGATCTCGCTCTGGTGGTCATATCTGA
ATCAGATAAGGCGTTGCTTGGAGCCGCCAGCCCCTACTACACTGCGAAAGCCACATTGATGAGCCAAGGCGT
GCCGGTGCAGGCTATTACCATTGAGACTATCAACAGGCTCAACCCCTACACCTTGAATAATCTGGCACTTTC
CCTTTACGCAAAACTCGGCGGGATACCTTGGACCCTGTCAGTTCAACAGCGACTGGTCCACGAGATAATTGT
AGGGATAGGGTCTGCGAGAGTGGGCTTCGACCGCCTCTCAGAGCGGGAGAGGCTTGTCGGCATCACGACCGT
GTTCTCCGGGGACGGATCATACCTTCTTGGCAATGCAACGACGGAAGCCAGCAGTACCGAATATAGGTCTCG
CCTTCTGGAGAGCCTTAGGGCGACTTTGGCAGAGTTGCGAAGACGATTTGGCTGGCAGCGGGGAGATAAATT
GAGGATTATCTTCCACCAAAGCTATAAGCGGTACAAGGAGACCGAAGCAACCGCCGTTAGCGACCTCATCGC
CGAACTTGATGAATTCGATGTGGAATTCGCGTTTGTGCAGATCAGTAGCGATCATGACTGGAAGTTGTTCGA
TGAGAGTGCCACAGGCGTTACGTATCAGTCCCGGCAAAAGGGAGCGAAGGTGCCGGAACGCGGAGTCATAGT
CCCTCTCGGACCTCGCGCTGCGCTGATCACGTTGGTGGGTCCGCATCAACTGAAAACCGACCTGCAAGGGTG
CCCCTCCCCCATACTGGTGTCTATCCACCCGAGCTCAACTTTCAAGGATTTGAGTTACGTGTCAAAGCAGGT
GTTCGACTTGACCTTTATGAGTTGGCGAAGCTTTAACCCAAGCACGCAGCCCGTTTCCGTGAGTTATCCCAA
CATGGTGGTGGATCTGCTCGGTAACCTGCGGCAAATCCCCAACTTCAATCCCGACATTCTGACGACAAAACT
GAGGGAGTCTAGGTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
307 20 GGTGTCGTGAGGATCCATGCCAAAGAAAAAAAGGAAAGTCGAGGACCCCAAAAAGAAGCGAAAAGTGGGCAG
CGGCTCCTTGGACAATTACATACTGACCGAGTACAAGGCCGGCATCCACGCCAGCGAGATCAAGATACACAT
CTACCGGATGCCCGTCAAGGATCTTGAGAAAATCGACTATGAGTACGGGAAGTACACACGCGACCTCAGACA
AAAAAACAGGAAGACGATATCCTTTTACCGCTCTCTGATCGGCAGCTTTGAGAAGCTCACCATCGTGCCCAA
GGGATACGAGAAGTACGAGTATAGATCAATTAAACTCGACCAGAGTGAGGAGTCACTCCAGGAGAGGAAACT
GCTGGAGAGGCTGATCTTCGACGGCCTTAGGGACAGCAATAGGAACCACTTTATGAGCACCGAGCAGAGCAT
CATCGAGAAAGAGCCCATCAAGTCCCTGAGCAAGTGCAAAATCCACCGGGGTATCTACATAGACATCACCGT
GAAAGAGAAAGGCGACATCTTCATCGGTTTCGAGCTGAAGCACTCCATCCAGAGCACCCACACGATTATCAA
GGCTCTGAAGGAGAAGAAACTGAACAAGGGCGATAAGGTGTTTGACTTTCTGAACAGCGCCCACTACGAGTT
CGAGGGGATTAGCGACAAAACCATCAGCGACCCCCTTCCCGAACTGGGCAACAAGAGCATTATCCAGCACTA
CAAAACGAAACCCAGCATCTACTGCCACCTCGTGAAAAAACCGAACATGCCCGCCATCCTGGTACGCAGCAA
GAGCGGCAAGGTGTATCCTTACCCCCCACAGCTGCTTAAGAAGGAGTGCCTGATGAAGGATGTGCCGGCTAA
GGAGCACAGCTCTATCAAGCTGAACCCCAACGATAAGATCAACTACAGCATTGAGATCATGAAGAGAATCAT
AGATGCGTTCGAGAACAGGTATTTCCCCATCGGCTTTGAAAAGAACAACCTGAACATCGCCAAGCTCGGATA
CAGGAGGAGGCTGGTCCCGGATCCCCTGCTGAGGATTGGCAACGGAGCCACCTGCAACCACAGAGACCTCAA
GGGTGCCTTCCTTAGGCACAAGATTTATGACAGCGTGAGCTCCCCTATCTACTACCAGCTTCTGCTTGACCA
ACCCTTCGAAAGGGAGTGGCAGAAAAAGATGAGCGAAGCGTTCATTACGAAGATGGAAAACCGGAGCAGGCA
GTGGGGCATAAAGCTTCAGTGTACCGGGAACCAGATCCTCCCTACCTCTAACCCGTACGCGCTGAGACTGCA
TCTTAAGGACATCAACCTGGATACCGACATCATTAGCGTGGTCCTGTTGGACGAGACCAAACAAGAAGGCGA
GGAGGTTTACTCTACCATCAAAAAAGAGCTGGGTGGCACCAGGGGCGCACATACCCAGGTAATCCTGATCGA
TAGCCTGAAGAACGAATACACTATCCCCCAGATACTGTTGGGAATCTACACCAAGGCTGGATTGCAGCCCTG
GGTCTTGCACCAGCCGTTGCACGCCGACTGCTACGTTGGCTACGACGTGAGCCATGAAAATGGCAGGCACAC
CACTGGCATAGTGCAAGTGTTCGGCAAAGACGGGTCACAGATCTTCAGTCAGCCCATTAGCAGCGCGGAGGC
CGGAGAGAAGGTGTCAAAGGAGACCATTCAGACTATGGTGATACACGTTCTTTACTATTACCAGAAGAAAGT
TGGCAAGATGCCACAGCACATTGTCTTCCACAGGGACGGCCGAGGATACGTAGAGGAGATAGACTGGATTAA
AGACATATTGAGTAATAGGGACCTCACCAACGGCCAAAGCATCGCTTTCGATTACATCTCAGTGATCAAAGA
GTGTGGTCGGCGCATGGCTTACTTTGACGACATAAAGAAGAAGTATGTGAACGTGCCCGGGATTGCCTACCT
GGACGACAACGCCCAAAAGGCCTATCTTTGCAGCACCAATCCATACGAAAAAGTAGGGATGAGCAAACCTAT
TAAGATTGTGAAGAAGATTGGCGAGATGACCCTGGAGCAGATCGTAGAAGACATCTATCACCTGAGTTTTAT
GAATATCGACACCGATAGGAAGGTGAGGCTGCCCGTGACTACCAATTACGCCGATAAGTCTTCAACGTTTTT
CTCTCGCGGCTATCTGTCATCACAAAAGAAAGGAATTGGCTTCGTATAGTAACTCGAGGTTAACTTGT
308 69 GGTGTCGTGAGGATCCATGCCCAAGAAGAAGAGAAAGGTCGAGGACCCGAAAAAGAAGCGAAAGGTAGGTAG
TGGTTCCATGGTCGGCGGCTATAAAGTCAGCAATTTGACAGTGGAAGCGTTCGAAGGTATCGGGAGTGTCAA
CCCGATGCTGTTTTACCAATACAAAGTCACCGGAAAGGGAAAGTACGATAATGTGTATAAGATTATCAAAAG
CGCACGGTACAAGATGCATTCTAAGAACCGATTCAAGCCCGTGTTCATCAAGGACGACAAACTGTACACCCT
CGAGAAGCTCCCGGATATAGAAGACCTGGATTTCGCAAACATTAACTTCGTGAAAAGCGAGGTTCTCAGCAT
AGAGGATAATATGTCAATTTATGGCGAGGTGGTGGAATACTATATCAATCTCAAGCTGAAAAAAGTGAAGGT
GTTGGGAAAATACCCCAAGTACAGGATCAATTACAGCAAAGAGATTCTCAGTAATACGCTGCTGACACGAGA
GCTCAAAGACGAGTTTAAGAAATCAAATAAGGGTTTTAACCTGAAACGGAAGTTTAGAATTTCCCCCGTGGT
GAATAAGATGGGCAAAGTGATACTCTATTTGTCCTGCAGTGCTGATTTCAGCACCAACAAGAACATTTACGA
AATGTTGAAAGAGGGCTTGGAGGTTGAGGGGCTGGCCGTTAAGAGCGAGTGGAGCAATATCAGTGGCAACCT
GGTGATCGAGAGCGTACTGGAAACCAAGATATCCGAGCCCACTAGCCTGGGCCAATCCCTGATAGACTACTA
TAAGAATAACAACCAGGGCTATAGGGTGAAGGATTTCACCGATGAGGATCTGAATGCCAACATTGTCAACGT
GAGAGGAAATAAGAAGATCTATATGTATATTCCGCACGCGTTGAAGCCGATAATCACCCGGGAGTACCTGGC
CAAGAACGATCCAGAGTTTTCTAAGGAGATCGAGCAGCTTATCAAGATGAATATGAACTACCGATATGAAAC
CCTCAAGTCATTTGTGAATGACATCGGGGTCATTGAAGAGCTGAACAACCTGAGCTTCAAAAACAAATACTA
CGAAGATGTGAAACTGCTGGGTTACTCCAGCGGCAAAATAGACGAACCCGTCCTGATGGGGGCAAAAGGGAT
CATAAAGAACAAAATGCAGATTTTTTCCAATGGATTCTACAAACTCCCCGAAGGCAAGGTACGATTTGGCGT
TCTGTACCCAAAAGAATTTGATGGCGTGTCAAGGAAAGCTATCCGCGCCATTTATGACTTCAGTAAGGAGGG
CAAATACCACGGCGAAAGCAACAAGTATATCGCGGAACACCTGATAAACGTGGAGTTCAATCCAAAGGAGTG
CATATTTGAGGGATACGAACTGGGCGATATCACCGAATACAAGAAGGCGGCTCTGAAACTTAATAACTACAA
CAATGTCGACTTCGTAATCGCAATAGTCCCGAACATGTCCGACGAAGAGATAGAGAACAGCTACAATCCGTT
CAAGAAAATATGGGCCGAACTGAATCTGCCCAGCCAGATGATTAGCGTCAAGACGGCCGAAATCTTTGCCAA
TAGCAGGGATAACACGGCGCTTTACTACCTGCATAACATCGTCCTCGGTATCCTGGGTAAGATAGGAGGGAT
TCCCTGGGTGGTTAAAGACATGAAGGGCGACGTGGATTGCTTCGTTGGACTCGATGTCGGCACCAGGGAGAA
GGGCATACATTACCCCGCCTGCAGCGTTGTGTTTGACAAGTACGGCAAGCTTATTAACTATTACAAGCCTAA
CATCCCGCAGAACGGAGAGAAGATTAACACAGAAATACTTCAGGAAATTTTCGACAAGGTGCTCATAAGCTA
TGAGGAGGAGAATGGAGCCTACCCGAAGAATATCGTGATCCACAGGGACGGCTTTAGCCGAGAGGACCTTGA
CTGGTATGAGAACTACTTCGGTAAGAAAAACATAAAGTTTAACATCATCGAAGTCAAAAAGTCAACTCCGTT
GAAAATCGCCAGTATAAACGAGGGAAATATCACGAATCCTGAAAAGGGTTCCTACATCCTGCGCGGCAACAA
AGCCTACATGGTGACCACAGATATTAAGGAAAACCTGGGAAGCCCAAAGCCCCTGAAGATAGAAAAGAGCTA
CGGCGACATAGACATGCTCACAGCTCTCAGCCAAATATACGCACTCACGCAAATCCATGTGGGGGCGACCAA
AAGCCTGCGCCTCCCAATCACCACCGGCTACGCCGACAAGATTTGCAAGGCGATCGAGTTCATCCCCCAAGG
GCGCGTGGACAACCGCCTTTTCTTTCTGTAGTAACTCGAGGTTAACTTGT
309 76 GGTGTCGTGAGGATCCATGCCAAAAAAGAAGAGAAAGGTAGAGGATCCCAAGAAGAAACGCAAGGTGGGGTC
(Helicase) CGGCAGTATGGACCGCGAGATCATTGAAAACTTCAACCCCAGCGACCCCAGGACCGAGGGCGAGAAGTATCT
GATGGATAACTTTTCAACCTCCCCCAGGTTTAATGGCTGGACAATATTTGAGCAGCCCCACATCAACTCAAT
GAAGCCCGACTTCATCTTGCTGCACCCCCACAAGGGCATCATAATCATAGAAGTGAAGGACTGGAACCTCAG
CAGCGAGACATATGAGAACGGCGGTTACATCTGGGGGGAAAACGGCGAGAGGATTAAGAAAAACCCCATCAA
TCAAGTAGAAAACTACAAAAACTCTATACTCAAGATGGAACTTACAAACAGCATCGAATTTAGTGAAGTGTT
CGGCGACAAATACTTCGCGTGCATAGAAACGGTGGTATACTTTCACAAAGCCAACAAAATTCAAGCCGAGAA
CTTCTGCAGGAGGAACAATAACTACACCAAGATCTGGACCAAGGACGAGTTCGACTACATATGCAATATCAA
TTACAAACTGAAGGGCAGTTGTCACACCTATGCCCTGAGCTACGAAAAAAGCACCCTTGAAGACAACAGAGG
TATGCTGAGTAAACTGGTGGAGGAGCTCAAGTGCAATCTCCAGTACAGTGACTACAACTATGAACGACGCCA
ACCGATTAAGTTGACCTATGAGCAAGAGAAGTTGGCGAGGCTGCAAAAGAATTCAATCAGGAGGTGGAGCGG
CGTGGCAGGCGCTGGCAAGTCCCTGAGTCTGGCGCAAAAAGCCGTGAACGCCCTGAAGGAGGACCATAGCGT
TCTGATCCTGACCTACAACATAACCCTGAGGCACTACCTGCGCGATCTGTGCTCTCAACAGTTCGGACCCGG
CTCCTACAAAGGCGAGCGCAAGAAGCTGAGGAGCGACCTGACCATCTGTCACTTTCATGACTTTTTGAGAAT
CATCATGGCCGAGTACGAGATCGAGGTCGAACATGACGAAGACGACAACTTCACCCAGCACTGGATAAACAA
GATCGACAGTTGCATAAAGGTGAACGGCATCAAGAGCCACCTCAAGTACGACTATATCCTGATCGACGAGGG
CCAAGACTTTGAAGGCGAATGGATTAGGTTCCTGAAGCAGTTCTTCACCGAGGTGGGTGAGATCTTTATCGT
GTACGACAAGGCCCAGGATCTCTACGAGCATGGCGTGTGGATCGAAGACAGCAACCAAATCAAAAACATCGG
CTTTAAGGGCAAGCCCGGGAACCTGAAAATCAGTATGAGGATGCCTGAGAAGATGGTGTACCTGGTGCAGGA
CATCAGAAATGAGTTCAAGATAGATGAGGAGGAGATCACCCCAAACGTGAACAGCCAGCAGAGCTTCATCGA
GATAACCAAGTGGATTAACTGTATGCCCCTGACGCTCACTGAAAAGCTCGACCAGATTGAAATACAGGTGGA
CTTTCTGCGCCGAAACAACAACAGCCTGGAGGATATCACGATCATTACGACCAACGAGGAGACCGGAGTGGA
GATAGTGAATAGGTTCAAAAGCAGGGGTATCAAGACCAGCCACGTCTACGATATGGAGAAGCGGGGGAACCA
GGCCAGGCGAAGGATGGAAAAATGGAAATTCCAGGGCGGCACCGGCAGACTGAAGATTTGTAGCTATCACAG
CTATAAGGGCTGGGAGACTCCGAACATCATCCTTGTGCTGGACGAGCCGAGCACAAAGTATGAAGACGGCAT
AATTAGTAAGGGGGAGTATAACGAGAAGAACATTTTCGACGCTATCTTCATTAGCATGTCCAGGGTGAAAAG
GAAAGCCCAAACCGGTGAGTTTAGCTTTACGTGCCTGAATTATCTTAGCGAATACAATAAGATTGAGGGCCT
CTTCCACTAGTAACTCGAGGTTAACTTGT
310 75 GGTGTCGTGAGGATCCATGCCTAAGAAAAAGCGGAAAGTTGAAGACCCCAAAAAGAAACGAAAAGTCGGAAG
(Helicase) CGGCTCACTGGGGCTGAATAATGAGTCCAAAGAGTTCTTTAAGGGCATTAGCCGCATTTGGAGAAATTACAA
GGACTACACCTACCTTGACGGGATTAAGCTGAGCCAGGCGCAGATCGATATCATCGAGAAGGAGGAAGACCA
ATTGCTTATAGAGGGCTACGCCGGCACCGGTAAGTCCCTGACCCTTATATACAAGTTCATTAACGTGCTGGT
TCGGGAAGATGGGAAGAGGGTGCTGTATGTGACTTTTAACGATACGCTGATCGAGGATACGAAAAAACGCCT
TAGTTATTGCAACGAGTACAACGAGAATAAAGAGAGGCACCACGTAGAGATTTGCACATTCCATGAGATCGC
CAGTAATATCCTGAAAAAAAAGAAGATCATAGACAGGGGTATTGAGAAACTGACGGCTAAAAAGATAGAAGA
TTACAAAGGTGCCGCTCTCCGCAGAATTGCGGGAATCCTGGCTAGGTACATCGAGGGGGGAAAGTATTATAG
CGAGTTGCCTAAAGAGGAACGCCTCTACAAGACACATGACGAGAACTTTATCAGGGAGGAGGTGGCCTGGAT
CAAGGCCATGGGCTTTATAGAAAAGGAGAAGTATTTCGAGAAAGATCGCATTGGGAGGTCCAAGAGTATCAG
GCTGACGCGCTCACAACGCAAAACTATATTCAAGATATTTGAAAAGTACTGCGAAGAGCAAGAAAACAAATT
CTTCAAAAGCCTCGACTTGGAGGATTACGCCCTGAAGCTCATCCAGAACATAGATAATTTCGATGACCTTAA
GTTCGACTACATTTTTGTGGACGAGGTACAGGATCTCGATCCCATGCAAATTAAGGCGCTGTGTCTGCTGAC
CAATACGAGCATCGTGCTGTCAGGCGACGCGAATCAGCGGATTTACAAGAAATCTCCCGTGAAGTACGAGGA
GCTCGGCCTCAGAATCAAAGAGAAGGGGAAACGGAAAATTCTGAACAAGAACTATCGGTCCACGGGTGAGAT
TGTCAAGCTCGCGAACTCAATCAAGTTCTTCGACGAGTCCATCAATAAGTATAATGAAAAGCAGTTCGTAAA
ATCCGGTGATCGCCCGATCATCCGGAAGGTGAACGACAAAAAGGGTGCGGTGAAGTTCCTGATCGGCGAGAT
CAAAAAAATCCACGAAGAGGACCCCTACAAAACAATCGCCATCATCCACCGAGAGAAAAACGAGCTTATCGG
CTTCCAAAAGTCCGAGTTCCGAAAGTACCTGGAAGGCCAGCTGTACATGGAAAAATTCAGTGACATCAAGTC
CTTTGAGTCAAAGTTTGATTTGAGGGAAAAGAACCAGGTGTTCTACACCAACGGCTACGATGTAAAGGGGCT
GGAATTTGATGTGGTGTTCATCATAAACTTCAACACGGCCAACTACCCACTGAGTAAAGAGCTGAAGAAAAT
CAAGGACGAAAACGACGGCAAGGAAATGACGCTCATTAAAGACGATGTGCTCGAGTTTATCAATCGCGAGAA
GAGGCTGCTGTACGTAGCTATGACCAGGGCCAAAGAAAAGCTGTATCTCGTGGCCGACTGCAAAAACAGCAA
CATCAGCAGCTTCATCTACGACTTTAACACCAAGTACTATGAGGCACAAAATTTCAAGAAGAAAGAGATAGA
GGAGAACTACAACCGGTACAAGATTAACATGGAGCGCGAATACGGCATCATCATTGAGGACGACGACTCCAA
CAACGTTAAGAACAATGACACGAAACAAGAGAACAAGTTTAATACCGAATCTAAGGAAAAGGGCAAAGATGA
CATCGACAAGATAAAGGTGTTTTTCATCAACAAGGGAATCGAGGTGGTGGACAACCGAGATAAGAGCGGGTG
CTTGTGGATCGTCGCCGGGAAGGAAGCGATCCCTCTTATGAAGAAGTTCGGTGTCCTGGGCTATAACTTCAT
ATTCATCGCAAACGGCGGTCGGGCATCTAAGAACCGGCCAGCCTGGTACCTCAAGAATAGCTAGTAACTCGA
GGTTAACTTGT
311 14 GGTGTCGTGAGGATCCATGCCTAAGAAGAAGCGGAAGGTGGAAGACCCGAAGAAAAAACGAAAGGTGGGCTC
CGGAAGCATGAACAACACCATAAACAAAATAGACTTCGGCGCGTTTCTGAGATCATTCAAGCAGAACCTGGA
CGGTAGCTTTTCTTTCCTTCTGGGAGCAGGCGCGAGTGTGAGCAGCGGCGTACAGTCTGCAAGCGACTGCAT
TTGGGACTGGAAAAAAGACATTTTTCTGGCCCAAAACCTTCAATTTGAGGAGTTTCTGGACATCCATAGTGA
CTTCTGTAAAGATAAAATCCAAAAGTGGTTGGATGAGCAGGGCGTGTTTCCCAAGCGAGACTCAGAGGAAGA
GTACGTGTTTTATGCCGAGAAAGCGTACCCAATGGAACAGGACAGGACCAAGTATTTCGAGAACCTTTGCGC
GGACAAAACCCCCTACATAGGGTATAAACTGCTGATGCTGCTGAACAAATACGGAGTTCTGAAATCCGTGTG
GACAACGAATTTTGACGGTCTGATAGAACGCGCAGCGCACCAAGCCGATCTGACGCCCATCGCCGTTACCCT
CGACAACCCCGAAAGGATTAGCCGAAACGAGAGTAAATCTGAGCTGCTCTACGTGGCACTCCACGGTGACTA
CAAGTATAGCAAGCTGAAGAACACAGCCCAAGAGCTGGACGCGCAAGAAATTCTCTTCACCGAACGCCTGAA
GTCTTACTTCATCGATAAGAATTTGGTGGTGATCGGTTACAGCGGTCGAGACAAAAGTTTGATGCACACCTT
GTGCGAGGCTTTTATGACGAAGGGGTGCGGTCGGCTTTACTGGTGCGGCTACGGTAACAAGATTACCTCTGA
AGTGCAGAACTTCCTCAACAGAATAAACGATTCAGGTAGGGAAGCCGTGTACGTGGACACCGATGGGTTCGA
TGCCACCCTCGTGTCTATTATGAAGTTTTGCTACGAGGATCAATTCGACAAGAAAATCGAAATCGGCAAGTA
TCTCAAGGGCCTGTCAAGGGTGAAGCATATTATCCCTTTCAGCGTTGAGAATACCACGTTCACCGGCTGCGC
CAAGACCAACCTGTACCCCTTGATCATCCCCCAAGACATATTCCAGTTCGAGATAGAGAGCCCCGAAGGTAG
CAGCAAATGGACCTTCATTAAAGAGAAGATTAAGGGCAAGGACATTATCGCTGCCCCTTACGAGAAAATAGT
CTACGCATACGGGCTGCCAAACTCAATCTACAACGTATTCAGTAAGGAGCTGATCGGCGAGATCAAGAGGGT
TCCCATCAGCCTGAGTAACATCAAAGACAACAGCACCCTCAAGAATATCATCCTGAAGGTGCTGATATGTTC
TCTGAGCAGTAACGCGGGACTCAGGGCGAGTATGAGCAAGAAGATCATCTGGAATGAGAAAGAGAGGTTCCA
GAGCAACGTTTTTAAGGCAATAAAGATCGACATCGTTTTCATCAATAGCGAAAAGTACGCCCTCATCTCAAT
CACCCCTACCCTCTATTTCAACAAGGAGGGCAACTACACGACGCTGCAGAAGCAGGAAATTACGCGGAGCTA
CATTGACAAGCTGTACAATAAGATTTATGAGGAAACCCTTTGTTACTGGGAGGCCATCCTGTTTAAGCAGCA
GACCAAGATCTGCTTCGACTACCCGCTCAATTCCGGGAACGGCTGTTTCTTCAAGGTTAGCTCTAACAGGGG
CGAAGCCCTGTTCAATAATCCGAATAAGCCGTACGTGATTACTAACGACATCATACTTAAACGCAAAATCTA
CGAAGGCATCATAATCGACGAGCCCCTCCTGAACTTCTCAGGGTCAACCAGCGCCCACATCATTATGGACTC
CAATCCGATGCGCGGTCTCAACAACAATAACCCATATGATCACTTCATTGCAAGCAAGTTTAGGGACGTTTC
TATCCACATCGGAGTCGTGTGTCCCTGTACATATAGCGACAGGTTTTTTAGCTTTCTGAACGAGCTGCAAAG
TCCGATAAAGAATAACAATCCTAACTCAGACTACATCCAGAACTATAACGGATTCAGCCAGATATACGCAAG
CATTCTTAATATCCCAGCGATCAACAGCCAATACTGGATCTCATGCCGCGAAGAGCAGGATAACAGCATCTC
TTTGGCTAGGAACCTGTGTAAATACGCGAACCAGATGGCCACTAACATGCCAGGTATAATAGTTACCTTCTT
CATTCCTAACAGCTGGAGCAACCACAAGAGTTTCAAAGAATGTGGCGAGGTATTCGACCTCCACAGTTACAT
CAAGGCTTTCGCCGCACAGCACGGTTTTACAACCCAAATCATTGAAGAGCGAACTCTCACAAATCTCTCCAT
GAAAAAGGAGATCTATTGGTGGCTGAGCCTGGCGTTCTTTGTAAAGGCTATGCGAGTACCATGGACCCTGGC
CAATCTGGACCAGAACACCGCCTTCGCCGGCATCGGCTACTCCCTGAGCAAAAAGCAAAGCGGCAAATTCAA
TATCGTTATCGGCTGTAGCCATATCTATAATTCTGAGGGCCAAGGCCTGAGGTACAAGCTCTCAAAGATAGA
TAATCCAATCTTGGACCGGAAAAACAACCCGTACCTGACCTATAATGAGGCGTATAAGTTGGGCGTGAACAT
ACAGAATCTGTTCATTCAGAGCATGGACAAACTCCCGAAGCGAGTAGTGATCCACAAAAGGATCCCGTTCCT
GGAGGACGAGATAAAGGGCATTACCGAGGCGTTGGCCCAGGCCAACATCACGAATGTTGACCTCATCACTAT
CACGATCGAAAAGAACATCAGATGCCTGGATCAGTTCTTCTACAATGGTCAAGCCAAGAACAGCAACTTCCC
ACTGCATAGGGGCACCTGCATGAAGCTCAGTGATACCGAGTGTCTGTTGTGGACCCACGGCGTGGTGGACTC
AATTAAGGCGGGCAGGAACTACTACTCTGGTGGCAAGGGTATCCCCTCCCCCCTCCGCATATCAAAGTTTTA
CGGCGCAGGCTCTATGAAGACTATATGCAACGAAATCCTGGGGTTCACAAAGATGAATTGGAATAGCTTTAA
CTTCTATACCAAGCTTCCCGCGACCATCGACACCAGCAACACGCTGGCGCAAGTGGGGAACATGCTCGATAA
TTACAACGGTATTACATACGATTACAGGTATTTCATCTAGTAACTCGAGGTTAACTTGT
312 26 GGTGTCGTGAGGATCCATGCCTAAGAAGAAGCGAAAAGTTGAAGACCCCAAAAAAAAGCGCAAGGTCGGGAG
CGGATCTATGATGGGAGCCAGCGATGAGTATTCCTTTTACGCTGAAAAGGCCTATCCCATAGAAGCGGACAG
GCAAAAGTACTTCGAACAGCTGGCGTACAACAAAGCCCCCTACATTGGCTATAAACTCTTGTGTCTGCTGAA
TAACGCGGGGCTGATAAAGTCTGTTTGGACCACAAATTTTGATGGCCTGACGGAAAGGGCCGCTCACCAAAT
GAACATCACCCCCATCTGCATTACCCTGGACGACCCCGAGAGGATTTTTAGGAATGAGAACTCTCACGAACT
GCTGTATATCGCCCTTCACGGCGATTACAAATATAGCAAGCTCAAAAATACCACCCACGAGCTGGACACCCA
AAACAATATCTTCAGAGACGCACTGAAGCGATACTTCGTGGATAAGAATCTTATTGTCATAGGATACAGCGG
CCGAGATAAAAGCCTGATGAACGCACTTAAAGAGGCATTTTCCCAATCCGGCTCCGGGCGACTGTACTGGTG
TGGCTTCGGGGACGATATATGCAGCGACGTTAAGGAATTGATAGACATCGCCAGGAGCAATAATCGGATTGC
CTACTTCATCCCGACGGACGGCTTCGATAAGACCATGCTCCAACTTAGTCGCGCCTGTTTCGAGGACGACAT
TGTGAAGCAGGAGGAAATCAAAAAGCTGATCAAGTCCACGATCAAGAAGGACGAGACGAAGACCAGCTTCCG
AATCGAGAGCAGCAGGAACGATAAACTTATTAAGTCTAACCTGCATCCCGTGGCGTTCCCCAAGGACGTGTA
CCAGTTCGAGATTAAGACTAACGGCGAGCATCTGTGGAACAACATAGACCAGATCATTGGCGGCAATAAGGA
CATAGTTGCCGTACCGTTCAAAGGTAAGGTGTTCGCTGTCTCAAGCATTGCGAAAATCAAGGAGAGGTTCGG
GGGCTATATCAAGGGGGAAATATTGAAAGACCCGATTGGCGTCGATGACATCCGCAAAGTATCTGTGTTCCA
GCGGCTTATGATGAAGAGCATCCTGATTGGAATCTCTGAGTTGGCAAATCTGGAAACTGATGGAAAGTGGCG
CCTTTGGAAAAAGAACACCCTGAGGCGAATCGTAAACGGCACGGAGTATTTCATCGCCGACGCTGTAGAGCT
GTCCTTTTTCTTCGGAAAAGATACCAAGTTTGCCTATCTCAGCATCAAACCGACCATTTACATTTATACACA
TAGCGACGAATTCATACCGAAGGATATAAAGCTGCAATTCACAAAGGAGAAGTTCGACCGACTCTATAATGC
ACAATACGACCAATCCCTGGAGGAGTGGAATAATCTCATCTTCCACAACAACAGCCTGAGGTTCACCTTTCC
CGTACTGACCACCTCCGACATGAGCTTTAGCATCAGCAACAATGTGGCCTTCTCAGGAATTAAGGTTTTGAG
TGACAAGTATAAGAGCTACCCCGTTTCTATCGAGCAGAAGCGCATAGTTTTCAAGGGCGTGGAGTTCCTGGA
GCCCCAGCTGCTGTTTCAAAATAAGAACAGCAACTTCAAGTCACGCGACTTCCATCCCATGAGGGGATTGAT
TAACCACTACCCCTTCGACTACCAGAACAATGGGATCACCAACACGTTTAATGTCAAACTCGGCGTGTTGTG
CTCCTCTAAGTACTCTACTAGGCTGTACGAGTTTCTCATGAAATTGAATGCCCAACATAAAGCGCCCGAGAA
AAACGAGTACATAATTGACTATGCTGGATTCAACCAAATCTACAACATCCCTATTGAGATACCGCTGGTAAA
CGACGAGAAGTGGATGGACGTAAAGTTTAATAGCAGCGTGAGTATCAAAGACGACGCTCTCAACCTGGCAAG
AATCATATGCACCCAGATCGAGGCGCTTCACGAGTCTTACAAAACTGACATGACCATCGTGATCTTCATTCC
CAACGAGTGGCAACCCTACAGACATATCGAGGAGGACACATGGGTTTTTGACCTCCACGACTACATCAAAGC
ATATAGCGCTCAGAAAAGAATTTCCACGCAGTTCATAGAGGAAGATACTCTGAACGATTCATTGACGTGCCA
GATATATTGGTGGCTCAGCCTTAGTTTTTACGTGAAATCCTTGCGGACGCCGTGGGTTCTGAATGCTAACAA
TAATGAGACCGCTTACGCGGGCATCGGCTACAGTATAAAGAATAACAACGGTGAGGCGTCAATTGTCCTCGG
GTGTAGCCATATTTACGACAGCCACGGCCAGGGCCTCAAGTACAAATTGAGCAGAGTGCAGGACTGCTACAT
CGACAACAAGCGGAACCCCTACCTGAGCTACAATGAGGCCTACAACTTTGGCATAAGTATCAGGGAGCTCTT
TCTGCACAGCATGGAGTACCTGCCAAAAAGGGTAGTAGTGCATAAACGCACCGAGTTCAAACCCGACGAAGT
GAATGGCATTGTCGACTCACTGCAGATAGCGGGTATCGAGAATATAGACCTTATCTCCATCAACTTCGAGCG
GGAAGTTAAATTCATGTCCACTAAATCCAACTACGGGCAGTTGCAAATCGATAACTTTCCCATACGCAGGGG
CACCTGTATCGTGGTGAACGACTATGAAGCCCTTCTCTGGACCCATGGAATTGTGCCGAGCGTTAAGTCCGA
TAACAGGACCTTCTATCTGGGCGGACGATCTATTCCTAGCCCTCTTATCATTAAGAAGCATTACGGTAAGAG
CGATATCAACGTTATCGCTACAGAGATACTGGGTCTTACCAAGATGAATTGGAACTCTTTTGATCTCTACAC
GAAGCTGCCGGCCACCATCGATAGCTCTAATCAAATCGCGCGGATCGGGAACCTGCTGACTAGGTTCGAGGG
CAAGACCTATGATTACCGGTTTTTCATTTAGTAACTCGAGGTTAACTTGT
313 46 GGTGTCGTGAGGATCCATGCCCAAAAAGAAACGGAAGGTGGAGGACCCGAAGAAAAAGCGCAAAGTAGGTAG
CGGCAGTATGCGATTGGGGCACATAGGCAACGGCTGTTACAGGGAAGGCGTTAAAGCACAATTCCAGACACG
AGAGAGGGAGGATGCCGGTTCAAGGGCTGCGGCTGCCCAACCCCCGATTAAGCAATTCGGATACACCGATAG
ACTCGGCCTGAACCTCGCCCCCATAAGGTTTTCTAGCGAAGAGTTTGAAGCCGGACGGACGGTGTACCGCGA
CGAGGAACAGTACCGAGCTCTTAGGGAAGCCCATCAAGCCACCCATGCCTTTAGGTATGACGCAAGGGACGC
GGCTATATACGACATCCCTATGGCAGAAGGGGTGGCGCCTCTGGGTACTCCCGTGAGGATCAAAACTAAGGA
CCACCTCGCTCTGCTCGGCAAAGCGGCTAACCACGCGCTGCTCGATTGGCTCGCACCACGCAGAACCATTCT
GCGGAGGGCGAGACCTCTTCAGTGCTGGGGCAACAGGAAGGCCTCACTGTTGTCAGCCGCCGTGCGGGATCA
AGGACTTGCCGAAACAAAGGGTCTGGATGTTCTGGTAAGGCATTCTTTTGATTTGAGGGCTTTGGGCGCACC
TCACCAGGGTGCTGAACCGTACCTTGCCCTGATGTTGGACGTGAGTACGAGCAATGAGCTGGAGATACCTGT
GGGCGAGCTTCTGCGCGAGAGATTCGACCCCATCGGTCGATACGTTTGTGCCAGAGCCGACTCTGGCCAAGA
TAACGTACTTGCTAGGTTGGAAACACTGGGTAGGGTCGTGGGTGTGGATGGTGGTAAGCTTCAACTGAACGA
CTTTACCGGAGAAGAATTCGTGGACGCTGATTCAGTCACGTTGGAGCCTAGATTGGAGAATCTCGATGCGCT
CATTCGCCACTTCTATCCCAGGGATGCGCCAAAAATCCTGGAGGGCCTTCGCAAAAGGAGAGTGCCTTTCTC
CACCGCGAACGACAAGCTGGCGAAGATACGAGAAGTGCACGGAGGAGTAGCCGGCCACCTTGAAACGATTAG
GATCGCTGGCATGGCTATAGAGGTGGGTGCCCTGCTGCAGAGAGGCTCTAACCTGTTTCCCCCACTCATAAG
CACGGACCGGCCTGGATTTCTGTTCGGCGCTCAAGGTAGGGAAACTGGCGCGTTCCCCGACGTGGGGGTGAA
GCAGCATGGGCCCTACAAGTACATGCAACACGAGCGCAATGAACCTGTGATCGCCATCATCTGCGAGAGCAG
GTTTCGGGGTCGGATAGACCAACTCGCCCGAACACTTCGCGATGGTGTCGCGGAAGATGCCTGGCAAGACGC
GATGAGGGGCAGAAATAAGGTGCCGGAAAACCCCTTTAGAGGCGGGCTGATCGGTAAATTGAGATTGTCTCG
GGTGCAGTTTGAGTTCGAAGAAGTAACCGAGCCCACTCCCGAAGCCTATCGCGAGGCCATCCTTCGGCTGCT
TGCGAGACTCCCAGAGACACCCGACCTCGCGTTGGTTCAAATACGAGCGGATTTTAAGCAGCTCCGCAACGA
CAGGAACCCATACTTCGCTGCAAAGGCCGCATTCATGACGGTGGGAGTGCCCGTGCAGTCCGTACAAGCCGA
GACTGCGGACATGCAGCCCAGTAATTTGGCCTACATGGCCAACAACCTGGCCCTCGCCGCCTACGCAAAATT
GGGCGGTAGTCCGTTCGTGATCTCCACACGCATGCCGGCGACGCATGAGCTCGTGGTTGGCTTGGGCTACAC
AGAGGTGTCAGAAGGACGCTTTGGACCGAAGTCCCGATTTGTAGGCATCACCACCGTGTTCCAAGGCGATGG
CAGGTACTTGGTGTGGGGGCAAACTAGAGAAGTAGAATTTGAAAACTACGCCGACGCTCTCTTGGCGAGTCT
GAAGACTACCATCGACACAGTGCGCAAGGACAATAACTGGCAGCCACGCGATCGAGTGAGGTTGGTATTCCA
CGTGTATAAGCCCCTTAAACATGTCGAGATCGACGCTATCAAACAGTTGGTGCAGGAGTTGCTGAAGGGCGA
ACATGAAGTGGAGTTCGCATTTCTGGACATCTCCCGCTTCCACGATTTTGCCCTTTTCGATCCTTCCCAAGA
GGGCGTGAATTACTACGCTGACCGCAGACGACTGCTGAAAGGCGTGGGCGTCCCCCTTAGGGGTATCTGCCT
CCAACTGGACGAAAGGAGCGTGCTCTTGCAGCTGACAGGCGCTAAGGAGGTGAAGACCAGTGAACAAGGTCT
GCCCAGGCCCCTGCGACTGACGTTGCATTCCGAGAGTGATTTTAGGGACCTCACATACTTGGCGCGACAGGT
GTACAGCTTTAGCTACCTCTCCTGGCGCAGCTACTTCCCGGCCATAGAGCCGGTGAGCATTACCTACAGCAG
ACTTATTGCCAATGCACTTGGCAACCTTAAGAGCATCCCGAACTGGAACAGCACATTCTTGACAGCTGGCCC
ACTGAGGTCAAGGATGTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
314 49 GGTGTCGTGAGGATCCATGCCGAAGAAGAAAAGGAAAGTGGAGGACCCCAAGAAAAAGCGCAAGGTTGGCAG
CGGGTCCCTGGAGAACCTCACCATAAACATAATCCCCTTCAAGCACCCCAGCATCCAAAAAGAATTTGGCTT
CTATACCGAGAAGAAGGAGGGCTATTTCCCCATTCATAGGACCGAGTTGCCCAACGAGCTGTGGGACAACCA
GAAAGAGGAAGTGGTGAAGCACAAGTTCTACTACACGAACTTTGAAGACACGGAGGATTGCGTTCTGAAGAC
CAAGGTGGACCTGTATAGTAGCACTAAGTTTGCCAAGCATCTGTACACGCGATTGGTGTACCAGTATTTCAT
TGGGATAGCGGATGCAATCCAGTTCAACTACGTGGGTGACATAGAGGTTTGGCTGCTGGATGCGAAAGCCAG
CACCACCAAATACAATAGCTACAACAAGTATACCCTGAAAATAGAGTTTAGCGGTCTGACCAAGAGCCCCGC
TCTCCTCCTCAGCTATGACAACACTAGTAAGGTAGCGACTACGAGCATAGACGAAATCAACATTCCCACCGA
GTACTTCAAGACCGTCGTGTATAACAAAGAAATCCAGAGGTTCAAGTACCTGACCGAGGACGCGAAACAACA
CCTCGATCAAGTGTATCCCCTGCTCAACATACCGTTGAAAAACCATCTTGAGATTCCTCACACCGTTCCCCG
CAAGGGCAACAGGTATAAGCCCTACTTTAACCACATTACGACTTTTTACAATAACTATTTGAACACCGACGA
ATTCAGGGCCATCCTGCCCCTTGATGAGAATGGATTCTTCAATATCCCAGAGGACAGCATTTTGAAAACTAG
CAAAAATTCTAACAACCTCCGGTTCTATAAGAAAGTCGGAGTAGATCCCAAGGCTGGAATGAAGAAGCCCGG
TCCCTACAAGGCCTCCCCCCACGACAACGTGAACCTGTTCTTTATCTATCACAAACCCGACGCACATGAATA
CGCCAAAACGTTGCATGACTACTTCATGGAGGGGTACAAAAAGTTCTTTCCCCCCCTCAAGAACGTTATCCG
GCAGCCGCTGTTCCTGGACAAAGGCACCTCACTTGCATTTGAGAGCTTCGACAGCTGCATCGCCGAGCTGAA
AACCCATCTGTTCGACCTCAAAAAAAAGCCCAATACCCGGTACGTGGCCATCTACGTGAGCCCCATCCATAA
GGAGGACGAAGACAATAAACACCTGTACTACCAGGTCAAAGAAGAGCTGCTTAAACATGACATCACCAGCCA
GGTGATTTACAAAGAGTCCATCAAAGATAAATACTTCGGCGCTTTCCTCGAGAATATCGCACCAGCTTTGCT
TGCAAAGATCGACGGCATTCCCTGGCGACTGGACAGGGAGTTGAAACAGGAACTGATCGTAGGCGTCGGCGC
CTATAAAAGCAGCGTCACCAACACAAGGTTCGTTGGAAGCGCCTTTTGCTTTAACAACAAAGGAGAGTTCAA
GAGCTTTGACTGCTTCAGGGAGAAGGAATTCGATCTGATTGCCGGGAAAATCGGCAAGCAGGTGCTCACCTT
CATTGAGGAGAACGAGAACAAGTTGGAGAGGCTGATCATCCATTATTTCAAGCCTTTCAACAAGGATGAGAT
AGATCTCGTGCAGGAGACCCTCGGCCTGCTGAAGCTGGAAATCCCCATCATCATCGTGACTATCAATAAGAC
CGAGAGCTCCGATTACGTCGCTTTTGACACCAACGACGACGCCCTGATGCCCCTGAGCGGCACCATTATCGA
GATAGCACATCTGAAGTATCTGCTGTTCAATAACGCGAAGTACAGCAGCATCGGCTTCGCCAAAGACCACCC
CTTCCCCGTTAAGCTCAGTCTGTACTGCACCGACCAGGATTACTTCGAGGACATCGCCATCGTCAAGGAGCT
CATAGATCAGGTTTATCAGTTTTCTAGGATGTACTGGAAGAGCGTCAAGCAGCAAAACCTGCCCGTGACAAT
CAAATACCCCGAGATGGTGGCCCAAATCTTCCCACACTTTGAGGGCGATAAACTGCCTGATTTTGGAAAAAA
CAATCTCTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
315 77 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGAGGAAGGTTGAGGACCCCAAAAAGAAGCGCAAAGTAGGTAG
(Helicase) CGGCTCCATGCTGACCAATAATCAGATTGTGCTGGAGCAGGAACTTCTGGGAAGCATATTCAAAAACAATAA
CCTGATGCTGAAAGCCCGAGAGAAGATAAAACCGGAGATGTTCCTGTATAGCAAACACATGAACATTTACCT
GGGCATCCTCGACATGGTGGCCAACAAGCTGGAGGTGGACCTGATCACCTTTCTCGAGCACCATAAGAAAAG
GGTGGGGGATATGGATGGCGTAACTTACGTGACCGAGATCTACACCTGCAGCGCGTCCGACATTGGCTTCAA
TACAAAACTTGACATGCTGGTGAACAACTACAAACGGCATCTGTATGTGGAGATGAAGGACAAAATCAACAG
TGATATGAGTCTTGAGGAGATCGAGAGCGAGGTTGAAGGGGTGAAGGTAAAGGTGCACAAATGCAACATCAA
GAAAGAACTGGATATAGACAAGCAATATGACGATTACATCAACTGGCTTTACGACGAAAACAGAGACAAGGG
GATGAAAAGCGGCCTGACCTATCTGGACAAGTATCTCGGCAACTTCCAGAAGGGCAGGCTCGTCACCGTGTT
CGCCAGGAGCGGCGTCGGCAAGACCACGTTCAGCTTGCAGCTGGCCGCCAATATGGCTCTGAAGGGCCACAA
GATATTCTACGGGAGCGCAGAGATGACCCGCAACCAGGTCTTTAACAGGATCGTGGCCTCAGGTTTGAGCCT
TAGCGCGAAGGCGATTGATGAGGACACCATCCTGAAGGAGGACAAGGAGAGCATCGCCAAGTTTATGACCAA
GGTTATCAACAACAAGTTCTACGTGTCAACCGAGACCGACTTCGAAAAGTTCATCGACGAGATAAAGGTTTA
TAAGCTGCAGAACAGTCTGGACGTGGTGTTCGTGGACTACATTAACAAGTACATCGACTTCACCGACAGGGA
CATGTTGACCAACAAACTGGGGAAGATCAGCGGCATGCTCAAGAGCCTGGCCATGGAAGAGGATATCTGCGT
GGTGCTGATGGCCCAGGCCAATAGAGTGATTGACAAGAAGGTGGGTGACAATGCCGTCGAAAAAATCGACAG
CAGCGACATCCAGGACAGCGCCAGAATCGAGCAAGACAGCGACCAAGTGATCGGCCTGTACCGGAACGTGAA
GCTCGATGATAAAATGTATAGGGAGAACCTGTTCAATCAGGGCAAGCTCAAGTATAATTCCAAGAACGCCGA
CGACAATCCGGAATGCATGAACGCTGTGATCATTAAGAACAGGCATGGCGACCGAGGCACGTGTGCACTGAG
GTGGCACGGCAGGTACAGCAGGGTCAGCGACTTCTAGTAACTCGAGGTTAACTTGT
316 66 GGTGTCGTGAGGATCCATGCCTAAGAAGAAGAGGAAGGTCGAAGATCCCAAAAAGAAACGAAAGGTTGGATC
AGGGTCTCTTCACCTTAACTACCTCCCATTGCGCTTTACCGCCGATATATTCAAGGGTGGTGCTTTGACATT
TCCCGAAGGCAGCGAGAAAAACTGGACCAGCGACGATCCAATCAGCAAGGAGCTGAGCAAGTTGCGAGAGAA
ACACGGAGATAGTCATGTCTTCCACCGGATGGGAAACAAAATTGCATGTATCCCCGTTGTGGAGAACGCCAT
TGCTATAGGCACCGAGACGGATTTCAACATCATTAGTGACTTTCAGCTGGCTAATGCTCTTGCTCGCAGCGC
CCTCCACAGGTACTTCAAAGCTGCGGGAAGGGAGACTGTAATTGGGTTCCGACCCGTAACCCTTCTCTTGGA
AAAACACAACTTGGCCAGCAACAGGAAGGACGTGTTCGGCATTTTCCCCGAGTACACTCTGGACGTCAGGCC
TCTTGCACCACATGAGGGCGACATAGCGAGCGGAGTGCTTATCGGCTTTGGAATAAAGTATGTTTTCCTTCA
GAACGTAGCCGAGCTGCAGGCACAAGGGGTGAGTGCCGCAGGGATGTACGCCGTGAGGCTGGTAGACGAGAG
CGAACATCAATTTGACCGGGCCTACCTGGGAAGGATTGATCGGTTCACAAAAGATAACGTGACGCTCGTTGA
CAGCGATTACGCGGAATATCCCGCCGACCAGTGTTACTTCGAGGGAAGCAGGACCAACATCGAAGCCGTGGG
CCGAAGTCTCCTGGGGAAAGACTATGATGCCTTCAGCTCAAGCCTTTTGCAGGAGAGCTACAAAGTGACCGG
AGCCCCCAACCAAACCCAACGACTGCACCAGTTGGGCGCGTGGCTCGAGGCCAAGAGTCCGATCCCCTGCGC
CGTTGGTCTGGGAGTACGGATTGCAAAAAAGCCGCATGAGTGCTCACGAGGCAACGACGCCGGGTACAGCCG
CTTTTTCGACAGCCCCAAGTGCGTGCTGCGGCCTGGCGGCTCTCTGACCGTGCCCTGGCCGGTCGACAAGCA
GATAGATCTCAATGGCCCTTACGACGCTGAGAGCTTTCCCAACAAGAGGGTACGAATTGCCGTCATCTGCCC
TCAGGAATTCACCGGGGATGCGGAAGAGTTCCTCCGGAAGTTGAAGGAGGGCCTTCCTAACGCACCGGACGG
CAGTCCGTTTCGCAAGGGCTTTGTTCGAAAGTACCATTTGTCTAGCTGTGACTTCACGTTCCATGAGGTTAA
GCGGAGCTCAAACAGTGACGACATCTACAAGGATGCGTCCCTTGAGGCACTGAAGCAGAAGCCAGATATGGC
AATCGCCATAATCCGGTCCCAATATCGCGGGCTGCCCGATGCTTCTAATCCCTATTACACGACAAAAGCTAG
GCTGATGGCCCAGGGCGTACCAGTTCAACTGCTGAACATAGAGACCATCAGGAGGAAGTCTTTGGACTACAT
TCTGAATAACATCGGTCTTGCGATGTATGCCAAACTTGGAGGAATCCCTTGGACCCTCACCCAGAATAGCGA
CATGGCGCACGAGATCATCGTCGGGATAGGGTCAGCCCGGCTCAATGAGAGCAGGAGGGGTGCTGGCGAGAG
GGTCATCGGGATCACGACCGTGTTCAGTGGTGACGGACAGTACCTCCTCGCCAACAACACCCAGGAAGTTCC
CAGCGAAGAGTACGTAGACGCATTGACTCAGTCTCTTAGCGAGACAGTATCAGAGCTTAGGAGCCGGTTCGG
TTGGCGCCCTAAAGATCGAGTGAGGTTCATATTCCACCAGAAGTTTAAGAAGTACAAAGACGCAGAGGCGGA
GGCGGTTGATAGGTTTGCACGCTCACTGAAAGATTTTGACGTGCAATACGCCTTCGTGCATGTGTCTGATTC
TCATAACTGGATGCTGCTGGACCCAGCTAGTCGGGGGGTGAAATTCGGCGATACGATGAAGGGCGTCGCCGT
CCCTCAGCGGGGACAATGTGTGCCCCTGGGGCCAAACGCTGCGCTGCTTACTTTGAGCGGTCCGTTCCAGGT
AAAGACCCCACTGCAAGGCTGTCCGCACCCCGTGCTGGTGTCAATTCATGAGAAGAGCACTTTTAAGTCTGT
TGATTACATAGCCCGCCAAATCTTCAATCTCAGCTTCATCAGTTGGAGGGGCTTTAACCCTAGCACCCTCCC
AGTGTCCATTTCCTACTCCGACATGATCGTAGACCTCTTGGGACATCTTAGACGCGTTAAGAATTGGAATCC
GGAAACCCTGTCTACCGCTCTTAAGGAACGAAGGTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
317 15 GGTGTCGTGAGGATCCATGCCCAAAAAGAAACGCAAGGTCGAGGACCCTAAGAAGAAGAGGAAAGTAGGGTC
TGGCTCTATGCAACTGAACTATTTCCCCATCCAGTTTGACTTTTCTGACTACCAGGTCATCACGCAGCCCTA
CTCCGACGAGAGATTGAAAGAACTCAGGCAGGCCTACAACGCCAGCTATTCCTTCTTTCGGGACGGCAACCT
TATCGTAATTTCCAATAAAGAGGACGAGGAAAACCAATTGACGGGCAACGTCGAAAACCGCAGCGTGTTCGA
CGATGCCAAAGTTACCGCCAGCATGGTCAAGCATATATTCTTTAGGACGTTCAAGGACAGGTTCCAAGGCTT
CATCCCCGTGGACTTTTACCCCTTCCGATTCTACAGCAGACAAGAGAAGGACGACCTTATTCTGAACCACCT
GCCCGAAAAACTTAAGCATAAAATCGCCTTTAAGAAACTGATCGAGGTGCAGCTCAGGGAGACGAATCTTAA
TTCAACCCAGGGCTTTGCTTTCGTCGTCAACATCAGGAGAAATTGGGTGTTTAACATTTCCTGTCTCGAGCT
TTATCAGGAAGGCTTTGACCTCACAGATTTTGAAGTGCTCCATGCGGAGACGCTTCCCGGGTTGGACAATAT
CCTGGCCCCGAACGAGGACTTCGTTGGCCTTCTCAAGAGCATCAACGGCGAGACTGCCATTGTGAGCACTAG
CGAGGGTGCCCGCTCCTATTCACTGCAGGAGCTCTTCATTCGCAAGACTAAGCACAACATACAGGCGTACCT
CAACTTCGCCACCGGGGAAAAAAAGTGCGACCAGATCCTTGCAGCCGTGTCCCAGGAACGAATCCGGAAGCA
GAACCCCGTGAATCAATTCAGCGAGATATCCAACATCGCGAAGCATCTTTTTTCAGACAAAGGCAATCCAGT
GCTGTTCCAGAATATGGATGGCTTTTGTTTTAAAGTTGACACCACGCCGATGCAGGTACAAAACTCCATGAA
CCTGCAAACTCCCACGTTCATCTACGACCACGCGGGTACCAAGACGAACACCCGCAACGCGGACCAGGGGCT
GAGCTACTACGGCCCCTACGATAGCCTCACCTTCGACATTAAGAAGCCAAGAGTTCTCTCTATCTGCCATAA
GACCAACCGAGGCTCCTTTACGCGCTTCCTCCACGACCTCAAAGACGGGCTCCCCAATAGCAGCTGGTTCAA
GAAGGGCCTCCTGAAGAAGTACGAGCTTCAAGAGGTGAATTACCTCATCCAGGAGATCAGCGACTACAGGTT
GGAGGACTACCTGGAAGTGATCTCAAACTACGATGATGAGAAGCCGCACCTGGCAATCATCGAAATTCCAGA
TAGGTTCAAAAAACTGTCCGACCGGGACAACCCCTATTTCAAGATTAAGGCAAAGCTGCTGAGCCTTGAGAT
TCCCGTACAATTTGTGCGCAGCACGACTTTGAGCAGCTACAGCGAATACATACTTAATCCGCTTGCATTGCA
AATCTATGCGAAACTCGGCGGCACGCCTTGGGTTCTTCCGGCCCAACGCTCCGTTGACCGCGAAATCGTTAT
TGGCATAGGTCACTCATGGCTTCGGAGTGGCATGTATAAGGGTGCTGAAAACAGCAGGGTGGTCGGCATTAC
TACGTTTATGTCTAGCGATGGCCAATACCTCCTGGGCGACAAGGTGAAAGACGTGCCTTACGAGTCTTACTT
CGAGGAGTTGCTGAAGAGTCTCAAAAGTAGCATAAGCAGACTCTCCGATGAGTATGCCTGGCAGGATGGCGA
CACAGTGCGCCTCATTTTCCACATCTTCAAACCCATCAAGAACGTTGAGTTCGATGTCATTAGCCAGCTTGT
GAAGGACATCAGCCAGTTCAACATAAAGTTCGCGTTTGTGACCATTAGCAAGTCACACCCGTCTATTCTCTT
TGACACGAGTCAGCAAGGCGAGAAAAAGTACGGCTCTAACCAGGTGATAGGGCAGTACATCCCTCAGAGGGG
TAGCAATATCTTCATAGATGACGAAACCAGCCTGGTGCAGATGCTGGGCGCCAGGGAACTTAAAACTGCCAA
ACACGGGATGAGCACCCCAATCCAAATCAAACTTAGGACACCGCAGGGTAACCATAACGACCAAGAACTGAA
GGATTTGATGTTTTACGATCTTAACTACATTACCCAGCAGATCTATAGTTTTACTTACTTGAGCTGGAGGAG
CTTTTTGCCACGCGAGGAACCGGCCACAATGCTCTACTCCAACTTGATATCCCGACTTCTTGGGAAGATGAG
GAGCATCCCTGAATGGGATGCGGATAAGCTCAATTATACCCTTAAAAGGAAGAAATGGTTCCTGTAGTAACT
CGAGGTTAACTTGT
318 22 GGTGTCGTGAGGATCCATGCCCAAGAAAAAAAGAAAGGTGGAAGACCCTAAGAAGAAGCGCAAAGTGGGATC
CGGCTCTATGTTGGAGACGAATATCAGGGTGGTGCGGCCTGGTCCGCAGCTGTGCGTTCCTGTACGCAGGGT
GATCGTGTCCGGTCAAACCTTGGCTCCCGACCTCCTGGAGAGGCTGTGTAACCTGCTGCGAAGGAGGTACGG
CATTAGCGCCGCAAGAATACCGGGCTCCGTGAGCGAGCTGTTCGTTGCGACCGACCGGCAGGTGGAGAAGGT
GACACTGGAAGAAGATAACTGGCAACTGACCGCCGTGGACTCCAACGACCCTACTCGAATCATGTCCATCTC
TAACACGGACGATGAGAGCTTTATAAGCATCCTGATCGAACGCGCGCTCCTTGCCCAGATCGCCAGTCGAAG
CCTCTTTTGGACCCTCGACTCTCCTCGAATTTGGTATGAGAAGAACCCGTTCCAAAGGAATGAAGGCGTAGC
CGTCTACCACAGGTACGAGGTGGATGCGCTCCCCCTCGGCGACGCAGGCATTGGCATCTCAGTGGATGTTTC
AACGGCCTTTTTTAGCGAGCACACCCTGGAGTACTACTTCGCCCCCAACCTGATTAGCGGCGAGAGCAAGAC
GCGACAGGACGAATTCCACAAGTTCACCGGCCGACAAGCTGGTCAAAAGGGGACGCTGCTTTACAATAACGG
CAGGAGTAAGGTGAAGTGCTATTTCGAGAACAATAGGGTGGGCCTGACATGTGGCGCAACCGGCCAAATGAA
ACTCGAGGGAATCACGTATCCCAGCCTGTACCACTACTATGCGAGCAAGTATAGCGCATTGCAGATCAACGA
GAACGATGCCGCAGTGCAAGTGTCTTTCCCTGGCTTGGACCGCCCAGTTCCGGTAGCCGCCAGGCTCCTGTC
CCTCCGAGTGATGAACGACGACGTGCCCGATGGTCTGAGCTCCGTCGACAAGATCCCTCCAAGGAACCGCAA
GTACCTTATCGAGCAGTTTTGGAAGTGCCTGGAGCCGAGACCCTTCGGGAATGTGGCCCCTGGTGTCTTCGA
CGGCTTCTGGAGACCCAACAACGAAAGGGTGCATTACATCCAGCTGCCCGAGATTAACTTTGGACAAGGCCA
AAAAGCAGAACCGCCTGACGTACGCTCCGTTGCATCCATCAAAAACTATTTTAGGCGACGACTGGAATTGCT
GGGTCACGCGGGGTGTTACCACTTTCCGCCCTCAGCCCCCAGGACAATCTTCTGCGCCTACCCGCAGTCATT
GGGTGAGGAGATCCCGGAAAAGTTGGTGAACGGGATCGTCAATGTGCTGAACAAGTGGACCGGCCTCAGCTT
CTGTAGCAACCTGGTAAGCTACAGCACGGCCAGCGAGGCGTACGGTAAATTGAGGAGGGCCGAGAGTGCCGG
CGTGGTCCTGTTCATCTTGGACGAGGAGCCGGCAGTCTACTACGACGCGAGCTTCAATCTTGAGGGCTGGAG
GGTAAAGCGCGTAACCGAGCCTGTGCTGCGCCAGCAGCATAAGTATCTGACCAACGGCGTGTGGGACCGGAA
GAGGCAAGAGTATAGTTTGGGGAGGGGGCAGAGTCGCTGGGAAAGCTTCATCAATTTGATCGGATTGGACGT
TATCCAGCAACTCGATGCCATTCCGTATAGGATCCCCAACATCGGCCCCTACGAAGGCCAGCTGATAATCGA
CGTGGGGCATGACAGGCAATTCTTCGCCGTGTCACTGCTTATTGTGAGATCAGAAGACAAAGTGCCCGCATT
TAACATCAGCAGCCAGGTCCAGCACAAGGCGGATCATAAGCACGAAAGCATTAACCCGGTGCTGTTGAAGGA
CACCATCATTAACGTGTTCAAGACCGCCAAACGGAGGACTTTTGATCCTCTGACTAGCCTGTTGATCATGCG
GGATGGCAACGTGCAGGGCAGCGAGATCGGCGGGATAGACAACGCCCTGGTCGAACTTAGGCAACTTGGCAT
AATCTCCCCCGATGCGAGGCTGGACATCGTGGGCGTACACAAGGAATCTGTAAGCTCCATCAGGCTCTGGGA
CGTTGACGTAAGGGGGGAGGTAAGCAACCCGATCGAGGGCACCGGTCTGTCAGTCAACTCATCTCTGTACCT
GGTGGCGTGCACAGGTGAGGCCACGCTGACCCAAGGCACCGCAGAGCCCGTGGCCATCGTCGCAAACAACAG
GTGCCTGAGTATTGCCGATGCAGCCCTGAGCGCCTTTCTGGCAGCCCAACTGAACTGGAGCAGCCCGGGAGT
CGCCCAGCGCCTGCCCCTGCCTCTGAAAAGAACAGATGAGGAACTTACCGCTAGGAGCGATCAAGAAATTAG
GAGGATAAGGTAGTAACTCGAGGTTAACTTGT
319 32 GGTGTCGTGAGGATCCATGCCCAAGAAGAAGAGAAAGGTGGAGGACCCGAAGAAAAAACGAAAGGTTGGCAG
CGGCAGCGTGCAGCAGACAGTGGAGCTCACCCTCTACACAGAAAAACATCCCGACACCCACCCAGAGCTCGT
TTATGCCGACGAGTGTCCCGACCTGTGGCAACAGCACAGCGAGCTTACGGGGGACAAATCTCTGTTCTACTC
TCTTACGAACCCGGCAGAATGCAAGGGAACCCAGTACACAGTGCAAATCAACCTGAATAACCAGAAGCAGCG
AAGGATCGCCAAGCACATAATTAGCCAGCAACTGTATAATCACTTCCGCCAGACCCAAATCGCTACCTTCGA
CAAGATCGACAATGTGGAGGTGTGGACCAAGAACACCCAACAGCCTACCCAGAATTGCACGGAGTACCTGAG
GTTCAGCCTTATACCCCAATACGCCGTGTTCTCTGACTCATGGGAGCTGGTCGTGTCCTCAAATGGCATATC
CACCGTGTATAACAAGCCTTTGAGCGCACTGGACCTTCAGACCGACCGATTCAAGGTCGTCGTTGGAGGGGA
AGTGGTCAAGTACAAGAACCTGAGCCCCAATCAAAAGCAACAAATAGACGAGGCCTTCCCCAAAATCAATAG
GGAACTGGCCGCTGAACTGCATATTAACGAGAAACGCTTTCTCAATAAAGACAAGTATACGACCACCTACAA
CCACATTAACAACTTCGTGCGACAGCACCTTCTCACATCCGAGTTCCAGGCACTGTTTTGTCTGAGCGGCGA
GATGTTCAACGTACCCGAGGAGCGGATCGGCCAAGTGGCGAAGGGGGCGAACCTGTTGCAGTTTAAGGACGG
CAAGACCGGCATTGACCCATTCAGCTGTGTGTTCGGCAGCAAGAGCATGGACGCACTCGGCATCTACCAACC
CAGCCTGAAGCCCCAGGTGAAATTCTTTTTCATCGCCCAGCAAAGCGATATCAACGTGTGCAAAAGCCTGTA
CGATATTTTCACGAAGGGATACAAGCCCTACGTGGACACAGCCACTGGCGAGCAGAGGTACGTGTTCCCACC
CCTGGCGACGTGCATCAAGCAGCCCTTTTCAACCGACCCCAAGGGGAGCATTTACTTCAGCGACCCTCAAAA
TGCCCTGAGCGAGATCAAGAGCCAGCTTAACAATAAGCCTCTTGACCCCCAAACGCAGTATGTGAGCATATA
CGTGTCACCCATCCCTCGCGACGCCGTCAACAATCCCTACTACGGTCTGTACTTTCAGATTAAGGAGCTGCT
GCTCGAAAAGAGGATAACGTCTCAGGTGATCTATAAGGACCGCCCCAACAACCAGTACTTCAACTTCCATCT
GCCCAATATCGCGACTGCCATCCTGGCAAAAATAGGCGGCATCCCGTGGCAGTTGAACTCCCACACGACGAA
CAAAGATCTGGTGATAGGCGTGGGCGCCTTCCTTAGCGAAAAAGTTGGCGAGAGGTATGTGGGCAGCGCGTT
CAGCTTTAACCCCAACGGCCTGTTTAAGAACTTCGACTGCTGTAAAGCGAACGATCTCGAATCTATCGTAGC
CGGGATCAGAAAGGCCATCGGACACTTCGTTGTGGACAGCGAAACAAACCCCCAGAGGCTGATCATCCACTA
CTACAAGACCATGTCAAAGAGGGAGGCCAGGCCCATCACGCAGATGCTGAACACGCTTGGCCTCAACATTCC
TGTATTGATCGTCACAATAAACAAGACGGAGACCAGCGACATTGTTATGTTTGATGAGAAACAGCAGGGCTA
CATGCCCCTTTCAGGCACCGTACTGAAGATAAGGAACGATGATTTCCTGCTCTACAACAATAGCAGGTACAA
AGAGAACGAAAAGTCAGATATGCTTTTTCCAGTGAGGATCCGCCTGAGTAAGATCGTAAACCAATCCGACAA
AGACATCCCAATGACAGACGCCTTCAATTTGCTCAACCAAGTGTACCAGTTCTCACGCATGTATTGGAAGAG
CGTTAAGCAGCAAAACCTGCCGATCACGATAAAGTATCCAGAGATGGTGGCCGAGATAGTGCCACACTTTTC
AGAAGCCGAATTGCCGCAGTTCGGAAAGAATAATCTGTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
320 91 GGTGTCGTGAGGATCCATGAAAATTATAGATAAGGAAACCTTCATCAGAAGTTTTAAAGTTTTGAGCAATCA
ATCCTTTGACCTGTTCCTGGGCGCTGGCGCCTCCATATCTAGCGGTATCCCTTCCGGAGGCGACCTCGTCTG
GCATTTTAAGCGCGAAATACTGAATTCCAACGGGAAGATAAATATTAAAAAATTTCAAGATCTTAAGATAGA
AGATAATAAGAAGGTTATACAAAGTTTCTTTGAGGAGACTGAGGAGAACAACATTATTAATCCTTATTCCTA
TTATTTTAACAAATGTTATCCAGACCCCTTGATAAGAAAAGAATTCTTGACGAATCTTGTGAGGGACAAGAA
GCCTTCCATAGGATTTATGTGCCTGTCTGCTCTCGTGGAGCAGCAAAAAATCAACACAGTATGGACAACTAA
CTTCGATGACTTGATTGAGAAGGCGATTAACGGATTGAATTACAAGTCCTGTCAAATTGTCTCACCCGAGAA
TGCGGGCAGCGTGAATAACTTTCGAACTGATATCCCCACTGTTGTTAAGCTTCACGGAGATTTTAGGTATGA
CCCACTGCAGAATACTGACGAAGAGTTGCAGAAACTCGAAGAGTCCTTGCATAAGTATTTCGTAGAGGCAAG
CACAAAGAGGGGACTTCTCGTAATGGGCTATTCTGGGTCAGATGAGTCTGTGCTGCAAAGCCTTGAGAAGGC
GCTGGAAGAGAACAACGCGTTCCCTAAGGGACTCATTTGGTGCATCCCCAAAAGTGTCACCCCAAACCAACG
ACTGGTCCGAATTATATCTAAGGCTAATGAGCAGAACCAGCGGTCCGGATTTATGATTATCGACAGTTTCGA
TTATTTCTTGCATGAACTCTACAAAATATGCGACCTTACGAATGACTATATCGACTCTATTACCAAGGAGAG
ATTTGAAAAAAGGCAGTCATTTAGGCTTAACCAAACTCCGTCCTCTACTCTGCCAATCTTGCTGAACGCAAT
AAAAGCAAAGCACTTCCCGAAAAGTACCTTTCTGACTAAAACGAATATCTCAGGCATAGGTAAGTGGAAACG
CTTGCGAGACGCTATAGGAAATAGCTCTATAGTCGGATCTTTCGGTAAGAACGATTCTCTCAGACTTTTTGG
AAGTGAACAAGACATTAATAATGTACTTAAGAACTACTTGATTGATGATTTGAAGATCAGTGATATCCCAGA
GCACCTTTTTTTCCATTCTGATTCATTCTACATTGGCATGCTTTATGAACTGATTGAAAAGTGTTTGATTAA
AGATTATGGGCTGTCAGTATATGCAAAGGGGAGAACTATCAGAAAGTTCTATTCAATCAATAACCCGCTGCC
GGAATCTGAAATCGCAGATATTAAGAAGAGAAACAATAATTTTAACATCGACAAAAATATAAATGTATTTGA
GGCGTTCGAGTTCTCCATAGAATTCATTAATAAGGAGCTGTTCCTGTTGCTGTGTCCCACCATACATATTCA
GACTAAACTCGGAGGTGAGGTCAATCGCAATATCTCTCAGTACCTGTCAAACACAATCATCAGCAATAGGTA
TAATAACAAATATGGGAAAAAGCTGAATTGGTGGATTAACGAGCTCAAGAAGTATAACAAGGACTTGGTTTT
TAAATTGGGGGACTTTGAGATACGATTGACAGATTATTACTCCACGAGCGCTAAGCGCGTTAAAGATGACAT
CTACTGTTTTGACGGATTTACTAAGTTGAGTGAGCCCAGTATATATTTCCACTATCAAGACGAAGCAAAGCA
GAGTATCCATCCCATAAGTGGACTGAAGATACTCGGTCCATTGGAAGAATCATTCGAGGCAAACGGTACATC
TTCCACAGTCAACCTTGCCATCATTACTCCGGACTTTGGCTTCTCCAAACTCAAGGCGCACCTCGAAAGTTT
GCTTAATACAATTTCCCCTATATGGGAGAAGGAATACTTGAAGGAGTTCCCTGGTTTCGATAACGTTTTTAA
GAAGCACCTGATAATACCCAATTCTATTCAAAGCGAGTATGTAATCAGCATACCTAATAATGATGTAAAACA
GTTCTCAGCAATTCAATTCTACGACTACCTGAAGAGTAAGATCGACCGACTCGCTCTGAAGTCCAATGACAT
TGATTGTCTTGTAATATACATACCCGACCAGTGG+AGAACTTCCGAGAGCTGAAAAATGAAAACACATATTA
TGACCTTCACGACAGTCTTAAACTCTACTGCGTAAAAAAGGGGTTGCGAATCCAGTTCATCGAAGATAAAAG
CATTAATTATAAAGACCAAGCCAAGATCCGGTGGTGGCTGTCTCTGGGGCTCTACGTGAAGTCTAACGGCAC
TCCCTGGAAGATCAAAACAGATAATACAGAGACTGCCTTTGTGGGCCTCGGTTACGCTATACGACAAAATGT
TAAGAATAAGGTTGTTCTCGGGTCTTCACAGATTTTCGACGGTTATGGGAATGGTCTCAAGTTTCTTTTGCA
GCCCATAGAGAAGCCAATTTTTTACAATAAAAACCCCTTCATGAGCAAAGAGGACTCTTTTCGGCTTATCAG
TAATATACGAAACACATATCATAAGATCGATCCAGTTATCGGACTTAAGAAACTCGTGTTGCATAAGACAAC
TCATTTTACTTCAGAGGAGATGGAGGGGATCTCTAATGCTTTGGAAGGCATAGACAATATTGAACTCTTGCA
GATTCAGCAATTCTCATCATGGAGGGCAATTAAGCTTATGAAAAATGCCACAAAGCACGATTTTAATGGTTA
TCCGATCGATCGCGGAACTATAATTCAACTCGACGACTTCTCTTTCCTTCTGTGGACACACGGGCTTATAGA
GAACCAAGAGCTGAACGGTAAGTACTACCAGGGAAAAAGAGGAATACCGGCTCCGCTTCTTATTAAGAGATT
TAGAGGCACGGATCCAATAGAGACGGTGGCAAACGATATTCTTAAGCTGACCAAGATGAATTGGAATGGTGC
AGAGCTCTATAAAACCTTTCCTGTAACGATTGATTTCAGTAAAAAACTTTCAGTCATGGGGAAGTAGTAACT
CGAGGTTAACTTGT
321 0 GGTGTCGTCACGATCCATGCCAAACAAAAACAGCAAACTCCACCATCCCAAGAACAAACGCAAGCTCCGTTC
CGGTTCTATGCCTTCAGCTCAACGGTGCATCTGGGAGTGGAAGAGGGATATCTTCGTGACCAAGAATCCGAC
GCTCCGGCAGTCCGTGGATGAACTTAGCTTGCCAGGGACCAGGCGCATCGTACAGGGATGGATCGACCAGCA
AGCCCAATACCCGGAAGATGGGTCAGCAGACGAATATAGCTTTTATGCCGAAGAGTGCTACCCAACCTCTCA
TGACCGGCGAGCGTTCTTCCATCGCTTCATTGCCGAGGCGAGACCGCATATCGGCTACAAGCTGGTTGCGCA
GrTGGCAGAAGCAGGGTTCTTGAGAACCATTTGGACGACCAACTTTGACGGACTGGTTAGCAGAGCGTGCAC
AGCGGCTAACGTCGTGTGCGTGGAAGTGGGCATGGACACACCCCACAGGGCCTCACGACCGCAAGGGGATGA
CGAAGTCAGACTGGTGTCCCTCCACGGTGACTTTAGGTATGACCTGCTGAAGAACACCGCCAATGAGCTGCG
CGAGCAGGATTTGGCCCTTAGGGAGGAACTGCTGCACGAACTCAAAGACTACGACCTGGTGGTCATCGGATA
TTCAGGGCGGGACGACAGCCTTATGCAAGTGCTCTCTGCTGCCTACAGCGACCGCGCATCTTGTAGGCTCTA
CTGGTGCGGGTTTGGCGCGGAACCAGCACCGGAAGrGAGGCACCTTATTAAGAGCATCGACCCAGCCCGAGA
GAGCGCGTTCTACGTGGATACCGCCGGATTTGACGACGTAATGAGCAGGCTTGCACTCAGGCGACTGAGCGG
TGAAAGCCTCGAAAGGGCCCAGAAGCTCATAGAAAGCGTCACCCCGGTTGCTGGCAAAAAGATGGCCTTTAG
TGTTCCACCATTGGCCCCTAGCGCCTTGGTGAAGGGTAATGCCTACCGATTGACCTGTCCGGCAAACGTCTT
GAAACTTCATATCGAACTTCCCGAGCACGGTTCCTGGCGCGATTCGCTGTCCGAACGAATCACTCCACAAAG
GGGGCAGGCCGTTGTGTTCGAGAAGGGAGCACTGGTTTTGGCCGACATGGCGGTTACCGCTAAAGTTTTCGA
TGGATTTCTTAGGGTGAGCCCGACACGGGTGGAGATAAGTGACGAGAACATCATCGCTGACGGCCGGATCGC
CAGTCTTTACCGACGAGCTCTCGTGAGCAGTGCCGCAAAAGCGCTCCAGATCCAAACCGACCACAGGAGGAG
GATATGGGAGCCCGTGCACTATGATACAAGGCAACrCGACGATGTGACGTACCGCGTGCATCGAGCCGTCTC
CCTGACGATAGTAGGGATAGAGGGAGTGCCCCATGrGGTGCTGATGCCAGAGGTCGTCGCArCTACGTTGGC
GGGCGACCTTGCGCCGGTTGACAGTCAAAAGACTCTCCGCAATGCCATTTACGGGTTCCAACATAACGATAA
GTTTGATGCCGACCTCAGCTATTGGACCCACCGCCTTGTTGAGAAGGAGCTGGCTTCCAGCGGCGAGGGCGT
TTTCGrATTGAGCAAAGTGCCACTTTATGCGGGCCrGGCACAAAAAGGTAAAGCTCCTCTCCCACACAGGTT
TGCACGCCACGCTAAACAGCATGGAArTATrGTGCCCGACGCACCGCTTGTTTTCAGCGCCAAGGrTGGCTC
TGGAGAGGTACGAAACCCCAATCCGCTGCATGGGCTGGTGCAAAACCGGCCATGGGACCACTCTCTTACGGC
GTCTGGTTTGTGTCCGAGTACAGATGCTAGCGTGATCTGCCCCGCAGACGCTGCTCCGAGGTTTGAGAGATT
CCTCCAATCTATGCAGGAGGTAGCAAGACCAAGCCAGAGCGAGACGGACTATTTGCATGATTTTCCCGGCTT
CCCTGCGGCCTTTGGACTGCCACTCCGAATGCCCGrGAGAGGGGACGCAAACTGGATTACCATCGACGACGG
AGTGAGCACCGATGCCCTGACAGGGGCTAAGCAACTGGCGCACCGAGTGTGCCAAGCACTCGACCACCTCCG
CAGAGCAAGGCCCTCTGACACGGCGATCGTGTTCGrTCCCAGGAGATGGGAACCATATAAGGTAGrGGACAC
GCAGCACGAAAGATTCAATTTCCACGATTACATTAAGGCCTACGCGGCCAGGCACAGTCAGAGCACGCAGTT
CGTCAGAGAAGAGACCATCCAAAGCCAATACGTGTGTAGGGTCCGGTGGTGGTTGAGTTTGGCACTGTATGT
TAAGGCTATGCGGACCCCCTGGCGGCTGGATGCGCTTGATGAGAATACGGCTTTTGTTGGTATAGGGTACTC
CCTGGACCCAGACGCAGGGACGGGCAACCATGTACTGCTCGGCTCCAGCCACCTGTATTCTGCGAGGCGTGA
GGGATTGCAGTTTAGGCTGGGCCGAArCGAGAATCCCGTGGTGCGAGGAAGGAACCCCTTCATGAGCGAGGA
CGACGCAAGGAGGACCGGAGACACCATCCGGCAGCTTTTCTACGATAGCAAAATGCATATTCCGACAAGGGT
GGTGATACACAAGAGGACAAGGTTCACTGACGAGGAGCAGAGGGGGTTGGTACAAGGATTGGACGGTGTGAG
GAATATCGAGCTGATAGAGATCAACCAGGAAGAGAGCTTGCGATATCTCAGCAGCCAGATGAAGGACGGCAG
ATTTGAGATCGACAAGTTCCCCCTGTTCAGGGGTACCACAATAGTTGAGTCAGATGACACTGCATTGCTGTG
GGTGCATGGAGCCACACCCAGCGCCGTGAACAAGTACTGGAGGTACTACCAGGGGAAGCGCCGCATTCCGGC
GCCATTGAGGATTCGAAGGTTCCTCGGGCAAAGCGACGTAGTGCAGATCGCGACCGAGATCTTGGGACTGTC
TAAAATGAACTGGAATACGCTTGACTACTATTCAAGGATGCCTGCGACTCTGGATTCTGCAGGCAGTATTGC
CAAGTTCGGGTCATATCTTGATGGGTTTACGAGCGCACCCTATGATTACAGACTTCTGATCTAGTAACTCGA
GGTTAACTTGT
322 6 GGTGTCGTGAGGATCCATGCCTAAAAAGAAACGCAAGGTAGAGGATCCCAAGAAGAAAAGGAAGGTGGGGAG
CGGGAGCGTTCACGCATTGCTCGCTCTGCTCGCGAACCGAGCCGGTGGAAGGACCGCCAGAATGGGAGACAG
CTTGCTCACGTGGAGCCCTCCTGAGTCTCTGCTGCTTGAAGGGACCCTGAGCTGGCGCGGCAACACCTACAC
ATACCGGCTTCGCCCACTGGCGAGAAGGGTGCTCAACCCTAGGAATCCCAGTGAGAGAGACGCCTTGTCCGC
GTTGGCGCGACGACTCCTCCGAGAAGTGCTTGAGCAATTCAGGCGCGAGGGGTTTTGGGTTGAAGGTTGGGC
CTTTTACAGGAAGGAGCACGCACGGGGTCCCGGGTGGCGCGTGCTGAAAGGTGCGGCGCTGGATCTGTGGGT
TTCAGCCGAGGGGGCCATGGTATTGGAGGTGGATCCGACTTATCGAATCCTGTGTGACATGACACTCGAGGC
GTGGCTTGCACAGGGACATCCACCCCCGAAACGCGTCAAGAACGCGTACAACGACAGGACATGGGAACTCCT
GGGTCTGGGTGAGGAGGACCCGCAAGGCATTCTTTTGCCAGGCGGGCTGAACCTCGTCGAGTACCACGCTAG
TAAGGGCAGAATCAGAGACGGCGGGTGGGGTCGGGTTGCGTGGGTGGCAAATCCTAAAGACGCCAAAGAGAA
GATCCCGCATTTGACGAGCTTGTTGATCCCCGTCTTGACCCTGGAAGACCTGCATGAAGAGGGGGGCTCTAA
CTTGGCCCTCTCCATCCCGTGGAATCAAAGGCAAGAGGAAACCCTTAAAGTGGCCCTGTCCGTGGCTCGCCG
ACTCGGCGTCGAACACCCCAAGCCCGTCGAGGCCAAAGCCTGGAGGATGAGGATGCCAGAGCTTCGCGCACG
ACGCAGGGTGGGTAAGCCAGCGGACGCCCTTAGAGTGGGGCTGTACCGGGCTCAAGAGACTACCCTCGCACT
GCTTCGGCTCGATGGCGGCAGAGGATGGCCTGACTTTCTGCTTAAAGCATTGGAGAACGCTTTTAGGGCCAG
CCAGGCTAGGCTTCATGTTAGGGAAATCCACGCGGATCCTAGCCAGCCCCTTGCATTTAGAGAAGCCTTGGA
AGAAGCGAAAGAAGCAGGTGTGCAGGCTGTCCTCGTACTCACCCCCCCACTGAGTTGGGAGGAGCGACACCG
CTTGAAAGCACTGTTCCTCAAAGAAGGACTCCCAAGTCAACTTCTGAACGTCCCCATACAGAGGGAGGAAAG
GCATCGGTTGGAAAACGCCCTGCTCGGGCTCCTGGCGAAAGCGGGTCTCCAAGTAGTCGCCCTTGAGGGCGC
ATACCCTGCTGATTTGACAGTTGGATTTGATGCCGGAGGCCGCAAGTCCTTTAGGTTCGGAGGTGCCGCATG
TGCTGTCGGCTCCGACGGAGGTCACTTGCTGTGGAGTCTGCCGGAAGCCCAAGCGGGCGAACGGATACCAGG
CGAAGTAGTTTGGGACCTGTTGGAGGAGGCGTTGCTGGTGTTTAAGAGAAAAAGAGGGCGGTTGCCCAGCCG
GGTGCTTCTGCTGAGGGATGGCAGGCTTCCCAAGGACGAGTTCACCCTGGCACTTGCAAAGCTGAGGCAGCT
CGGCATTGGCTTCGACCTCGTGTCCGTAAGGAAGAGTGGAGGCGGAAGGATTTATCCGACCCGGGGAAGATT
GCTTGACGGCCTTCTGGTGCCCGTTGAAGAGAGGACTTTTTTGCTCCTGACGGTGCATAGGGAGTTCAGAGG
CACCCCACGGCCCCTCAAATTGGTACACGAAGAAGGTGAGACACCTCTGGAGGCTCTCGCAGAGCAGATCTA
CCACCTGACGAGGCTGTATCCTGCATCAGGTTTCGCATTTCCCAGACTGCCCGCACCCCTGCACTTGGCAGA
TAGGCTCGTGAAAGAGGTGGGCCGATTGGGCGTGAGGCATCTCAAGGAAGTAGACAGGGAAAAGCTGTTCTT
TGTATAGTAACTCGAGGTTAACTTGT
323 50 GGTGTCGTGAGGATCCATGCCGAAAAAGAAGAGGAAGGTTGAAGATCCCAAGAAGAAACGAAAGGTGGGGAG
CGGCAGCGTGAGGCTGGTAAACCAGAAAGAGAAACCGGAAGGCGACTACGTGTATGGCTACACTCTCCCAAT
AGACCCCAGTAACAGGAACATGAGGCAGCCCTTCTGGATAAGCATGGATAAAAAGGAGGGCTATGAAGCTCA
TTTCGTTGGCCCCTATGAGAACATTGAGTTGACCAAGAGCGTGATCTTCTGGGACCTTCTGAGGAGGACCAG
GGAGCAACTCAGCAGCGATAAGTTCACGGAATCAAGAAAAAAGTTCTTTAAGGAGATCTACTTCCCCCTTAA
CCTCTACAATGAGGGCAGCCAAGGGCTCGCCGTGCAACCCTACTACCTGAAGATTGATCAGCAATTTGGACT
GCTGGTGGATTTTCAATTCAAACTTGACAAAGATTTCACCTTCAGCCGGAAGATTCAACAGCTCAGTCTGAC
ATTGGATGGGAAGAACCGGAGGAACCTCAACTACTACGTCGACAGGATAACCAAAACCAACCAATTCATCAA
GGCCCTCTGGAACATCATTGGCACCTTCTCCCATAATGAAAACAAGGAAAACTACACGCTGAGGAACGACTT
CTACCCCTGCGCCGCAAGCAGGCTGCGGTCTCGAATGTATCTCTTTTCCAATGGCAGTGAATCCAGGAGCCA
GTTCAATGGCTTGAAGGAATACGGCCCACTCCGACCCCTGACAGCCAATCCGACACTGCTGTTTGTGTTCCG
GGAACAAGACCGCGACGCCGCGAGAAAACTGGCGATGGCACTTAAAGGCAGCAAAAAGCAAGATCAATACAG
CTTCCCCGGGTTCAACTCCCTGTTTAAAGCGGACCTGTTGATCGACGGAAATCCCATGGTCTTGAAAGACTT
TTCTATCGAGAGCAGCAGGGAGGTGTTGGCCAGGGTGACAACATCAACATCCAGCTTGTTGCCCATTTTCAT
CCTGCCCAACCGCGAGGGCGACGGCTACCTGGAGCACAAAGCCATCTTCGCCGAGAACGGCATACCTACTCA
AGCGTGCACACTCCAAGTCATTCAGGACGACGTGACCCTTAGGTGGAGCGTCCCCAACATCGCCCTGCAAAT
ATTCTGCAAAGCGGGTGGCTGGCCCTGGAAAGTGCAGAGCCCCGTAACCGACAACGCCCTGATTATAGGCAT
AAGTCAGAGCCACAAGTTGAATTATAGTGACGGTAAGACAACTGTGGACAAGCACTTCGCTTTTAGCGTGCT
GACTGATTCAAGCGGCCTCTTTCAGAAAATTCAGGTGCTGAGCGAGCAGAAGACGGAGGAGACCTACTTCGA
ACAACTGAAGCTGAATCTCAAAAGCATCCTGAACGCCAATAGCAAGAACTACCAACGCATCGTGATCCACAC
CTCATTTAAGCTCAAATACAAAGAAATAAGTGCAATCGAGGAAGTTGTTAGCGAATTTGCAAGGAACAGCAA
CAGCGCCGACTGCAAGTTCGCCGTTGTGAAGGTTAATCACAAGCATAGGTACTTCGGGTTTAATCGGGAAGT
GAATAGCTTGGTGCCCTACGAGGGAACCGTGTGTAAGCTGGGCGATAGAGAGTACCTGGTCTGGTTCGAGGG
TATCTATCAGGAGAAGCCGACCGTTACCAAAGCATTTCCGGGTCCCACCCACATCGAATTTCTTAAAATCGG
GTCTAATAACGTGATTAGCGACGACCTTTTGTTGCAAGACCTGATGAACTTGAGCGGAGCGAACTGGAGAGG
CTTTAATGCGAAGAGTGCTCCGGTATCCATCTTTTACTGCCACCTGGTGGCCGACATCGTGCATGATTTCCA
AATCAAAGGCCTCCCTATGCCCGCCATAGATCTTATACGACCCTGGTTCATCTAGTAACTCGAGGTTAACTT
GT
324 11 GGTGTCGTGAGGATCCATGCCTAAGAAAAAGCGAAAGGTCGAGGATCCAAAGAAGAAACGGAAGGTGGGCAG
CGGCTCCATGCAAGAACACCTGAAGACGAACATACTGAACTTTAAATGGCCCAACTCTGCTCCGACCATCTA
CCTGACATTGGAGGACATTGAGGGGAGCCACCCTATCCACAAAAGCAAATTTTCTAGACAGATAAAAGAAGT
GTTCCCCGACGCGGATTTGAGTAACAAGGACCAGATCTTTACGACATTCACGACCGAAATCCCAGACGCCCC
AAGCATAAAACTCTTGAACGTGGACGGCCGAGAATTGCGGATCTATAAACAGTTCCTCAAGCACAAGCTGCG
GTCATATTTCAAATCTAAGGACTACATCGTGGTCAAGAATTTCGTGGGCGACGTTCAAGTGTGGATGCCGAG
CAAAAAGGGTAACACCGCAGATTACAACCTGTACTATAAGTTTAGCTTTAAGATCCAATTTGCCAAACTGAC
GGACCTCCCCGAGCTGATCGTAAGCTACGATGGCACCTCCAAGGTGCTCACGACGTCCGTTAAGGACATCGA
AGATTCAGAGCTCATCAAGCGATGCGTCTACGGCCAAAAGACGTTTAACTACCAAATGGACTTGGACACCGA
AGAGAAGCAAGAGTTTTACAACGCGATACAGTTTGACCAGGCCTACCCAATTTTCAACCTTTCCCTGGCAAG
GGCACTCGACATCCCCATAGAGGAGCCAATAAGGCCGATCAACAAATACCAAAAATACGTAGCCCTGATTAA
CAATTTCGCAACTAATTACCTTTTCAAGGAGGACTTCAAGGTTATCTTCCCGTTTAAAACAGACACGTTCAT
CGACGTGCCTATAAATCGGATAAATCACATCGACCCCCAAGTCGGCCTGTTGGAATTCGGAAAAGATCAATA
TGGCAACAAGAAAACCCACCTGGTACCTAAAAAGGCAATGAACATCTTGAATCCATACCGGCGACCTAATAA
TCAGAACATCAAAATCTTTTTCATCTGTCACACAAGCCACAAAGACTCCGTGCTCAGCTTCTATCAGAATCT
GAAGGAAGGAGTAAACACGGAGAAGAACTACTACAAAGGACTTGAAGCCTACGTGAACATTAAGGCAAGTAG
TAGCAAGGAGCATTTTATCGAGTTCACGAACGAGAATGACCCCATCCCGGAGATCGTGGAGAAGCTTGAGAG
CCTCACATTTGATCATGACAATGTTCTCTACGCGGCGTTCTATCTCTCCCCCTTCGACAAATTCACCCAGAA
TCCGGAGGACCGGGAAATTTACATCCAAATAAAGGAGTTGTTCCTGAACGAAGGTATCGTGACCCAAGTTGT
CGATTACGAGAAAATGGTCGTCAATATCGAGAATCAGTATAACTTCCAGTTCAGCCTGCAAAACATGGCCCT
CGCCATTCATGCTAAGCTGGGCGGTGCCCCGTGGAAGCTGGCCGTGACCGACAAGAAGGAATTGGTCATCGG
GGTTGGAGCGTTTACAAATCAAGGCGAGAACAGACGCTATATTGCTTCCGCCTTCTCCTTTCAGAATAACGG
CCTCTTCCGCAAGTTCGAGTACTTCGATCAAAGCGAGACCGACCTCCTGGCTGGCAGTATCTGCAAAGCCAT
CCGCGACTTCACCAGCGTAGCGGAGGCAGATAAGGTCGTTATCCATTTCTATAAGGAGATGAGTTACGAGGA
GCTTAAACCCATCATTCGGGGCATGCACACGCTTGGGCTGAAGATACCCCTTTACATACTTAACATAAACAA
GACTGAAGCCGAGGATATTATCGCCTACGACCTGAATTGGAACAAAAAGCTGATGCCCGTCAGCGGCACCTA
CATTCGCATCTCCGAAAATCATTTCCTGCTCTTCAATAACGCACGATATCCTAATTCCCAACGGTACGCCGA
CACGGATGGTTACCCGTTTCCCATTAAGATTAAGGTCAGCTCTCCGGACGAGGATGCCTTTGAAGATGCAGA
TGTGGTCCTGGAGCTGCTTACTCAGGTTTATCAATTTAGTAGACTGTATTGGAAAAGTCTTCGCCAACAAAA
TGTACCTATCACCATCAAGTACCCAGAGATGGTAGCCCAGATTGCCCCCCATTTCAACAACGGGGTGCCCGA
CGATGCCAAGGATGCTCTGTGGTTCCTGTAGTAACTCGAGGTTAACTTGT
325 48 GGTGTCGTGAGGATCCATGCCCAAGAAGAAGCGGAAGGTGGAAGATCCGAAGAAAAAGAGGAAGGTTGGCAG
CGGGAGCATGACTGAGGACTTGTACCTCGACTACGACGCGTTCCTGCGGAGCTTTAAAAGAAACATAGATGT
GCCGCACTCCTTTCTCCTGGGAGCAGGTACATCCATTAGCAGTGGCATCCAGACCGCCTACGATTGTATCTG
GGAGTGGAAAAAGGACATTTACCTCTCCAAGAACATCAACGCCGCTGAGTTCTATAAGAACCATAAGGACGA
GGCGGTAAGAAAGAGCATCCAAAAGTGGCTGGATAACCAAGGTGAATACCCAGTTCTCGACAGCACGGAGGA
GTATTGCTTTTATGCCGAAAAGGCCTATCCCATCCCCGAGGACCGCCGCAAGTATTTTCTGTCTCTTATCGA
AAATAAGGAGCCCTACATAGGGTATAAGCTCCTCTGTCTGCTGGCCGAGCGCAGCATTGTAAAGGCTGTCTG
GACTACTAATTTCGATGGCTTGACCGTCAGGGCTGCTCATCAGAACAAGTTGACGCCCATTGAGATAACCCT
CGATAACTCTGATAGAATATTTCGCAACCAGTCTACCAAGGAATTGCTCACAATTGCGCTGCATGGTGACTA
CAAATTCTCTACGCTGAAAAATACGGAGAAGGAGCTCGACAACCAGAACGACACATTCAAACAGCAGCTGGG
GACGTATCACGTGGACAAGAATATGATCGTAATAGGCTACTCAGGGCGCGACAAGAGCCTCATGGACGCCAT
CAGCGAGGCCTTCAGTACGCGGGGTGCAGGGAGGCTTTATTGGTGCGGCTATGGCGAGACGATCCCCAACGA
GGTTAGCGAGCTCATACTGAAAATCAGGTCCCAGGGTCGCGATGCATACTACATATCAACGGATGGATTTGA
CAAAACGCTGATACACCTGTCTAAAAGTGCGTTCGAAGACAACCCCGAGATTACGAAAAACATCCAACTCGC
GCTCGAAAACAGCGCGGACGAAGAGTACTTTAAGACTGACTTTTCACTGAACTTTAGCAAGCCGGATAAGTT
CATCAAGTCAAACCTCCACCCCATCGTGTTCCCGAAAGAAATCTTTCAATTCGAGCTTGACTTCAAGGAGGA
CAAGCCTTGGCAACTCCTCAAAACTATTTCACGCGAGACAAACATTTGCGCCGTGCCGTTCAAGGGTAAGGT
GTTCGCACTGGGCACGCTTACTGACATTGGGAACGTCTTCAAGAACCGCCTGAAGAGTGATATAAAGCGCGA
AGCAATTAGCACCTCCGACGTGGATAATGTGAGTGCCTTTAAATCTCTGATGCTGCAGGCTGTGCTGAAGTT
TTTCATTGGTATCGAAGGCGTGGAGTCCAACCTCAAAGACAGATTGTGGCTTACCAACGCGGAGCAGCTCGT
GGGTGATATTAGTGTGCATAAGGCTATCCACCTCAGCCTGTACTTCGACAAAAACAAAGGATTCGCTTACCT
GTCCTTCACCCCCACCGTACAACTCATCTCTCCTGAGGAAATCAGCAAAATCCAGAAGCAGAGAATCTCTAA
GAGTAAACTCGAGAAGCTGTTCAATGACAAGTATGACGAGATATTGGAGTTCTGGAACCAAAAGCTCTTTAA
CAATAGCCAAATCAAGTTCGAGTACCCGATCAGCTCAGGTAGTGGGTTTGAGTTCAAAATCTCCGCCAACAC
CGCATTTGGGGAGATAAACGTATTGGACCCCAACTTTCGCTCCTTTTCCCCTAGAAATTATGACCCGAAGCG
CACACAGTTTAAGGGCGTGCAGTTCCTCGAACCGCAGCTGATATTCCGCAACATCAGTACTAATGTGGAATT
TAAGGACTACCACCCGATGAGGGGGCTGGTGAACAACCGACCGTTCGACGTGAACCTGAACGGTATAATTCA
TTCTAACGAAATAAACCTCACGGTCATCTGCGGCAAGTCATACGCCAACGACCTGTATGAATTCCTGAGCAA
GCTCCAAGTGAAGCACGCCACTGAGAATGTCAACCCGGACTATCTTATTGAGTATCCGGGCTTCCAAAGTGT
GTTCAACCTGCCACTCAACATACCCCACTTTGACTCTTCCGAGAAGTGGTACGACATCGACTTCGTAGCTGA
CAATAACGGGGAGAACCACGAGAATGCCATTAAGCTTGCCAGACTCATCACCACCAAGATCGACCAGATTGC
CTCTACACAGAACCAGAGCACGGTCGTGGTGTTTATTCCAAATGAATGGCAGTTGTTTGAGGGGTACCTGAA
TCAGGGGGAGAGTTTCGATTTGCACGATTACATCAAGGCATTCAGCGCTAGTAGGGGCATTTCAACGCAGCT
CATCCGCGAGGATACACTGGCGGATACGTTGAAGTGCCAGATCTACTGGTGGCTGAGCCTCTCATTTTACGT
TAAAAGCCTGCGAACTCCTTGGATTCTGAATAATCAAGAAAAGAACACGGCCTACGCCGGGATCGGTTATAG
CGTGACTAAAATACAGGACCGGACGGAAACGGTGATCGGCTGTTCCCATATTTACGATTCCAACGGCCAGGG
GCTCAAGTATCGGTTGAGTAAAATTGACGACTACTTCCTTGACAATCGCAATAATCCATTTCTTAGCTATAA
GGATGCGTTCCAATTCGGTGTGTCCATACGGGAATTGTTTTACCAGTCCCTGGACAAATTGCCTGAGCGGGT
AGTTATACACAAGCGGACCCGATTTACCGATGATGAGATCAATGGTATTAAGGCGTCTCTGAACAAGGCGGG
GATTAAGAAGATTGACCTGGTGGAGATTAACTACGAGACGGACGCCCGCTTCGTGGCCATGTCCGTATACCA
GAATGCACTGCAGGTAGACCGATTCCCTATCAGTCGGGGTACTTGTATAGTCACAAATAAGTACACTGCCCT
TTTGTGGACGCACGGGATTGTCCCAAGTGTACGGCAGCCAAACTACAAGTTCTACCTTGGCGGTAGAAGCAT
ACCGGCTCCGATCAAGATCACAAAGCATTATGGTGATAGTAATATAGACGTTATCGCCACCGAAATCCTTGG
GCTGACCAAAATGAACTGGAACTCCCTTGACCTTTATAGCAAACTTCCCTCTACGATCGACTCCAGCAATCA
GATCGCTCGGATTGGCAAACTGCTCTCCCGGTACGAAGGCAAGACGTACGACTATCGATTGTTTATCTAGTA
ACTCGAGGTTAACTTGT
326 31 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGCGGAAGGTTGAGGACCCAAAAAAGAAGAGGAAAGTTGGCAG
CGGGAGCATGGAAAATCTGACCCTGAATATCATCCCTTTCAGCCACCCCGTGCAGGAGCTTGAGATCGGCTT
CTATAAGCAAGAGAAACAGGGATGCTACAGCCTGTGGAAGGGCGAGTACCCGCAGTCATTCTGGGACGACTT
CAACGAGGAAATGCAAAATTGCGACAAACTCTACACCAACTTCATTGACACGGAAAACTGTGATTACAAAGC
CAGTGTGGACTTTAGCAAAAACAGACGCCTGGCGGTCCATTACTACAGCAGGCTGATCTACAACTACTTTGA
AACAGTGGCAGATGCCGTGAAAATCAACTTCGTGAAAGATATCCAGATATGGTTCAAGGACGAGACCAAGAG
CACCGCCGTCTATACCAGTTACAAGCGGTTCACGATCAAGGTCCAGTTCCATAAGGTGACCGAGTCCCCAGA
GCTGTTGATCAGCTTCGATGGCAATACCACGGCCTATAACAAAAGTCTGGCCGAGTTGGACGATTTCCCTCC
CGAGCTGATTAACTACGTTAAGTACAATACCCAAGTGGTGAAGTACGAGTTCGCCGAGGACGCTATTAAGCA
GCATATCGAGGAGCTGTACCCGATCCTGAGCAACCCCATCAGGGACTACCTTAAGATTGCCAGGCCCGATTT
TAAGAGGGGCAACAAGTATAAGCCCTACTACAAGAACATTACAGACTTCTATCACAACCACCTGAACTCCAA
AGAGTTTAAAGCTATCCTGCCTATCTCCGAAGACGGTTTCTACAAAATGCCTAAGCACAAGGTTCACAAAAC
CAGCTTCAATAGCAATAAACTGAGATTTTTCAATAACACGGACATCGTGCCCCACAACGGGATGAAAAACAT
CGGCCCCTATAAGGCGTCCCCCCACCCCAACGTGAGGTTCTTCTTCATCTACCATAAGCCAGACCGAAACTT
CGCCGTCAAGACGCTGTACGAATACTTTACGGAAGGGTACAAGAGCCCAGAGGGCTACCTTTACTTCAAGCC
TCTCAAAACCTACATTAAACAGCCCTTTCTCATCGACAAGGATACCAGCATCGCGTTCGAAAGCCCGGAAAG
CGCTCTGCGCGAAGTCAAGCAGGGTTTGCTTAACCTGGAAAAGCAGCCCAATACGAAATACGTCGCTATCTA
TGTGACCCCCATACATAAGACCGAGACCGACGAGCAGAGGAAGATGCTTTATTACCAGGTCAAGGAAGAATT
GCTCAAGCACGACATATCAAGCCAGGTGATATACAAGGACAACATTGGACATAAGGATTTTAGTTTCTATCT
GCCCAACATCGCCATCGCCCTGCTGGCCAAGATCGATGGAATCCCCTGGAGGCTGGACAGAGACACTAAGGA
GGAACTTATCGTGGGCGTAGGCGCATTCACAAGCCTGAACCACAATATCAAATATGTAGCTAGCGCCTTCTG
CTTTAACAACAATGGGGAATTCAAGGGATTCGACTGCTTCAAAGCGAATGAAACCGAACTTTTGGCTGGCAC
CATCGGCAAGCAAATCCTGAAGTATGTGGTGGACAACGGCGAGAGCGCCAAGCGCCTGATAATCCACTTTTA
CAAAAAGATCAGTAACAAGGAACTCGAGCCCATAAAGAAAATGCTGAACAAGCTGAACCTGACCATCCCCGT
AGTGATAGTGACTATCAACAAGACGACCTCAGAAGATAACGTGGCGTTTGACACCAGCAGCCATAACCTGAT
GCCCGTGAGCGGCACCTACCTCAAAATAGGATGGGACCAGTACCTCCTTTTCAACAACACGAGATACAACGC
CAGCGACACCGAGAAGGATAACCCCTTCCCTGTAAAGCTGAGCTTCTCTAGCACCGTAGACAATTACTTCGA
CGACAGGAAGGTGGTCGAGGAATTGATCGACCAGGTGTATCAGTTCTCCCGCATGTATTGGAAGAGCGTGAA
GCAACAGAACCTGCCCGTTACCATCAAGTACCCCGAGATGGCGGCAGAGATCTTCCCATTTTTTGAAGGCGA
TAAGCTGCCCGACTTCGGAAAGAATAACCTTTGGTTTCTGTAGTAACTCGAGGTTAACTTGT
327 2 GGTGTCGTGAGGATCCATGCCGAAGAAAAAGCGCAAGGTAGAAGACCCTAAAAAGAAGCGGAAAGTTGGCAG
CGGGTCAATGAACACGCCTTTGACGCATTACGTGCTCACCGAGTGGGAATCCGATACAAATACTAATGTATT
GCACATCCACCTGTACACCCTCCCCGTTAGGAACGTGTTCGAGCAGCACAAGGAGAACGGTAACGCATGTTT
CGATCTTCGCAAGCTGAATAGGAGTCTGATCATCGACTTCTACGACCAATATATCGTGAGCTGGCAGCCTAT
AGAAAACTGGGGCGAGTACACCTTCACCCAGCACGAATACCGCAGTATAAACCCAACAATACTGGCCGAGAG
GGCCATCCTCGAACGACTCCTCTTGCGGACAATCGAAAGCGTCCAGCCCAAGAAGGAGATCGCAGCTGGTTC
CCGCAAGTTTACCTGGCTGAAGGCAGAGAAGGTCGTGGAGAACATTAGCATCCACAGGGTAATCCAGTGCGA
CGTAACCGTGGACTACGCCGGCAAGATCTCTGTGGGCTTTGACCTCAATCACAGCTATAGGACAAATGAGAG
CGTGTACGACCTCATGAAGTCTAACGCCATCTTTAAGGGAGACCGCGTGATAGACATTTACAATAACCTGCA
CTACGAGTTTGTAGAGATTTCCAACTCCACAATAAATGACTCCATCCCCGAGCTCAACCAAAGTGTCGTCAA
CTACTTTACGAAGGAGCGAAAGCAAGCATGGAAAGTGGATAAGCTGGAACAGAGCATGCCAGTCGTGTACCT
CAAGGCATTCAACGGCAGTAGGATTGCATACGCGCCTGCGATGCTCCAAAAAGAGCTGACCTTTGAGAGTCT
CCCGACCAACGTAGTACGGCAGACGTCAGAAATATTCAAGCAAAATGCCAATCAGAAAATCAAGACCTTGCT
GGATGAAATCCAAAAGATTCTTGCCCGCACCGACAAGATCAAATTCAACAAGCAGAAGCTGTTGGTTCAGCA
GGCCGGCTACGAGATACTTGAACTGTCCAACCCAAACCTCCAGTTTGGGAAGAACGTTACTCAGACGCAACT
GAAGTATGGACTGGATAAAGGCGGAGTTGTGGCCTCCAAGCCGCTCAGCATCAATCTTCTGGTCTACCCGGA
ACTTATAGACACCAAGCTCGATGTGATCAACGATTTCAATGACAAACTGAACGCTTTGTCCCACAAATGGGG
CGTGCCCCTGAGTATCCTGAAGAAGTCTGGAGCGTACCGCAACAGACCCATTGATTTCACTAACCCCCACCA
GCTCGCGATTCTGTTGAAGGAACTGACCAAGAACCTTTTCCAGGAACTCACGCTTGTGATAATACCGGAAAA
GATCAGCGGCATGTGGTACGATCTGGTTAAAAAGGAATTTGGCGGCAATAGCAGTGTTCCGACGCAATTTAT
CACCATCGAGACACTTCAGAAGGCAAACGACTATATTCTGGGGAACCTGCTCCTTGGCCTCTATAGCAAGTC
CGGCATCCAACCATGGATTCTTAATAGCCCCCTTAGCTCCGACTGCTTCATCGGTCTGGACGTATCACATGA
GGCGGGTCGCCACAGCACCGGGATAGTCCAAGTCGTAGGAAAGGACGGGCGCGTGTTGTCATCCAAGGCGAA
TACGAGCAATGAAGCCGGCGAGAAGATCCGCCACGAGACCATGTGCCAAATAGTGTATAGCGCCATCGACCA
GTACCAGCAACACTACAACGAGAGGCCTAAGCACGTGACCTTCCACCGCGACGGTTTTTGCAGGGAGGACCT
GCTGTCACTCGACGAGGTGATGAACTCCCTGGATGTCCAGTACGACATGGTGGAGATCATCAAAAAAACCAA
TCGGCGAATGGCACTGACCGTCGGCAAACAAGGATGGGAAACCAAGCCAGGACTGTGCTACCTGAAGGACGA
GAGCGCCTATCTGATCGCCACCAATCCGCACCCGAGGGTGGGCACCGCGCAACCCATCAAGATTATCAAGAA
GAAGGGGAGCCTCCCTATCGAGGCCATTATACAGGACATCTACCACCTGAGCTTCATGCATATCGGCTCACT
GCTTAAGTGCCGACTCCCCATCACAACTTATTACGCCGATCTGTCTAGCACCTTCTTTAACCGCCAATGGCT
TCCGATCGATAGTGGCGAGGCCCTTCACTTCGTGTAGTAACTCGAGGTTAACTTGT
328 35 GGTGTCGTGAGGATCCATGCCTAAGAAGAAGCGCAAAGTCGAAGACCCCAAGAAAAAGCGAAAGGTGGGCTC
TGGCAGTATGATTAACAAACTGCAATTCGACGAGTTTCAGAGGGCCATAGGTATTTCTAAGAACGACACCTT
CAGTCTTTTGCTCGGAGCGGGTTGCAGCATCAATAGTGACATCCCTAGCGCGGAAGACTGTATATGGGAGTG
GAAGCGAGATATTTACAAAACAAATAACAGTTCTAGCTTCGGCTGGATTGACAATTACAAGAATCCCAAGAC
TCAGGAGATCATTCAGAACTGGCTCAACAACCAAGGCATCTATCCCGAACGCGGCTGCAAAGAGGAGTACAG
CTTTTACGCCTACAAATGCTATCCCATCGACGAACATAGGCGACAGTATTTTCAGAAAATCTGTAGTGGTAA
AAAGCCATCCATCGGGTACAAACTTATTCCCCTGCTTGCCCGAAAGGGCATGCTTGATAGCGTGTGGACCAC
GAATTTGGACGACCTCGTGGTGACCGCCTGTATAGGCAACGGGATCCAGGCGATCGAAATCACGCTCGACTC
CGTGCAAAGGTTGAACAACCGGCCTCAGAACCGACATGAGCTTCCTGTGATCAAACTCCACGGAGATTTTAA
GTATGGCGATCTTAAAAACACCGAGGAGGAACTCCTCAATCAGGATAAAACGTTCAGGGAGAGACTTATTGA
ATACGTACAAGACAAGCACCTGATCGTGCTCGGCTACAGTGGCCGAGACACCAGCCTGATGGACACACTTAA
AGAGGCCTACTCAAAACAGGGGGGTGGAATTCTGTACTGGTGTGGATATGGTGACAACATAAACTCCGACAT
CGCCGAACTGATTCAAATAGCCACTAAAAATGGCCGACGAGCCTTTTACATCCCCACTGATGGTTTCGATTC
TACGCTCCGGAAAATCACACAGATAGTGGTCGAGGATGATAACAACCTGAAAAAAGAGCTTCTCGAGCTTCA
CCAGACCAGCAATATCAATGACACTATCACACCTTTTGATCTGAAGTGCGAGAGGGTGAATAAGCTGTTGAA
GTCAAACATATTCCGGATTAGCTTTCCAGACGAAGTGTTCGTTTTCGATGTGAGCATCAGCGATAAACCCTG
GAAGTTCGTGGACGAAAGGACTCTTGAGCGCAACGATATTAGCGCCGTTCCCTATAACAAGCAAATCTGGGC
ATTCGGTAGGCTTGACATCATAAAAGACATCTTCAAAGACGTGATGAACTCAGACATTCAGCGAAAACCCCT
GGCAAACATCAAGATATACAACACGGCGGTTAGTCGGCTGTTGCTTACTACGATTTGCAAGATACTGGCGCT
GCAGAGCAACCTTAAGACCGACTATAAGGGTAAGATATGGACCGAGAACAACAGTAAGTCCATTTCCGGCCA
CATAGTATACAATGCCGTGCTGCTGTCCTTTGATCGGATAAGCGGTGAGTATTACCTTAGCCTCAACCCCGA
CTTCGTGCTGGCTAACCCCAACATTGAGAAGAGTAGCATACAGACCATAGGACTGTTCTTCTTCCAGAAGCT
GTGGAATCAGCAGTTTAACGAGTACATTAACTATTGGAGGGAAATTTTGTTGAAAAAGAATAATGAGTACGA
GTTCCCCATAAATAGCGGAACCGGCTTCAAGTTCAAGATCAAGAACATCCCAGTGTTCACTAACATCTGCGA
CCTGAATAACCCTCGCATCAACAATCACAACGTGTCCAGCCACCACCTGCTGCTTCAGGGGGTGCAATTTAA
GGAAATCCCGCTGCTTTTCAGCACCAACAATGGCAACCGCACGGCCACCGACACCCACCCTATGAGAGGACT
TCTCATAAACAAACCGTATGAAACGGGCGTCAACGACTTCCTCGAAAAGTCTATCACCCTGGGAATCATAAG
CCCCAGTCAGGACGCCCTCAGGTTCTACCAATTCCTGGAAAACCAGAACTCTAAAATCAAAAAGCACAACGA
CAAGGACAACTACATAATAGACTACGAAGGGTTTTTCGCCATCTACGGCGTTAGTCTCAGCTTCCCAACACC
TAACGACAACGAGTGGGAAAGGATCAACGAACCGCTGATTATGGGCATCAAGGAGACCGCCCAACAGATAAA
GCAACTGATATGCGACAGCATCGTGAAGATCTCAAGCACGACCAGGAGAAAAATCATCGTCATCTATATCCC
CCAACGCTGGGAGCCCTACACCTCTTACCAGCTCGATGGTGAGTCATTTGACCTCCATGACTACGTGAAAGC
GTTCTGCGCGGAGAAAGGGATTATGAGCCAACTCATTCGAGAGAAGACCATTAACGATACTATCCAAAAATG
CCAGATACATTGGTGGTTGTCTCTGTCATTTTTCGTAAAATCCTTCCGGACCCCATGGATTCTCGCAAATAC
TAACAACACCACCGCCTTCGCGGGTTTGGGGTACAGTGTAGAAAACAAGAAGGATATTAACGGACATATTGT
GCTGGGGTGTAGCCACATTTACAGCTCAAACGGAGAAGGGCTCAAATACAAGCTGGCCAAAATAAGTAATGA
TAAGATTCAGTGGAGGCATAAGAAGCCGCACCTCTGCTACGACGACGCGTATGAGTTTGGCAAGTCAATTGT
GAACCTGTTCTACGAATCTATGAACGAACTGCCAAAAAGGGTGGTCATCCACAAGAGGACCTTCTATACCGA
TGAAGAGAAACAAGGGATCATAGACTCCATTAGCGACAATAAGAAAATAGAGAGCATCGACCTCATCGAGAT
CAACTTTGAAAACAATATAAAGTACGCCTCTAGCAAAATCCACGACGGAAAGGTAGACATTGACGGATTTAG
CGTATCTAGGGGAACCTGCATACAACTCAGCTCTAAGGAGGCGCTCCTGTGGGCGCATGGAGTGATTCCTAG
CGTCATTAACCCTAACTGGAACTTCTACCCTGGCGGCAGGTACATACCTAAACCACTTAGGATCATTAAACA
TTACGGTACAGGTAGCTTGGAACAGATCGCGAACGAGATTCTGGGCCTGACTAAAATGAATTGGAATAGCCT
GAACATGTACAGCCAATTGCCTGCCACAATTTCAAGCTCCAATGATATAGCTAGGATAGGTAAATTGATAGG
GGCGAACAGTATGCACGAATACGACTACCGATACTTCATCTAGTAACTCGAGGTTAACTTGT
329 9 GGTGTCGTGAGGATCCATGCCGAAGAAGAAACGAAAGGTTGAGGACCCCAAAAAGAAAAGGAAGGTGGGGAG
CGGCAGCATGAATAACATACCCATCAGGCTGAACTTTTTCGCCCTGAAGAACCAGAACATTAGCTTCAGGAT
CTACAGGCAGGACTTCAACGGCCAGAAAAAACAGGACGGGTACTACAGGACCAAGCTGCCCATCAACGACTC
TTCTGACACCTACGCGGAGTACTGGGTGACAACCCAGCCCAAGGATGGCTTCGAGAGGGTGTACTGCCTGGG
TTCCTCAAACCCTAAGCTCACCGTCCGAATCATGTGGGAGAGCTTCCTGGATAGGGTCCAGAAGTCCCTGAG
CTCCGACGAATATATCCTTTACGGTAACGGATTTAGCCGGAAGGTCGCCGTGATCATCGGCAGGCACAGGGA
GGGCAATGAGGTGATCCAGATAGAGCCCTATTACCTGAAGGCCGAGAAGAAGTTCGGCTTTCTGGTGGACTT
CGCATTTAAGAAGGCCAAGGACGTGCCCTATAGCATCAGGGTTCAGCAGCTGAGCCTGTCACTGAACAAGTA
TGGGAAGAGCAACGCCGACTACTATAGCGACAAGCTGGATAAGATAAAGTTCTTTATGCAGAAGTTTAAGCA
GAGGCTTTTCCCATTTAGCTTGGATAACGAGGATTACGACATCGAGAACGAGCTGTATCTGATGAGGAGCTA
CCCGCTCAAGATGAAGACCTACATATTCTCTAATGGCAAGGAAAGCAACAGCCAGGTGCAGGGTCTCAAAAC
CTACGGACCGCTGGCGAATCTCGATAAGGAGCCACTGTTCGTGTTCATGTTCGAGTCCCAGGACAGGAACGA
GGCCCTGGAGCTCTATTCTAGCCTGCTGGGCAAGACGTACACCAACATATTTGCTGGCATGGAGAGCGTGTA
CAAAATCAAACTCGCAAAAGAGAATGTGAAGCACATCATCATCCCCAGCCTTACCAAGGAGGGTCTGCAAGT
GGTGGAGCAAGAGCTGCAAACTATCGTGGAGAGTCATCAGGACAAGAAGGTGATTGGGATATTTGTAATGAA
TGAAAAGGTGCCCTCATCCATCACCGGTTTCAGCCCCTACCACTACGTCAAGTACATCTTCACAGAGAAACG
CATTCCCCTCCAGACAGTGAGGTGCGAGAGGATCGCTGCCAGGGATGGCCTCAAATGGAGCGTTGGCAACAT
CGGCCTCCAAATTTTCGCTAAATTGGGCGGCATCCCCTGGAAAGTCAAGCCGAGTAACGATAAGTGCATCAT
TTTTGGCCTGGGCTGCGCCCACAAAAAAGACGAACTGGGAAACATTAACAAATACTTCGCCTACAGCGTGTG
CATGGACAGCAGCGGCATTTACCGAAAGATTAATGTGCTCGGCGATGCAAAGGAGCGCACTGATTACATCCT
TCAACTGCGGGAGAACATCAAAAGCGTGATAAGCGAGAATCTGGACGGGAGCATTGAAAAGTGCGTGATTCA
CCTGCCCTTCAAAATTAAGAACGACGAGATCAGGTACATAAAATCCAGCGTGCAGGAGATCGCGCACCTGTA
TTCCGACATAGAATTTCAATTTATCAAGATCAACACGGACAACAAGTTTTTCGGATACGCTGAAAACAACAG
CAAGGTACCCTACGAGAGCAGCTACATACAACTGAGCAGCAACGAGTTCCTGGTGTGGTTCGAAGGCCTGCA
GTACGGGAAGGAGCTGGTGAAGAAAAAGGTAGGTAACCCCGTGCACATTGAGTTCATGCAGATCGATGAGTT
GGATCCCGAAAAGAAGCGGCGATATCTGCAGGATATCATAAACCTGAGCGGTGCCAACTGGCGAGGTTTTAA
CGCCAAACTGTCTCCAATCAGCATCTACTACCCCAACATCATAGCCAATTTCATTTCAGAGTTCAGGGAGTT
CCAGCCCGAAGGCGACGTGGACCTGACCAACTTTTACATTCCCTGGTTCCTGTAGTAACTCGAGGTTAACTT
GT
330 10 GGTGTCGTGAGGATCCATGCCCAAGAAGAAGCGCAAAGTAGAGGACCCTAAGAAAAAACGCAAGGTCGGCAG
TGGCAGCATGCATAACATCGAAATCAACACCTTCGTCAACAGCTTTGCCATTAAACCCAACAACTCCATGTC
CTTCCTGCTCGGCGCAGGCGCGTCTATATCCTCCGGGATCCTGTCTGGCGGACAGATGGTGTGGGACTTTAA
ACGGAACCTCTATTGTGCGTCCAAAAACATACGCACCAGCAATTTTCCCGATATGAGCAAAAAGAATGCGCA
GGACGAGATCCAACGCTTTTTTGATGGGCAGGCCGGAAATCCTAGCCTGTGGTCCTCCGAGGAGTATAGTTT
CTACTTCGAGAGGTGTTATCCGGCGAGGAAAGACAGGGAGCTGTACATACAGAACAAGGTACGAGACGTCAA
GCCGTCATTGGGGTATCTCTGCCTCGGGGAATTGATCATACACGAGAAGATCGGTGTAGTATCAACCACAAA
CTTTGATGACCTGGTGTTGGCCGGCATCCATTCAATAAGACCGGACCTGAGTGTGAAGACCATCAGCAGTGC
CCTCAAAAATAGCACGGGATTCTTCGTGAACGACGGGTTCCCGAACATCATTAAGCTGCACGGCGATTACTT
GTACGATAAGCTGAAGAATACCGATAAGGAGCTGCAAAAGCTCGAGACGGAGATCAGCGGAATTTTTCGAGA
TGCCGTCAAGAGTGGCGGGCTCATCGTACTTGGCTACGCCGGCAACGACAACAGCGTGATGAGCGTCCTGGA
GGAGCTCGTAAGCTCCGGGCAAATCAGGTACGGCGTGTTCTGGTGCCAACCGAAGGGCTTCCCCCTGTCCAA
GCGAGCGCGGGAGTTTATTGAGAAGGCTTGCGCCTACAATGAGGAATCCGGGGTTGTCGAGATCAACAATTT
TGACGACTTTATGTACCGCCTGTTCCTTACACTCAACATCCAAAACTCATTTATCGACAGCATGTGGGAACA
GAGCGGCATGAAGCAGCCGATCCTCTATGAGAATATCGGACGACACAAGTCCACCGCCGTGACGAACGCCCT
GTGCGCCCTGCAGTACCCCCGAAAATGCTACGTCTTCAACGCGAATATATCAAGCTGGAAGGAACTGCGCGA
GACGATAAACGACACGTGCGTGGCAGTGCTGTATAAGGGCATGGTTTGGGCGCTGGGCAGCAAAGCAGGCAT
CGTGCATGCGTTCGCCGGGAAGATCAATGGAGACATATACGAACTCGACATCCCGTTGTACATGATGAAACT
CGAGGATTCTGACATCCTGGGCATGTTTTACGACATCATAGGACGCGGCCTTCAGCGAAAGGGGCTGGTGAG
CTACGGTAATAGGAAACATCACAAATACTTCAACCCCTCCAGCAAACGGTTCAAGAACGGTCAAAACATCTA
CGACGCGGTCAAGATATCACTGAGTTTCGTGGACGATCAGCTCGTGCTCATCCTGCTGCCTACGGTGCATCT
GCTGAAACGCGACGGGACGGAGCTGGAGAAATTTGACTACCAAAAATTGGTGTCCCAGGAGATGGCAACACA
CTACAACAAAGTGGTGGACAGCGAGATAGAGATCTGGCTGAAATTCATCTCTAATAACGGCAAGATAATCTT
TGAGCTGGGGAACGCAATACTGGAATTTAACAACGTCCGCATCCAGTACTCTGGTAACGGTAACCTCAGCAA
GTGCTACCAGGTGAGCGAGCCCGAGCTCACGTTCAGTTACGAAAAGGACAACTGCATCGCTACCAACCAACT
GCGGGGTCTGATCAACTATGGACCCATAGAGACTTACGTGAACAAAGCCATCAGGTTGGCTGTACTCAGCCC
TAAGGAGTGTGCCGCGGACATTTGGAAACACCTGCAGAAGTTGAATGAGCATCACGTCACCTCCCTTATTCA
GGATGCAAATTTTCTGCCGGAGTACACCGGCTTTCAGAACGTTTTTAGGTGCAACCTTGACATTCCCAATGG
GAACGATGTGCATAGGTTCAAAGGCTACAGTATAGACAAGGTCATGCAACTCAACGCAAAGAGCTACTTTTA
CGGGATCTGCAAGTACATTGATGCATTCGAGACACAAAGGAGCCAATACGACCTCCTCGTCATCTATATACC
TAAGCAGTTGACCCACATCCGAGAGGCCAAGAATAACTTCGAATATTTCGACCTGCACGACAGCCTGAAGAT
TTATTGCGCTGGTAAAGGTATAGTCACGCAGATCATCGAGGAACACAGTGTTTATACTAACAATGACACCGC
CAAGATCATATGGGGTCTCTCAACGGCCATATTCACCAAGACCGCCGGAAGGTTGTGGAAACCCAGACGCTA
TTCCATGAACACCGCTTACGTCGGCCTGTCATATGTGCAGAGCGTTAAGAACAACGAGAAAGTCAGCATCGG
TTGCAGTCAGCTGTTCGACGCCGAAGGCAATGGAATGAAGCTTTACCTGAGACCCTTGATGAACCCCCAGAT
AATTCAAAATAACCCTTTTATGCGGAGCGACGACGCTTGCAGGCTTATGTCAAACCTTAAGCGGATGTATGA
CGACAGTGTCCCGCTCTACAAACTGAATAGGATCGTGATCCACAAAACTACGTTCTTCACTAAAGAAGAGAT
GGAAGGCATCACCAAAGGGCTGGCTGGAGTGGATGACATAGAGTTGCTCCAGATCCAGGAGTTCACAGCTTG
GCGAGCAATACGCTTCGACTACGACAAGATCGCACCGTTTCCGATACAGAGGGGCACAGTGATTCTGGGGTG
GGGCCACTTTAGTTACTTGGATACCTGGAAGTGTACCACCTAGTAACTCGAGGTTAACTTGT
331 7 GGTGTCGTGAGGATCCATGCCTAAGAAGAAGCGAAAAGTGGAAGACCCAAAAAAGAAAAGGAAGGTGGGTAG
CGGCAGCATGAACGCCGTGACCGTGGGCAGCACCCCAAGCGCCCAGGTACTCGTCGGTGTTCAGCCATACGA
CGAAACCACCCTGGAGAGCCTGAGAAGTAAACACCGCGGAGACTATCTCTTTAAAAGGGGGGGAGAGAACGG
CGATAGCATACTTGCTGTGGCCCTGAAACCGAGTCTGCCGGTCATCGGAGCAACCGAGGAGGATGTAATTCT
TGCCGAGAGCCCATGGTTGTTGGCTCCACTTGCCTTGGAGACTTTGCTGCAATGCTTCGTGAGGCTTCAAAG
GCCCATCCTGAAAGCTAGGCATCCCCTGAGAGTGCTCTCACAAAAACCGGCAAATCTTTTCCCAGCCGATGC
GGGGGTCCCCCAGTGGCTGCAGAGGAGACTGGTGCTGGAATTCGACACGCGCACTGTTAGGGACAGGTCAGA
CGCTGCCTCTGTCGTGCTGGCATGTGGCGTGAGGACTCGGAATTTGATTGATGCCGACTGCGCGACACTGAT
AGCAGCCGGTGTCCCCCTTGTGAATCGATACGTGGTGACGAGGCACCCTGCGGATGATCCCCGAGTGCAGGG
CTATTTGAGGCTCGCCGGGAGGGTGACCAGGATAGATGGCCCCAACCTGTACTTGGAGGATCATGGCGATGG
AGCAGCTGTGATCAAGGCCTCCATGGCCTATCTGGAGCCCAGGAGGGAGAACGTGATTTGGTGTGCCCACCA
TTTGCTGGGGAGAAATGCGGATAGAGTACTGGCGGAAGCGGATAACGCAGCCGCAAAGCACTTGAGCGGTCC
CGAACGATTGGCCGTAGTGAAGAAGACTTTCGACTACCTTAGGAGCCAGAACATCGAGCTTGCGCCTGGAGT
GCCCCTCACTCTGGGTAACGTTGTGGGGAATGACAAGGGTTCTTGGATCTTCCGGACGGAAACTCTGCCCAA
GCCCCACCTGGTGTTCGACCCGAGCGGGACCCGGATCGATAGGTGGAATGAGAGGGGATTGGACGCTCACGG
GCCCTATGATCAAAGGACCTTCACCCCTAAACAACTGAGGATTGCCGTCATATGTCAACTGCCCTACGAAGG
CCAGGTCGATGCGTTCCTGGCAAAATTTCTCGACGGCCTTCCAGACGTGAAGACCGGCTACGGGGACCGGGC
CAGGGCGCCTTATGCCAAGGGGTTCATCAGGAGGTACGGTCTGGAGAAGCCCAAGGTGAGCACCTTCGCAAC
AAAAGGCGCTACTGCTAAGGACTATGCCGCTGCATGTAGGGCGGCTGTGGAGGACGCAACCGCAAGCGGCTT
CGAGTGGAATCTGGCTATCGTGCAGATCGACAAGGATTTCAAGGAGCTGAGTGACGTGGAGAATCCCTACTT
CACCACCAAGGCCCTGCTGCTGAAGCATCGGGTGCCCGTCCAAGAGGTGACGCTGGAGACGATGAGGTTGGC
AGACGAACAGCTGGTGTACGTGTTGAACAACATGAGCGTAGCCACCTACGCCAAAGTGGGCGGTACTCCCTG
GCTCTTGAAAGCGCAACCAACCGTGGCCCATGAGTTGGTAGTTGGAATCGGAAGCCAGACTTTTAGTGCCTC
AAGGCTGGGTGAGAAAGAGAGGGTTGTAGGCCTTACCACCGTGTTCTCCTCCGACGGGAAATACCTGCTGGA
CGACCGGACTAGCGCCGTTGATTACGACAACTATAGCGAAGAGCTGTTTAAGAGCTTGTCCCGGTCAATAGA
ATCAGTAAGGATCGCCGATAACTGGCGAAGTACGGACAGTGTCAGGCTGATTTTCCATGTTTTCAAGCAGAT
GGCGGACGAGGAAGCCGACGCGGTTGACAAGTTGGTGCAAAAGCTGGGTTTGGCACAGGTTAAGTTCGCGTT
TCTGCACATCGTGGATGACCACCCATTCGCCCTGTTTGACGAGAAGAACATAGGTACAAAGACATGGGGTGG
GATATTCAAGGGCGTCTTGGCACCGGAAAGGGGCCTCGCGGTAAACCTCTCTGGGGCCGAAACCCTGTTGTG
CTTCACAGGCGGCAGGGAACTGAAACAGGCGAAGGATGGCCTGCCCGTGCCTAGTCTGCTGCGACTGCACCA
CAGGAGTACGTTCAGGGACATGACCTACCTGACGGGGCAAGCCTTCAACTTCAGCTGTCACACCTGGCGCAT
GTTCACACCCGCTCCTGTTCCCATCACAATACATTACAGCGAGCTGATGGCGCGACTCCTTACGGGCCTCAG
GCACGTCCCGGATTGGGATCCAGACACAATGCTGACCCCCATCAGTCGAACCCGGTGGTTCCTGTAGTAACT
CGAGGTTAACTTGT
332 13 GGTGTCGTGAGGATCCATGCCCAAGAAGAAGCGAAAGGTAGAGGACCCAAAGAAAAAAAGGAAGGTGGGCTC
CGGATCTCTGGACAGTTTCCACCTCGTGCAGACAGAGAAAAAGGCCATCGCAATGCCAAAGCAGAAGCTTGC
GGTTAATGCACTCCCCATTAGCCTGAAAGAGCAGGAGCAGCACAAGCTGTTCTTTTTTAGCAAGGAAAAGCA
GGGCGAGCGAGCCCCGCTCACCAGGAAAGAATATCCTGACAGCTTCGCCAAGAGGTACCCCAAGAGCTCCAA
AGAGTACGACGTGCTGTACACGGACTTCACCCCAGAGCCAGCTGAGGATGGGTTTGAAATTGATATCGACCT
GGAGGAGGCACCTGGCCTTGCCAAGCACTACTTGCACAAAAGGATCTTTGAGGCCTTTAAGGGAGTAGCTGA
CTTCAGAAAGCGGGATTTCATCAACGGTGTGGAGCTTTGGTTCAGGGACAAACCCGCCGACGAAGTTAATTT
CCGGGCCTACAAGAAGTTTAAGATTACCACCCGCAGAACTTGGTTCTCCGCAGGCTGGGCCCTGTTCATACA
ATACACCGGCCATTCCTTTATTCACCCGGTGGCGATCAATAGCGAAGAGGCCGCAGTGGACACTACGGAACT
CACGCGGGTTGCTTATAACCGACACATCTTCCACTACGAGGAGATCCCCGAAGACAAACTGAGTGAGATAGA
TTTCAGTAAGATGTACCCCGTGGTGAACTTCAACATTAGGGATAAAATGCAGCAGTTCCCCGTTATCGATCC
ATTCAAAAACAAGGTCAAGGAATATGTCGACGAAATAGACAGGTTCAAGAACATGTATCTGATCGCGCCAGC
GGTTGAGGAGGTGCTTCCGTTTACTTTCAACGACGACAACTGGTGCGAGATCAAGATCGGCACCTACCATAC
CGTGCCCAATGCCGGTTCCAAATTGGTTTTCCGCGATGGGCAAACCGAGATACACCCGTTCTACGGTATCAG
GAACCACGGCCCTTTCATGCCCCCCAAACACAGCCACATAAGGTTTTTGTTTATCATGAGCAAGAGGGACAT
CAAGGGCGCTGGTAAGCAATTCTATGAATACTTGAAGGGGGAGGTAAAAGGAGTGGACGGGTTCAACAGGTA
TGCTAATATACCGTCATCCCTGAGGGGTGAGATGATCGAGTTTGAGAACGAGCAAAACCCCCTGCCGGAGAT
TATCGACGGCTTGAACAACATGGAGCGAGAAGCGGGCGTGGCCTACTTCGCCTTCTATATCAGCCCCATCGA
CCGAGAAGTGAGGAACAGGAAGGAGAGGTTGGTGTACTACAGGGTTAAGGAGGAGCTGCTGAAGAGAAAGAT
TGCCTCACAAGTGGTAGAAAGGAGCACTATCGAGAAGGCCGACTTCCGCTACAGCATCCCCAACATCGCCGT
TGCCACAGTGGCCAAGCTGGGAGGCATCCCGTGGAAGCTTACTCAACCCCCAGAAGCAGAGCTGATCGTGGG
CATAGGCGCATTCCAGCCACGCGAGTTCGACAAGCGATATCTGGGCAGCGCCTTTTGCTTCCAAGGCGACGG
AACCTTTAGCGGCCTGAGGTGTTTCACCAAGGACGAACCCCATATGCTTGCTGGCAGCATCAGGGAAGCGGT
TCAAAGGTACGCCGATGAAAACAGGCAAGTGGAACGGCTGGTTATCCATTTCTACAAAACCATGAGCTATGA
CGAGAGGAAGCCGATCCTGGCCACCTTGAAAGAACTCGGCCTGGACATTCCCGTTGTGGTGGTCACTATCAA
CAAGACTGAATACGAGCAGACAATCCTCTTTGACCTGAATTCTAGCATGAGGCTGCCGCTGAGTGGTACCTA
TTTCAGCCAGCGCAGGGACGACATCCTGCTGAGCAACAACACCAGGTACCGCAAAGACAGCGAGGTGAAGAG
GGGTTTCCCTTTTCCCGTGAGACTGCAGCTGTGGTGCTCCAAGGAGGGCCTGCTGGACGACGAGGGTTTTAG
GGAGCGACTGATCACCCAAGTGTATAGGTTTTCTCGGCTTTACTGGAAGAGCGTGTCTCAACAGAATCTGCC
CGTGACCATTAAGTATCCCGAGATGCTGGCCGAAAAGTTCCCATACTTTAACTCAAGGAGCCTTCCTAGCTT
CGGCGAAAAAAGCCTGTGGTTCTTGTAGTAACTCGAGGTTAACTTGT
333 3 GGTGTCGTGAGGATCCATGCCGAAAAAGAAGCGGAAAGTTGAGGACCCCAAGAAAAAGCGCAAGGTGGGCAG
CGGCTCCATGCTTATCTGGCAATTCAAGAGAATGCTCTACTGCCAGGCCAACAACATCAAAGAGGAAAAATT
CAAAGACCTGGAGAGCGAGCGAAATCAAAACACTATCCAGAGCTATTTTGACCTGAAGGGCGGCTATCCGGA
AAGATATAGCCAGGAGGAATACTCCGCTTATTTCGAGCATTGCTTCCCGAAGTCTATCAACCGGAAGTATTT
CATGCAGAAAATAGTAGAGGGCCGAAATCCGAGCATAGGTCACAAGTGTTTGGGTGCCCTGTTCGACTGCAA
AAAGGTAAACCACATCTGGACAACCAACTTCGACGAGCTCATCGAGAATGGGATTAAAAGCGTCAACAATGC
CAGCAGCTTCGAGGTCATTAGTATCGACAATCAGAGGCAGCTGGCCAACCTCAACAACTACCCAAGGGTGGT
AAAACTTCACGGCGACTACAGGTACGACAAGCTCCAAAATACCGTTGACGAACTGCAGACGCTGGAGAAGGA
CCTCCATAAGTACTTCGCCGATGTGCAAAGCAAGACCGGCTTGATTGTGATAGGCTACGGCGGAAACGACCA
GAGCATCATGTCCGCCTTTGAAAAGACTTTGGAGGCCGACAACCCGTTCCCGTTTGGGCTTTACTGGTGCGT
GAGGACGGGCCAGAAAACCAACAAGAAGGTAATCGAATTCATAGAGAAGGTTCACCAGAAGAACAAGGAAAA
GCTTGCTGCGTTCATCGAAATCGACTCTTTTGACGATTTTCTTTATGAGCTGTATAAGACGAACAACCTTGC
CAACGATCACATTGAAAATATCGCCAAAAGCCGCTTCGAAAAAAGGAAGGCTTTTACAGCCCCCCAGATCGG
CACCTCCTTTACGCCTATAAAGCTTAACGCCATAAAGGCCAAGACTTACCCGAAAAGCATCTATTCCTTTAA
AACTGACCTCAAGGGGGGCAAGGATGACTGGGATAAACTCAGGGAAATCATTAAGGACCAACCGGTGAGCGC
GGCTCTGACCAATGAAAACACGGTCGCCTTCGCAAGTGTCAACGACATCAAGAAACTCTTCTCACACACACT
GAAGTCAGAGATCACCACCGTGGACATAGATGACAAGTTGATCTATCGGCAGGAGTCTTTCTACCTGGGCAT
GCTTTACGATCTGATAGAGCACAACCTCCTGAAGAAGTTCAAGTTGGAGAAAGTGCCCAACAATAGGCTCCG
CAAGTATTATAGCAAAAACTACAAGCTGAATACCGAGGAGCTTCAGAAGTCCAAGATCAAGACCAGCCTGTC
CGTCTACGAAGCGTTCGAGATTCAAATAGAATTCCACAATAAAGAGCTGTTCCTCATTATCCTTCCGTCCAT
CCACATAGACGACAAAGCCGGGCTGAGCCGATTTGAGAAACAGGAGATAGCCAATAAGATCATAAGCAAAAG
GTGGAACCGCATGGTTAACAACCAGCTTAGGTTCTGGCTGGGGCTCCTTAAGAACGATAACACTAACATAGA
GTTCAGCATCGACAGTTTCAAGATTGATTTGGAAGAAAAGTTCTCCGGCGTCGGGAGCTTTACATCCTCTTA
CTACATCTTTAAGGGCGCGTTTATTTCCAACGAACCCAAGCTTAGCTTCCATATCTCCGACAGCAATTACAA
AACAGTGCACCCCCTGAAAGGCCTCAAGAACTTCGGTCCACTGGATTACTCATTTGAAAGCAAACAGACCAA
TCAGCAGGCTATTAAACTTGGTATAATCACTCCGATCAGCGGCATGCAACGGATACTCAAACACCTGAACGA
ACTTAATAACGAGATCCGCGCAGCTACGGAAAAGGAGTACCTGACCGATTATTACCCCTTTAGCAACATCTA
CAAGAGATACCTTGACATCCCGCAGAATAAGGATAGTAAATTCTTGGAACTCGTGAATGAAGCCGAAGTGAA
CAAACTGAACCACCTCGAGTTTTATGACTTCCTCAAACGCAAAATTGATTACTTCTATACAATTAGGGGCGA
GTTCGACGTGCTTGTGTTGTATTTTCCCAAAGGCTGGACTAAGTTCCGCGAGCTGAAAAATGACAGTGTCTA
CTTTGATCTGCACGACTCCATCAAGCTGTACTGTGCTAAGAAGAATATCAAGATCCAATTCGTGGAAGATAA
GAGTATAGACTACCTCGACCCGGCCAAGGTTAAATGGTGGTTGAGCCTCGGCTTGTATGTCAAAGCGAACGG
GCTGCCCTGGCGGAACGTGGTCGTAAACGAAAGCACCGCGTTTGTCGGGCTCGACTTCGCGGTCCAGCGAAT
AAACAACAGTAACAAGTACGTGCTGGGTAGCTCACAGATCTTCGACAGCTCCGGACAAGGACTCAGGTTTCT
GTTGCAGCCCATCGAACACCCTGTGTTTATCGGTAAAAACCCCTTCATGAGCAAGGAAGATGCGCGACGGAT
GATTCTTAAATTGAAGGAAGCGTATTTTAGGATTGACGGTAACTCCAAGCTGGAAAAACTGGTGGTGCACAA
AGTACTGCATTACACAAATGATGAGATGACCGGCATTTCCGAGGCGCTGGAAGGTATTGAGAACATTGAGCT
TCTGCAAATACAGAAGTATAGTAAGTGGAGGGCAATTAGAGGGGACATCGATCGGTATACGGGAAAGGTGAA
GACCGACCCGCACAATTTCCCGATCCAACGGGGGACAGTGATCCAGCTCGACGACTTCTCTTTCCTTCTGTG
GACACATGGAAGTGTACAGGAAGACGACGTGGCTGGTAGGCACATGAATTACTACCAGGGTAAGCGCGGGAT
TCCCGCACCACTTCTCATACGGAGGTTTCGCGGCACCGATCCGATTGAAATGACCGTGCGAGACATCCTGTC
ACTCACCAAGATGAACTGGAACGGAGGCGAACTTTACAAGACTCTGCCGGTGACCCTGGATTTCTCTAAACG
GCTTTCTAAGTATGCGAAGCAGGCAGAGACCCTCCAGGCAATACCCTACGACTTTCGGTTCTTCATGTAGTA
ACTCGAGGTTAACTTGT
334 51 GGTGTCGTGAGGATCCATGCCAAAGAAAAAACGAAAAGTAGAAGACCCTAAAAAGAAGCGGAAAGTAGGGTC
AGGCTCTATGCTTCAACTGAACGGCTTTAGCATCGAAATCGCCGGAGGTTCCCTGACTGTCTTGAAATCTAA
AATCGCGCCTACCGACGTTAAAGAAACCCGCAGGAGCCTGGAAGACGACTGGTTCACCATGTATCACGAGGG
CCACTTGTACTCACTTGCAAAAAACAGCAACGCATCCGGCGGATTGGGTGAGACCGAGCTCCTGGTCCTGTC
TGATCATCTGGGTCTTAGGTTCGTTAAGGCTATGTTGGACCAAGCCATGAGGGGCGTATTCGAGGCCTACGA
CCCCGTTAGAGATAGGCCCTTCACATTTCTGGCGCGAAACGTAGATCTCGTAGCCCTCGCGGCAGAAAACCT
CGAGTCCAAGCCCAGCCTTCTCTCCAAATTCGAGATCAGGCCCAAGTACGAACTGGAGGCCAAGGTAGTGGA
ATTCAGACCGGGCGAGCTGGAACTTATGCTGGCGCTCAATCTGACTACACGGTGGATCTGCAACGCCTCCGT
AGACGAGCTCATTGAGAAGAACATACCGGTCCGAGGAATGCACCTGATCCGACGGAACCGGGAGCCGGGACA
GAGAAGCTTGGTTGGCACCTTCGACCGCATGGAAGGCGACAACGCCCTGCTGCAGGATGCTTACGACGGACA
AGACAAGATAGCAGCCTCACAGGTGAGGATCGAGGGGAGCAAGGAAGTCTTCGCGACCTCTCTGAGGAGGCT
CTTGGGCAATCGCTATACCAGTTTCATGCACTCCGTGGATAACGAGTACGGCAAGTTGTGCGGGGGTTTGGG
GTTCGACGGCGAACTTAGGAAGATGCAGGGATTTCTCGCGAAAAAGAGTCCTATACAACTGCACGGAGGTGT
AGAAGTGTCCGTGGGGCAGAGGGTACAACTTACCAATCAGCCTGGGTATAAGACAACAGTTGAGCTTTTGCA
GTCAAAGTACTGCTTTGACAGAAGTAGGACGAAGCTCCACCCCTACGCCTGGGACGGGCTTGCTCGATTCGG
CCCATTCGACAGGGGCAGCTTCCCGACGCGATCCCCCAGGATTCTGCTCGTGACACCCGACTCCGCGAGCGG
TAAGGTCTCTCAAGCTCTGAAGAAATTCCGCGACGGGTTCGGCAGCAGCCAGAGCAGCATGTATGACGGCTT
CCTCGACACCTTTCACCTCAGTAATGCTCCTTTCTTCCCCCTTCCCGTGAAGCTGGACGGCGTGCAGCGCAG
CGACGTGGGCAAAGCTTATCGAAAGGCGATCGAAGATAAACTCGCACGAGACGACGACTTCGACGCCGCCTT
TAACATTCTCCTGGACGAGCACGCCAATCTGCCGGACAGCCATAACCCCTATCTGGTCGCCAAGTCCATCCT
CCTCTCCCACGGCATCCCAGTGCAAGAAGCACGAGTGAGCACTCTGACGGCCAACGAATACAGCCTGCAACA
CACCTTCAGGAATGTCGCCACAGCCCTGTACGCCAAAATGGGTGGTGTCCCATGGACCGTTGACCACGGGGA
GACCGTGGACGATGAGCTGGTAGTAGGAATCGGAAACGCGGAGCTTAGCGGGAGCAGGTTCGAGAAAAGACA
GAGGCACATCGGAATCACGACAGTGTTTAGGGGGGACGGCAACTACCTGCTTAGCAACCTCAGCAAAGAGTG
CCGATACGAGGATTACCCGGACGTACTCCGGGAGAGTACCATCGCCGTGTTGAGGGAGGTTAAGCAAAGGAA
CAATTGGTTGCCGGGTCAAACCGTGCGAATCGTTTTCCACGCCTTCAAGCCTCTGAAAAACGTGGAGATTGC
CGACATCATCGCGAGCTCTGTAAAGGAGGTAGGCTCCGAACAGACCATAGAATTTGCATTCTTGAATGTTTC
CCTCGACCACTCCTTCACCCTTCTGGACATGGCTCAAAGGGGAATAACGAAGAAGAATCAGACCAAGGGGAT
ATACGTTCCCAGGAGGGGCATGACAGTCCAGGTTGGGCGCTACACCAGGCTTGTAACCAGCATCGGTCCGCA
CATGGTAAAAAGGGCAAACCTTGCCCTCCCGCGACCCCTGTTGATTCACCTGCACAAGCAGAGCACCTATCG
GGACCTGAGCTATCTGAGCGAACAGGTTCTGAACTTTACCACCCTGTCCTGGAGGAGCACCCTCCCCAGCGA
GAAGCCTGTTACCATTCTCTACTCATCACTGATAGCCGACTTGTTGGGAAGGCTCAAGTCAGTGGATGATTG
GAGCCCCGCAGTGTTGAATACCAAACTGAGGAATAGCAAATGGTTCCTGTAGTAACTCGAGGTTAACTTGT
335 28 GGTGTCGTGAGGATCCATGCCAAAGAAGAAGAGAAAGGTTGAGGATCCCAAGAAAAAGCGGAAGGTCGGCAG
TGGCAGCCTGGGAGCCGGTGCCAGCATCAGTTCCGGCATCCAAAGCGCTAATGACTGCATTTGGGACTGGAA
GTACTCTATCTACCAAACTAACTCCGGCAGTCAACGAGTGGCCCTCGTGGACCCTAAGAAATCCGACGCCTC
CAAGTCTATCATCCAGAAGTGGCTGGATAATCAACCGAAATTCTCACAGATCGAAGCCCATCAGGAGTACAG
CTTCTACGCCCAGGCGGCTTACCCCATTGAGGCGGACCGAATCAAATACTTTCAGAATCTCTTCCAGGGGAA
GTCCCCCTATATCGGCTACAAATTGCTCTGCCTGCTGAACAAGTACGGTGTAGTGAAATCTGTGTGGAGTAC
CAACTTCGACGGCCTGGTCGAACGGGCAGCACAGCAAGCCAACATCACCCTGATCGCCATCAATCTTGACTG
TGTTGACCGCATATATCGAGCAGAAAGCGTGAATGAACTTCTGTATATCGCGCTCCACGGGGACTACAAGTT
TAGTACCATAAAGAATACCGCGAATGAGCTCGACAGCCAGCACACCGAGTTCGTATCTGCCATGTGCCGGTA
CTTCGTCGATAAAAACTTGATCGTCATGGGATACAGCGGACGCGACAAGTCACTTATGGACGCCCTGGTCCA
AGCGTTTAGCAAGAAGGGTGGGGGGAGACTTTATTGGTGCGGCATGGGCGAGACCATCACGATCGAGGTGCA
AAACCTGATACAGAGAGTGAGGACCGCAGGCCGGTCAGCTTATTATGTAGATACCTCTGGGTTTGACAACAC
CATGCTGTCACTGGTAAAGTACTGTTTTTCAGAGGACGTCGCCAAACAGCGAGAAATAAACGAAATTTTGAA
AATTGTGGAACCGGAGCAGATTACTCCGTTTGAGATTCAAAAGAGCCAGAACAAACGGTATCTCAAGAGCAA
CCTGCTGCCAATCGTGCTTCCCAAGGAACTCTTTCAGTTTCAGATCTCTTATAACGACACGGCGGACAGGTG
GGGATTCTTGCGCGAGAGGATTAAGGAGCGGGAAATCATAGCAGTCCCGTACCAGGACAAAGTATACGCAAT
CAGCACGGTCTCCATCATTAACGACGTTTTCAAGGACTGTCTCGTAAGCGAGATTGAGCGCACGTCCATCTC
TCTGAATGAGATCGAGCGCAATGGCTGCTTCAAAGAGCTGTTCCTCAAGGCTATTCTCTACGGGTTTAGCCA
AATCCGGAATCTGGGCATCAACTACCGCCACGGCATCATTTGGAAGAAGGAGGCGCTCTACACTGAGCCCGG
CAAGACCGTACACGAGGCCATAGAATGCGGCTTGTCTTTTATACCGCAAGCGAACTACGCTTTGATTAGCAT
CACACCAAGTTTGCACATCGAATCCAGCAGCCCGATCGAAAAAGAGAAGAAACAAGAGTATAACAGGCGGTA
CCTTGACAAGATGAGGAATAAAGAGTACGAGGAAAAGATCCAGGAGTGGTGCAACATACTGTTCTCCGGTAA
CAAGCTCGTTTTTGACATCCCGCTGCAAAGCAACAACGACTTGAAGTTCTTCATTTCCAGTAATAGGGGTTT
CGCCGAGGTATACAATTACGGTAAGGACATCGAGAAGAGCTACACGCCCAATGCTTACAATACGAAACAGAC
CATTTACTACGGCATGCAAATCGAAGAGCCTCAGTTGGAGTTTATCAACTCCATAATCAGTAGGCCGTTCTA
TGACGTTAACCCAATGAGGGGCCTCTCAAATCACAAACCATTCGACGCGGACTACTATGACAAGTTCCCCCA
GGATGTGTGTTTGGGCATTGTGTGTCCGACCAGCTACAGCCTGATGTTCTCAGAATTCCTGAAGCGCCTGAA
CACTAAGATCCCAGCACCGAAGTCATCCGACTACATCCACAACTATATTGGCTTTAACAGCATCTACAACTG
CAGGCTGGACATACCGGACATCAATGCCGATCGCTGGGTGAGCATCGGCGACAACCCCCAGAACGCGGAGGA
ATTGGCCCGCAACATCTGTATGGAAGCAAAAAAGCTGAGTGAACAATATCCGGGCATCGTGGTTAACATATT
CATCCCTACTATCTGGAGCAACTACAGAAACTTTAAACACAACGGTGAATTCTTCGACCTGCATAACTACAT
TAAAGCATTTGCGGCACAAAATCGCTTCACCACGCAACTCATCGAGGAGAAAACTGTTTGTAACACGATGAT
GTGCGAGATATCCTGGTGGCTTTCCCTTGCCCTTTTCGTTAAGACCCTGAGGACTCCGTGGACACTGGCTGA
CCTTAACCCCAACACCGCCTACGCGGGGATAGGGTATTCAGTTAAAAAGCAGGCCAAGGGCAGGACAGAGAT
CGTACTGGGGTGTAGCCACATTTACAATGCGCAGGGACAGGGACTCAAGTACAAACTGAGCAAGGTCGAGCA
CCCACAGTTCGACAAAAAACGGAACCCATTCTTGAGCTTCGAGGAAGCCTTCAAATTCGGGATGGATATTCT
TAATTTGTTCCAGAGTGCAATGGAAAAACTGCCGCAGAGGGTGGTTATTCATAAACGGACGCCTTTTAGGGA
AGAGGAAATAGAAGGGATTACCAGCGCCCTCAAGCGGGCAGGGATCACGGAGGTGGACCTGATCACTATAAC
GCAGGAGCGAAACATTAAGTTTATAGCACAGGTTGTCTCCTTCGGCCAACTCAATACCGACGGCTATCCCGT
CAACAGAGGCACTTGCATCAAGCTTAGCTCTCGCAATGCACTCCTTTGGACCCACGGCGTCGTCCAGAGCAT
TCGAGACAAAAGACGGTACTACCAGGGGGGCAGGTGCATTCCGAGCCCGCTGAAAATCACTAAGTATTACGG
CAACGGCGATCTCCAGACTATAGCTAAGGAGATCATCGGTTTCACGAAGATGAATTGGAATAGCTTCAACTT
CTATACGAAGCTGCCAGCGACCATTGACACTAGCAACACCCTGGCCCAAGTGGGCAACCTTCTCAGGAACTA
TAATGGCACCACCTACGATTATCGCTACTTTATCTAGTAACTCGAGGTTAACTTGT
336 43 GGTGTCGTGAGGATCCATGCCGAAAAAGAAGCGGAAAGTAGAGGACCCGAAGAAAAAACGCAAGGTGGGCTC
CGGGTCTATGGCCAACCATACCTTTAACATCCTGACTTTCAACCACCCCCAGGAGGAACAGACCTTCTACTT
CACGGACCAGGAGCAAGACAACCTGACCCGCATCTACAAGAGCCTGGTGCCCGACGAGGTCATCGAGAAATA
TGGCGAGCAGGATCACTACTACACCTCTTTCACCGTAGAGAAGGATGGTTTCCTGGCCGTCAGCAAGCCCAC
AACGCCCCTGTTCGAGACCAAGACTACGGAGGCGGGCGAGGAGAGGAGCTATACCATCAGGAATTCAACGTT
CAGCAGCAGCGTGTTGAAACGGTACTACAACAGCCTTATCCACAGCCACTTCAAGGAGAAGGGCTTCCTGGT
GAAGCCCAACTTCGTGAGCGACACGGAGGTGTGGCTGCCTAGCGCCAAGCAGGACACGACCGGCAAATACAA
AATATTCGACCGCTTTAGCCTGAAGGTGCAGTTCAAGACCGTCTCTGATTCCCTGGAGTTGCTCGTCACGTT
CGAGGGGAAGTCAAAGATATTCAAAGTACCTGTTAGCACCCTGCTGGAGGATGTGAGCCCCACGGACATCAA
CTGGGTTGTGTACGAAAAGGGATTGTACAGGTTCGACGAACTCCCGGACAGCGGCAAGAGGGAGTATGACAA
GGTTTACCCCGTGTGGACCTTCGAGATCAGGGACGCGCTTATGCAGGGCACCGAAGCCCCAGACAAGACCAA
CAAGTACAAAAAGTTCAGGGAGGGCATCGACAAGTTCTATAACCAGTATCTGAACACAGAGGAGTTCAAAGC
CATCATTCCAATCACGTCTAATGGCTTCATCCCGGTCAATAAGATCAATGTCGGTAGTGTGAATAATAGTAG
CAACAGGCTGCTGTTCGGGGAACAAAAGAGCGGTATCGTGCCAATGGACGGCATGAAGGAACATGGCCCATT
CGACTTTTCCAGCACCAGCAAGATCCATTTCTTCTTTATCTTTCATAAAGACGACCAGCACATCGCCCAAAA
GATGGATGGCTATTTCAAAGGCAGCGAGTTCGGGTTCAAGGGACTCACCAAATTCATACACACCCCCTATCA
CACCGAGAAAGGATTCTCAATCAGGTTTGAGGACCGCGACAATCCGTGGCCCGAGATCTACGAAGCCGTCAC
TAACAAGCACTTCGAGTCCGACATACAATACATTGCGATCTACATCAGCCCCTTCAGCAAAAACAGCCCCGA
CAAGAGTCGGCGCAAAATCTATTACAAGCTCAAAGAACTGCTCTTGAAAGAAGGCGTGAGCAGCCAGGTGAT
TGACGGCGAGAAGGTGATGACCAACGAGAAGTATTACTACAGCCTCCCCAACATAGCAATCGCCATTCTGGC
CAAGTTGAATGGCACCCCTTGGAAACTGGACACCAAGCTGAAGAACGAACTGATCGTGGGAATCGGCGCCTT
CCGCAACAGCGAGGTTGACATTCAATATATCGGCAGCGCGTTCTCTTTCGCAAACAACGGCAAGTTTAATCG
CTTTGAGTGCTTCCAGAAGGACCAGACGAAAGAATTGGCGGGAAGCATCATACGGGCGGTGAAGGAGTACGC
CAACGTAAACACCGGCATTAAGAGGCTTGTGATCCACTTTTACAAAAGCATGCGACAGGATGAGCTCCAGCC
GATCGAGGACGGCCTTAAAGACCTCGGCCTGGACATTCCGGTATTCATCGTATCTATCAATAAAACAGAAAG
CAGTGATATCGTGGCGTTCGATAACAGCTGGAAGGATCTGATGCCGATGAGCGGCACATTCATTAAAGTGGG
GTACAACAAATTTCTCCTGTTCAACAACACCAGGTATAATCCAAAGTTTTACAGCTTCCACGACGGGTTCCC
CTTCCCCATCAAACTTAAGATTTTTTGCACTGAAAAGGAACTCGTGGAGGAGTATAAAACGGTTAAAGAGCT
GATCGACCAGGTGTACCAATTTAGCCGCATGTACTGGAAGTCTGTCCGCCAGCAGAACCTGCCCGTGACCAT
TAAGTATCCGGAAATGGTGGCCGAAATGTTGCCTCACTTTGACGGGAATGAGATACCTGAATTCGGTAAGGA
CAACTTGTGGTTCCTGTAGTAACTCGAGGTTAACTTGT
337 74 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGCGAAAAGTAGAGGATCCAAAGAAGAAACGGAAGGTCGGCAG
CGGAAGTGTGAACCATTACTATTTTTCCGAATGCAAGGCGGACGAGAAAGCCAGCGACATAGCCATCCACCT
TTACACCGTGCCCCTGTCCAACCCCCATGAGAAATACAGCTATGCGCACAGCATCGCCTATGAATTGAGAAA
ACTCAACTCATACATAACCGTGGCCGCGCACGGTCAGTACATCGCGTCTTTCGAGGAGATATGCCACTGGGG
CGACCACAGGTACATACAGCACGAACATAGACCAATCCAGTGCAGCCTCCCGATGGAGAGGACCATACTGGA
AAGACTCCTCAAGAAAGAGCTCGAGAATAGGTGCAAAAGCAGCTATAAGATGGACAACGACCTTTTCCGGTT
GGCTAACGAGCAAAGCATGCACGTGGGCGAGATCAGCATACACCCAGCGATCTACATCTCATTCAGCGTGGA
GGAAAATGGTGACATATTTGTTGGCTTCGACTACCAGCACCGGTTCGAGTACCGCAAAACACTCCAAGACGT
CATCAACAACGATCCCTCCCTGCTTAAGGAAGGCATGGAAGTGGTGGACCCCTTCAATAGAAGGGCCTACTA
TTACACTTTTGTGGGCATGGCCGATTATACCGCCGGACAGAAAAGCCCCTTCCTGCAGCAGTCTGTGATCGA
CTATTATCTCGAAAAGAATGAGCTGTGGAAGCTCAAGGGTGTGCACGAAAAAACCCCCGTGGTGCACGTCAA
GAGCCGAGACGGTCACTTGCTCCCGTATCTGCCGCACCTGCTCAAATTGACATGTTCATACGAACAGCTCTT
GCCCAGCATGACCAAGGAAGTCAATCGCCTGATTAAGCTGAGCCCCAACGAGAAGATGAGTAAGTTGTATAC
GGAGATGTTTCGATTGCTCCGGCAGCAACAGGTGCTGACCTTCAAGAAGGAAAACGTGCGAGCCGTCAACCT
CGGCTACGATGTGAATGAACTTGACAGCCCGATCATGGAGTTCGGACAAGGCTACAAGACAAACGAGATCTA
TCGAGGCCTGAAGCAGAGCGGAGTATACGAGCCCAGCTCAGTGGCCGTGAGCTTTTTTGTTGACCCCGAGCT
TAACTACGACCCCCAGAAGCGGAAAGAAGTAGGTTGCTTCGTCAAAAAACTGGAGAGCATGAGCGAGGCCCT
GGGAGTAAAACTGAACATAAGCGACCAGCCCCGACAACTTTATGGCCAGCTCCCCAAGGACTTTTTCAAGCA
GGACAACCTCTCATATCATTTGAAATCTATCACCGACCAGTTCAGGGGAACGGTGGTGGTTGTTATCGGCAC
TGAAGAGAACATCGACCGGGCATACGTTACAATCAAAAAGGAATTCGGCGGCAAGGAGGATCTGATGACCCA
GTTTGTCGGCTTCACCTCCTCCCTCGTCACGGAGAACAACATTTTTCACTACTACAACATCCTGCTCGGCAT
CTATGCGAAAGCTGGTGTTCAGCCCTGGATACTCGCCAGCCCAATGCACTCAGACTGTTTCATTGGACTCGA
CGTAAGCCACGAGCACGGTAAGCACGCATCAGGGATAATACAAGTGATTGGACGGGACGGCAAGATTATCAA
ACAAAAGAGCGTTGCGACAGCAGAGGCCGGAGAGACTATTGCCAATAGCACGATGGAAGAAATCGTCAACGA
AAGCATTTATTCCTACGAGCAGATCTACGGGGCCAAACCGCGCCACATAACATTCCATAGAGACGGGATCTG
TCGCGAGGACCTCGATTTTCTGCAAGCGTATTTGCGGAGTTTCCAAATCCCATTCGACTTCGTAGAAATCAT
AAAGAAGCCGCGACGCAGAATGGCGATATACTCTAATAAGAAGTGGGTCACGAAACAGGGAATATACTACAG
TAAGGGCAACACCGCTTATCTGTGTGCCACGGACCCCAGAGAATCCGTGGGTATGGCGCAACTTGTCAAGAT
CGTACAGAAGACTAACGGATTGAGCGTTCACGAGATAGTGAGCGACGTGTATAAGCTGTCCTTCATGCACAT
ACACAGTATGCTCAAGACCAGGTTGCCTATCACGATACACTATAGCGACCTCAGCTCAACGTTCCACAACCG
GGGCTTGATCCATCCCCGGTCCCAACATGAGAGAGCACTCCCGTTCGTGTAGTAACTCGAGGTTAACTTGT
338 68 GGTGTCGTGAGGATCCATGCCCAAAAAGAAACGAAAGGTAGAAGATCCCAAGAAAAAAAGGAAAGTGGGAAG
CGGAAGCATGGAGAACCTGGCTCTTAGTGCGCTGCAACTGGACTCTAAGCTCGACCGCTACATCGTGTGCAG
GTACAGAATCGTGTACCAGAAGCGAGACGAGACCATTCCCGGCGAACAGTTGGCCCGGAAGGCGGCCTACGA
GATCCAGAAAGCGAATGACTTCGCCCTTTTGACCAACCTCGGCAATCAACACATCGTTTCCCTCAAGCCCAT
CTCACAGAGGGGCATTGAAAGCACCCACCTTCAGGCGAATCTCATCGAAGACGGGGACCTGGAGCTCGATTG
CTCCATCGAACAACATCAGCAGGCACTCCAGCGGCTCGTGAACCAGGACATCAATAAAGCTGCGTGGAAGCT
TAAGAAGAGCTCACAGGGCAAACTCGATTACAAAAAGGCAGCTAGCGGGAACACCGAGATCTTTGAGCCAAT
TCATAGCACTCGAATCAACGCCCGAGCCACGTATCTTGACGCTTTTTGCTCACTGCAGCTTAGCCCCGAGGT
GCTTGCTAATGGAACCGTACTGATAGGGCTGCATCTCAAGCACAATCTGGTAGCAAAGTCTGACATCTCTTT
GCAGTGGATCATTGATAAAAGGCCCGATTGGCTGCAGAGCATCAAGAAGGTGCGGCACAGGTACTTCGATCC
CGGCAAAGCGCCCCTGGTCGCCGAATTCCTGAGGGTGGAGGACTCCCTGAATGGCAACAGCGTCTTGCCCCA
CATGGGCCAGAGTCTTGTTTCATACCACCAAGCGAAGGGACTCTTGTCAGAAAGACAGCTCGCAGAGGCCAC
GAAGAGCGTGCTGATAAAGGTAAAATACGGCAAAAACGAGGCGGACCACATCGCATCTCTGGTTGAACCAAT
GTTTGATTTCGACACGCTCAGCAAGATCGATAGTATCTTCCTTAACAAGTTGGCAAAGGACCTGAAGTGGAG
CCTGAACGACAGGATACGCACTTCCGCGAAAATGGTGAAAGGCTTGTATCTCCCAAACTTCAACTGCAAGCT
GGAACAGGTTGACTATCAGATCCTTCACAGGCAGCGACTTAATCACCAACAGATGCTTCAATTCGCCAACGG
GGCGAAATCTTCAAGAGAGCAGGACGTGCTGCGACATAAGGCGTTCGGCAACATGACGCGCACACAAGTTAT
CCCGCTTATTGCGGGCGAGAAGAACAATACAGAACAAAATAAGCAGCTCCTGTGCAACGCATACCAAGCATT
GCAACAACTGACCACCACGGAATTGCCTCCGTTCACCAAGTTCCCCAACCCCGTAGAGAACGCAGCCGAGCT
GGACGCAAGACTGAATGAACGGTGTCCCCCAAATGCGATACTGCTCATCGGCCTTATCGACAAAAGCGACAA
AGTGGCGATCCGCGACACCGCGTTTAGCTACGGTCTTGCAACCCAGTTCATGCGCCTGGATCACAGACCGAA
CGTCTACAGCCCCTCATATTTCAACAACGTGGCGGCTGGTTTGTTTTCCAAAGGTGGCGGGCAGCTCTGCGC
CATTGATGACATGCCGGGTGAAACCGACTTGTTTATCGGTCTCGACATGGGAGGGATCTCTGTAAGGGCACC
AGGCTTCGCGTTTCTGTTTCTGCGATCTGGTGCGCAGTTGGGGTGGCAACTCGCGGACAAACAACAGGGAGA
AAGGATGCAGGATGAGGCCCTGATGTCACTGTTGGACAAGTCTCTCACCACCTACCTGAGAAGCTGCTCTGG
TGAGCTTCCTAAGCGCATAACCCTCCATAGGGATGGCAAGTTCTACGAAAGCATAGAAGTGATCGAGCAGTT
TGAGCAGAAGCACGGCGTGAAAGTAGATGTGCTGGAGGTTCTGAAAAGCGGTGCTCCGGTTTTGTATAGACG
AAGCCGCATGGCCGACGGAACCAAGGAGTTTAGCAACCCCAATGTGGGCGACGCGATCTATCTCAGTGATCA
TGAGATGATCCTGAGCACGTATAGCGGCGAAGAACTCGGAAAGATATGGGGTGACAAGGTCAGCGTCAGGCC
TCTTAGGCTGCGCAAGAGATACGGTGATGTGAGCCTGGAGACCCTGGCACATCAAGTGCTCGTGCTGTCTAG
GATACACGGCGCTAGCCTGTATCGCCATCCTCGACTGCCCGTGACCACGCACCACGCCGACCGATTCGCAAC
ACTGAGGCAGGAAACATGCATAGACGCCCTCTCTAAGATGGACCGGCTCTGTCCGGTCTACCTGTAGTAACT
CGAGGTTAACTTGT
339 56 GGTGTCGTGAGGATCCATGCCTAAGAAAAAGCGCAAGGTTGAGGACCCGAAAAAGAAGAGGAAGGTCGGCAG
CGGGAGCATGCAGCTGAACTACTTCCCCATAAAGTTTGAGTTTGAAGAGTACCAGATAAAAACTGAGCCCTA
CAGCGAAGAACGACTTAAAGAGTTGAGGGCCAGTTACAACGCCACCCACTCCTTTTTTAGAAATGGAGACAA
TATATGCATTAGCAACAAGGAAGGCGAGGACATTAGTCTGACCGGCGAGGTGATACCGAAAAGAATTTTCGA
CGACAGTCAAGTGACCGCCTCATTGATAAAGCACTTGTTTTTCAGGACGTTCAAGGAGAGGTTCCCCAACTA
TATTCCTGTGGACTTTTACCCCTTCCGCTTCTTCTCCGCCCAGGCTAAAGACGACATCATCTATAACGCCCT
GCCCGGCAACCTCCGGAAACGAATCGCTTACAAAAAGCTGATCGAGGTTCAGTTGCGGCTGACGGAAATAAA
CGGCATCAAGCAGTTTGGCTTCCTGATCAACATTAAACGAAATTGGGTGTTCAACAAGTCATGCTTCGAGCT
CCACTCCGAGGGCTACAACCTGATCGGGGTGGACGTGCTGTACGCCGAGGAACTGCCGGGGTTGACCGAGGT
GCTGGCCCCAAACGAAGAGCTTTTGGGCGTAATCGCGGAAATCGTGGACGACAATGCCAGGATAGAAACCAA
CGAGGGCATTAAGGAGTTCCCTCTGAACCAGTTGTTCATCAAGAAAAGCAAGTACAACATTGGCAATTACCT
TAGCTTCGCGATCTCTCAGCAAAAGAGCGACGAAATAATGAATCTTATCGAGAGCAAACGCTCCGACATCTA
CAATACCAAGGGTCTTTACGACGAGATCTTGAAAATTGCGAACCATCTTTTTTGCGAGAACAGCGCACCCAT
ACTGTTTCATAATAAGGACGGATTCTGCTTTACTGTCGATTCCCAGCCGCTCAGTGTGACGAACAGCATGGA
ATTGAAGACTCCAACATTCATATACGATCCAGCGGCCACGAAGACGAATTCTAGCAATCCCGACTTGGGCCT
GTCCAATTACGGGCCCTACGACTCCAGCATTTTTGACATAAAGATACCCAACGTGTTGTGCATCTGCAATAG
GAATAATCGAGGCAACTTTACAAAGTTTCTGTCTAACCTGAAAGACGGGATACCTCAAAGCCGCTATTTCCA
GAAAGGCCTCCAGAAGAAATACGACCTCCAGGATGTGATCCTCAATATCCGAGAAATCCAGGCCTATAGCAT
CGCCGACTACCTTAACGCCATCAGGGACTACGATGAGAACAAGCCTCATCTGGCGATCATCGAGATCCCTGC
CAGCTTCAAGAGGCAGGCCGACGTGGCGAACCCCTACTACCAAATTAAGGCCAAGTTGTTGAGCCTGGAGAT
TCCCGTGCAATTCGTTACCAGCGAGACCATCGGTAACCACAACGAGTATATCCTGAACTCTATCGCGCTGCA
GATCTACGCAAAGCTCGGCGGGACCCCGTGGGTCCTGCCCTCTCAACGCAGCGTTGACAAAGAGATAATCAT
CGGAATAGGCCATTCCTGGCTTAGGCGCAACCAGTACGCTGGCGCAGAACAGAATAGGGTAGTGGGGATCAC
GACCTTTATGAGCTCCGATGGCCAGTACCTTCTGGGTGACAAGGTCAAAGATGTTGCCTTCGAGAACTATTT
TGAGGAGCTTCTGAAAAGCCTGAAGCAAAGCATCCAGAGGCTCAGCACAGAGCAGGGCTGGAGCGATGGCGA
CACCGTGAGGCTGATATTCCACATATTCAAACCGATAAAGAACACTGAATTCGACGTGATCAGTCAGCTTGT
CAGAGACATCACGCAGTACAAGATTAAGTTCGCATTCGTAACCATCAGCACTGTGCACCCTTCCATGTTGTT
CGACATTAATCAGTCCGGTATCGCCAAATACGGTTCCAATATCATGAAGGGACAATACATACCAAACAGGGG
CAGCAACGTTTTCCTGGACGAGAAGACATGCATCGTACAGATGTTCGGCGCGAACGAACTGAAAACGGCCAA
GCAAGGCATGAGCAAGCCCATCCTTATAAACATTCGCACCCCCCAGGGGAACTACAATTCAAGCGACCTGAA
CGATCTCCTGTTTTATGACCTGGGGTACATCACACAACAGATATTTAGCTTTACCTACCTCAGCTGGCGGTC
CTTCTTGCCCGGTGAAGAGCCGGCGACTATGAAGTACAGTAACCTCATTTCCAAACTTCTCGGGAAGATGCG
GAACATCCCTAACTGGGACGCCGACAATCTTAACTACGGCCTGAAACGGAAAAAGTGGTTCCTGTAGTAACT
CGAGGTTAACTTGT
340 4 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGCGAAAGGTAGAGGACCCCAAAAAGAAACGCAAAGTGGGCTC
CGGAAGCCTGAAGCTGAACCACTTCCCCCTTAATCCCGACCTCCCCCTGTACATCACAGAATATGCCCACCG
GAACCCGCGAGCGTTGCTCGGATTCGTTAGGGGCCAAGGTTTCTGGGCGCAACAGGTCGGAGAACAGGTACA
AGTGTACCACGGTAGACCGCAGCCCACGTTCAGGGGAGTTCAGGTGATCAGCCATACCAGGTTGGACCCCGA
CCATCCGGCTTTTGACCAAGGCGTTTTGAGCCTCATCCGACAAGCACTGGTGAGGGCGGGATACGTGCTGAC
CTACAGGGAGAGGATGGCTATTCATCCCAGACTGGAGAGGGTTGTGCTGAGACCCCCGGACCGGCACCCAGC
AGAGTTGACCGTCCATGCACATCTGCGATGGGAATGGGAGCTTGAAAGGCACAGCGGACAACGCTGGCTGGT
TCTTCGACCCGGCAGGCGACATCTGAGCGCCCTTCCATGGCCCGCAGAAGCAGTACAAATGTGGTCCGCCGC
TCTTCCGGCCACCTGCCAGAAGCTGCACGCCCTTTGTCTGGACCGAGGCCAACAGATGGCCCTTTTGCGGCA
AGAGGACGGCTGGCACTTCGCCAATCCCGGTGCTGCCACTCAAGGAAGGTGGCACCTGTCCTTTAGCCCCCA
GGCCCTTCACGAGCTGGGACTGGCACAGGCTGCGCACCATGCGGCTGCATTTAGGTGGGACGAGGTACAGCG
ACTCGTGCAACTGACTGACCTGTGGAAGCCCTTCGTGACCTCTCTGGAGCCCCTTGAGGTAGCTGCCCCCAT
CATTGCCGGGAAAAGGCTGAGGTTTGGACGGGGTCTTGGCCGCGATGTCACGGAGGTGCACAAGCGAGGTAT
CCTGGAACCACCCCCACTGCCCGTGCGACTGGCTGTCGTGTCTCCCCATCTTCCTGATGAGCACGCGAACGC
CCAGTTGAGGCGGGAGTTGCTTGCTCACCTCCTCCCGCGACACCAAGTACTGAGATCAGCGGAGAGCCGGCA
AGGCCTCCACGAGCACCTGAGGAGGCAAGATCAGGACGATACCCTGTATACCTTTTGGTCAGGCGGCGAGTA
CAGGAAGCTGGGCTTGCCCCCCTTCGATCTCGCACGAGGCCTGCACACCTACGACCCAGCTAGCGGCCAGCT
GCAACAACCGGCTGCCCTGGCACCAGCACCCGCGCAGGCCACGCAAGCGGGTAGGCAGCTGATAGCCCTGGT
GGTGTTGCCCGACGACCTGACGCGGTCTGTCCGGGACACCCTGTTTCAGCAGCTCCAGCAGTTGGGCCTTAG
GTGTCTGTTTAGTGTGAGCAGGACCCTGCTGCACCGACCACGCACAGAGTATATGGCATGGGTAAACATGGC
CGTCAAGTTGGCTAGGACTGCAGGGGCCGTGCCTTGGGACCTGGCAGACCTGCCCGGTGTCACCGAGCAGAC
GTTTTTCGTAGGCGTTGATCTGGGGCATGACCACACCCACCAACAGTCCCTCCCGGCCTTCACCCTGCACGA
CCATAGGGGACGCCCTCTTCAAAGCTGGACGCCTCCCCGACGCACCAATAATGAGAGGCTGTCATTGGCCGA
GCTTAAGAAGGGGTTGCATAGGCTTCTTGCACGCAGGAGCGTGGACCAAGTGATCGTGCATCGAGACGGCCG
ATTCCTTGCTGGCGAGGTGGACGACTTCACTCTGGCGTTGCATGATCTCGGCATCCCGCAGTTTAGCTTGTT
GGCAATaAAAAAAAGCAACCACAGCGTGGCGGTGCAAGCAGAGGAAGGATCCGTGCTTAGCCTGGACGAACG
ACGATGCCTTCTTGTTACTAATACCCAAGCCGCGCTTCCGCGGCCCACGGAGTTGGAACTGGTCCATAGCGA
CAGGCTTAGTTTGGCGACCCTGACCGAACAAGTATTCTGGCTGACCCGCGTCTTCATGAACAACGCGCAGCA
TGCGGGCAGCGATCCAGCCACCATCGAATGGGCCAACGGCATAGCCAGGACTGGACAGCGAGTGCCCCTGGC
CGGGTGGCGGCTGTAGTAACTCGAGGTTAACTTGT
341 27 GGTGTCGTGAGGATCCATGCCCAAGAAAAAGAGGAAGGTCGAAGATCCTAAAAAGAAAAGGAAAGTCGGGTC
CGGTAGCATGCCCACCCAGTTCCAGGAGGTGGAAGTGATACTCAACCGCTTCTTTGTAAAGAAACTGTCTCG
GCCCGACCTTACGTTCCATGAGTACCAATGCCAGTTCACCCAGGTTCCAGAGCAAGGCAGCGAACAAAAGGC
CATCAGCAGCGTGTGCTACAAGCTCGGTGTGACCGCCGTGAGGCTGGGCTCATGCATCATCACCAGGGAGCC
CATAGACCCTGAAAGGATGCGCACCAAAGATTGGCAGTTGCAGCTGATCGGATGCCGAGAGCTGAGCTGCCA
AAACTACCGAGAGAGGCAAGCTTTGGAGACTTTCGAGCGAAAAATCCTGGAGGAAAAGCTCAAGGAAACATT
TAAGAAGACCATCATCGAGAAGGACTACGAGTTGGGCCTGATCTGGTGGATATCAGGCGAAGAGGGACTGGA
AAAAACCGGTCACGGGTGGGAAGTGCACAGGGGCAGGCAAATAGACCTCAAGATCGAGACGGACGAAAAGTT
GTACCTGGAGATCGACATACATCACAGGTTCTACACCCCCTTCAAGCTGGAGTGGTGGCTGAGCGAATACCC
CAACATCCAAATCAAGTACGTGCGCAACACGTACAAGGACAAGAAGAAATGGATACTGGAGAATTTCGCCGA
CAAGAGCCCCAACGAGATTCAGATAGAGGCCCTTGGCATCAGCCTTGCGGAATACCACCGGCAAGAAGGTGC
TACCCAGCAGGAAATCGACGAGAGTAGGGTTGTGATCGTCAAAAAGATCTCTGACTACAAGGCGAAACCCGT
GTATCACCTGTCTCAGAGGCTGTCCCCGATACTGACCATGGAGACCCTTGCCCAGATCGCCGAGCAGGGTCG
GGAAAAGAAGGAGATACAGGGCGTGTTCGATTACATTAGGAAGAACATCGGCACGAGGCTGCAGGAGAGCCA
GAAGATCGCGCAGGTCATTTTCAAGAATGTTTATAACCTTAGCAGCCAGCCCGAGATCATGAAGGTGAACGG
TTTTGTAATGCCACGCGCGAAGTTGTTGGCAAGGAACAATAAGGAGGTCAACCAGACCGCTAGGATCAAGAG
TTTCGGCTGCGCTAAGATCGGAGAAACGAAGTTCGGATGTCTCAATCTGTTCGACAACAAACCGGAGTACCC
GGAGGAGGTACACAAGTGCTTGCTGGCGATTGCGCGGAGCAGTGGGGTCCAGATAAAGATAGATAGCTACTT
CACGGGGAGCGACTACCCGAAAGATGACTTGGCCCAGCAAAGGTTCTGGCAACAGTGGGCGGCACAAGGAAT
AAAGACGGTGCTGGTCGTGATGCCCTGGTCCCCTCACGAGGAGAAGACAAGACTGCGGATCCAAGCTCTTAA
AGCCGGCATCGCAACTCAATTTATGATCCCCACGCCCCAGGATAACCCATACAAAGCATTGAACGTTGCTTT
GGGTCTGCTCTGCAAAGCCAAATGGCAACCCGTTTACCTGAAGCCCCTGGATGACCCCCAGGCCGCAGACCT
GATCATCGGCTTCGACACTTCTACCAACAGGCGGCTCTACTACGGTACAAGCGCCTTCGCGATTCTGGCGAA
CGGCCAGTCACTGGGCTGGGAGTTGCCTGACATCCAGAGGGGCGAGACATTTAGCGGCCAAAGTATATGGCA
GGTAGTGAGCAAACTTGTGCTGAAATTCCAAGACAACTACGACAGCTACCCTAAGAAAATTCTGCTTATGAG
GGATGGACTGGTTCAAGACGGCGAGTTTGAACAGACCATAAGAGAGTTGACCCACCAAGGGATCGACGTGGA
CATCCTGAGCGTGAGGAAGAGCGGTAGTGGCAGGATGGGAAGAGAACTGACAAGCGGCAATACTGCCATCAC
CTATGACGACGCCGAAGTGGGAACCGTGATATTCTATTCTGCCACCGACTCATTCATACTGCAGACAACCGA
GGTAATTAAGACAAAAACGGGCCCACTCGGTTCCGCGCGACCGCTCAGAGTGGTTAGGCACTACGGGAACAC
CCCGCTTGAACTGCTCGCGCTGCAAACGTACCACCTGACCCAATTGCATCCCGCCAGCGGCTTTCGGAGCTG
TAGGCTCCCCTGGGTTCTGCACTTGGCAGACAGGAGCAGCAAGGAGTTCCAACGGATCGGTCAAATTTCATT
GCTCCAGAACGTGGATAGGGAGAAGCTGATTGCAGTGTAGTAACTCGAGGTTAACTTGT
342 24 GGTGTCGTGAGGATCCATGCCTAAGAAAAAAAGAAAAGTCGAGGATCCCAAGAAGAAGCGGAAGGTGGGGTC
CGGGTCTATGCTCACACAAGAACAATTTATACGCAACTTTAGCGTTATGGCCAATGGTGAAGTAGACTTCTT
TCTTGGTGCCGGTGCATCTATTGCGAGTGGAATCCCAACTGGGGGTGGCTTGATTTGGGAATTTAAGAGGAC
ACTGTACTGTAGCGAGTGCGGCATCAGCGCCGAAAAGTACAAGGACCTGTCACTCCCAAGCACGCGCAAAAC
GCTCCAGGACTACTTCGACATTAAAGGGTATTGCCCCAAACAATATGCGCCTGAGGAATACAGCTTCTATTT
CGAGCAATGTTACACCGATCCCATGGCCCGAAAGAGGTTCATCGAGAATATGGTTAGTGGGAGGGAGCCAAG
TATAGGTTACCTTTGTCTCGCGGAGGCCGTTATGCAAGGCAAAGTTAAAAACATTTGGACTACCAACTTCGA
TAGCCTTCTGGAGAATGCCCTCCATAGGCTTTACCCCATGAACAACGTTTTGGTGTGCTCCGAGGCTAATAG
AGGCAGTGTGTGCCTGCTCAACCCGACGTACCCAGTCATAGGCAAGCTCCACGGCGACTATCGCTATGATTG
GCTCAGGAACACCGAGGACGAATTGCAGCGACTCGAGACCAGCCTTAAAGGTTACGCGTCCAGCCAACTTAC
AGGGAAACAACTCGTCGTTATAGGATATAGCGGGAACGATGAGAGCATTATCAGTTTCCTCAAGGATTGCAT
AGATAACCCGGCACTGCTTACCAAGGGTCTGCTGTGGGCTGTACGACGCGGTTCCTGGGTAAACCCGAGGGT
TAATGAGCTGATAGAACGGGCGCACAAAATTGGGAAACCAGCCGACGTGATCGAGATCGATGGCTTCGACCA
ATTGATGTTCTCAATATACCAGATCCAGAACTACCATAATGAGATTATCGACGGCCAAGGCAGGCTCCTCCA
GGTCGGATCTGACATCCGCCTCACGGGGAAGCCCGTGGACAGCTTTGTCAAGCTGAACGCTTACAAGGCTGA
GTACTGCCCCCTTTGTAACGTGTTCGAGACAGACATCACATCCTGGAAGGAACTTCGGACCATAACCGGCAG
CAGTGACATCATCGCCGGTCTGTTCTCCAAACATATCTATTCTCTGTCTTCCGCAGACAAATTGAAGACCGT
GTTCAGCAAGCACTTTCTCTCTAGCATTAACAAGGAGGAGGCTCCCGAACGGGACATTCGACGGAACGAGAG
TGTGTACATTGGATTGATTTACCAGCTTATTAAGCGGACCCTGCTTTCAAAAGGGATGGTGTCCTTCGCTAA
GAATAAGGTCTATAACCCCGACAGCTGCCGCAGCGAGCAAGGCTACCAAGTTTTTGACGCCCTGGAGATCGC
GGTCAGCTTCGTTGATGGAAACCTGTACCTGAATCTTATGCCCACGGTACATGTGAGAGGCTCAAATGGCGA
GAGTCTCGACAAAGAGTCCTACCAAATACAAGTCAACCATGTGGTCAGCACAATCTACAATAAGCAATACAA
TGAGAAACTGCGGTTCTGGGAGAGCTTGTGTCTGGACAGTGGTAGAATAATCTTCGAGAACGACGGCTTCAG
CATATCATTTGTCGCTCCCGCTGTCTCCCTGGGCGGCAACAATCGAAGAGCTAAGTGGCTTTCCATGCCGTC
CTGCAAGTATGACGAACCACTCATGTGCTTCTCAGACACTGACAAAAGCAAACGAGTTATTAACCAACTGAA
GGGACTCTGCCAGTACGGGCCAATCGACTGCTCTTATATGCGGGATAGCACCACAAGGCCCAGCGTTAGGCT
GGCCGTTCTGAGCCCGAACCAGGACATGGACCGAATTCTTGCACACCTCAATAAACTCAACACCCACGTCCA
AAACAGGGGCAGCGATAATTTCCTGCCCCACTATGAGGGCTTTGAGCAAGTTTACAGAAGGGCTCTGAGCGT
CCCTACGAAGGAGCAGAGCAACATCTGCATCGGATACAACGTGAACGCCATCCTCAAAATGTCTCCTGCAGA
GTTTCTGGCTTTTATGAAGCGGGGTATAGAGAAATACTCCCTTCGGTCAAGCGATTTCGATATACTCGTTAT
TTACATCCCAGAGTCATTCGCGCATTTCCGGACAGCAACCGAAATTAGTAGCGACTACAATCTGCACGATGC
GCTCAAACTGTATGCCACGGATAAGGGGATTATCCTTCAACTCATAGAGGAGAAATCTGTGAAGTCATACGA
CCCCTGCAAAGTAATGTGGGGCTTGTCCACCTCACTCTACGCGAAGGCGACAGGGGTACTTTGGCATCCAGA
GGCAATTAGAAATGACACGGCCTACATAGGGATAAGCTACGCTTTCAGCGAAGAGAAAAGGATTTGTATAGG
CTGCAGTCAGCTGTTCGACTCAACCGGGACAGGTATTCGGATGGTCCTTAGAAAGATAAACAATCCGATATT
TCTGGGGCGATCCAACCCCTACATGAGGGAAGACGACGCTCGAATTATGATGACCGAGCTCAGGGAGCAGTA
TTACCACAGCGCACCTGTGAATACTCTCAAGAGGGTCGTGATCCATAAGACCACGCCCTTCATACGGGATGA
GATAGCCGGTATAATGCAGGCATTTAACGGCATCGAGGTCGAGCTGGTTCAGATTCAAGACTATTGCTCTTG
GAGAGGCATACGCTTCGGCGGTGAGCCTGGGAAAACGGCGTTTGGGTTCCCGGTGAAGCGAGGTATGGCCGT
AAAACTCGACCGAGAAAGCTTCCTGCTCTGGACCCACGGCTGCGTGATTCACCCGGAACTGTCAGGCACGCA
TAACTATTTCAAAGGTTCACGCGGTATCCCAGCACCCCTCCTGGTCCGCAGGTTTGCGGGTAACGCAAGTGG
CGACACATTGGCAAAAGAGATTCTGATGCTTACGAAGATGAACTGGAACTCCGGTGACAGTCTGTACAAAAC
CCTTCCCGTGACCCTGGATTTTGCGAAAGTTCTCGCCCGCATGTCTAAGCAAGATGAGGCGATCTTTGATAA
GGCGTACGACTTCAGGTTTTTCATGTAGTAACTCGAGGTTAACTTGT
343 62 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGAGAAAGGTGGAAGATCCCAAGAAAAAGAGGAAGGTGGGTAG
CGGGAGCATGAGGGAAACCAACATCTACGAGCTCAGCGGCCTCGAAACCGTGAGTACCAGCTACAGACTTTT
CGAGTTGCAGGGCGCGCCAGAGTTCTCTCCTGAGTATTATGCTGGTGTGAGCCGCCTCGTGAGGACGCTTAG
CAGGAGACACCAGGCACCCTTCACCAGTATCCAACGGGGCGAGACCATGTTGCTCGCTGCACCCGAGGCCCT
GAGCGGTGATCTCGCAGAACACCATAATCTGGCACGCTGGGTGGCGACCCTGAAGTCACTTGGAGATAGCAT
AGAGATAGACTGCAGCGTGAGCGGAGATGAGCTGGACCCCATAAGGCTGCGATTCCTGAACTTCATGATCCA
ATCTCCATTGTTCAACCACGGCGAGCTCTGGCAGCCCAGGGCCGGTGATGCCTTCTACTACCGGAAGCCTGC
CGACACGTTCGACGGAATCGAACTGTTTGAGGGTATTGCCGTGAGGGCCGTGCCCTACCCAGGAGGCGGGTT
CGGCGTTATGCTCGACGCGAGGACTAAGCTGATCTCACAGCGGGCTGTGGGCGCCTACGCGGACCCGAATTT
CATAAGGAGGCTGAAAAACACTAGCTGCCTGTACCGAATGGGAGACATCTGGTACGAGATAAAGATCAGTGG
CGCGAATCAGACCGTTTCTCACCCCATCCTGTTTAAGGACAACCAGCCCGTGTCACTCAAAGCCTACCTGCA
CGAACAAGCACGGCAGCCAATCCCCAAGTCTCTGATTGATCTTAAAGGTGACGGCGTGGTGTTGACCTATCG
CGGCAGCGATAGCGCCGAGGTCAAAGCGGCACCCGCGGAACTTTGTTTCCCCATAGTAGACACCCATAGCAA
GAGGGGTGCCCGGCACCAGAGAAGGAGCATCCAAGCCCCACACATCCGACGCAGCAAGGCTTACCGATTCAA
GCAAAGGTTCTTGCGGGACATCAAAATAGGAAATGCCGTGTTGAGCGTGGCCGACCAACCCGCAGCCCTCAA
GACCAGGCCCATCGACTTGCCCGAGCTGCAATTCGGCTCCAATAGGATTCTGTACGGCACGGACAGGGGCGG
AGACCGAATCGACCTTCGCCAGTATGCCAAGAATCGGCGAACGCTGCTGGAGCGCGCAGACGTGGGCTTCTT
TGAGACTTCTCCCCTGGAGCCCCAATGTTTGGTACTTCCTAAGAGCGTGATGAACGCATGGGGCAACGAGTT
CGTTCGAGACCTGACTGCCGAAGTGAAGCGACTCCACCCCACCGGTAACTACAAGCCAACCGTAATCGCGTT
TGATGATGTCAGCGCAACCGTGGACGCCAGGAGCCAAGCAGAAGCCATCTTCAAGCTCGCGGAAGACGGGGA
TCTCCCTCCAGGCGACTGCGCCATTATGATACACCGAACCAAAGGAAAGGCAAGAGCGCAGGAGGAGCTGCC
CGCACTTCTTATAAACAAGCTGAGAAAGAGCTACGGAGTGAATGCCGCCATATTCCACGCGACTGTCCCCGG
CAACGCCTACCGAAGGGAAAGCGCCAGCGATGGCGCTCGCTATGTGCGCAAGCGGGATGAGAAGGGCAGGTT
TAGTGGATACCTGACCGGAGCGGCGCTTAACAAGATTCTTCTGCCCAACGCCAAGTGGCCCTTCGTGCTCAA
GGACGAGTTGGTGGCAGATATAGTGGTGGGCATAGATGTGAAACATCACACCGCAGCTCTCGTTTTGATCGC
CGAAGGCGGGAGGATTATCAGGCACACTCTTCGCCTCAGCACCAAGAACGAGAAACTCCCTGCTGGTATCGT
GGAAACGAAGCTGGTGGAACTGATTTCAAATGAAGCACCACACCTGAGCAGGCTCACCAAAACAATCGCCAT
CCATAGGGACGGCAGGATTTGGCCCTCCGAGCTTAAGGGATTGCGAGCAGCCTGTAGGAAGCTTGCCGACGA
CGGCCACATCGATCCTGCGTTCGATCTGAACGTCTTCGAGGTGAGCAAAAGTGCCCCTGCTAGGCTTAGGCT
GTTTAGCGTCGACCGCAGTGCTGGCAGAAAGCCGAGGATTGAAAACCCGGAACTGGGGGACTGGATGATGCT
GACAGAAACCGACGGCTACGTTTGCACGACCGGTGCTCCGCTGTTGAGAGGTGGTGCGGCTAGACCCCTGCA
TGTAAAGCAGGTCGCAGGTGATATGAGCTTGCAGGACGCCCTTTCCGACGTGTTCCGACTGAGCTGTCTGAC
CTGGACTAGGCCCGAGTCATGTAGCAGGTTGCCTATCAGTTTGAAGCTCTGCGATATGCTGCTGATGGACGA
GGGAACTGCCCACGACGAGGACGAAATCCTTCATGCTAACGACGACACCCCAGCCGTTAGCGCCTAGTAACT
CGAGGTTAACTTGT
344 55 GGTGTCGTGAGGATCCATGCCCAAAAAGAAGCGAAAAGTAGAGGATCCAAAGAAAAAGCGGAAGGTCGGGAG
CGGCTCCATGGCGTTTAGGCCCGGTGAACGAGTCAGACCGCAGCTCGCGCTGAATGCGATCAGGGTCCTTAC
ACCCCCTGGCACCATCCCCGCCAGTGTAGTCCAATTCGACAGAGCGCTGCTGCACGCATATCTTGACAGACC
CGAGAACGACGTATTCGCTACCCGACACGGGGAGACTGATATGGCGGTCGTACCCCTGACCAGCGGTGCGAA
CCTGCCAACGGACAGAATGGGGCTTCCAGCTGCAGAGCACCTCAGGCTGGTATCTGCGCTGACAAGAGAAGC
TGTGTTTCGCCTCCTCGCGGCCAGCCCGGAAGCGGATCTGCTGATCCGGCGACGCCCACCGACCGTCGCGGG
GAAGAGAGAAAACGTACTTGCAGAGGACATTGGGCTCCCGGACTGGTTGAAGAAAAGACTTGTGCTGGAGTT
CGACACGCGCATATTGCAACCACCGAGAGGGGACGCCTACGTGGTGCTGACGTGTAGTAAAAGGCTGCGCAC
GACAATAGACGCGAGTTGTCGCACCCTTCTGGAACTCGGTGTACCACTGACGGGTGCCGCAGTCAGCTCCTG
GAGGGAAGATCCTGACCCCAAGGTGAGCCGGCGATTGGCCTACGCTGGGCGCGTTGTAGAAGTAGGGCAGGA
CACGCTCACTCTGGACGACCACGGAGCTGGTCCGAGTGTTGTCTCCAGCGAAGACGTGTTCCTCGAGCCGAC
TCGAGCAAACTTCAACAAGGTGGTGGAAGTGATAACCCAGGGTAACTCCGAACGAGCCTTCAAGGCCGTACA
AAAAGCAGAAGCCGAATGGCACGGCGGGAGGCGGACAATCGAAATAGTGCATGGTGTCCTCAACCAACTCGG
CAACCGGTCAATGGTTCTTGCCGATGGCGTGCCTCTGCGGCTCGGGGGCTTGATAGACCAAGCGGTCGATAG
CGACGCATTCCCCCCAGCCGAGGCGGTGTGGCGCCCTAAGCTCTCATTCGACCCCGTGCACAGCCCCGAGAC
ATCAAATTCCTGGAAACAGCAGTCACTGGACAGGACGGGCCCTTTCGATAGGCAAACCTTTGAAACAAAGAG
ACCGCGAATCGCGGTTGTCCATCAGGCCGGAAGAAGGGAGGAAGTGGCTGCGGCGATGCGCGATTTCCTCCA
CGGAAGGCCTGACATCGCCAGCGATACGGGCCTGGTTCCCCACGGTTCAGGACTCCTCGGACGCTTTAGGCT
CCACGAACCCGAAGTGAGATACTTTGAGGCCGCAGGCAGGGGGGGACCCGCTTATGCCGACGCAGCACGGAG
TGCGCTCAGGGACGCGGCGTCAAGGGACGAACCATGGGACCTCGCAATGGTGCAGGTAGAGCGGGCGTGGCA
AGATCGCCCACATGCCGATAGCCCGTACTGGATGAGCAAGGCAACGTTTCTCAAGAGGGATGTGCCGGTGCA
AGCCCTTAGCACAGAAATGTTGGGTCTTGATGCATTTGGGTACGCGAACGCACTTGCGAACATGTCACTTGC
AACGTATGCGAAACTGGGCGGTGCCCCGTGGCTTTTGTTTGCCAGGTCACCAACCGACCATGAACTGGTGGT
CGGGCTCGGAAGCCACACTGTAAAAGAGGGCCGAAGGGGTGCGGGTGAGAGGTTTGTCGGTATCGCGACCGT
ATTCAGCAGCCAGGGCCATTATTTCTTGGATGCCAGGACAGCCGCGGTCCCGTTTGAAGCCTATCCTGCTGC
CTTGAGCGACAGCATCGTTGACGCGATCAAAAGGATTGGACGAGAGGAAGCCTGGCGACCAGGCGAGGCCGT
CAGGTTGGTCTTTCACGCCTTCACCCAGTTGAGCCGAGAAACCGTTCAGGCAGTGGAGAGAGCAGTAGCAGG
CATCGGGGCCACCAACGTAAGCTTCGCGTTTCTGCACGTTGTCGAAGATCACCCGTTTACCATGTTTGACCG
AGCGTGGCCAGACGGAAAGGCGACATTCGCCCCTGAAAGAGGTCAGGCGCTTCGACTCTCCGAGCGCGAATG
GTTGTTGACACTTACCGGCAGGCGCGAAGTTAAGAGCGCCAGTCACGGGCTGCCTGGGCCGGTTCTGTTGCG
ACTTCATGACAGCAGCACCTATAGAGACATGCCCGTGCTCGTCCGACAAGCATCCGACTTCGCCTTCCACTC
TTGGCGCAGTTTTGGACCCAGCGGACTCCCCATCCCGTTGGTTTACGCGGACGAAATTGCAAAACAGCTCAG
CGGCTTGGAAAGAACCCCCGGATGGGACACGGATGCGGCTGAGGGTGGCCGGGTTATGAGAAAGCCTTGGTT
TCTGTAGTAACTCGAGGTTAACTTGT
Example 10: RHDC Expression and Purification A synthetic codon-optimized gene encoding Argo # was cloned into the pETM-30 expression vector. The subcloned Argo plasmids were transformed into Escherichia coli BL21 (DE3) (New England Biolabs) according to manufacturer's instructions. Strains were cultivated in LB medium (Cart Roth) containing 50 μg/ml Kanamycin (Carl Roth) in a bacterial shaking incubator at 37° C. and 150 rpm. After overnight incubation, the preculture was used to inoculate expression cultures (150 ml) with a starting OD600 nm of 0.05. The cultures were incubated at 37° C. and 150 rpm until OD1600 nm of 0.6-0.8 was reached. AGO protein expression was induced by adding 1 mM of isopropyl-b-D-thiogalactoside (IPTG) (Sigma Aldrich). Expression was continued in a bacterial shaker at 30° C. and 150 rpm for 6h. Cells were harvested by centrifugation at 500×g for 10 min at 4° C. The pellet was frozen and stored at −80° C. The frozen cells were thawed at 4° C. and resuspended in 25 mL Buffer I (50 mM Tris/HCl pH 7.5, 0.5 M Sodium chloride, 5% Glycerol) supplemented with 1 mM Phenylmethanesulfonyl (Carl Roth) and 5 mM β-Mercaptoethanol (Sigma Aldrich). The resuspended cells were disrupted by sonication with a Branson Digital Sonifier (Model 102C, 3 mm tip). Sonication: Step 1: 25% amplitude: 5 sec ON, 2 sec OFF for 2 min; repeat twice; pause for 3 min after each cycle; Step 2: 35% amplitude; 5 sec ON, 2 sec OFF for 30 sec. The lysed pellet was kept on ice during sonication. The lysate was centrifuged for 15 min at 15000×g at 4° C., after which the supernatant was used for His-Tag affinity chromatography purification. The Ni-NTA agarose (Qiagen) was equilibrated in 10 CV (column volumes) Buffer I supplemented with 5 mM β-Mercaptoethanol and after centrifugation (50×g for 5 min) diluted with Buffer I in a 1:1 ratio. The cleared lysate was incubated with 350 μl of the diluted Ni-NTA agarose suspension on a rotary wheel (30 min at 4° C.). After centrifugation (50×g for 5 min) the Ni-NTA agarose beads were transferred to an empty Bio-Spin Chromatography column (Biorad). The column was washed with 60 CV (column volume) of Buffer I supplemented with 5 mM β-Mercaptoethanol. The His-tagged AGO protein was gradually eluted with Buffer I supplemented with 5 mM β-Mercaptoethanol and increasing concentrations of imidazole (Elution fraction (EF) 1: 25 mM-11 CV; EF 2: 50 mM-11 CV; EF 3: 75 mM-11 CV; EF 4: 125 mM-2.5 CV; EF 5: 250 mM-2.5 CV; EF 6: 250 mM-2.5 CV; EF 7: 250 mM-2.5 CV).
Argo proteins and empty control (only expression vector-control for protein prep impurities) were purified, run on SDS-polyacrylamide gels and stained for 1 h in coomassie blue then de-stained in a solution containing water/acetic acid/methanol. The protein was quantitated using Image J, FIG. 15A. FIG. 15B, FIG. 15C, FIG. 15D, and FIG. 15E.
To determine if the sonication protocol initially utilized for Argo #441 was functional using other Argo sequences, Argo #17 and Argo #30 together with Argo #41 were tested to see whether sonication conditions hold true for other Argos. As used herein, Argo sequences can be referred to interchangeably as AGO # or Argo #. Sequences for the Argo # can be found, for example, in Table 18. The Control cleavage assay was done with 2.5 uL of each prep. Since AGO #17 and AGO #41 showed ssDNA cleavage, the concentration of used protein preps with Image 3 using BSA standards was evaluated at: Argo #41: 0.58 μg/reaction. Argo #17: 0.15 μg/reaction, and Argo #30: 0.53 μg/reaction. Based on this, 0.3 μg protein/reaction was utilized, FIG. 16.
TABLE 20
Argo Protein Quantification
MW [kDa] μM μg/μL μg/mL
Argo#4 108.62 1.486 0.16 161.36
Argo#7 117.17 0.200 0.02 23.45
Argo#8 114.12 — — —
Argo#9 106.86 3.313 0.35 354.01
Argo#10 137.98 — — —
Argo#16 104.72 0.295 0.03 30.86
Argo#17 115.23 0.487 0.06 56.11
Argo#19 118.25 — — —
Argo#20 114.38 4.114 0.47 470.50
Argo#21 128.66 1.260 0.16 162.16
Argo#23 125.36 0.331 0.04 41.48
Argo#25 115.64 — — —
Argo#26 144.52 — — —
Argo#27 116.49 3.819 0.44 444.93
Argo#29 118.77 0.445 0.05 52.91
Argo#30 111.47 1.852 0.21 206.49
Argo#41 118.42 1.920 0.23 227.31
Argo#63 118.35 — — —
TABLE 21
Lysis Conditions
Lysis Condition Reagents
1 50 mM Tris/HCl pH 7.5
FIG. 13A 500 mM NaCl
5% Glycerol
1 mg/mL Lysozyme
100 μg/mL DNase I
5 mM β-Mercaptoethanol
1 mM PMSF
2 50 mM Tris/HCl pH 7.5
FIG. 13B 500 mM NaCl
5% Glycerol
1 mg/mL Lysozyme
1 μg/mL DNase I
5 mM β-Mercaptoethanol
1 mM PMSF
3 50 mM Tris/HCl pH 7.5
FIG. 13C 500 mM NaCl
5% Glycerol
1 mg/mL Lysozyme
Benzonase (1:10000)
5 mM β-Mercaptoethanol
1 mM PMSF
4 50 mM Tris/HCl pH 7.5
FIG. 13D 500 mM NaCl
5% Glycerol
1 mg/mL Lysozyme
Benzonase (1:20000)
5 mM β-Mercaptoethanol
1 mM PMSF
5 B-PER Lysis Buffer
FIG. 13E 1M NaCl
5 mM β-Mercaptoethanol
1 mM PMSF
500 μg/mL Lysozyme
Sonication: no nucleases
20% Amplitude
(5 sec ON, 1 sec OFF)
2 min; 2 cycles
6 50 mM Tris/HCl pH 7.5
FIG. 13F 500 mM NaCl
5% Glycerol
5 mM β-Mercaptoethanol
1 mM PMSF
Sonication: no nucleases
35% Amplitude
(5 sec ON, 1 sec OFF)
2 min; 1 cycle
Example 11: Argonaute Activity Assay For activity assays, elution fractions containing Argo protein (EF5) were diluted with Buffer 1, containing 5 mM β-Mercaptoethanol and 250 mM Imidazole to a final protein concentration of 30 μg/mL. A total of 10 μl protein sample was mixed with 0.25 μM sgDNA or sgRNA in 18.5 μl of reaction buffer (Ago preloading step: 0.3 μg protein, 0.25 μM sgDNA/sgRNA, 20 mM Tris/HCl, 5 mM MnCl2; 250 mM NaCl. 83.3 mM Imidazole, 1.6 mM β-Mercaptoethanol, 1.6% Glycerol). The reaction was incubated at 37° C. for 15 min. After pre-incubation, ssDNA (0.25 μM) or dsDNA (100 ng) templates (1 μl) were added and incubated for 1 h at 37° C.
AGO protein preps: DNase I or Sonication lysis (Lysis Condition 6)
Elution fraction 4 (EF4): 125 mM Imidazole
Elution fraction 5 (EF5): 2501 mM Imidazole
sgDNAs (Table 25):
D1 . . . targeting sgDNA
D2 . . . targeting sgDNA
NT . . . non-targeting sgDNA
Template: 90 nt ssDNA (Table 24)
Expected cleavage products for D1: 66 bp, 24 bp
Expected cleavage products for D2: 69 bp, 21 bp
Final Buffer Concentrations MnCl2: 5 mM Tris/HCl, pH 8: 15 mM NaCl: as indicated
Imidazole: 32.25 mM (EF4), 62.5 mM (EF5) Incubation Time: Pre-incubation (AGO+sgDNA): 15 min at 37° C. Incubation: 1 hour at 37° C.
To inactivate ssDNA cleavage assay reactions, samples were incubated with TBE urea sample buffer (Biorad) in a 1:1 ratio at 95° C. for 10 min, ssDNA cleavage products were resolved on 15% TBE Urea gels (Invitrogen). Gels were incubated for 15 min with SYBR gold Nucleic Acid Gel Stain (Invitrogen) and visualized using a UVsolo TS Imaging System (Biometra, Analytik Jena). dsDNA cleavage assay reactions were inactivated with Proteinase K solution (20 μg/reaction) (Qiagen) for 20 min at room temperature. Samples were mixed with 6× loading dye (New England Biolabs) before they were resolved on a 1% agarose gel, containing ethidium bromide. As a marker, a 1 kb Generuler Marker (agarose gels) or an in-house prepared ssDNA marker (urea gels) were used, FIG. 14A, FIG. 14B and FIG. 14C.
To determine if ssDNA cleavage occurs at increased temperatures due to nucleic acid unwinding as a result from the heat, Argo prep, was heated to 95° C. for 30 min prior to running of the cleavage assay, FIG. 14D. The undigested plasmid was used as a control to see whether the protein stability is affected by a higher T, FIG. 18. Based on the ssDNA cleavage assays, dsDNA cleavage assays are currently being evaluated and optimized.
To determine Argonaute cutting efficiency utilizing truncated guide polynucleic acids, elution fractions containing Argo protein (EF5) were diluted with Buffer I, containing 5 mM β-Mercaptoethanol and 250 mM Imidazole to a final protein concentration of 30 μg/mL. A total of 10 μl protein sample was mixed with 0.08 μM sgDNA or sgRNA in 30 μl of reaction buffer (protein, truncated sgDNA/sgRNA (Table 22). Tris/HCl, MnCl2; NaCl, Imidazole, β-Mercaptoethanol, and Glycerol). The reaction was incubated at 37° C. for 15 m. After pre-incubation, ssDNA (0.8 μM) template (1 μl) was added and incubated for 1 h at 37° C., FIG. 26A and FIG. 26B.
TABLE 22
Truncated sgDNA
sgDNA No Sequence SEQ ID NO
sgDNA21 GCTGCCATCCAGATCGTTATC 345
sgDNA20 GCTGCCATCCAGATCGTTAT 346
sgDNA19 GCTGCCATCCAGATCGTTA 347
sgDNA18 GCTGCCATCCAGATCGTT 348
sgDNA17 GCTGCCATCCAGATCGT 349
sgDNA16 GCTGCCATCCAGATCG 350
sgDNA15 GCTGCCATCCAGATC 351
sgDNA14 GCTGCCATCCAGAT 352
sgDNA13 GCTGCCATCCAGA 353
TABLE 23
dsDNA Cleavage Assay
SEQ
ID Sequence
NO ID DNA Sequence
354 PCR TCAAGCCTCAGACAGTGGTTCAAAGTTTTTTTCTTCCATTTCAGGTGTCGTGACGCCACCATGGAGAGCGACG
amplicon- AGAGCGGCCTGCCCGCCATGGAGATCGAGTGCCGCATCACCGGCACCCTGAACGGCGTGGAGTTCGAGCTGGT
t- GGGCGGCGGAGAGGGCACCCCCGAGCAGGGCCGCATGACCAACAAGATGAAGAGCACCAAAGGCGCCCTGACC
GFP TTCAGCCCCTACCTGCTGAGCCACGTGATGGGCTACGGCTTCTACCACTTCGGCACCTACCCCAGCGGCTACG
AGAACCCCTTCCTGCACGCCATCAACAACGGCGGCTACACCAACACCCGCATCGAGAAGTACGAGGACGGCGG
CGTGCTGCACGTGAGCTTCAGCTACCGCTACGAGGCCGGCCGCGTGATCGGCGACTTCAAGGTGATGGGCACC
GGCTTCCCCGAGGACAGCGTGATCTTCACCGACAAGATCATCCGCAGCAACGCCACCGTGGAGCACCTGCACC
CCATGGGCGATAACGATCTGGATGGCAGCTTCACCCGCACCTTCAGCCTGCGCGACGGCGGCTACTACAGCTC
CGTGGTGGACAGCCACATGCACTTCAAGAGCGCCATCCACCCCAGCATCCTGCAGAACGGGGGCCCCATGTTC
GCCTTCCGCCGCGTGGAGGAGGATCACAGCAACACCGAGCTGGGCATCGTGGAGTACCAGCACGCCTTCAAGA
CCCCGGATGCAGATGCCGGTGAAGAATAACTGTGCCTTCTAGTTGCCAGCCATCTGTCCCCATGGGCGATAAC
GATCTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAA
TGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAG
GGGGAGGATTGGGAAGACAATAGCAGGCATGC
355 PCR GAAAAACTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCAGGATTATCAATACCATATTTTTGAAAA
amplicon- AGCCGTTTCTGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAAGATCCTGGTATCGGTCTG
Kanamycin CGATTCCGACTCGTCCAACATCAATACAACCTATTAATTTCCCCTCGTCAAAAATAAGGTTATCAAGTGAGAA
ATCACCATGAGTGACGACTGAATCCGGTGAGAATGGCAAAAGTTTATGCATTTCTTTCCAGACTTGTTCAACA
GGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAACCGTTATTCATTCGTGATTGCGCCTGAG
CGAGACGAAATACGCGATCGCTGTTAAAAGGACAATTACAAACAGGAATCGAATGCAACCGGCGCAGGAACAC
TGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATATTCTTCTAATACCTGGAATGCTGTTTTCCCGGGG
ATCGCAGTGGTGAGTAACCATGCATCATCAGGAGTACGGATAAAATGCTTGATGGTCGGAAGAGGCATAAATT
CCGTCAGCCAGTTTAGTCTGACCATCTCATCTGTAACATCATTGGCAACGCTACCTTTGCCATGTTTCAGAAA
CAACTCTGGCGCATCGGGCTTCCCATACAATCGATAGATTGTCGCACCTGATTGCCCGACATTATCGCGAGCC
CATTTATACCCATATAAATCAGCATCCATGTTGGAATTTAATCGCGGCCTAGAGCAAGACGTTTCCCGTTGAA
TATGGCTCAT
356 Linearized AGCCTGAATGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCG
Plasmid TGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGC
#89 CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGAC
CCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGA
CGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTA
TTCTTTTGATTTACAGTTAATTAAAGGGAACAAAAGCTGGCATGTACCGTTCGTATAGCATACATTATACGAA
CGGTACGCTCCAATTCGCCCTTTAATTAACTGTTCCAACTTTCACCATAATGAAATAAGATCACTACCGGGCG
TATTTTTTGAGTTGTCGAGATTTTCAGGAGCTAAGGAAGCTAAAATGGAGAAAAAAATCACTGGATATACCAC
CGAGTACTGCGATGAGTGGCAGGGCGGGGCGTAATTTTTTTAAGGCAGTTATTGGTGCCCTTAAACGCCTGGT
TGCTACGCCTGAATAAGTGATAATAAGCGGATGAATGGCAGAAATTCGAAAGCAAATTCGACCCGGTCGTCGG
TTCAGGGCAGGGTCGTTAAATAGCCGCTTATGTCTATTGCTGGTTTACCGGTTTATTGACTACCGGAAGCAGT
GTGACCGTGTGCTTCTCAAATGCCTGAGGCCAGTTTGCTCAGGCTCTCCCCGTGGAGGTAATAATTGACGATA
TGATCCTTTTTTTCTGATCAAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTA
ACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTT
CTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGC
TACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTTCTTCTAGTGTAGCC
GTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTG
GCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGC
GGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCT
ACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGG
GTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTC
GCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAA
CGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGAT
TCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCG
AGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTA
ATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTC
ACTCATTAGGCACCCCAGGCTTTACACTTTATGCTCCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAAC
AATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCGCGCAATTAACCCTCACTAAAGGGAACAAAA
GCTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCCACTGTGGAATTCGCCCTTTC
AAGCCTCAGACAGTGGTTCAAAGTTTTTTTCTTCCATTTCAGGTGTCGTGACGCCACCATGGAGAGCGACGAG
AGCGGCCTGCCCGCCATGGAGATCGAGTGCCGCATCACCGGCACCCTGAACGGCGTGGAGTTCGAGCTGGTGG
GCGGCGGAGAGGGCACCCCCGAGCAGGGCCGCATGACCAACAAGATGAAGAGCACCAAAGGCGCCCTGACCTT
CAGCCCCTACCTGCTGAGCCACGTGATGGGCTACGGCTTCTACCACTTCGGCACCTACCCCAGCGGCTACGAG
AACCCCTTCCTGCACGCCATCAACAACGGCGGCTACACCAACACCCGCATCGAGAAGTACGAGGACGGCGGCG
TGCTGCACGTGAGCTTCAGCTACCGCTACGAGGCCGGCCGCGTGATCGGCGACTTCAAGGTGATGGGCACCGG
CTTCCCCGAGGACAGCGTGATCTTCACCGACAAGATCATCCGCAGCAACGCCACCGTGGAGCACCTGCACCCC
ATGGGCGATAACGATCTGGATGGCAGCTTCACCCGCACCTTCAGCCTGCGCGACGGCGGCTACTACAGCTCCG
TGGTGGACAGCCACATGCACTTCAAGAGCGCCATCCACCCCAGCATCCTGCAGAACGGGGGCCCCATGTTCGC
CTTCCGCCGCGTGGAGGAGGATCACAGCAACACCG
AGCTGGGCATCGTGGAGTACCAGCACGCCTTCAAGACCCCGGATGCAGATGCCGGTGAAGAATAACTGTGCCT
TCTAGTTGCCAGCCATCTGTCCCCATGGGCGATAACGATCTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCT
GGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCAT
TCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCAAGGG
CGAATTCCACATTGGGCTGCAGCCCGGGGGATCCACTAGTTCTAGAGCGGCCGCACCGCGGGAGCTCCAATTC
GCCCTATAGTGAGTCGTATTACGCGCGCTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGC
GTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCG
ATTAAATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAA
ATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTCAGAAGAACTCGTCAAGAAGGCGATAGAAGGCG
ATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCACGAGGAAGCGGTCAGCCCATTCGCCGCCAAGTTCTT
CAGCAATATCACGGGTAGCCAACGCTATGTCCTGATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGAA
TCCAGAAAAGCGGCCATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCATGGGTCACGACGAGATCCTCG
CCGTCGGGCATGCTCGCCTTGAGCCTGGCGAACAGTTCGGCTGGCGCGAGCCCCTGATGTTCTTCGTCCAGAT
CATCCTGATCGACAAGACCGGCTTCCATCCGAGTACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGAA
TGGGCAGGTAGCCGGATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGATGGATACTTTCTCGGCAGGA
GCAAGGTGAGATGACAGGAGATCCTGCCCCGGCACTTCGCCCAATAGCAGCCAGTCCCTTCCCGCTTCAGTGA
CAACGTCGAGCACAGCTGCGCAAGGAACGCCCGTCGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGCAG
TTCATTCAGGGCACCGGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCCTGCGCTGACAGCCGGAACACG
GCGGCATCAGAGCAGCCGATTGTCTGTTGTGCCCAGTCATAGCCGAATAGCCTCTCCACCCAAGCGGCCGGAG
AACCTGCGTGCAATCCATCTTGTTCAATCATTAGTGTCCTTACCAATGCTTAATCAGTGAGGCACCTATCTCA
GCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCT
TACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAA
CCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGT
TGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCG
TGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATC
CCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTG
TTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGA
CTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAAT
ACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAA
CTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCAT
CTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGC
GACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTC
ATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAG
TGCCACCTTAATCGCCCTTCCCAACAGTTGCGC
TABLE 24
ssDNA Cleavage Assay
SEQ
ID Sequence
NO ID DNA Sequence
357 Template TGCACCCCATGGGCGATAACGATCTGGA
(90 nt) TGGCAGCTTCACCCGCACCTTCAGCCTG
CGCGACGGCGGCTACTACAGCTCCGTGGTGGACA
358 Template TGCACCCCATGGGCGATAACGATCTGGA
(60 nt) TGGCAGCTTCACCCGCACCTTCAGCCTGCGCG
TABLE 25
sgDNA/sgRNA
SEQ
ID Sequence
NO ID Nucleotide Sequence
359 sgDNA 1 GCTGCCATCCAGATCGTTATC
5′phosphorylated
360 sgDNA 1* GCTGCCATCCAGATCGTTATC
unphosphorylated
361 sgRNA 1 GCUGCCAUCCAGAUCGUUAUC
5′phosphorylated
362 NT gDNA CCCGAATCTCTATCGTGCGG
5′phosphorylated
363 sgDNA21 GCTGCCATCCAGATCGTTATC
5′phosphorylated
364 sgDNA20 GCTGCCATCCAGATCGTTAT
5′phosphorylated
365 sgDNA19 GCTGCCATCCAGATCGTTA
5′phosphorylated
366 sgDNA18 GCTGCCATCCAGATCGTT
5′phosphorylated
367 sgDNA17 GCTGCCATCCAGATCGT
5′phosphorylated
368 sgDNA16 GCTGCCATCCAGATCG
5′phosphorylated
369 sgDNA15 GCTGCCATCCAGATC
5′phosphorylated
370 sgDNA14 GCTGCCATCCAGAT
5′phosphorylated
371 sgDNA13 GCTGCCATCCAGA
5′phosphorylated
372 sgDNA Kan 1 CTATTAATTTCCCCTCGTCAA
5′phosphorylated
373 sgDNA Kan 2 TCTCACTTGATAACCTTATTT
5′phosphorylated
374 sgDNA Kan 3 GATCGCAGTGGTGAGTAACCA
5′phosphorylated
375 sgDNA Kan 4 GGAAGCCCGATGCGCCAGAGT
5′phosphorylated
376 sgDNA Kan 5 CCTGATGATGCATGGTTACTC
5′phosphorylated
Example 12: Mammalian Cell DNA Cutting Assay Split fluorescence protein (FP) systems may be used as protein tagging tools in visualization of protein localization in living cells. In this assay a split fluorescence protein system is used to assess DNA cutting activity of different proteins/constructs. An overview of the assay is shown in FIG. 18. Briefly, a cell line was constructed with a frameshift within a fluorescent protein which may be repaired by non-homologous end joining, repaired cells then display fluorescence. In the self-complementing split GFP1-10/11 systems, two fragments (G1-10 and G11) can associate by themselves to form a functional GFP signal. A study by Feng et al (2017) showed that the insertion of a 96 bp linker between G1-10 and G11 minimally affects the fluorescence of GFP signal. Therefore, we deleted 2 bps of the linker to frameshift the linker and GFP11 fragment, so that the GFP signal was turned off. Different target sites may be selected within the 94 bp linker for DNA cutting. If the linker is cut or nicked insertions or deletions from non-homologous end joining repair, or from homology directed repair, can make the linker and GFP11 in-frame and GFP signal can be detected. The sequence of the GFP1-10/11 system used was engineered from the sfGFP reported previously (Cabantous, S., Terwilliger, T. C., Waldo. G. S. (2005) Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein. Nat Biotechnol. 23, 102-7).
This construct was used to make a stable mammalian cell line, 6808. An SFFV promoter was used to control the reporter protein expression and mCherry was used as an expression marker to represent the expression of the GFP1-10/11 system with inserted 94_linker. For generation of lentivirus. HEK293T cells were transiently transfected the pHR constructs, pCMV-dR8.91, and pMD2.G at a ratio of 9:8:1, respectively. Viral supernatant was collected 72 h post-transfection, passed through a 0.45 μm filter, and concentrated 10× using the Lenti-X Concentrator (Clontech) by incubating overnight at 4° C.
The 6808 reporter cell line was generated by transducing HEK293T cells with lentivirus expressing the above described architecture, examples of this architecture are also shown in FIGS. 19-21 and in FIG. 35. Single cells were sorted by fluorescence activated cell sorting (FACS) using a BD FACS Aria2 for mCherry marker expression to identified transformed cells.
The 6808 reporter cell line was validated using a Cas9 system to target the 94_linker. 6808 cells were seeded at a density of 1×105 per well in 12-well plates per well. For transient transfection of cutting and nick experiments, cells were transfected 1 day after seeding with 1.5 μg total of plasmid (sgRNA and Cas9 or Cas9n are on the same plasmid) per well using TranslTLT1 transfection reagent (Mirus) at a ratio of 6 μL transfection reagent for the 1.5 μg plasmid. Transfected cells were collected after 72h transfection to analyze the GFP expression. To analyze GFP expression, cells were dissociated using 0.05% Trypsin EDTA (Life Technologies) and analyzed by flow cytometry on a BD LSRII. Flow cytometry data was analyzed using FlowJo. 10,000 viable cells were analyzed for each sample, Selected sequences are provided in Table 26.
A range of control experiments were performed using untransformed HEK293T cells (FIG. 22A), and 6808 cells further exposed to: no plasmids. Cas9 alone, Cas9 and non-targeting guide RNAs. Cas9 with non-targeting guide RNAs and single-stranded oligodeoxynucleotide donors spanning the double stranded break (ssODN_3 or ssODN 4), or a Cas9 nickase (nCas9) with or without non targeting guide RNAs, and single-stranded oligodeoxynucleotide donors (ssODN_3 and ssODN_4) (FIGS. 228-K). The treated cells were analyzed by Fluorescence-activated cell sorting with a GFP fluorescence cut off of 105. As seen in FIGS. 22A-K the control experiments showed very low rates of fluorescent cells, well below 0.1% in all cases. FIG. 23 shows the results of an experiment using Cas9 and a guide RNA targeting the 94_linker (sgRNA6819, shown in FIG. 19), 17.2% of cells gained fluorescence as a result of this treatment. FIG. 24 shows the results of an experiment using a Cas9 nickase and a guide RNA targeting the 94_Linker (sgRNA6821, shown in FIG. 20), in this case 8.23% of the cells gained fluorescence. The number of fluorescent cells can be further increased by treating the 6806 cells with a Cas9 nickase, a guide RNA targeting the 94_Linker and ssODN_3 or ssODN_4 donors. These treatments resulted in 46.3% (FIG. 25A) and 54.2% (FIG. 25B) of cells becoming fluorescent respectively.
To analyze the forms of DNA repair occurring in the different treatment conditions DNA from GFP positive cells was collected and sequenced. Since multiple copies of the reporter fragments were integrated in the cells, the NHEJ and HDR percentages in the GFP positive cells were analyzed by MiSeq.
Transfected cells were collected after 72h transfection to analyze the GFP expression. GFP positive populations cells were bulk sorted by fluorescence activated cell sorting (FACS) using a BD FACS Aria2. 1 million GFP positive cells of each sample were collected to prepare the total DNA (DNeasy Blood & Tissue kit, QIAGEN). The amplicons were fixed at 300 bp and the sgRNA targeting site was in the region that sequencing can efficiently cover. PCR amplifications were performed with KAPA HiFi PCR Kit (KAPABIOSYSTEMS) following the manual. PCR conditions: 95° C. 5 min; 98° C., 20 s. 64° C., 20 s, 72° C. 20 s, 23 cycles. 72° C., 5 min. PCR products were checked by gel electrophoresis for the right amplicon. Then 10 PCRs for each sample were pooled and run on a 75 bp paired-end Miseq sequencing run.
FIG. 27A shows the results of a sequencing reaction performed on untreated 6808 cells, only 0.5% of the reads showed modifications consistent with non-homologous end joining repair, while 99.5% of the reads showed unmodified DNA. FIG. 27B shows results of sequencing reaction performed on 6808 cells treated with nCas9, a non-targeting guide RNA and ssODN_4, only 0.3% of the reads showed modifications consistent with non-homologous end joining repair, while 99.7% of the reads showed unmodified DNA. FIG. 28 shows results of sequencing reaction performed on 6808 cells treated with nCas9 and sgRNA6821. Interestingly 2.1% of the reads showed modifications consistent with non-homologous end joining repair, while 97.9% of the reads showed unmodified DNA. FIG. 29 shows results of sequencing reaction performed on 6808 cells treated with nCas9, sgRNA6821 and ssODN_4 donor, 35.8% of the reads showed modifications consistent with homology directed repair, 0.6% of the reads showed modifications consistent with non-homologous end joining repair, 0.7% of the reads showed modifications consistent with mixed homology directed repair and non-homologous end joining repair, and 62.8% of the reads showed unmodified DNA. FIG. 30 shows results of sequencing reaction performed on 6808 cells treated with Cas9 and sgRNA6825, 95.7% of the reads showed modifications consistent with non-homologous end joining repair, and 4.3% of the reads showed unmodified DNA. FIG. 31 shows results of sequencing reaction performed on 6808 cells treated with Cas9, sgRNA6825 and ssODN_4 donor; 10.9% of the reads showed modifications consistent with homology directed repair, 82% of the reads showed modifications consistent with non-homologous end joining repair, 0.9% of the reads showed modifications consistent with mixed homology directed repair and non-homologous end joining repair, and only 10.9% of the reads showed unmodified DNA.
The 6808 cell assay was used to assess DNA editing activity of different Agos as described herein. The reporter cell line 293T 6808 was seeded at 100K per well in a 12 well plate with 1 ml DMEM medium with 5% FBS. Cells were grown for 24 hours before the transfection using the recipe list in Table 27. 72 hours after transfection, cells were trypsinized from the plate, filtered through 70 uM cell strainers and analyzed by FACS as described above. FIGS. 32A and 32B show the results of the assay. As seen in FIG. 32A and FIG. 32B some of the Ago proteins resulted in significantly higher percentages of GFP positive cells than the negative controls.
TABLE 26
Sequences used in the 6808 cell assay.
SEQ ID
Description Sequence (5′ to 3′) NO:
Non-target guide GGCTGGCGCGGTATGGTCGGC 377
RNA (6823 and
6824)
ssODN_03 ACAAACAGTCCTGAGCAAAGATCCAA 378
ATGAAAAAGACGTTGGTGGTGGCGGATCAGAAGGAGGCGGT
AGCGGCCCTGGTTCGGGAGGGGAAGGTTCTGCTGGGGGAGG
GAGCGCTGGCGG
ssODN_04 CCGCCAGCGCTCCCTCCCCCAGCAGAA 379
CCTTCCCCTCCCGAACCAGGGCCGCTACCGCCTCCTTCTGA
TCCGCCACCACCAACGTCTTTTTCATTTGGATCTTTGCTCA
GGACTGTTTGT
94 linker AGACCCCCCGCCAGCGCTCCCTCCCCCAGCAGAACCTTCCC 415
CTCCCGAACCAGGGCCCGCTACCGCCTCCTTCTGATCCGCC
ACCACCAACGTC
92 linker GACGTTGGTGGTGGCGGATCAGAAGGAGGCGGTAGCGGCCT 416
GGTTCGGGAGGGGAAGGTTCTGCTGGGGGAGGGAGCGCTGG
CGGGGGGTCT
ssODN_03 ACAAACAGTCCTGAGCAAAGATCCAAATGAAAAAGACGTTG 417
GTGGTGGCGGATCAGAAGGAGGCGGTAGCGGCCCTGGTTCG
GGAGGGGAAGGTTCTGCTGGGGGAGGGAGCGCTGGCGG
ssODN_04 CCGCCAGCGCTCCCTCCCCCAGCAGAACCTTCCCCTCCCGA 418
ACCAGGGCCGCTACCGCCTCCTTCTGATCCGCCACCACCAA
CGTCTTTTTCATTTGGATCTTTGCTCAGGACTGTTTGT
sgRNA6819_ GGTGGCGGATCAGAAGGAGG 419
Targeting
sgRNA6821_ GATCAGAAGGAGGCGGTAGC 420
Targeting
sgRNA6823_ GGCTGGCGCGGTATGGTCGGC 421
Targeting
sgRNA6824_ GGCTGGCGCGGTATGGTCGGC 422
Targeting
sgRNA6825_ GATCAGAAGGAGGCGGTAGC 423
Targeting
(FIG. 35)
TABLE 27
Recipe for 6808 cell assay with Ago proteins
Optimized condition using 6808
cell line in 12 well plate
Positive control Plasmid 6821 1.5 ug
ssODN 0.8 ug
Transit 6 ul
Opt medium 200 ul
complete assay Ago plasmid 1 ug
gDNA 0.25 ug
ssODN 0.8 ug
pSLQ1339 1 ug
sgRNA1 for dCas9 0.75 ug
Transit 6 ul
Opt medium 200 ul
TABLE 28
Expression Vector utilized in ssDNA cleavage assay
SEQ ID
NO: Sequence
384 TACTGGAACGTTGTGAGGGTAAACAACTGGCGGTATGGATGCGGCGGGACCAGAGAAAAATCACTCAGGGTCAATGCCA
GCGCTTCGTTAATACAGATGTAGGTGTTCCACAGGGTAGCCAGCAGCATCCTGCGATGCAGATCCGGAACATAATGGTGC
AGGGCGCTGACTTCCGCGTTTCCAGACTTTACGAAACACGGAAACCGAAGACCATTCATGTTGTTGCTCAGGTCGCAGAC
GTTTTGCAGCAGCAGTCGCTTCACGTTCGCTCGCGTATCGGTGATTCATTCTGCTAACCAGTAAGGCAACCCCGCCAGCCT
AGCCGGGTCCTCAACGACAGGAGCACGATCATGCGCACCCGTGGGGCCGCCATGCCGGCGATAATGGCCTGCTTCTCGC
CGAAACGTTTGGTGGCGGGACCAGTGACGAAGGCTTGAGCGAGGGCGTGCAAGATTCCGAATACCGCAAGCGACAGGC
CGATCATCGTCGCGCTCCAGCGAAAGCGGTCCTCGCCGAAAATGACCCAGAGCGCTGCCGGCACCTGTCCTACGAGTTGC
ATGATAAAGAAGACAGTCATAAGTGCGGCGACGATAGTCATGCCCCGCGCCCACCGGAAGGAGCTGACTGGGTTGAAG
GCTCTCAAGGGCATCGGTCGAGATCCCGGTGCCTAATGAGTGAGCTAACTTACATTAATTGCGTTGCGCTCACTGCCCGCT
TTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGC
GCCAGGGTGGTTTTTCTTTTCACCAGTGAGACGGGCAACAGCTGATTGCCCTTCACCGCCTGGCCCTGAGAGAGTTGCAG
CAAGCGGTCCACGCTGGTTTGCCCCAGCAGGCGAAAATCCTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGT
CTTCGGTATCGTCGTATCCCACTACCGAGATATCCGCACCAACGCGCAGCCCGGACTCGGTAATGGCGCGCATTGCGCCC
AGCGCCATCTGATCGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCATTTGCATGGTTTGTTGAAAACC
GGACATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAATTTGATTGCGAGTGAGATATTTATGCCAGCCAGCCAG
ACGCAGACGCGCCGAGACAGAACTTAATGGGCCCGCTAACAGCGCGATTTGCTGGTGACCCAATGCGACCAGATGCTCC
ACGCCCAGTCGCGTACCGTCTTCATGGGAGAAAATAATACTGTTGATGGGTGTCTGGTCAGAGACATCAAGAAATAACGC
CGGAACATTAGTGCAGGCAGCTTCCACAGCAATGGCATCCTGGTCATCCAGCGGATAGTTAATGATCAGCCCACTGACGC
GTTGCGCGAGAAGATTGTGCACCGCCGCTTTACAGGCTTCGACGCCGCTTCGTTCTACCATCGACACCACCACGCTGGCAC
CCAGTTGATCGGCGCGAGATTTAATCGCCGCGACAATTTGCGACGGCGCGTGCAGGGCCAGACTGGAGGTGGCAACGCC
AATCAGCAACGACTGTTTGCCCGCCAGTTGTTGTGCCACGCGGTTGGGAATGTAATTCAGCTCCGCCATCGCCGCTTCCAC
TTTTTCCCGCGTTTTCGCAGAAACGTGGCTGGCCTGGTTCACCACGCGGGAAACGGTCTGATAAGAGACACCGGCATACT
CTGCGACATCGTATAACGTTACTGGTTTCACATTCACCACCCTGAATTGACTCTCTTCCGGGCGCTATCATGCCATACCGCG
AAAGGTTTTGCGCCATTCGATGGTGTCCGGGATCTCGACGCTCTCCCTTATGCGACTCCTGCATTAGGAAGCAGCCCAGTA
GTAGGTTGAGGCCGTTGAGCACCGCCGCCGCAAGGAATGGTGCATGCAAGGAGATGGCGCCCAACAGTCCCCCGGCCAC
GGGGCCTGCCACCATACCCACGCCGAAACAAGCGCTCATGAGCCCGAAGTGGCGAGCCCGATCTTCCCCATCGGTGATGT
CGGCGATATAGGCGCCAGCAACCGCACCTGTGGCGCCGGTGATGCCGGCCACGATGCGTCCGGCGTAGAGGATCGAGA
TCTCGATCCCGCGAAATTAATACGACTCACTATAGGGGAATTGTGAGCGGATAACAATTCCCCTCTAGAAATAATTTTGTT
TAACTTTAAGAAGGAGATATACCATGAAACATCACCATCACCATCACAACACTAGTAGCAATTCCATGTCCCCTATACTAG
GTTATTGGAAAATTAAGGGCCTTGTGCAACCCACTCGACTTCTTTTGGAATATCTTGAAGAAAAATATGAAGAGCATTTGT
ATGAGCGCGATGAAGGTGATAAATGGCGAAACAAAAAGTTTGAATTGGGTTTGGAGTTTCCCAATCTTCCTTATTATATTG
ATGGTGATGTTAAATTAACACAGTCTATGGCCATCATACGTTATATAGCTGACAAGCACAACATGTTGGGTGGTTGTCCAA
AAGAGCGTGCAGAGATTTCAATGCTTGAAGGAGCGGTTTTGGATATTAGATACGGTGTTTCGAGAATTGCATATAGTAAA
GACTTTGAAACTCTCAAAGTTGATTTTCTTAGCAAGCTACCTGAAATGCTGAAAATGTTCGAAGATCGTTTATGTCATAAAA
CATATTTAAATGGTGATCATGTAACCCATCCTGACTTCATGTTGTATGACGCTCTTGATGTTGTTTTATACATGGACCCAAT
GTGCCTGGATGCGTTCCCAAAATTAGTTTGTTTTAAAAAACGTATTGAAGCTATCCCACAAATTGATAAGTACTTGAAATCC
AGCAAGTATATAGCATGGCCTTTGCAGGGCTGGCAAGCCACGTTTGGTGGTGGCGACCATCCTCCAACTAGTGGATCTGG
TGGTGGTGGCGGATGGATGAGCGAGAATCTTTATTTTCAGGGCGCCATGGCTGGCAAGGCACACAGGCTGAGTGCTGAG
GAACGGGACCAGCTGCTGCCAAACCTGCGGGCCGTGGGGTGGAATGAACTGGAAGGCCGAGATGCCATCTTCAAACAGT
TCCATTTTAAAGACTTCAACAGGGCTTTTGGCTTCATGACAAGAGTCGCCCTGCAGGCTGAAAAGCTGGACCACCATCCCG
AGTGGTTTAACGTGTACAACAAGGTCCATATCACCTTGAGCACCCACGAATGTGCCGGTCTTTCTGAACGGGATATAAACC
TGGCCAGCTTCATCGAACAAGTTGCCGTGTCTATGACATAGGTACCGGATCCGAATTCGAGCTCCGTCGACAAGCTTGCG
GCCGCACTCGAGCACCACCACCACCACCACTGAGATCCGGCTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGC
CACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTA
TATCCGGATTGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACC
GCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTC
A
AGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGA
TGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACT
CTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTAT
T
GGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTCAGGTGGCACTT
TTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAATTAATTCTT
A
GAAAAACTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCAGGATTATCAATACCATATTTTTGAAAAAGCCGTTTC
TGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAAGATCCTGGTATCGGTCTGCGATTCCGACTCGTCC
AACATCAATACAACCTATTAATTTCCCCTCGTCAAAAATAAGGTTATCAAGTGAGAAATCACCATGAGTGACGACTGAATC
CGGTGAGAATGGCAAAAGTTTATGCATTTCTTTCCAGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACT
CGCATCAACCAAACCGTTATTCATTCGTGATTGCGCCTGAGCGAGACGAAATACGCGATCGCTGTTAAAAGGACAATTAC
AAACAGGAATCGAATGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATATTCTTCT
AATACCTGGAATGCTGTTTTCCCGGGGATCGCAGTGGTGAGTAACCATGCATCATCAGGAGTACGGATAAAATGCTTGAT
GGTCGGAAGAGGCATAAATTCCGTCAGCCAGTTTAGTCTGACCATCTCATCTGTAACATCATTGGCAACGCTACCTTTGCC
ATGTTTCAGAAACAACTCTGGCGCATCGGGCTTCCCATACAATCGATAGATTGTCGCACCTGATTGCCCGACATTATCGCG
AGCCCATTTATACCCATATAAATCAGCATCCATGTTGGAATTTAATCGCGGCCTAGAGCAAGACGTTTCCCGTTGAATATG
GCTCATAACACCCCTTGTATTACTGTTTATGTAAGCAGACAGTTTTATTGTTCATGACCAAAATCCCTTAACGTGAGTTTTC
GTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTG
CAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGC
TTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCG
CCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCA
AGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACG
ACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGT
ATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCC
AGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTG
TGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGC
GAGGAAGCGGAAGAGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATATGGTGCACTC
TCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATACACTCCGCTATCGCTACGTGACTGGGTCATGGCTGCGCC
CCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCG
TCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGGCAGCTGCGGTAAAGCTCATCAGCG
TGGTCGTGAAGCGATTCACAGATGTCTGCCTGTTCATCCGCGTCCAGCTCGTTGAGTTTCTCCAGAAGCGTTAATGTCTGG
CTTCTGATAAAGCGGGCCATGTTAAGGGCGGTTTTTTCCTGTTTGGTCACTGATGCCTCCGTGTAAGGGGGATTTCTGTTC
ATGGGGGTAATGATACCGATGAAACGAGAGAGGATGCTCACGATACGGGTTACTGATGATGAACATGCCCGGT
