Patents by Inventor Michael H. Shapero
Michael H. Shapero has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20150010905Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.Type: ApplicationFiled: June 13, 2014Publication date: January 8, 2015Inventors: Keith W. JONES, Michael H. SHAPERO, Stephen P. A. FODOR
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Publication number: 20140378340Abstract: Novel methods and kits are disclosed for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences, for example, to discriminating between alleles at polymorphic positions in a genome. Complexity reduction can be accomplished by extension of a capture probes followed by amplification of the extended capture probe using common primers. The capture probes may be locus specific and allele-specific. The amplified sample may be hybridized to an array designed to interrogate the desired fragments for the presence or absence of a polymorphism. In some aspects the methods employ allele-specific extension of oligonucleotides that are complementary to one of the alleles at the 3? end of the oligonucleotide. The allele-specific oligonucleotides are resistant to proof reading activity from a polymerase and may be extended in an allele-specific manner by a DNA polymerase with a functional 3? to 5? exonuclease activity.Type: ApplicationFiled: August 27, 2014Publication date: December 25, 2014Inventors: Michael H. SHAPERO, Keith W. JONES
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Patent number: 8808995Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.Type: GrantFiled: January 11, 2012Date of Patent: August 19, 2014Assignee: Affymetrix, Inc.Inventors: Ketih W. Jones, Michael H. Shapero, Stephen P. A. Fodor
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Publication number: 20130017966Abstract: The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. This selective adaptor ligation allows for selective amplification of a subset of the fragments using primers complementary to the adaptor sequence. In another aspect primers that are complementary to a subset of the fragments after adaptor ligation are used for amplification. Amplified fragments may be analyzed to genotype polymorphisms by hybridization to an array of probes that are complementary to target sequences that will be amplified.Type: ApplicationFiled: February 3, 2012Publication date: January 17, 2013Applicant: Affymetrix, Inc.Inventors: Michael H. Shapero, Keith W. Jones
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Publication number: 20120214704Abstract: Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to normal tissue. The methods may be used to diagnose cancer and other diseases associated with chromosomal anomalies.Type: ApplicationFiled: April 30, 2012Publication date: August 23, 2012Applicant: Affymetrix, Inc.Inventors: Jing Huang, Keith W. Jones, Michael H. Shapero
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Publication number: 20120142551Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.Type: ApplicationFiled: January 11, 2012Publication date: June 7, 2012Applicant: AFFYMETRIX, INC.Inventors: Keith W. Jones, Michael H. Shapero, Stephen P.A. Fodor
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Patent number: 8190373Abstract: Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to normal tissue. The methods may be used to diagnose cancer and other diseases associated with chromosomal anomalies.Type: GrantFiled: October 12, 2010Date of Patent: May 29, 2012Assignee: Affymetrix, Inc.Inventors: Jing Huang, Keith W. Jones, Michael H. Shapero
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Patent number: 8133667Abstract: The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. This selective adaptor ligation allows for selective amplification of a subset of the fragments using primers complementary to the adaptor sequence. In another aspect primers that are complementary to a subset of the fragments after adaptor ligation are used for amplification. Amplified fragments may be analyzed to genotype polymorphisms by hybridization to an array of probes that are complementary to target sequences that will be amplified.Type: GrantFiled: November 17, 2008Date of Patent: March 13, 2012Assignee: Affymetrix, Inc.Inventors: Michael H. Shapero, Keith W. Jones
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Patent number: 8114978Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.Type: GrantFiled: December 2, 2008Date of Patent: February 14, 2012Assignee: Affymetrix, Inc.Inventors: Keith W. Jones, Michael H. Shapero, Stephen P. A. Fodor
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Publication number: 20120010087Abstract: Novel methods and kits are disclosed for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences, for example, to discriminating between alleles at polymorphic positions in a genome. Complexity reduction can be accomplished by extension of a capture probes followed by amplification of the extended capture probe using common primers. The capture probes may be locus specific and allele-specific. The amplified sample may be hybridized to an array designed to interrogate the desired fragments for the presence or absence of a polymorphism. In some aspects the methods employ allele-specific extension of oligonucleotides that are complementary to one of the alleles at the 3? end of the oligonucleotide. The allele-specific oligonucleotides are resistant to proof reading activity from a polymerase and may be extended in an allele-specific manner by a DNA polymerase with a functional 3? to 5? exonuclease activity.Type: ApplicationFiled: July 5, 2011Publication date: January 12, 2012Applicant: AFFYMETRIX, INC.Inventors: Michael H. Shapero, Keith W. Jones
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Publication number: 20110029251Abstract: Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to normal tissue. The methods may be used to diagnose cancer and other diseases associated with chromosomal anomalies.Type: ApplicationFiled: October 12, 2010Publication date: February 3, 2011Applicant: AFFYMETRIX, INC.Inventors: Jing Huang, Keith W. Jones, Michael H. Shapero
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Publication number: 20110009294Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.Type: ApplicationFiled: December 2, 2008Publication date: January 13, 2011Applicant: Affymetrix, Inc.Inventors: Keith W. Jones, Michael H. Shapero, Stephen P.A. Fodor
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Patent number: 7822555Abstract: Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to normal tissue. The methods may be used to diagnose cancer and other diseases associated with chromosomal anomalies.Type: GrantFiled: December 5, 2005Date of Patent: October 26, 2010Assignee: Affymetrix, Inc.Inventors: Jing Huang, Keith W. Jones, Michael H. Shapero
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Publication number: 20090239764Abstract: Methods for detecting genomic rearrangements are provided. In one embodiment, methods are provided for the use of paired end tags from restriction fragments to detect genomic rearrangements. Sequences from the ends of the fragments are brought together to form ditags and the ditags are detected. Combinations of ditags are detected by an on-chip sequencing strategy that is described herein, using inosine for de novo sequencing of short segments of DNA. In another aspect, translocations are identified by using target specific capture and analysis of the captured products on a tiling array.Type: ApplicationFiled: March 11, 2009Publication date: September 24, 2009Applicant: Affymetrix, Inc.Inventors: Andrew Sparks, Michael H. Shapero, Glenn K. Fu, Keith W. Jones
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Publication number: 20090117573Abstract: Methods are provided for multiplexed amplification of selected targets and analysis of the amplified targets. In preferred aspects the amplification and analysis take place on the same solid support and preferably in a localized area such as a bead or a feature of an array. In preferred aspects the analysis is a determination of sequence at one or more locations in the amplified target. The methods may be used for genotyping, sequencing and analysis of copy number.Type: ApplicationFiled: September 15, 2008Publication date: May 7, 2009Applicant: Affymetrix, Inc.Inventors: Glenn K. Fu, Michael H. Shapero, Pei-Hua Wang
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Publication number: 20090075345Abstract: The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. This selective adaptor ligation allows for selective amplification of a subset of the fragments using primers complementary to the adaptor sequence. In another aspect primers that are complementary to a subset of the fragments after adaptor ligation are used for amplification. Amplified fragments may be analyzed to genotype polymorphisms by hybridization to an array of probes that are complementary to target sequences that will be amplified.Type: ApplicationFiled: November 17, 2008Publication date: March 19, 2009Applicant: Affymetrix, Inc.Inventors: Michael H. Shapero, Keith W. Jones
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Patent number: 7459273Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.Type: GrantFiled: August 5, 2004Date of Patent: December 2, 2008Assignee: Affymetrix, Inc.Inventors: Keith W. Jones, Michael H. Shapero, Stephen P. A. Fodor
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Publication number: 20080293589Abstract: Methods are provided for amplifying a plurality of pre-selected target sequences from a complex background of nucleic acids. The targets are selected for amplification using splint oligonucleotides that are used to modify the ends of the fragments. The fragments have known end sequences and the splints are designed to be complementary to the ends. In one aspect the splint brings the ends of the fragment together and the ends are joined to form a circle. In another aspect the splint is used to add a common priming site to the ends of the target fragments. Specific loci are amplified and can be subsequently analyzed.Type: ApplicationFiled: May 27, 2008Publication date: November 27, 2008Applicant: Affymetrix, Inc.Inventor: Michael H. Shapero
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Patent number: 7452671Abstract: The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. Selective adaptor ligation allows for selective amplification of a subset of the fragments using primers complementary to the adaptor sequence. In another aspect primers that are complementary to a subset of the fragments after adaptor ligation are used for amplification. Reduced complexity samples generated by the disclosed methods may be interrogated for the genotypes of SNPs in the sample.Type: GrantFiled: May 1, 2006Date of Patent: November 18, 2008Assignee: Affymetrix, Inc.Inventors: Michael H. Shapero, Keith W. Jones
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Publication number: 20080254453Abstract: Methods of analyzing DNA to identify regions of the genome that are methylated in a genomic sample are disclosed. In one aspect genomic DNA is fragmented using a restriction enzyme with a degenerate recognition site, methylated restriction fragments are separated from unmethylated fragments by affinity purification. The complexity of the methylated fragments is reduced by amplification of a subset of the fragments using adaptors that ligate to a subset of the fragments. The amplified product is fragmented, labeled and hybridized to an array of probes. The hybridization pattern is analyzed to determine methylation status of cytosines.Type: ApplicationFiled: April 12, 2007Publication date: October 16, 2008Applicant: AFFYMETRIX, INCInventors: Michael H. Shapero, Shivani Nautiyal