Polymorphisms associated with hypertension

Abstract

The invention discloses a collection of polymorphic sites in genes know or suspected to have a role in hypertension. The invention provides nucleic acids including such polymorphic sites. The nucleic acids can be used as probes or primers or for expressing variant proteins. The invention also provide methods of analyzing the polymorphic forms occupying the polymorphic sites.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This application derives priority from U.S. Ser. No. 60/084,641 filed May 7, 1998, which is incorporated by reference in its entirety for all purposes.

BACKGROUND OF THE INVENTION

[0003] Hypertension, or high blood pressure, is a common disease affecting 50 million Americans and contributing to over 200,000 deaths annually from stroke, myocardial infarction, and end-stage renal disease. The disease is multifactorial and numerous genetic and nongenetic components, such as salt intake, age, diet, and body mass, are suspected to contribute. A specific cause of hypertension can typically be identified in only a small percentage of patients. Other patients with abnormally high blood pressure of unknown cause are said to have essential hypertension.

[0004] The existence of a genetic component to hypertension is known from twin studies, which have revealed a greater concordance of blood pressure in monozygotic twins that in dizygotic twins. Similarly, biological siblings have show greater concordance of blood pressure than adoptive siblings raised in the same household. Such studies have suggested that up to about 40% of the variations in blood pressure in the population are genetically determined.

[0005] There is a substantial pool of candidate genes that may contribute to the genetic component of hypertension. Because blood pressure is determined by the product of cardiac output and vascular resistance, candidate genes may act through either pathway. Physiologic pathways which are know to influence these parameters include the renin-angiotensin-aldosterone system, which contributes to determination of both cardiac output and vascular resistance. In this pathway, angiotensinogen, a hormone produced in the liver, is cleaved by an enzyme called renin to angiotensin I, which then undergoes further cleavage by angiotensin I-converting enzyme (ACE) to produce the active hormone angiotensin II (AII). All acts through specific AT1 receptors present on vascular and adrenal cells. Receptors present on vascular cells cause vasoconstriction of blood vessels. Receptors present on adrenal cells cause release of the hormone aldosterone by the adrenal gland. This hormone acts on the mineralocorticoid receptor to cause increase sodium reabsorption largely through a renal epithelial sodium location. Other candidate genes are those of peripheral and central adrenergic pathways, which have dominant effects on cardiac iontropy, heart rate and vascular resistance; a variety of renal ion channels and transporters, which determine net sodium absorption and hence intravascular volume; calcium channels and exchangers and nitric oxide pathways, whose activity influences vascular tone. Another candidate gene encodes atrial natriuretic factor precursor, which is cleaved to atrial natriuretic peptides, found in the heart atrium, an endocrine organ controlling blood pressure and organ volume.

[0006] For some of the above candidate genes, variant forms have been identified that occur with increased frequency in individuals with hypertension. For example, a number of the polymorphisms have been reported in the angiotensinogen gene (AGT). In one of these, an M/T substitution at position 235, the T allele occurs more frequently in individuals with hypertension suggesting that this polymorphic form is a cause of hypertension or in equilibrium dislinkage with another polymorphism that is a cause. Jeunmaitre et al., Am. J. Hum. Genet. 60, 1448-1460 (1997). Two other genes within the renin-angiotensin-aldosterone system also have variant forms correlated with specific forms of hypertension, that is, aldosterone synthase gene and the gene encoding the &bgr;-subunit of the epithelial sodium channel induced by the mineralocorticoid receptor. Lifton et al., Proc. Natl. Acad. Sci. USA 92, 8548-8551 (1995).

[0007] Despite these developments, only a minute proportion of the total repository of polymorphisms in candidate genes for hypertension has been identified, and the primary genetic determinants of hypertension remain unknown in most affected subjects, as does the nature of the interaction between different genetic determinants. The paucity of polymorphisms hitherto identified is due to the large amount of work required for their detection by conventional methods. For example, a conventional approach to identifying polymorphisms might be to sequence the same stretch of oligonucleotides in a population of individuals by dideoxy sequencing. In this type of approach, the amount of work increases in proportion to both the length of sequence and the number of individuals in a population and becomes impractical for large stretches of DNA or large numbers of persons.

SUMMARY OF THE INVENTION

[0008] The invention provides nucleic acids of between 10 and 100 bases comprising at least 10 contiguous nucleotides including a polymorphic site from a sequence shown in Table 1, column 8 or the complement thereof. The nucleic acids can be DNA or RNA. Some nucleic acids are between 10 and 50 bases and some are between 20 and 50 bases. The base occupying the polymorphic site in such nucleic acids can be either a reference base shown in Table 1, column 3 or an alternative base shown in Table 1, column 5. In the some nucleic acids, the polymorphic site is occupied by a base that correlates with hypertension or susceptibility thereto. Some nucleic acids contain a polymorphic site having two polymorphic forms giving rise two different amino acids specified by the two codons in which the polymorphic site occurs in the two polymorphic forms.

[0009] The invention further provides allele-specific oligonucleotides that hybridize to a nucleic acid segment shown in Table 1, column 8 or its complement, including the polymorphic site. Such oligonucleotides are useful as probes or primers.

[0010] The invention further provides methods of analyzing a nucleic acid sequence. Such methods entail obtaining the nucleic acid from an individual; and determining a base occupying any one of the polymorphic sites shown in Table 1 or other polymorphic sites in equilibrium dislinkage therewith. Some methods determine a set of bases occupying a set of the polymorphic sites shown in Table 1. In some methods, the nucleic acid is obtained from a plurality of individuals, and a base occupying one of the polymorphic positions is determined in each of the individuals. Each individual is then tested for the presence of a disease phenotype, and correlating the presence of the disease phenotype with the base, particularly hypertension.

[0011] In another aspect, the invention provides nucleic acids comprising an isolated nucleic acid sequence of Table 1, column 8 or the complement thereof, wherein the polymorphic site within the sequence or its complement is occupied by a base other than the reference base show in Table 1, column 3. Such nucleic acids are useful, for example, in expression of variant proteins or production of transgenic animals.

[0012] The invention further provides methods of diagnosing a phenotype. Such methods entail determining which polymorphic form(s) are present in a sample from a subject at one or more polymorphic sites shown in Table 1, and diagnosing the presence of a phenotype correlated with the form(s) in the subject.

[0013] The invention also provides methods of screening polymorphic sites linked to polymorphic sites shown in Table 1 for suitability for diagnosing a phenotype. Such methods entail identifying a polymorphic site linked to a polymorphic site shown in Table 1, wherein a polymorphic form of the polymorphic site shown in Table 1 has been correlated with a phenotype. One then determines haplotypes in a population of individuals to indicate whether the linked polymorphic site has a polymorphic form in equlibrium dislinkage with the polymorphic form correlated with the phenotype.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIGS. 1A and 1B depict computer systems suitable for storing and transmitting information relating to the polymorphisms of the invention.

DEFINITIONS

[0015] A nucleic acid can be DNA or RNA, and single- or double-stranded. Oligonucleotides can be naturally occurring or synthetic, but are typically prepared by synthetic means. Preferred nucliec acids of the invention include segments of DNA, or their complements including any one of the polymorphic sites shown in Table 1. The segments are usually between 5 and 100 contiguous bases, and often range from 5, 10, 12, 15, 20, or 25 nucleotides to 10, 15, 30, 25, 20, 50 or 100 nucleotides. Nucleic acids between 5-10, 5-20, 10-20, 12-30, 15-30, 10-50, 20-50 or 20-100 bases are common. The polymorphic site can occur within any position of the segment. The segments can be from any of the allelic forms of DNA shown in Table 1. For brevity in Table 1, the symbol T is used to represent both thymidine in DNA and uracil in RNA. Thus, in RNA oligonucleotides, the symbol T should be construed to indicate a uracil residue.

[0016] Hybridization probes are capable of binding in a base-specific manner to a complementary strand of nucleic acid. Such probes include nucleic acids, peptide nucleic acids, as described in Nielsen et al., Science 254, 1497-1500 (1991).

[0017] The term primer refers to a single-stranded oligonucleotide capable of acting as a point of initiation of template-directed DNA synthesis under appropriate conditions (i.e., in the presence of four different nucleoside triphosphates and an agent for polymerization, such as, DNA or RNA polymerase or reverse transcriptase) in an appropriate buffer and at a suitable temperature. The appropriate length of a primer depends on the intended use of the primer but typically ranges from 15 to 30 nucleotides. Short primer molecules generally require cooler temperatures to form sufficiently stable hybrid complexes with the template. A primer need not reflect the exact sequence of the template but must be sufficiently complementary to hybridize with a template. The term primer site refers to the area of the target DNA to which a primer hybridizes. The term primer pair means a set of primers including a 5′ upstream primer that hybridizes with the 5′ end of the DNA sequence to be amplified and a 3′, downstream primer that hybridizes with the complement of the 3′ end of the sequence to be amplified.

[0018] Linkage describes the tendency of genes, alleles, loci or genetic markers to be inherited together as a result of their location on the same chromosome, and can be measured by percent recombination between the two genes, alleles, loci or genetic markers. Loci occurring within 50 centimorgan of each other are linked. Some linked markers occur within the same gene or gene cluster.

[0019] Polymorphism refers to the occurrence of two or more genetically determined alternative sequences or alleles in a population. A polymorphic marker or site is the locus at which divergence occurs. Preferred markers have at least two alleles, each occurring at frequency of greater than 1%, and more preferably greater than 10% or 20% of a selected population. A polymorphic locus may be as small as one base pair. Polymorphic markers include restriction fragment length polymorphisms, variable number of tandem repeats (VNTR's), hypervariable regions, minisatellites, dinucleotide repeats, trinucleotide repeats, tetranucleotide repeats, simple sequence repeats, and insertion elements such as Alu. The first identified allelic form is arbitrarily designated as a the reference form and other allelic forms are designated as alternative or variant alleles. The allelic form occurring most frequently in a selected population is sometimes referred to as the wildtype form. Diploid organisms may be homozygous or heterozygous for allelic forms. A dialletic polymorphism has two forms. A triallelic polymorphism has three forms.

[0020] A single nucleotide polymorphism occurs at a polymorphic site occupied by a single nucleotide, which is the site of variation between allelic sequences. The site is usually preceded by and followed by highly conserved sequences of the allele (e.g., sequences that vary in less than {fraction (1/100)} or {fraction (1/1000)} members of the populations).

[0021] A single nucleotide polymorphism usually arises due to substitution of one nucleotide for another at the polymorphic site. A transition is the replacement of one purine by another purine or one pyrimidine by another pyrimidine. A transversion is the replacement of a purine by a pyrimidine or vice versa. Single nucleotide polymorphisms can also arise from a deletion of a nucleotide or an insertion of a nucleotide relative to a reference allele.

[0022] A set of polymorphisms means at least 2, and sometimes 5, 10, 20, 50 or more of the polymorphisms shown in Table 1.

[0023] Hybridizations are usually performed under stringent conditions, for example, at a salt concentration of no more than 1 M and a temperature of at least 25□C. For example, conditions of 5×SSPE (750 mM NaCl, 50 mM Na Phosphate, 5 mM EDTA, pH 7.4) and a temperature of 25-30□C. are suitable for allele-specific probe hybridizations.

[0024] An isolated nucleic acid means an object species invention that is the predominant species present (i.e., on a molar basis it is more abundant than any other individual species in the composition). Preferably, an isolated nucleic acid comprises at least about 50, 80 or 90 percent (on a molar basis) of all macromolecular species present. Most preferably, the object species is purified to essential homogeneity (contaminant species cannot be detected in the composition by conventional detection methods).

[0025] Linkage disequilibrium or allelic association means the preferential association of a particular allele or genetic marker with a specific allele, or genetic marker at a nearby chromosomal location more frequently than expected by chance for any particular allele frequency in the population. For example, if locus X has alleles a and b, which occur equally frequently, and linked locus Y has alleles c and d, which occur equally frequently, one would expect the haplotype ac to occur with a frequency of 0.25 in a population of individuals. If ac occurs more frequently, then alleles a and c are in linkage disequilibrium. Linkage disequilibrium may result from natural selection of certain combination of alleles or because an allele has been introduced into a population too recently to have reached equilibrium with linked alleles.

[0026] A marker in linkage disequilibrium can be particularly useful in detecting susceptibility to disease (or other phenotype) notwithstanding that the marker does not cause the disease. For example, a marker (X) that is not itself a causative element of a disease, but which is in linkage disequilibrium with a gene (including regulatory sequences) (Y) that is a causative element of a phenotype, can be used detected to indicate susceptibility to the disease in circumstances in which the gene Y may not have been identified or may not be readily detectable. Younger alleles (i.e., those arising from mutation relatively late in evolution) are expected to have a larger genomic sequencement in linkage disequilibrium. The age of an allele can be determined from whether the allele is shared between ethnic human groups and/or between humans and related species.

DETAILED DESCRIPTION

[0027] The invention provides a substantial collection of novel polymorphisms in several genes encoding products known or suspected to have roles in biochemical pathways relating to blood pressure. Detection of polymorphisms in such genes is useful in designing and performing diagnostic assays for hypertension. Analysis of polymorphisms is also useful in designing prophylactic and therapeutic regimes customized to underlying abnormalities. As with other human polymorphisms, the polymorphisms of the invention also have more general applications, such as forensics, paternity testing, linkage analysis and positional cloning.

[0028] I. Novel Polymorphisms of the Invention.

[0029] The invention provides polymorphic sites in 75 candidate genes, known or suspected to have roles in hypertension. A gene was designated a candidate based on known or suggested involvement in blood pressure homeostasis and/or hypertension in one of the following biochemical pathways: renin-angiotensin, neural, or hormonal pathways regulating blood pressure; regulation of vascular constriction, growth, and repair; ion and other small molecule transportation pathways in the kidney; and, regulation of glucose metabolism. Experimental evidence supporting selection of candidate genes included blood pressure physiology, animal models with altered blood pressure (including transgenic and knockout mouse or rat animal models), and human genetic linkage and association studies.

[0030] To maximize the chances of identifying informative single nucleotide polymorphisms (SNPs), DNA samples from 40 Africans and 35 U.S. individuals of Northern European descent were screened to include both a range of human genetic diversity and hypertension phenotype diversity. Human genetic diversity is greater within African, as compared to European, Asian or American, populations (The History and Geography of Human Genes (Cavalli-Sforza et al., Eds., Princeton University Press, Princeton, N.J., 1994)). There are also significant differences in the prevalence and phenotype of hypertension between Africans (or US Blacks) and Northern Europeans (or US Whites). Hypertension has a greater prevalence, an earlier onset and a higher frequency of salt-sensitive cases in populations of African descent. The individuals sampled were selected from the top and bottom 2.5th percentile of a normalized blood pressure distribution. Regression analysis was performed within each community sample, of systolic, diastolic and mean arterial blood pressure against age and sex, and calculated the ranked frequency distribution of residuals. Equal numbers of individuals were selected from both ends of this latter distribution to maximize potential genetic differences it the genes screened for SNPs.

[0031] 874 SNPs in 75 individuals were identified at a frequency of one SNP per 217 bases. 387 SNPs were in coding sequences, 150 in introns, and 337 in 5′ and 3′ UTRs. Of coding sequence chances, 178 and 209 SNPs led to synonymous and nonsynonymouse substitutions in the translated protein. On average, 12 SNPs were identified per gene, with the number ranging from zero (HSD11) to 54 (PGIS), with ten genes harboring 20 or more SNPs.

[0032] A large collection of polymorphisms of the invention are listed in Table 1. The first column of the Table 1 lists the gene and exon in which a given polymorphism occurs. For example, ACEEX13 means that a polymorphism occurs in exon 13 of angiotensin I-converting enzyme. AGTEX2 means that a polymorphism occurs in exon 2 of the angiotensinogen gene. The full names of the 75 genes shown in Table 1 are shown in Table 3. Sequences of each of the genes are available at http//www.ncbi.nlm.nih.gov/Entrez/nucleotide.html. The second column of Table 1 shows the position of a polymorphism. Numbering of nucleotides follows that of previously published reference sequences with nucleotides in sequence tags shown in column 8 being assigned the same number as the corresponding nucleotide in a reference sequence when the two are maximally aligned. In general, nucleotides in exons are numbered consecutively from the first base of the exon. Column 3 shows the base occupying the polymorphic position in a previously published sequence (arbitrarily designated a reference sequence). Column 4 of Table 1 shows the population frequency of the reference allele. For example at position 138 of exon 13 of ACE, a C nucleotide occurs in 63% of the population. Column 5 of the table shows a nucleotide occupying a polymorphic position that differs from previously published sequences. An allele containing such a nucleotide is designated an alternative allele. Column 6 of the Table shows the population frequency of the alternative allele. Column 7 of the Table shows the population frequency of heterozygosity at a polymorphic position. For example, for the polymorphic position at position 138 of exon 13 of the ACE gene, 37% of the human population are heterozygous. A high frequency of heterozygosity is advantageous in many applications of polymorphisms. The eighth column of the table shows a polymorphic position and about 15 nucleotides of flanking sequence on either side. The bases occupying the polymorphic position are indicated using IUPAC ambiguity nomenclature. For polymorphisms occurring in coding regions, columns 9 and 10 of the Table indicate the codons of the reference and alternate alleles including the polymorphic site. These columns are left blank for polymorphisms occurring in noncoding regions. Column 11 indicates whether the change between reference and alternate alleles is synonymous (i.e., no amino acid substitution due to polymorphic variation), nonsynonymous (i.e, polymorphic variation causes amino acid substitution). If the polymoprhic site does not occur in a coding region, column 11 characterizes the polymorphic site as “other.” For polymorphic sites occurring in noncoding regions column 12 indicates the type of region in which the site occurs (e.g., 5′ UTR, intron). For polymorphic sites occurring in coding regions, column 12 indicates the amino acid encoded by the codon of the reference allele in which the polymorphic site occurs. Column 13 indicates the amino acid encoded by the codon of the alternative allele in which the polymorphic site occurs.

[0033] The polymorphisms shown in Tables 1 were identified by resequencing of target sequences from unrelated individuals of diverse ethnic and geographic backgrounds by hybridization to probes immobilized to microfabricated arrays. About 190 kb of genomic sequence from 75 candidate genes in 75 humans (150 alleles) or about 28 MB total was analyze. The sequence included 87 kb coding DNA, 25 kb intron and 77 kb of 5′ and 3′ UTR sequences. Multiple target sequences from an individual were amplified from human genomic DNA using primers complementary to published sequences. The amplified target sequences were fluorescently labelled during or after PCR.

[0034] Polymorphisms were identified by hybridization of amplified DNA to arrays of oligonucleotide probes. Each genomic region was amplified by the polymerase chain reaction (PCR) in multiple segments , ranging from 80 bp to 14 kb, by both conventional and long PCR protocols. 205 distinct PCR products, averaging 3 kb, representing all 75 genes were pooled for each individual for each chip design

[0035] The strategy and principles for design and use of arrays of oligonucleotide probes are generally described in WO 95/11995. The strategy provides arrays of probes for analysis of target sequences showing a high degree of sequence identity to the published sequences described above. A typical probe array used in this analysis has two groups of four sets of probes that respectively tile both strands of a reference sequence. A first probe set comprises a plurality of probes exhibiting perfect complementarily with one of the reference sequences. Each probe in the first probe set has an interrogation position that corresponds to a nucleotide in the reference sequence. That is, the interrogation position is aligned with the corresponding nucleotide in the reference sequence, when the probe and reference sequence are aligned to maximize complementarily between the two. For each probe in the first set, there are three corresponding probes from three additional probe sets. Thus, there are four probes corresponding to each nucleotide in the reference sequence. The probes from the three additional probe sets are identical to the corresponding probe from the first probe set except at the interrogation position, which occurs in the same position in each of the four corresponding probes from the four probe sets, and is occupied by a different nucleotide in the four probe sets. Arrays tiled for multiple different references sequences were included on the same substrate.

[0036] The labelled target sequences were hybridized with a substrate bearing immobilized arrays of probes. The amount of label bound to probes was measured. Analysis of the pattern of label revealed the nature and position of differences between the target and reference sequence. For example, comparison of the intensities of four corresponding probes reveals the identity of a corresponding nucleotide in the target sequences aligned with the interrogation position of the probes. The corresponding nucleotide is the complement of the nucleotide occupying the interrogation position of the probe showing the highest intensity (see WO 95/11995). The existence of a polymorphism is also manifested by differences in normalized hybridization intensities of probes flanking the polymorphism when the probes hybridized to corresponding targets from different individuals. For example, relative loss of hybridization intensity in a “footprint” of probes flanking a polymorphism signals a difference between the target and reference (i.e., a polymorphism) (see EP 717,113, incorporated by reference in its entirety for all purposes). Additionally, hybridization intensities for corresponding targets from different individuals can be classified into groups or clusters suggested by the data, not defined a priori, such that isolates in a give cluster tend to be similar and isolates in different clusters tend to be dissimilar. See WO 97/29212, filed Feb. 7, 1997 (incorporated by reference in its entirety for all purposes). Hybridizations to samples from different individuals were performed separately.

[0037] II. Analysis of Polymorphisms

[0038] A. Preparation of Samples

[0039] Polymorphisms are detected in a target nucleic acid from an individual being analyzed. For assay of genomic DNA, virtually any biological sample (other than pure red blood cells) is suitable. For example, convenient tissue samples include whole blood, semen, saliva, tears, urine, fecal material, sweat, buccal, skin and hair. For assay of cDNA or mRNA, the tissue sample must be obtained from an organ in which the target nucleic acid is expressed.

[0040] Many of the methods described below require amplification of DNA from target samples. This can be accomplished by e.g., PCR. See generally PCR Technology: Principles and Applications for DNA Amplification (ed. H. A. Erlich, Freeman Press, NY, N.Y., 1992); PCR Protocols: A Guide to Methods and Applications (eds. Innis, et al., Academic Press, San Diego, Calif., 1990); Mattila et al., Nucleic Acids Res. 19, 4967 (1991); Eckert et al., PCR Methods and Applications 1, 17 (1991); PCR (eds. McPherson et al., IRL Press, Oxford); and U.S. Pat. No. 4,683,202 (each of which is incorporated by reference for all purposes).

[0041] Other suitable amplification methods include the ligase chain reaction (LCR) (see Wu and Wallace, Genomics 4, 560 (1989), Landegren et al., Science 241, 1077 (1988), transcription amplification (Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989)), and self-sustained sequence replication (Guatelli et al., Proc. Nat. Acad. Sci. USA, 87, 1874 (1990)) and nucleic acid based sequence amplification (NASBA). The latter two amplification methods involve isothermal reactions based on isothermal transcription, which produce both single stranded RNA (ssRNA) and double stranded DNA (dsDNA) as the amplification products in a ratio of about 30 or 100 to 1, respectively.

[0042] B. Detection of Polymorphisms in Target DNA

[0043] The identity of bases occupying the polymorphic sites shown in Table 1 can be determined in an individual (e.g., a patient being analyzed) by several methods, which are described in turn.

[0044] 1. Allele-Specific Probes

[0045] The design and use of allele-specific probes for analyzing polymorphisms is described by e.g., Saiki et al., Nature 324, 163-166 (1986); Dattagupta, EP 235,726, Saiki, WO 89/11548. Allele-specific probes can be designed that hybridize to a segment of target DNA from one individual but do not hybridize to the corresponding segment from another individual due to the presence of different polymorphic forms in the respective segments from the two individuals. Hybridization conditions should be sufficiently stringent that there is a significant difference in hybridization intensity between alleles, and preferably an essentially binary response, whereby a probe hybridizes to only one of the alleles. Some probes are designed to hybridize to a segment of target DNA such that the polymorphic site aligns with a central position (e.g., in a 15 mer at the 7 position; in a 16 mer, at either the 8 or 9 position) of the probe. This design of probe achieves good discrimination in hybridization between different allelic forms.

[0046] Allele-specific probes are often used in pairs, one member of a pair showing a perfect match to a reference form of a target sequence and the other member showing a perfect match to a variant form. Several pairs of probes can then be immobilized on the same support for simultaneous analysis of multiple polymorphisms within the same target sequence.

[0047] 2. Tiling Arrays

[0048] The polymorphisms can also be identified by hybridization to nucleic acid arrays, some example of which are described by WO 95/11995 (incorporated by reference in its entirety for all purposes). One form of such arrays is described in the Examples section in connection with de novo identification of polymorphisms. The same array or a different array can be used for analysis of characterized polymorphisms. WO 95/11995 also describes subarrays that are optimized for detection of a variant forms of a precharacterized polymorphism. Such a subarray contains probes designed to be complementary to a second reference sequence, which is an allelic variant of the first reference sequence. The second group of probes is designed by the same principles as described in the Examples except that the probes exhibit complementarily to the second reference sequence. The inclusion of a second group (or further groups) can be particular useful for analyzing short subsequences of the primary reference sequence in which multiple mutations are expected to occur within a short distance commensurate with the length of the probes (i.e., two or more mutations within 9 to 21 bases).

[0049] 3. Allele-Specific Primers

[0050] An allele-specific primer hybridizes to a site on target DNA overlapping a polymorphism and only primes amplification of an allelic form to which the primer exhibits perfect complementarily. See Gibbs, Nucleic Acid Res. 17, 2427-2448 (1989). This primer is used in conjunction with a second primer which hybridizes at a distal site. Amplification proceeds from the two primers leading to a detectable product signifying the particular allelic form is present. A control is usually performed with a second pair of primers, one of which shows a single base mismatch at the polymorphic site and the other of which exhibits perfect complementarily to a distal site. The single-base mismatch prevents amplification and no detectable product is formed. The method works best when the mismatch is included in the 3′-most position of the oligonucleotide aligned with the polymorphism because this position is most destabilizing to elongation from the primer. See, e.g., WO 93/22456.

[0051] 4. Direct-Sequencing

[0052] The direct analysis of the sequence of polymorphisms of the present invention can be accomplished using either the dideoxy-chain termination method or the Maxam-Gilbert method (see Sambrook et al., Molecular Cloning, A Laboratory Manual (2nd Ed., CSHP, New York 1989); Zyskind et al., Recombinant DNA Laboratory Manual, (Acad. Press, 1988)).

[0053] 5. Denaturing Gradient Gel Electrophoresis

[0054] Amplification products generated using the polymerase chain reaction can be analyzed by the use of denaturing gradient gel electrophoresis. Different alleles can be identified based on the different sequence-dependent melting properties and electrophoretic migration of DNA in solution. Erlich, ed., PCR Technology, Principles and Applications for DNA Amplification, (W. H. Freeman and Co, New York, 1992), Chapter 7.

[0055] 6. Single-Strand Conformation Polymorphism Analysis

[0056] Alleles of target sequences can be differentiated using single-strand conformation polymorphism analysis, which identifies base differences by alteration in electrophoretic migration of single stranded PCR products, as described in Orita et al., Proc. Nat. Acad. Sci. 86, 2766-2770 (1989). Amplified PCR products can be generated as described above, and heated or otherwise denatured, to form single stranded amplification products. Single-stranded nucleic acids may refold or form secondary structures which are partially dependent on the base sequence. The different electrophoretic mobilities of single-stranded amplification products can be related to base-sequence difference between alleles of target sequences.

[0057] III. Methods of Use

[0058] After determining polymorphic form(s) present in an individual at one or more polymorphic sites, this information can be used in a number of methods.

[0059] A. Association Studies with Hypertension

[0060] The polymorphisms of the invention may contribute to the phenotype of an organism in different ways. Some polymorphisms occur within a protein coding sequence and contribute to phenotype by affecting protein structure. The effect may be neutral, beneficial or detrimental, or both beneficial and detrimental, depending on the circumstances. By analogy, a heterozygous sickle cell mutation confers resistance to malaria, but a homozygous sickle cell mutation is usually lethal. Other polymorphisms occur in noncoding regions but may exert phenotypic effects indirectly via influence on replication, transcription, and translation. A single polymorphism may affect more than one phenotypic trait. Likewise, a single phenotypic trait may be affected by polymorphisms in different genes. Further, some polymorphisms predispose an individual to a distinct mutation that is causally related to a certain phenotype.

[0061] The polymorphism shown in Table 1 are analyzed for a correlation with hypertension, the metabolic processes that lead to hypertension, and response to drugs used to treat hypertension. For purposes of these studies, hypertension can be defined as a dichotomous trait (e.g., diastolic blood pressure greater than 90 mm Hg), as a continuous scale of increasing severity based on blood pressure values, or as several intermediate phenotypes. Because it is likely that the causation of hypertension in the population is heterogenous, use of intermediate phenotypes can increase the strength of correlations identified. Some useful subtypes for association studies are mendelian forms of human hypertension, forms characterized by increased erythrocyte sodium-lithium countertransport, forms characterized by altered urinary kallikrein levels, and forms characterized by sensitivity of blood pressure to increases or decreases in sodium intake.

[0062] Correlation is performed for a population of individuals who have been tested for the presence or absence of hypertension or an intermediate phenotype and for one or polymorphic markers. To perform such analysis, the presence or absence of a set of polymorphic forms (i.e. a polymorphic set) is determined for a set of the individuals, some of whom exhibit a particular trait, and some of which exhibit lack of the trait. The alleles of each polymorphism of the set are then reviewed to determine whether the presence or absence of a particular allele is associated with the trait of interest. Correlation can be performed by standard statistical methods such as a &kgr;-squared test and statistically significant correlations between polymorphic form(s) and phenotypic characteristics are noted. For example, it might be found that the presence of allele A1 at polymorphism A correlates with hypertension as a dichotomous trait. As a further example, it might be found that the combined presence of allele A1 at polymorphism A and allele B1 at polymorphism B correlates with increased erythrocyte sodium lithium counter transport, an intermediate phenotype in development of hypertension.

[0063] B. Diagnosis of Hypertension

[0064] Polymorphic forms that correlate with hypertension or intermediate phenotypes are useful in diagnosing hypertension or susceptibility thereto. Combined detection of several such polymorphic forms (for example, 2, 5, 10 or 20 of the polymorphisms listed in Table 1) typically increases the probability of an accurate diagnosis. For example, the presence of a single polymorphic form known to correlate with hypertension might indicate a probability of 20% that an individual has or is susceptible to hypertension, whereas detection of five polymorphic forms, each of which correlates with hypertension, might indicate a probability of 80% that an individual has or is susceptible to hypertension. Analysis of the polymorphisms of the invention can be combined with that of other polymorphisms or other risk factors of hypertension, such as family history or obesity, as well as measurements of blood pressure.

[0065] Patients diagnosed with hypertension can be treated with conventional therapies and/or can be counselled to undertake remedial life style changes, such as a low fat, low salt diet or more exercise. Conventional therapies include diuretics (e.g., thiazides), which lower blood pressure by depleting the body of sodium and reducing blood volume; sympathoplegic agents (e.g., methyldopa and clonidine), which lower blood pressure by reducing peripheral vascular resistance, inhibiting cardiac function and increasing venous pooling in capacitance vessels; direct vasodilators (e.g., hydralazine, minoxidil,, diazoxide and sodium nitroprusside), which reduce pressure by relaxing vascular smooth muscle; agents that block production or action of angiotensin (e.g., captopril, enalapril and lisinopril), and thereby reduce peripheral vascular resistance; and adrenergic neuron blocking agents (e.g., guanethidine, reserpine, propranolol) which prevent release of norepinephrine. See, e.g., Basic and Clinical Pharmacology (Ed. Katzung, Appleton & Lange, CT, 1989).

[0066] C. Drug Screening

[0067] The polymorphism(s) showing the strongest correlation with hypertension within a given gene are likely to have a causative role in hypertension. Such a role can be confirmed by producing a transgenic animal expressing a human gene bearing such a polymorphism and determining whether the animal develops hypertension. Polymorphisms in coding regions that result in amino acid changes usually cause hypertension by decreasing, increasing or otherwise altering the activity of the protein encoded by the gene in which the polymorphism occurs. Polymorphisms in coding regions that introduce stop codons usually cause hypertension by reducing (heterozygote) or eliminating (homozygote) functional protein produced by the gene. Occasionally, stop codons result in production of a truncated peptide with aberrant activities relative to the full-length protein. Polymorphisms in regulatory regions typically cause hypertension by causing increased or decreased expression of the protein encoded by the gene in which the polymorphism occurs. Polymorphisms in intronic sequences can cause hypertension either through the same mechanism as polymorphisms in regulatory sequences or by causing altered spliced patterns resulting in an altered protein. For example, alternative splice patterns have been reported for the human angiotensin II receptor gene (Curnow et al., Molecular Endocrinology 9, 1250-1262 (1995)).

[0068] The precise role of polymorphisms in hypertension can be elucidated by several means. Alterations in expression levels of a protein (e.g., sodium-calcium ion channel) can be determined by measuring protein levels in samples groups of persons characterized as having or not having hypertension (or intermediate phenotypes). Alterations in enzyme activity (e.g., renin), can similarly be detected by assaying for enzyme activity in samples from the above groups of persons. Alterations in receptor transducing activity (e.g., angiotensin II receptor, &bgr;-3-adrenergic receptor or bradykinin receptor B2) can be detected by comparing receptor ligand binding, either in vitro or in a cellular expression system.

[0069] Having identified certain polymorphisms as having causative roles in hypertension, and having elucidated at least in general terms whether such polymorphisms increase or decrease the activity or expression level of associated proteins, customized therapies can be devised for classes of patients with different genetic subtypes of hypertension. For example, if a polymorphism in a given protein causes hypertension by increasing the expression level or activity of the protein, hypertension associated with the polymorphism can be treated by administering an antagonist of the protein. If a polymorphism in a given protein causes hypertension by decreasing the expression level or activity of a protein, the form of hypertension associated with the polymorphism can be treated by administering the protein itself, a nucleic acid encoding the protein that can be expressed in a patient, or an analog or agonist of the protein.

[0070] Agonists, antagonists can be obtained by producing and screening large combinatorial libraries. Combinatorial libraries can be produced for many types of compound that can be synthesized in a step by step fashion. Such compounds include polypeptides, beta-turn mimetics, polysaccharides, phospholipids, hormones, prostaglandins, steroids, aromatic compounds, heterocyclic compounds, benzodiazepines, oligomeric N-substituted glycines and oligocarbamates. Large combinatorial libraries of the compounds can be constructed by the encoded synthetic libraries (ESL) method described in Affymax, WO 95/12608, Affymax, WO 93/06121, Columbia University, WO 94/08051, Pharmacopeia, WO 95/35503 and Scripps, WO 95/30642 (each of which is incorporated by reference for all purposes). Peptide libraries can also be generated by phage display methods. See, e.g., Devlin, WO 91/18980. The libraries of compounds can be initially screened for specific binding to the protein for which agonists or antagonists are to be identified, or to its natural binding partner. Preferred agents bind with a Kd<&mgr;M. For example, for receptor ligand combinations, the assay can be performed using cloned receptor immobilized to a support such as a microtiter well and binding of compounds can be measured in competition with ligand to the receptor. Agonist or antagonist activity can then be assayed using a cellular reporter system or a transgenic animal model.

[0071] The polymorphisms of the invention are also useful for conducting clinical trials of drug candidates for hypertension. Such trials are performed on treated or control populations having similar or identical polymorphic profiles at a defined collection of polymorphic sites. Use of genetically matched populations eliminates or reduces variation in treatment outcome due to genetic factors, leading to a more accurate assessment of the efficacy of a potential drug.

[0072] D. Other Diseases

[0073] The polymorphisms in Table 1 can also be tested for association with other disease that have known but hitherto unmapped genetic components (e.g., agammaglobulinemia, diabetes insipidus, Lesch-Nyhan syndrome, muscular dystrophy, Wiskott-Aldrich syndrome, Fabry's disease, familial hypercholesterolemia, polycystic kidney disease, hereditary spherocytosis, von Willebrand's disease, tuberous sclerosis, hereditary hemorrhagica telangiectasia, familial colonic polyposis, Ehlers-Danlos syndrome, osteogenesis imperfecta, and acute intermittent porphyria). Phenotypic traits also include symptoms of, or susceptibility to, multifactorial diseases of which a component is or may be genetic, such as autoimmune diseases, inflammation, cancer, diseases of the nervous system, and infection by pathogenic microorganisms. Some examples of autoimmune diseases include rheumatoid arthritis, multiple sclerosis, diabetes (insulin-dependent and non-independent), systemic lupus erythematosus and Graves disease. Some examples of cancers include cancers of the bladder, brain, breast, colon, esophagus, kidney, leukemia, liver, lung, oral cavity, ovary, pancreas, prostate, skin, stomach and uterus. Phenotypic traits also include characteristics such as longevity, appearance (e.g., baldness, obesity), strength, speed, endurance, fertility, and susceptibility or receptivity to particular drugs or therapeutic treatments.

[0074] Such correlations can be exploited in several ways. In the case of a strong correlation between a set of one or more polymorphic forms and a disease for which treatment is available, detection of the polymorphic form set in a human or animal patient may justify immediate administration of treatment, or at least the institution of regular monitoring of the patient. Detection of a polymorphic form correlated with serious disease in a couple contemplating a family may also be valuable to the couple in their reproductive decisions. For example, the female partner might elect to undergo in vitro fertilization to avoid the possibility of transmitting such a polymorphism from her husband to her offspring. In the case of a weaker, but still statistically significant correlation between a polymorphic set and human disease, immediate therapeutic intervention or monitoring may not be justified. Nevertheless, the patient can be motivated to begin simple life-style changes (e.g., diet, exercise) that can be accomplished at little cost to the patient but confer potential benefits in reducing the risk of conditions to which the patient may have increased susceptibility by virtue of variant alleles. Identification of a polymorphic set in a patient correlated with enhanced receptiveness to one of several treatment regimes for a disease indicates that this treatment regime should be followed.

[0075] E. Forensics

[0076] Determination of which polymorphic forms occupy a set of polymorphic sites in an individual identifies a set of polymorphic forms that distinguishes the individual. See generally National Research Council, The Evaluation of Forensic DNA Evidence (Eds. Pollard et al., National Academy Press, DC, 1996). The more sites that are analyzed the lower the probability that the set of polymorphic forms in one individual is the same as that in an unrelated individual. Preferably, if multiple sites are analyzed, the sites are unlinked. Thus, polymorphisms of the invention are often used in conjunction with polymorphisms in distal genes. Preferred polymorphisms for use in forensics are diallelic because the population frequencies of two polymorphic forms can usually be determined with greater accuracy than those of multiple polymorphic forms at multi-allelic loci.

[0077] The capacity to identify a distinguishing or unique set of forensic markers in an individual is useful for forensic analysis. For example, one can determine whether a blood sample from a suspect matches a blood or other tissue sample from a crime scene by determining whether the set of polymorphic forms occupying selected polymorphic sites is the same in the suspect and the sample. If the set of polymorphic markers does not match between a suspect and a sample, it can be concluded (barring experimental error) that the suspect was not the source of the sample. If the set of markers does match, one can conclude that the DNA from the suspect is consistent with that found at the crime scene. If frequencies of the polymorphic forms at the loci tested have been determined (e.g., by analysis of a suitable population of individuals), one can perform a statistical analysis to determine the probability that a match of suspect and crime scene sample would occur by chance.

[0078] p(ID) is the probability that two random individuals have the same polymorphic or allelic form at a given polymorphic site. In diallelic loci, four genotypes are possible: AA, AB, BA, and BB. If alleles A and B occur in a haploid genome of the organism with frequencies x and y, the probability of each genotype in a diploid organism are (see WO 95/12607):

Homozygote: p(AA)=x2

Homozygote: p(BB)=y2=(1−x)2

Single Heterozygote: p(AB)=p(BA)=xy=x(1−x)

Both Heterozygotes: p(AB+BA)=2xy=2x(1−x)

[0079] The probability of identity at one locus (i.e, the probability that two individuals, picked at random from a population will have identical polymorphic forms at a given locus) is given by the equation:

p(ID)=(x2)2+(2xy)2+(y2)2.

[0080] These calculations can be extended for any number of polymorphic forms at a given locus. For example, the probability of identity p(ID) for a 3-allele system where the alleles have the frequencies in the population of x, y and z, respectively, is equal to the sum of the squares of the genotype frequencies:

p(ID)=x4+(2xy)2+(2yz)2+(2xz)2+z4+y4

[0081] In a locus of n alleles, the appropriate binomial expansion is used to calculate p(ID) and p(exc).

[0082] The cumulative probability of identity (cum p(ID)) for each of multiple unlinked loci is determined by multiplying the probabilities provided by each locus.

cum p(ID)=p(ID1)p(ID2)p(ID3) . . . p(IDn)

[0083] The cumulative probability of non-identity for n loci (i.e. the probability that two random individuals will be different at 1 or more loci) is given by the equation:

cum p(nonID)=1−cum p(ID).

[0084] If several polymorphic loci are tested, the cumulative probability of non-identity for random individuals becomes very high (e.g., one billion to one). Such probabilities can be taken into account together with other evidence in determining the guilt or innocence of the suspect.

[0085] F. Paternity Testing

[0086] The object of paternity testing is usually to determine whether a male is the father of a child. In most cases, the mother of the child is known and thus, the mother's contribution to the child's genotype can be traced. Paternity testing investigates whether the part of the child's genotype not attributable to the mother is consistent with that of the putative father. Paternity testing can be performed by analyzing sets of polymorphisms in the putative father and the child.

[0087] If the set of polymorphisms in the child attributable to the father does not match the putative father, it can be concluded, barring experimental error, that the putative father is not the real father. If the set of polymorphisms in the child attributable to the father does match the set of polymorphisms of the putative father, a statistical calculation can be performed to determine the probability of coincidental match.

[0088] The probability of parentage exclusion (representing the probability that a random male will have a polymorphic form at a given polymorphic site that makes him incompatible as the father) is given by the equation (see WO 95/12607):

p(exc)=xy(1−xy)

[0089] where x and y are the population frequencies of alleles A and B of a diallelic polymorphic site.

(At a triallelic site p(exc)=xy(1−xy)+yz(1−yz)+xz(1−xz)+3xyz(1−xyz))),

[0090] where x, y and z and the respective population frequencies of alleles A, B and C).

[0091] The probability of non-exclusion is

p(non-exc)=1−p(exc)

[0092] The cumulative probability of non-exclusion (representing the value obtained when n loci are used) is thus:

cum p(non-exc)=p(non-exc1)p(non-exc2)p(non-exc3) . . . p(non-excn)

[0093] The cumulative probability of exclusion for n loci (representing the probability that a random male will be excluded)

cum p(exc)=1−cum p(non-exc).

[0094] If several polymorphic loci are included in the analysis, the cumulative probability of exclusion of a random male is very high. This probability can be taken into account in assessing the liability of a putative father whose polymorphic marker set matches the child's polymorphic marker set attributable to his/her father.

[0095] G. Genetic Mapping of Phenotypic Traits

[0096] The polymorphisms shown in table 1 can also be used to establish physical linkage between a genetic locus associated with a trait of interest and polymorphic markers that are not associated with the trait, but are in physical proximity with the genetic locus responsible for the trait and co-segregate with it. Such analysis is useful for mapping a genetic locus associated with a phenotypic trait to a chromosomal position, and thereby cloning gene(s) responsible for the trait. See Lander et al., Proc. Natl. Acad. Sci. (USA) 83, 7353-7357 (1986); Lander et al., Proc. Natl. Acad. Sci. (USA) 84, 2363-2367 (1987); Donis-Keller et al., Cell 51, 319-337 (1987); Lander et al., Genetics 121, 185-199 (1989)). Genes localized by linkage can be cloned by a process known as directional cloning. See Wainwright, Med. J. Australia 159, 170-174 (1993); Collins, Nature Genetics 1, 3-6 (1992) (each of which is incorporated by reference in its entirety for all purposes).

[0097] Linkage studies are typically performed on members of a family. Available members of the family are characterized for the presence or absence of a phenotypic trait and for a set of polymorphic markers. The distribution of polymorphic markers in an informative meiosis is then analyzed to determine which polymorphic markers co-segregate with a phenotypic trait. See, e.g., Kerem et al., Science 245, 1073-1080 (1989); Monaco et al., Nature 316, 842 (1985); Yamoka et al., Neurology 40, 222-226 (1990); Rossiter et al., FASEB Journal 5, 21-27 (1991).

[0098] Linkage is analyzed by calculation of LOD (log of the odds) values. A lod value is the relative likelihood of obtaining observed segregation data for a marker and a genetic locus when the two are located at a recombination fraction &thgr;, versus the situation in which the two are not linked, and thus segregating independently (Thompson & Thompson, Genetics in Medicine (5th ed, W. B. Saunders Company, Philadelphia, 1991); Strachan, “Mapping the human genome” in The Human Genome (BIOS Scientific Publishers Ltd, Oxford), Chapter 4). A series of likelihood ratios are calculated at various recombination fractions (&thgr;), ranging from &thgr;=0.0 (coincident loci) to &thgr;=0.50 (unlinked). Thus, the likelihood at a given value of &thgr; is: probability of data if loci linked at &thgr; to probability of data if loci unlinked. The computed likelihoods are usually expressed as the log10 of this ratio (i.e., a lod score). For example, a lod score of 3 indicates 1000:1 odds against an apparent observed linkage being a coincidence. The use of logarithms allows data collected from different families to be combined by simple addition. Computer programs are available for the calculation of lod scores for differing values of &thgr; (e.g., LIPED, MLINK (Lathrop, Proc. Nat. Acad. Sci. (USA) 81, 3443-3446 (1984)). For any particular lod score, a recombination fraction may be determined from mathematical tables. See Smith et al., Mathematical tables for research workers in human genetics (Churchill, London, 1961); Smith, Ann. Hum. Genet. 32, 127-150 (1968). The value of &thgr; at which the lod score is the highest is considered to be the best estimate of the recombination fraction. Positive lod score values suggest that the two loci are linked, whereas negative values suggest that linkage is less likely (at that value of &thgr;) than the possibility that the two loci are unlinked. By convention, a combined lod score of +3 or greater (equivalent to greater than 1000:1 odds in favor of linkage) is considered definitive evidence that two loci are linked. Similarly, by convention, a negative lod score of −2 or less is taken as definitive evidence against linkage of the two loci being compared. Negative linkage data are useful in excluding a chromosome or a segment thereof from consideration. The search focuses on the remaining non-excluded chromosomal locations.

[0099] IV. Modified Polypeptides and Gene Sequences

[0100] The invention further provides variant forms of nucleic acids and corresponding proteins. The nucleic acids comprise one of the sequences described in Table 1, column 8, in which the polymorphic position is occupied by an alternative base for that position. Some nucleic acid encode full-length variant forms of proteins. Similarly, variant proteins have the prototypical amino acid sequences of encoded by nucleic acid sequence shown in Table 1, column 8, (read so as to be in-frame with the full-length coding sequence of which it is a component) except at an amino acid encoded by a codon including one of the polymorphic positions shown in the Table. That position is occupied by the amino acid coded by the corresponding codon in the alternative forms shown in the Table.

[0101] Variant genes can be expressed in an expression vector in which a variant gene is operably linked to a native or other promoter. Usually, the promoter is a eukaryotic promoter for expression in a mammalian cell. The transcription regulation sequences typically include a heterologous promoter and optionally an enhancer which is recognized by the host. The selection of an appropriate promoter, for example trp, lac, phage promoters, glycolytic enzyme promoters and tRNA promoters, depends on the host selected. Commercially available expression vectors can be used. Vectors can include host-recognized replication systems, amplifiable genes, selectable markers, host sequences useful for insertion into the host genome, and the like.

[0102] The means of introducing the expression construct into a host cell varies depending upon the particular construction and the target host. Suitable means include fusion, conjugation, transfection, transduction, electroporation or injection, as described in Sambrook, supra. A wide variety of host cells can be employed for expression of the variant gene, both prokaryotic and eukaryotic. Suitable host cells include bacteria such as E. coli, yeast, filamentous fungi, insect cells, mammalian cells, typically immortalized, e.g., mouse, CHO, human and monkey cell lines and derivatives thereof. Preferred host cells are able to process the variant gene product to produce an appropriate mature polypeptide. Processing includes glycosylation, ubiquitination, disulfide bond formation, general post-translational modification, and the like.

[0103] The protein may be isolated by conventional means of protein biochemistry and purification to obtain a substantially pure product, i.e., 80, 95 or 99% free of cell component contaminants, as described in Jacoby, Methods in Enzymology Volume 104, Academic Press, New York (1984); Scopes, Protein Purification, Principles and Practice, 2nd Edition, Springer-Verlag, New York (1987); and Deutscher (ed), Guide to Protein Purification, Methods in Enzymology, Vol. 182 (1990). If the protein is secreted, it can be isolated from the supernatant in which the host cell is grown. If not secreted, the protein can be isolated from a lysate of the host cells.

[0104] The invention further provides transgenic nonhuman animals capable of expressing an exogenous variant gene and/or having one or both alleles of an endogenous variant gene inactivated. Expression of an exogenous variant gene is usually achieved by operably linking the gene to a promoter and optionally an enhancer, and microinjecting the construct into a zygote. See Hogan et al., “Manipulating the Mouse Embryo, A Laboratory Manual,” Cold Spring Harbor Laboratory. Inactivation of endogenous variant genes can be achieved by forming a transgene in which a cloned variant gene is inactivated by insertion of a positive selection marker. See Capecchi, Science 244, 1288-1292 (1989). The transgene is then introduced into an embryonic stem cell, where it undergoes homologous recombination with an endogenous variant gene. Mice and other rodents are preferred animals. Such animals provide useful drug screening systems.

[0105] In addition to substantially full-length polypeptides expressed by variant genes, the present invention includes biologically active fragments of the polypeptides, or analogs thereof, including organic molecules which simulate the interactions of the peptides. Biologically active fragments include any portion of the full-length polypeptide which confers a biological function on the variant gene product, including ligand binding, and antibody binding. Ligand binding includes binding by nucleic acids, proteins or polypeptides, small biologically active molecules, or large cellular structures.

[0106] Polyclonal and/or monoclonal antibodies that specifically bind to variant gene products but not to corresponding prototypical gene products are also provided. Antibodies can be made by injecting mice or other animals with the variant gene product or synthetic peptide fragments thereof. Monoclonal antibodies are screened as are described, for example, in Harlow & Lane, Antibodies, A Laboratory Manual, Cold Spring Harbor Press, New York (1988); Goding, Monoclonal antibodies, Principles and Practice (2d ed.) Academic Press, New York (1986). Monoclonal antibodies are tested for specific immunoreactivity with a variant gene product and lack of immunoreactivity to the corresponding prototypical gene product. These antibodies are useful in diagnostic assays for detection of the variant form, or as an active ingredient in a pharmaceutical composition.

[0107] V. Kits

[0108] The invention further provides kits comprising at least one allele-specific oligonucleotide as described above. Often, the kits contain one or more pairs of allele-specific oligonucleotides hybridizing to different forms of a polymorphism. In some kits, the allele-specific oligonucleotides are provided immobilized to a substrate. For example, the same substrate can comprise allele-specific oligonucleotide probes for detecting at least 10, 100 or all of the polymorphisms shown in Table 1. Optional additional components of the kit include, for example, restriction enzymes, reverse-transcriptase or polymerase, the substrate nucleoside triphosphates, means used to label (for example, an avidin-enzyme conjugate and enzyme substrate and chromogen if the label is biotin), and the appropriate buffers for reverse transcription, PCR, or hybridization reactions. Usually, the kit also contains instructions for carrying out the methods.

[0109] VI. Computer Systems For Storing Polymorphism Data

[0110] FIG. 1A depicts a block diagram of a computer system 10 suitable for implementing the present invention. Computer system 10 includes a bus 12 which interconnects major subsystems such as a central processor 14, a system memory 16 (typically RAM), an input/output (I/O) controller 18, an external device such as a display screen 24 via a display adapter 26, serial ports 28 and 30, a keyboard 32, a fixed disk drive 34 via a storage interface 35 and a floppy disk drive 36 operative to receive a floppy disk 38, and a CD-ROM (or DVD-ROM) device 40 operative to receive a CD-ROM 42. Many other devices can be connected such as a user pointing device, e.g., a mouse 44 connected via serial port 28 and a network interface 46 connected via serial port 30.

[0111] Many other devices or subsystems (not shown) may be connected in a similar manner. Also, it is not necessary for all of the devices shown in FIG. 1A to be present to practice the present invention, as discussed below. The devices and subsystems may be interconnected in different ways from that shown in FIG. 1A. The operation of a computer system such as that shown in FIG. 1A is well known. Databases storing polymorphism information according to the present invention can be stored, e.g., in system memory 16 or on storage media such as fixed disk 34, floppy disk 38, or CD-ROM 42. An application program to access such databases can be operably disposed in system memory 16 or sorted on storage media such as fixed disk 34, floppy disk 38, or CD-ROM 42.

[0112] FIG. 1B depicts the interconnection of computer system 10 to remote computers 48, 50, and 52. FIG. 1B depicts a network 54 interconnecting remote servers 48, 50, and 52. Network interface 46 provides the connection from client computer system 10 to network 54. Network 54 can be, e.g., the Internet. Protocols for exchanging data via the Internet and other networks are well known. Information identifying the polymorphisms described herein can be transmitted across network 54 embedded in signals capable of traversing the physical media employed by network 54.

[0113] Information identifying polymorphisms shown in Table 1 is represented in records, which optionally, are subdivided into fields. Each record stores information relating to a different polymorphisms in Table 1. Collectively, the records can store information relating to all of the polymorphisms in Table 1, or any subset thereof, such as 5, 10, 50, or 100 polymorphisms from Table 1. In some databases, the information identifies a base occupying a polymorphic position and the location of the polymorphic position. The base can be represented as a single letter code (i.e., A, C, G or T/U) present in a polymorphic form other than that in the reference allele. Alternatively, the base occupying a polymorphic site can be represented in IUPAC ambiguity code as shown in Table 1. The location of a polymorphic site can be identified as its position within one of the sequences shown in Table 1. For example, in the first sequence shown in Table 1, the polymorphic site occupies the 15th base. The position can also be identified by reference to, for example, a chromosome, and distance from known markers within the chromosome. In other databases, information identifying a polymorphism contains sequences of 10-100 bases shown in Table 1 or the complements thereof, including a polymorphic site. Preferably, such information records at least 10, 15, 20, or 30 contiguous bases of sequences including a polymorphic site.

[0114] From the foregoing, it is apparent that the invention includes a number of general uses that can be expressed concisely as follows. The invention provides for the use of any of the nucleic acid segments described above in the diagnosis or monitoring of diseases, particularly hypertension. The invention further provides for the use of any of the nucleic acid segments in the manufacture of a medicament for the treatment or prophylaxis of such diseases. The invention further provides for the use of any of the DNA segments as a pharmaceutical.

[0115] All publications and patent applications cited above are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication or patent application were specifically and individually indicated to be so incorporated by reference. Although the present invention has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims. 1 TABLE 1 Heteroz Type of Alt Base Ref Alt ygosity Ref Alt amino acid Ref amino amino Gene/Exon Position Allele Freq (P) Allele Freq (Q) (H) Sequence Tag Codon Codon Change acid acid AADDEX1 305 G 0.98 A 0.03 0.05 ACGGGGGCGGAGCCRGAGCCGGAGCCGAC . . Other 5′UTR . AADDEX10 246 G 0.86 T 0.14 0.23 AAGCTTCCGAGGAAKGGCAGAATGGAAGC GGG TGG Nonsynonymous Gly Trp AADDEX12 43 A 0.94 T 0.06 0.11 GATCCGAGAGCAGAWTTTACAGGACATTA AAT ATT Nonsynonymous Asn Ile AADDEX13 173 C 0.70 G 0.30 0.42 GAAGCAGAAGGGCTSTGAAGGTGAGTGCT TCT TGT Nonsynonymous Ser Cys AADDEX15 74 C 0.73 T 0.27 0.40 CCTAGTAAGTACCGYGCTGCCTCCGCTCT . . Other Intron AADDEX16 1071 G 0.99 A 0.01 0.02 ATTCCTGTCATAGGRAAGGTATATCAGGA . . Other 3′UTR AADDEX16 1321 C 0.98 T 0.02 0.04 GCCCTGGGGCCCCTYGACATCACCGTCAT . . Other 3′UTR AADDEX16 1328 A 0.91 G 0.09 0.17 GGCCCCTCGACATCRCCGTCATTGATGGA . . Other 3′UTR AADDEX16 1478 A 0.89 G 0.11 0.19 CAGCCTGACTAGGTRCAGGCAAGCTTGTG . . Other 3′UTR AADDEX16 691 C 0.99 G 0.01 0.02 CAGCTTTGGCTGCASGTCACCCTCCTGAG . . Other 3′UTR AADDEX16 995 C 0.94 T 0.06 0.11 TATGCATGTCTGACYGACGATCCCTCGAC . . Other 3′UTR AADDEX2 31 A 0.98 G 0.03 0.05 TTTGATTCTGTAGGRACCTAGAAAGATTG . . Other 5′UTR AADDEX7 96 T 0.98 A 0.02 0.04 TTGGAGAAGTGGCTWATCATGACTACCAT TAT AAT Nonsynonymous Tyr Asn AADDEX9 173 A 0.93 T 0.07 0.13 ATTGGTGAGCAGGAWTTTGAAGCCCTCAT GAA GAT Nonsynonymous Glu Asp ACEEX13 151 T 0.75 C 0.25 0.38 CCAGCCAGGAGGCAYCCCAACAGGTGACA TCT CCT Nonsynonymous Ser Pro ACEEX13 202 A 0.75 C 0.25 0.38 AGGCAACAACCAGCRGCCAGACAACCACC AGC GGC Nonsynonymous Ser Gly ACEEX15 144 G 0.80 A 0.20 0.32 CTAGAACGGGCAGCRCTGCCTGCCCAGGA GCG GCA Synonymous Ala Ala ACEEX17 19 C 0.69 A 0.31 0.43 CTCAAGCCATTCAAMCCCCTACCAGATCT . . Other Intron ACEEX18 130 C 0.95 G 0.05 0.09 CAGCCACTCTACCTSAACCTGCATGCCTA CTC CTG Synonymous Leu Leu ACEEX21 150 T 0.98 C 0.03 0.05 CTTCCATGAGGCCAYTGGGGACGTGCTAG ATT ACT Nonsynonymous Ile Thr ACEEX22 19 T 0.99 G 0.01 0.03 AGCATGACATCAACKTTCTGATGAAGATG TTT GTT Nonsynonymous Phe Val ACEEX24 118 C 0.95 T 0.05 0.10 CAGTCCAAGGAGGCYGGGCAGCGCCTGGG GCC GCT Synonymous Ala Ala ACEEX24 16 T 0.57 C 0.43 0.49 TGCTCCAGGTACTTYGTCAGCTTCATCAT TTT TTC Synonymous Phe Phe ACEEX26 154 G 0.98 A 0.03 0.05 GGGCCTCAGCCAGCRGCTCTTCAGCATCC CGG CAG Nonsynonymous Arg Gln ACEEX26 174 C 0.90 A 0.10 0.18 TCAGCATCCGCCACMGCAGCCTCCACCGG CGC AGC Nonsynonymous Arg Ser ACEEX26 205 A 0.98 C 0.02 0.03 CTCCCACGGGCCCCMGTTCGGCTCCGAGG CAG CCG Nonsynonymous Gln Pro ACEEX26 224 G 0.94 A 0.06 0.11 GGCTCCGAGGTGGARCTGAGACACTCCTG GAG GAA Synonymous Glu Glu ADDBEX10 81 G 0.98 T 0.03 0.05 CTCCTGGAGCAGGAKAAGCACCGGCCCCA GAG GAT Nonsynonymous Glu Asp ADDBEX15 68 G 0.99 A 0.01 0.03 GCTCTGGTCCGGCCRTGTGCGAGTTCTTC CCG CCA Synonymous Pro Pro ADDBEX15 85 C 0.90 T 0.10 0.18 TGCGAGTTCTTCAGYGTTGCCCTCCACAT GCG GTG Nonsynonymous Ala Val ADDBEX17 147 C 0.98 A 0.02 0.04 GAGGAAATCCTCAGMAAAGGCCTGAGCCA AGC AGA Nonsynonymous Ser Arg ADDBEX3 138 G 0.89 A 0.11 0.19 GCTTCTCAGAGGACRACCCCGAGTACATG GAC AAC Nonsynonymous Asp Asn ADDBEX4 134 C 0.99 G 0.01 0.02 CATGGCCAGCACCTSCCACGCAGTCTTCC TCC TGC Nonsynonymous Ser Cys ADDBEX8 173 A 0.96 G 0.04 0.07 CCACCTGCAAGGTTRGCTTAGCTCTTCTG . . Other Intron ADDBEX9 69 T 0.99 C 0.01 0.02 GTAGAGGAGGCATTYTACAAGATCTTCCA TTT TTC Synonymous Phe Phe ADDG 2087 T 0.98 C 0.02 0.03 TGACATTGCACATCYAAATACCACATTTA . . Other 3′UTR ADORA2AEX1 429 C 0.97 T 0.03 0.07 GGTGTCACTGGCGGYGGCCGACATCGCAG GCG GTG Nonsynonymous Ala Val ADORA2AEX2 1230 G 0.97 T 0.03 0.06 TGCAGAAGCATCTGKAAGCACCACCTTGT . . Other 3′UTR ADORA2AEX2596 G 0.97 A 0.03 0.06 CCGCCAGACCTTCCRCAAGATCATTCGCA CGC CAC Nonsynonymous Arg His ADORA2AEX2741 C 0.92 T 0.08 0.15 GGAGTGTGGGCCAAYGGCAGTGCTCCCCA AAC AAT Synonymous Asn Asn ADRB3EX1 1020 C 0.96 T 0.04 0.07 GGCCCCGGTGGGGAYGTGCGCT ACG ATG Nonsynonymous Thr Met ADRB3EX1 1354 C 0.89 T 0.11 0.20 TGCGCCGCCGCCCGYCCGGCCCTCTTCCC CGC CGT Synonymous Arg Arg ADRB3EX1 1445 G 0.90 T 0.10 0.18 GGTAGGTAACCGGGKCAGAGGGACCGGCG . . Other Intron ADRB3EX1 44 A G GCTACTCCTCCCCCRAGAGCGGTGGCACC . . Other Intron ADRB3EX2 301 G 0.96 C 0.04 0.08 GTGGTAGTGTCCAGSTGCCGTGGAGCAGC . . Other 3′UTR ADRB3EX2 408 C 0.80 T 0.20 0.32 TGGTTCCATTCCTTYTGCCACCCAAACCC . . Other 3′UTR ADROMEX1 1197 C 0.98 T 0.02 0.04 TGGGACGTCTGAGAYTTTCTCCTTCAAGT . . Other 5′UTR ADROMEX1 154 G 0.98 T 0.02 0.05 ATGTTACCTTCCTTKCCTGACTCAAGGGT . . Other Promoter ADROMEX1 723 G 0.97 T 0.03 0.06 GGGCTCTTGCTGTTYTTCGCCAGGAGGCT . . Other Promoter ADROMEX1 981 G 0.99 A 0.01 0.03 GAGCAGGAGCGCGCRTGGCTGAGGAAAGA . . Other Promoter ADROMEX2 101 A 0.96 C 0.04 0.07 TCGCTCGCCTTCCTMGGCGCTGACACCGC CTA CTC Synonymous Leu Leu ADROMEX3 81 C 0.95 C 0.05 0.09 CTGCGGATGTCCAGSAGCTACCCCACCGG AGC AGG Nonsynonymous Ser Arg ADROMEX4 1033 T 0.95 C 0.05 0.09 ACCGAGTCTCTGTAYAATCTATTTACATA . . Other 3′UTR ADROMEX4 1292 A 0.98 G 0.02 0.05 TGTCCTGGGTGCGARTCAGGGCTTCGCGG . . Other 3′UTR ADROMEX4 1389 T 0.97 C 0.03 0.06 GCGAGCCTGGACTCYCGGGTTGCGCAACG . . Other 3′UTR ADROMEX4 388 G 0.98 C 0.02 0.05 CAAGCATCCCGCTGSTGCCTCCCGGGACG . . Other 3′UTR ADROMEX4 536 T 0.98 G 0.02 0.04 CGCTTCCTTAGCCTKGCTCAGGTGCAAGT . . Other 3′UTR ADROMEX4 918 A 0.91 G 0.09 0.16 ATTTTAAOACGTGARTGTCTCAGCGAGGT . . Other 3′UTR AEIEX1 298 G 0.95 A 0.05 0.10 GGGGCATGAGTCAGRGGTTTGCGAGCTGC . . Other Promoter AEIEX1 80 A 0.98 C 0.02 0.04 TCAAACCTTCATCCMCAAAGGAAGAGTCA . . Other Promoter AE1EX10 77 G 0.99 A 0.01 0.02 CGAGGGGAGCTGCTRCACTCCCTAGAGGG CTG CTA Synonymous Leu Leu AELEX11 181 C 0.95 T 0.05 0.10 GTCATCTTCATCTAYTTTGCTGCACTGTC TAC TAT Synonymous Tyr Tyr AEIEX11 191 C 0.99 T 0.01 0.03 TCTACTTTGCTGCAYTGTCACCCGCCATC CTG TTG Synonymous Leu Leu AEIEX11 228 A 0.98 T 0.02 0.04 CGGCCTCCTGGGTCWGTGCCAATACCTGT . . Other Intron AEIEX12 70 G 0.93 A 0.07 0.13 GTGTCGGAGCTGCTRATCTCCACTGCAGT CTG CTA Synonymous Leu Leu AEIEX12 71 A 0.96 T 0.04 0.07 TGTCGGAGCTGCTGWTCTCCACTGCAGTO ATC TTC Nonsynonymous Ile Phe AEIEX14 159 A 0.93 T 0.07 0.13 CCTTCYFCTTTGCCWTGATGCTGCGCAAG ATG TTG Nonsynonymous Met Leu AEIEX15 107 T 0.79 C 0.21 0.33 TTCTTCATTCAGGAYACCTACACCCAGGT GAT GAC Synonymous Asp Asp AEIEX16 92 C 0.97 T 0.03 0.06 GGCTGGGTCATCCAYCCACTGGGCTTGCG CAC CAT Synonymous His His AEIEX17 34 A 0.97 G 0.03 0.06 CCTACAGTAGGCTGRTTGTCAGCAAACCT ATT GTT Nonsynonymous Ile Val AEIEX17 40 A 0.99 G 0.01 0.02 GTAGGCTGATTGTCRGCAAACCTGAGCGC AGC GGC Nonsynonymous Ser Gly AEIEX17 72 C 0.94 T 0.06 0.11 ATGGTCAAGGGCTCYGGCTTCCACCTGGA TCC TCT Synonymous Ser Ser AEIEX19 132 G 0.96 A 0.04 0.07 TGGCCCTGCCCTTCRTCCTCATCCTCACT COT CAT Nonsynonymous Arg His AEIEX19 43 G 0.99 A 0.01 0.02 GGTGAAGACCTGGCRCATGCACTTATTCA CGC CAC Nonsynonymous Arg His AEIEX20 1007 G 0.99 A 0.01 0.03 AATCAGTGGACTCCRAGGGGACTGAGACA . . Other 3UTR AEIEX20 1213 A 0.64 T 0.36 0.46 ATTTGAGAGCCATTWTCCTCAACTCCATC . . Other 3′UTR AEIEX20 1542 T 0.94 C 0.06 0.12 AAAAATACAAAAATYAGCTGGGTGTCTCG . . Other 3′UTR AEIEX20 1628 G 0.95 C 0.05 0.10 CCCAGGAGGTGGAGSTTGCAGTGAGCCAA . . Other 3′UTR AEIEX20 1679 A 0.68 G 0.32 0.44 CTGGGCAACAGAGCRAGACCCTGTCTCAA . . Other 3′UTR AEIEX20 379 G 0.97 A 0.03 0.06 TCACTGGGGATCCCRTGCTGGAAGACTTA . . Other 3′UTR AEIEX20 418 C 0.99 A 0.01 0.03 CTCCCTCTTCCCAGMACAGGCAGGGGTAG . . Other 3′UTR AEIEX20 991 G 0.99 A 0.01 0.02 TTACTGAGGGCCCCRGAATCAGTGGACTC . . Other 3′UTR AEIEX4 17 C 0.98 T 0.03 0.05 CAATACTAACCGACYTCTGGTTTTCAGCT . . Other Intron AEIEX4 36 A 0.91 C 0.09 0.16 GTTTTCAGCTCACGMCACCGAGGCAACAG GAC GCC Nonsynonymous Asp Ala AEIEX4 89 A 0.78 G 0.23 0.35 ACCCGGGTACCCACRAGGTGAGGACCCCA AAG GAG Nonsynonymous Lys Glu AEIEX5 197 A 0.97 T 0.03 0.06 CTAGAGCTGCGTAGWGTCTTCACCAAGGG AGA AGT Nonsynonymous Arg Ser AEIEX8 35 T 0.99 C 0.01 0.03 TTCCCACAGGGAGAYGGGGGCACAGAAGG GAT GAC Synonymous Asp Asp AGTEX2 181 C 0.99 T 0.01 0.03 AGAGTACCTGTGAGYAGCTGGCAAAGGCC CAG TAG Nonsynonymous Gln STOP AGTEX2 354 C 0.99 T 0.01 0.03 GTCGGGATGCTGGCYAACTTCTTGGGCTT GCC GCT Synonymous Ala Ala AGTEX2 755 T G GGACTTCACAGAACKGGATGTTGCTGCTG CTG CGG Nonsynonymous Leu Arg AGTEX5 258 C 0.96 T 0.04 0.08 TGGCAAGGCCTCTGYCCCTGGCCTTTGAG . . Other 3′UTR AGTEX5 376 C 0.97 G 0.03 0.06 AGCTGGAAAGCAGCSGTTTCTCCTTGGTC . . Other 3′UTR AGTEX5 385 T 0.97 C 0.03 0.06 GCAGCCGTTTCTCCYTGGTCTAAGTGTGC . . Other 3′UTR AGTEX5 641 T 0.93 G 0.07 0.13 GCCTTCGGTTTGTAKTTAGTGTCTTGAAT . . Other 3′UTR AGTEXP1 101 G 0.99 C 0.01 0.03 CTGGCTGTGCTATTSTTGGTGTTTAACAG . . Other Promoter AGTEXP2 160 G 0.99 A 0.01 0.03 GGAACCTTGGCCCCRACTCCTGCAAACTT . . Other Promoter AGTEXP2 35 G 0.97 A 0.03 0.06 CCCTCTGCACCTCCRGCCTGCATGTCCCT . . Other Promoter AGTEXP3 158 A 0.71 G 0.29 0.41 CTCGTGACCCGGCCRGGGGAAGAAGCTGC . . Other Promoter AGTEXP3 173 C 0.96 T 0.04 0.08 GGGGAAGAAGCTGCYGTTGTTCTGGGTAC . . Other Promoter ALDREDEX1 162 A 0.86 T 0.14 0.23 GCGCCAAGATGCCCWTCCTGGGGTTGGGT ATC TTC Nonsynonymous lie Phe ALDREDEX1 71 C 0.41 G 0.59 0.48 AAAGGTACGCGCCGSGGCCAAGGCCGCAC . . Other Promoter ALDREDEX10 150 T 0.91 G 0.09 0.16 TTGCAAATGTAGTAKGGCCTGTGTCACTC . . Other 3′UTR ALDREDEX2 180 C 0.94 G 0.06 0.11 TGAAGCGTGAGGAGSTCTTCATCGTCAGC CTC GTC Nonsynonymous Leu Val ALDREDEX2 204 T 0.95 G 0.05 0.10 TCAGCAAGGTATCGKTCCGCGGTGGGGCT . . Other Intron ALDREDEX2 88 A 0.98 T 0.03 0.05 CGTCGGGTACCGCCWCATCGACTGTGCCC CAC CTC Nonsynonymous His Leu ALDREDEX3 28 A 0.95 T 0.05 0.10 GCCTCTCGCTGGCTTWGCTGTGGTGCACGT . . Other Intron ALDREDEX4 101 G 0.98 A 0.03 0.05 AACATTCTGGACACRTGGGCGGTAAGACA ACG ACA Synonymous Thr Thr ALDREOEX6 87 G 0.94 A 0.06 0.11 ACTGCCAGTCCAAARGCATCGTGGTGACC GGC AGC Nonsynonymous Gly Ser ALDREDEX9 67 C 0.99 T 0.01 0.02 CCAGGATATGACCAYCTTACTCAGCTACA ACC ATC Nonsynonymous Thr Ile ANPEX1 252 G 0.99 A 0.01 0.03 CCATGTACAATGCCRTGTCCAACGCAGAC GTG ATG Nonsynonymous Val Met ANPEX1 297 C 0.97 T 0.03 0.06 TAGGGCCAGGAAAGYGGGTGCAGTCTGGG . . Other Intron . ANPEX3 106 G 0.97 T 0.03 0.06 TCCTGTCCCCTGGGKTCTCTGCTGCATTT . . Other 3′UTR . ANPEX3 127 T 0.91 C 0.09 0.16 CTGCATTTGTGTCAYCTTGTTGCCATGGA . . Other 3′UTR . APOA1 101 C 0.76 T 0.24 0.36 GCCTTGCCCCAGGCYGGGCCTCTGGGTAC . . Other Promoter . APOA1 1016 A 0.76 C 0.24 0.36 CGTAACTGGGCACCMGTCCCAGCTCTGTC . . Other Intron . APOA1 1162 G 0.94 C 0.06 0.12 AGGTGTCACCCAGGSCTCACCCCTGATAG . . Other Intron . APOA1 1163 C 0.93 T 0.08 0.14 GGTGTCACCCAGGGYTCACCCCTGATAGG . . Other Intron . APOA1 1401 G 0.99 C 0.01 0.02 TGCAGCCCTACCTGSACGACTTCCAGAAG GAC CAC Nonsynonymous Asp His . APOA1 1576 G 0.98 C 0.02 0.04 TGTGGACGCGCTGCSCACGCATCTGGCCC CGC CCC Nonsynonymous Arg Pro . APOA1 1643 G 0.98 A 0.02 0.04 CTTGAGGCTCTCAARGAGAACGGCGGCGC AAG AAA Synonymous Lys Lys APOAL 1757 C 0.94 G 0.06 0.11 CAAGGCCTGCTGCCSGTGCTGGAGAGCTr CCC CCG Synonymous Pro Pro APOAL 2007 T 0.64 A 0.36 0.46 CTCCGTGCCCAGACWGGACGTCTTAGGGC . . Other 3′UTR APOA1 334 T 0.69 C 0.31 0.43 AACCATCGGGGGGCYTTCTCCCTAAATCC . . Other Intron APOA1 620 C 0.92 T 0.08 0.14 TTTGAAGGCTCCGCYTTGGGAAAACAGCT GCC GCT Synonymous Ala Ala APOA1 771 C 0.96 T 0.04 0.07 CTGGATGGAGAAACYGGAATGGATCTCCA . . Other Intron APOA1 840 G 0.99 A 0.01 0.02 GGGCTGCCCGATGCRTGATCACAGAGCCA . . Other Intron APOA2 1334 T 0.99 A 0.01 0.03 AGATTAGGCTTAAAWTGCAGAGAAAAAGT . . Other Intron APOA2 1412 G 0.82 C 0.18 0.29 AAGAACTGGGCCTTSAATTTCAGTCTCTA . . Other Intron APOA2 1414 A 0.95 T 0.05 0.10 GAACTGGGCCTTGAWTTTCAGTCTCTAGA . . Other intron APOA2 1459 C 0.99 T 0.01 0.03 AGCAAAGGTCTTGAYTCTATTCCTACCTA . . Other Intron APOA2 1672 C 0.94 T 0.06 0.11 AGGCTGGAACGGAAYTGGTTAACTTCTTG CTG TTG Synonymous Leu Leo APOA2 249 T 0.55 C 0.45 0.50 TGCTTCCTGTTGCAYTCAAGTCCAAGGAC . . Other Promoter APOA2 547 A 0.99 C 0.01 0.01 GACGCTGGCTAGGTMAGATAAGGAGGCAA . . Other Intron APOA4 1228 A 0.75 G 0.25 0.38 GACCAGGTGGCCACRGTGATGTGGGACTA ACA ACG Synonymous Thr Thr APOA4 1338 T 0.03 C 0.97 0.06 GGGACTACAGTGTGYGGTGGTGACGGGGA . . Other Intron APOA4 1479 C 0.98 T 0.03 0.05 CCACATATGTAAACYGGAAGTTTGGACCG . . Other Intron APOA4 1529 T 0.86 C 0.14 0.24 TTGCTTTGACGTTCYAGAGTTTGACAAAT . . Other Intron APOA4 1597 T 0.59 C 0.41 0.48 GGAGGAAAATGTCAYGTGAGCTGATTTCT . . Other Intron APOA4 1617 G 0.99 A 0.01 0.02 CTGATTTCTAATACRTTTCAGAAAGACAG . . Other Intron APOA4 1879 C 0.94 G 0.06 0.11 GATTCTGAGACAAASTATGTGGGAGATCC . . Other Intron APOA4 1961 G 0.96 A 0.04 0.07 CTGCACCACCATAGRGAGGGTGAACTCGG . . Other Intron APOA4 1998 T 0.63 C 0.37 0.47 AGCACTCACCTGTCYTAGCACGTGTGCAT . . Other Intron APOA4 2134 C 0.73 T 0.28 0.40 GAAGTGAACACTTAYGCAGGTGACCTGCA TAC TAT Synonymous Tyr Tyr APOA4 2138 G 0.99 A 0.01 0.02 TGAACACTTACGCARGTGACCTGCAGAAG GGT AGT Nonsynonymous Gly Set APOA4 2140 T 0.94 C 0.06 0.12 AACACTTACGCAGGYGACCTGCAGAAGAA GGT GGC Synonymous Gly Gly APOA4 2358 A 0.89 G 0.11 0.20 GCGCACCCAGGTCARCACGCAGGCCGAGC AAC AGC Nonsynonymous Asn Ser APOA4 2698 C 0.95 T 0.05 0.10 ATCTCGGCCAGTGCYGAGGAGCTGCGGCA GCC GCT Synonymous Ala Ala APOA4 2764 C 0.92 T 0.08 0.15 CTGAGGGGCAACACYGAGGGGCTGCAGAA ACC ACT Synonymous Thr Thr APOA4 2806 G 0.99 A 0.01 0.02 CTGGGTGGGCACCTRGACCAGCAGGTGGA CTG CTA Synonymous Leu Leu APOA4 2837 G 0.98 C 0.02 0.04 AGTTCCGACGCCGGSTGGAGCCCTACGGG GTG CTG Nonsynonymous Val Leu APOA4 2926 G 0.81 T 0.19 0.30 CATGCGGGGGACGTKGAAGGCCACTTGAG GTG GTT Synonymous VaL VaL APOA4 3058 T 0.16 G 0.84 0.26 CAGCAGGAACAGCAKCAGGAGCAGCAGCA CAT CAG Nonsynonymous His Gln APOA4 350 G 0.88 A 0.12 0.21 GCCAGCAGGGCCTCRAGGCATCAGTCCCG . . Other Promoter APOA4 637 G 0.96 C 0.04 0.08 TGGCGATAGGGAGASAGTTTAAATGTCTG . . Other Promoter APOA4 687 G 0.96 A 0.04 0.07 GTTCCCACTGCAGCRCAGGTGAGCTCTCC . . Other Promoter APOC1EX1 1020 G 0.93 T 0.07 0.13 TTGTATTTTCAGTAKAGACAGGGTTTCAC . . Other Intron APOC1EX1 1044 G 0.95 A 0.05 0.10 TTCACCGTGGTCTCRATCTCCTGACTTTG . . Other Intron APOC1EX1 1057 T 0.64 C 0.36 0.46 CGATCTCCTGACTTYGTGATCCGCCTGCC . . Other Intron APOC1EX1 1111 C 0.89 T 0.11 0.20 CAGGCGTGAGCCACYGCGTCCGGCCATTC . . Other Intron APOC1EX1 1376 G 0.57 T 0.43 0.49 GCACGCGCCTGTAGKCCCAGCTACTCGGG . . Other Intron APOC1EX1 1411 C 0.99 G 0.01 0.02 AGGCAGGAGAATCASTTGAACCCGGGAGG . . Other Intron APOC1EX1 432 G 0.97 A 0.03 0.06 AGGCTCTTCCTGTCRCTCCCGGTCCTGGT TCG TCA Synonymous Ser Ser APOC1EX1 462 C 0.61 G 0.39 0.47 GTGGTTCTGTCGATSGTCTTGGAAGGTAA ATC ATG Nonsynonymous Ile Met APOC1EX1 496 G 0.01 C 0.99 0.02 GGATGGGAGAATTGSGGAGTTTGGAGATT . . Other Intron APOC1EX1 713 C 0.99 T 0.01 0.02 ACCTCTGGGATTGGYTGTCCTGCTTCGAC . . Other Intron APOC2 1084 T 0.91 G 0.09 0.17 TCTGAGGACTCAAGKGCCAAGATGGAGGG . . Other 3′UTR APOC2 126 C 0.99 T 0.01 0.02 CAGGTCTCTGGACAYTATGGGCACACGAC . . Other 5′UTR APOC2 13 T 0.34 A 0.66 0.45 CTGGGACACCGAGCWCACACAGAGCAGGA . . Other Promoter APOC2 472 G 0.99 A 0.01 0.02 CCCAGAACCTGTACRAGAAGACATACCTG GAG AAG Nonsynonymous Glu Lys APOC2 553 G 0.99 A 0.01 0.02 TGGCCCATACCACCRACTGCATCCAGGAC . . Other intron APOC2 725 T 0.19 C 0.81 0.31 CCCAGGAGTCCAGGYCCCCAGACCCTCCT . . Other Intron APOC2 804 A 0.97 T 0.03 0.06 TGTGCTTTCTCCCCWGGGACTTGTACAGC . . Other Intron APOC2 819 A 0.82 C 0.18 0.30 GGGACTTGTACAGCMAAAGCACAGCAGCC AAA CAA Nonsynonymous Lys Gln APOC3 1148 T 0.95 A 0.05 0.10 CTGGGGACTAAGAAWGTTTATGAACACCT . . Other Intron APOC3 1322 G 0.71 A 0.29 0.41 CACGGGCTTGAATTRGGTCAGGTGGGGCC . . Other Intron APOC3 1468 A 0.97 C 0.03 0.06 ATACGCCTGAGCTCMGCCTCCTGTCAGAT . . Other Intron APOC3 1519 A 0.95 G 0.05 0.10 GGAGTGTGAACCCTRTTGTGAACTGCACA . . Other Intron APOC3 1637 T 0.96 A 0.04 0.07 GGCCCATGGAAAAAWTGTCCACCACAAAA . . Other Intron APOC3 1722 A 0.84 G 0.16 0.27 AGGAAAATGGGGCCRGGCGCAGTGGCTCG . . Other Intron APOC3 1728 A 0.73 G 0.27 0.40 ATGGGGCCAGGCGCRGTGGCTCATGCCTG . . Other Intron APOC3 736 A 0.85 G 0.15 0.26 AGGCGCAGTGGCTCRTGCCTGTAATCCCA . . Other Intron APOC3 1774 A 0.76 C 0.24 0.36 GAGGCCGAGGCAGGMGGATCCCCTGAGGT . . Other Intron APOC3 1817 T 0.69 C 0.31 0.43 CAACCTGGCCAACAYGGTGAAACCCCATC . . Other Intron APOC3 1931 C 0.98 T 0.02 0.04 TTGAACCCGGGAGAYGGAGGTTGCAGTGA . . Other Intron APOC3 1975 G 0.99 A 0.01 0.03 CTGCACTCCAGCCTRGGTGACAGAGGGAG . . Other Intron APOC3 2221 G 0.96 A 0.04 0.08 AGGGCTAAAACGGCRCGGCCCTAGGACTG . . Other Intron APOC3 2535 G 0.81 A 0.19 0.30 GCGTGCTTCATGTARCCCTGCATGAAGCT GGC GGT Synonymous Gly Gly APOC3 2854 C 0.70 T 0.30 0.42 CCCTGGGGAGGTGGYGTGGCCCCTAAGGT . . Other Promoter APOC3 429 A 0.69 C 0.31 0.43 GCAACCTACAGGGGMAGCCCTGGAGATTG . . Other 3′UTR APOC3 460 G 0.99 C 0.01 0.03 GGACCCAAGGAGCTSGCAGGATGGATAGG . . Other 3′UTR APOC3 636 G 0.96 A 0.04 0.07 TAAATCAGTCAGGGRAAGCAACAGAGCAG . . Other Intron APOC3 954 A 0.89 G 0.11 0.19 GTGCAAACAGCACCRCCTGGAGTTGCACA . . Other Intron APOC4 1150 T 0.39 C 0.61 0.47 AAGTGCTAGGATTAYAGGCGTGAGCCACT . . Other Intron APOC4 1246 A 0.33 C 0.67 0.44 AGGCTGGTCTTGAAMTCCTGACCTCAGGT . . Other Intron APOC4 1281 C 0.91 T 0.09 0.16 CCCGCCTTGGCCTCYCAAAGTGCTGGGAT . . Other Intron APOC4 1287 T 0.95 C 0.05 0.10 TTGGCCTCCCAAAGYGCTGGGATTACAGG . . Other Intron APOC4 1313 A 0.42 G 0.58 0.49 AGGCATGAGCCACCRCGCCCGGCCATGTA . . Other Intron APOC4 1406 G 0.87 A 0.13 0.22 ACAGGGCCAGGCACRGTGGCTCATGCCTG . . Other Intron APOC4 1446 G 0.91 A 0.09 0.16 CTTTCGGAGGCCGARGCGGGTGGATCGCA . . Other Intron APOC4 1587 C 0.29 A 0.71 0.41 CGGGAGGCTGAGGCMGGAGAATCACTTGA . . Other Intron APOC4 1782 G 0.96 C 0.04 0.07 ATAACCCTGAGGTASATATTATTACCCCG . . Other Intron APOC4 1794 C 0.94 T 0.06 0.11 TAGATATTATTACCYCGTTCTACAAAAGG . . Other Intron APOC4 1842 G 0.98 A 0.03 0.05 CAGGATAAGTCACCRGCCAAGGCACACAG . . Other Intron APOC4 1858 T 0.36 C 0.64 0.46 CCAAGGCACACAGCYAGCTACATGTGGCC . . Other Intron APOC4 1875 C 0.96 T 0.04 0.07 CTACATGTGGCCCCYGCGTGACGGCTGGT . . Other Intron APOC4 2206 A 0.92 G 0.08 0.15 TGAAGAGATGGCCCRGCCGGACGGGGTGG . . Other Intron APOC4 2237 C 0.94 T 0.06 0.12 CACATCTGTAATCCYAGCATTTTGGGAGC . . Ocher Intron APOC4 2276 T 0.65 C 0.35 0.46 TGGATCACTTCAGGYCAGGAGTTCGAGCC . . Other Intron APOC4 2345 A 0.74 G 0.26 0.38 ATTAGCCGGGCATGRTGGCAGATGCCTGT . . Other Intron APOC4 2366 T 0.51 A 0.49 0.50 ATGCCTGTAATCCCWGCTACTCGGGAGGC . . Other Intron APOC4 2767 G 0.99 A 0.01 0.02 AAGATGAGTCGCTGRAGCCTGGTGAGGGG TGG TGA Nonsynonymous Trp Stop APOC4 3027 G 0.98 A 0.03 0.05 TCACAGAGAGGAGCRGATAAATGGGGCAG . . Other Intron APOC4 3078 G 0.96 C 0.04 0.08 GCCTCCACTGTGATSTCCTCTCTCCTGTA . . Other Intron APOC4 3162 T 0.51 G 0.49 0.50 GGACCTGGGTCCGCKCACCAAGGCCTGGT CTC CGC Nonsynonymous Leu Arg APOC4 3252 A 0.91 T 0.09 0.17 TGGGGACAAGGACCWGGGTTAAAATGTTC CAG CTG Nonsynonymous Gln Leu APOC4 483 T 0.95 G 0.05 0.10 CTGAGAGTGAAGTGKGAATGTCACATTGG . . Other Intron APOC4 931 A 0.97 G 0.03 0.06 CCAGGCTGGAGTGCRGTGGCGTGATCflG . . Other Intron APOC4 968 C 0.76 T 0.24 0.36 CAAGCTCCGCCTCCYGGGTTCACGCCATT . . Other Intron APOER2EX1 454 6 0.98 C 0.02 0.04 CGCGGCAAGGACTCSGAGGGCTGAGACGC . . Other 5′UTR APOER2EX12 68 A 0.96 C 0.04 0.07 ACCAACTGTCCAGCMTTGACTTCAGTGGA ATT CTT Nonsynonymous Ile Leu APOER2EX13 55 G 0.99 C 0.01 0.02 CGAGGCCATTTTCASTGCAAATCGGCTCA AGT ACT Nonsynonymous Ser Thr APOER2EX14 162 G 0.98 A 0.03 0.05 GAAGAGGTGCTACCRAGGTAAGCAGACCT CGA CAA Nonsynonymous Arg Gln APOER2EX17 55 A 0.98 G 0.03 0.05 TACCTGATCTGGAGRAACTGGAAGCGGAA AGA AGG Synonymous Arg Arg APOER2EX19 1005 G 0.52 C 0.48 0.50 CAGAGTGCTCAGAAASTCAAGATAGGATAT . . Other 3′UTR APOER2EX19 1060 T 0.96 C 0.04 0.07 TAAAGTTCAGCTCTYTGAGTAACTTCTTC . . Other 3′UTR APOER2EX19 1149 A 0.98 T 0.03 0.05 TGCCATCCTTACAGWGCTAAGTGGAGACG . . Other 3′UTR APOER2EX19 13 G 0.51 A 0.49 0.50 GTTGTCTCCCCAGCRAGTGGCATTAAGCC CGA CAA Nonsynonymous Arg Gln APOER2EX19 602 A 0.93 G 0.07 0.13 TTTAGAGAAGTGAGRGTATTTATTTTTGG . . Other 3′UTR APOER2EX19 931 A 0.99 C 0.01 0.02 CCATGGCTGCTGTGMCTCCTACCAGGGCT . . Other 3′UTR APOER2EX9 116 G 0.99 A 0.01 0.03 TGCTCAAGAATGTCRTGGCACTAGATGTG GTG ATG Nonsynonymous Val Met APOER2EX9 157 G 0.99 C 0.01 0.02 AATCGCATCTACTGSTGTGACCTCTCCTA TGG TGC Nonsynonymous Trp Cys AT1EX5 1158 A 0.95 G 0.05 0.10 TGAGGTTGAGTGACRTGTTCGAAACCTGT . . Other 3′UTR AT1EX5 1226 T 0.92 G 0.08 0.15 TCCTCTGCAGCACTKCACTACCAAATGAG . . Other 3UTR AT1EX5 1242 A 0.53 C 0.47 0.50 ACTACCAAATGAGCMTTAGCTACTTTTCA . . Other 3′UTR AT1EX5 1249 A 0.99 G 0.01 0.03 AATGAGCATTAGCTRCTTTTCAGAATTGA . . Other 3′UTR ATIEX5 1473 G 0.91 A 0.09 0.17 CCTGCTTTTGTCCTRTTATTTTTTATTTC . . AT2EX3 1355 T 0.39 G 0.61 0.47 GTTTGTACAAGATTKTCATTGGTGAGACA . . Other 3′UTR AT2EX3 1361 G 0.69 A 0.31 0.43 ACAAGATTTTCATTRGTGAGACATATTTA . . Other 3′UTR AT2EX3 562 T 0.99 C 0.01 0.03 TATATAGTTCCCCTYGTTTGGTGTATGGC CTT CTC Synonymous Leu Leu AT2EX3 807 G 0.94 A 0.06 0.12 CTATGGGAAGAACARGATAACCCGTGACC AGG AAG Nonsynonymous Arg Lys AT2EX3 844 T 0.93 C 0.07 0.13 AAGATGGCAGCTGCYGTTGTTCTGGCCTT GCT GCC Synonymous Ala Ala AVPEX2 154 C 0.96 T 0.04 0.08 GGAGAACTACCTGCYGTCGCCCTGCCAGT CCG CTG Nonsynonymous Pro Leu AVPR2EX1 114 A 0.97 T 0.03 0.06 TCATGGCGTCCACCWCTTCCGGTAAGGCT ACT TCT Nonsynonymous Thr Ser AVPR2EX2 109 G 0.98 A 0.02 0.04 ACCCGGGACCCGCTRCTAGCCCGGGCGGA CTG CTA Synonymous Leu Leu AVPR2EX2 129 C 0.85 T 0.15 0.25 CCGGGCGGAGCTGGYGCTGCTCTCCATAG GCG GTG Nonsynonymous Ala Val AVPR2EX2 184 G 0.94 T 0.06 0.11 GGCCTGGTGCTGGCKGCCCTAGCTCGGCG GCG GCT Synonymous Ala Ala AVPR2EX2 444 C 0.87 T 0.13 0.23 CCGTCCCATGCTGGYGTACCGCCATGGAA GCG GTG Nonsynonymous Ala Val AVPR2EX3 112 C 0.95 T 0.05 0.10 TCTTTCAGCAGCAGYGTGTCCTCAGAGCT AGC AGT Synonymous Ser Ser AVPRIEX3 232 G 0.95 A 0.05 0.10 AAGGACACTTCATCRTGAGGAGCTGTTGG TCG TCA Synonymous Ser Ser AVPR2EX3 252 T 0.97 C 0.03 0.06 AGCTGTTGGGTUTCYTGCCTCTAGAGGCT . . Other 3′UTR . AVPR2EX3 46 A 0.50 G 0.50 0.50 GCCCCCTTTGTGCTRCTCATGTTGCTGGC CTA CTG Synonymous Leu Leu BIR 1069 C 0.98 T 0.03 0.05 CAGGACTGGCTGGAYCCACAGCTCTAGGG . . Other 3′UTR . BIR 1142 G 0.67 A 0.33 0.44 GGTGAGCCAGTCCTRAATTGGGTTGGGAG . . Other 3′UTR . BIR 1185 G 0.98 T 0.03 0.05 ATAACCCAGTACAGKTTCCTGCTGAGGCC . . Other 3′UTR . BIR 1265 G 0.95 A 0.05 0.10 GGAGGCTGAGCTGARGCTCGCCCAGCCTC . . Other 3′UTR . BIR 1295 C 0.24 7 0.76 0.37 CACCAGGCCCTGGCYGGGCTACATACCAC . . Other 3′UTR . BIR 1441 T 0.99 C 0.01 0.02 AGGGGCCCGCGGGCYGAGGCGAGGGTCAG TCA TCG Synonymous Ser Ser BIR 1521 C 0.26 T 0.74 0.38 TGTGGGCACTTTGAYGGTGTTGCCAAACT GTC ATC Nonsynonymous Val Ile BIR 1729 G 0.99 C 0.99 0.03 GGTGCCAGGTCGTASAGTGGGCTGTTGGC CTC CTG Synonymous Leu Leu BIR 1946 C 0.99 T 0.01 0.02 GCATGAAGCAGAGGYGGCCGTGGCGCAGG CCC CAC Nonsynonymous Arg His BIR 1960 G 0.75 A 0.25 0.38 CGGCCGTCGCGCAGRGCGATCACCGCATG CCC GCT Synonymous Ala Ala BIR 2463 T 0.22 C 0.78 0.34 ACGGTACCTGGGCTYGGCAGGGTCCTCTG AAG GAG Nonsynonymous Lys Glu BIR 2664 T 0.97 C 0.03 0.06 TGTGCTGGCCTCACVTCTGAGATAACTCC . . Other 5′UTR BIR 2894 T 0.99 G 0.01 0.03 TGGTGGTGCGCACCKGTAATCCCACCTAC . . Other Promoter BIR 2954 G 0.97 C 0.03 0.06 CCCGAGAGGCGGAGSTTGCAGTGAGCCAA . . Other Promoter BIR 3174 C 0.70 T 0.30 0.42 TCCCGCTAAGAGCCYTTCTCCCCGCCCAG . . Other Promoter BIR 369 G 0.97 A 0.03 0.06 CAACACTGCTCCAARGGTCCAGGCACGGG . . Other 3′UTR . BIR 510 T 0.99 C 0.01 0.02 CCTTCTGGACAAAGYGAGTGGCAGCCACT . . Other 3′UTR . BIR 657 T 0.92 A 0.08 0.14 CACAGAGCCCTCACWGCACGAGGCCGATG . . Other 3′UTR . BIR 981 G 0.98 A 0.03 0.05 TTGGAGCCACAGACRCAAAGCAGCAGCCC . . Other 3′UTR . BKRB2EX1 55 T 0.77 G 0.23 0.35 GGTGGGGACGGTGGKGACGGTGGGGACAT . . Other 5′UTR . BKRB2EX3 1513 T 0.93 C 0.07 0.13 ATCTCCAGGAGAACYGCCATCCAGCTTTG . . Other 3′UTR . BKRB2EX3 1833 G 0.95 A 0.05 0.10 ACTCAAGTGGGAACRACTGGGCACTGCCA . . Other 3′UTR . BKRB2EX3 747 0.093 A 0.07 0.13 AAGGAGATCCAGACRGAGAGGAGGGCCAC ACG ACA Synonymous Thr Thr BNPEX1 343 G 0.99 T 0.01 0.02 TTTCCTGGGAGGTCKTTCCCACCCGCTGG CGT CTT Nonsynonymous Arg Leu BNPEX2 15 C 0.97 G 0.03 0.07 TGAGGCTTGGACGCSCCCATTCATTGCAG . . Other Intron . BNPEX2 174 A 0.99 T 0.01 0.02 GTGGGCACCGCAAAWTGGTCCTCTACACC ATG TTG Nonsynonymous Met Leu BNPEX2 37 G 0.97 A 0.03 0.06 ATTGCAGGAGCAGCRCAACCATTTGCAGG CGC GAG Nonsynonymous Arg His BRS3EX1 424 G 0.95 A 0.05 0.10 AGAACTGAAGCAAARGAGTATCTGGATGT . . Other Promoter BRS3EX1 730 A 0.97 C 0.03 0.06 GTGCCATCTATATTMCTTATGCTGTGATC ACT CCT Nonsynonymous Thr Pro BRS3EX1 879 A 0.95 T 0.05 0.10 CTAACTTGTGTGCCWGTGGATGCAACTCA CCA CCT Synonymous Pro Pro BRS3EX2 144 T 0.94 A 0.06 0.11 GCTCTACCTGAGGCWATATTTTCAAATGT GCT GCA Synonymous Ala Ala BRS3EX2 80 T 0.98 A 0.02 0.04 CTCCAATGCCATCCWGAAGACTTGTGTAA CTG GAG Nonsynonymous Leu Gln BRS3EX3 173 T 0.94 C 0.06 0.12 GCCATGCATTTCATYTTCACCATTTTCTC ATT ATC Synonymous Ile Ile Other 5′UTR CAL/CGRPEX1+2 1063 T 0.98 G 0.02 0.05 CCCCAGTCACAGGCKCTGGGAGCAAAGAG . . Other 5═UTR . CAL/CGRPEX1+2 940 G 0.86 A 0.14 0.24 GTGCGATCAGGGACRGCGTCTGGAGCCCA . . Other 5′UTR . CAL/CGRPEX3 112 G 0.92 A 0.08 0.15 CTGCACTGGTGCAGRACTATGTGCAGATG GAC AAC Nonsynonymous Asp Asn CAL/CGRPEX3 120 G 0.99 T 0.01 0.02 GTGCAGGACTATGTKCAGATGAAGGCCAG GTG GTT Synonymous Val Val CAL/CGRPEX4 30 C 0.91 A 0.09 0.16 TGTTTTCCCTGCAGMCTGGACAGCCCCAG AGC AGA Nonsynonymous Ser Arg CAL/CGRPEX5 309 A 0.59 T 0.41 0.48 ATGTGGTTTTAAAAWATCCATAAGGGAAG . . Other 3′UTR . CAL/CGRPEX5 433 C 0.78 T 0.22 0.34 CAGACCAAGAAATAYAGATCCTGTTTATT . . Other 3′UTR . CAL/CGRPEX5 719 G 0.91 A 0.09 0.16 AAAGAGCAAGTGAGRTAATAGATGTTAAG . . Other 3′UTR . CHYEX1 158 T 0.86 A 0.14 0.24 TTGCCTTCTGGGAGWTATAAAACCCAAGA . . Other 5′UTR . CHYEX1 65 T 0.70 C 0.30 0.42 TCTAGGGGAACTTCYGATCAGAAACAGCC . . Other 5′UTR . CHYEX2 107 G 0.95 C 0.05 0.09 TTGTAACTTCCAACSGTCCCTCAAAATTT GGT CGT Nonsynonymous Gly Arg CHYEX2 168 A 0.92 G 0.08 0.14 GCTGACGGCTGCTCRTTGTGCAGGAAGGT CAT CGT Nonsynonymous His Arg CHYEX3 26 A 0.91 G 0.09 0.17 CCTTCTTCCTCACARCAGGTCTATAACAG . . Other Intron . CHYEX4 83 A 0.92 C 0.08 0.15 CTCCCCTTCCCATCMCAATTCAACflTGT TCA TCC Synonymous Ser Ser CHYEX5 274 C 0.89 T 0.11 0.19 TCCCTCAGCCACAAYCCTAAGCCTCCAGA . . Other 3′UTR CLCNKBEX10 33 G 0.56 C 0.44 0.49 CTCTGGCCACCTTGSTTCTCGCCTCCATC GTT CTT Nonsynonymous Val Leu CLCNKBEX13 12 C 0.94 T 0.06 0.12 GGAGGAGCTGCTATYGGGCGCCTCTTTGG ATC ATT Synonymous Ile Ile CLCNKBEX15 64 C 0.94 T 0.06 0.11 ACTGGCCAAGGACAYGCCACTGGAGGAGG ACG ATG Nonsynonymous Thr Met CLCNKBEX15 68 A 0.34 G 0.66 0.45 GCCAAGGACACGCCRCTGGAGGAGGTGGT CCA CCG Synonymous Pro Pro CLCNKBEX18 51 C 0.96 T 0.04 0.08 CCTCTTTGTGACGTYGCGGGGCAGAGCTG TCG TGG Nonsynonymous Ser Trp CLCNKBEX3 34 A 0.94 C 0.06 0.11 GGGAGATTGGGGACMGCCACCTGCTCCGG AGC CGC Nonsynonymous Ser Arg CLCNKBEX3 96 G 0.93 A 0.07 0.13 GTCTCTTTCTCTTCRGGCTTCTCTCAGAG TCG TCA Synonymous Ser Ser CLCNKBEX4 19 G 0.35 C 0.65 0.46 TGGAATCCCGGAGSTGAAGACCATGTTG GTG GTG Nonsynonymous Val Leu CLCNKBEX4 70 A 0.92 C 0.08 0.15 ACCTGGATATCAAGMACTTTGGGGCCAAA AAC CAC Nonsynonymous Asn His CLCNKBEX7 108 G 0.89 A 0.11 0.20 TTCCGGCTCCTGGCRGTCTTCAACAGCGA GCG GCA Synonymous Ala Ala CNPEX1 1018 C 0.91 A 0.09 0.16 GCAGCGCCAACTTTMTGCCTGTATGACTT . . Other 5′UTR . CNPEX1 144 G 0.98 T 0.02 0.04 GCCTTCACGCCTGGKGACAGCCACTGCAC . . Other 5′UTR . CNPEX1 1457 C 0.98 G 0.02 0.05 GCAGCACTGGGACCSTGCTCGCCCTGCAG . . Other 5′UTR . CNPEX1 578 G 0.91 A 0.09 0.16 ATTGTTCCCACAGARGGAGTTCACCAGCG . . Other 5′UTR . CNPEX1 592 G 0.94 A 0.06 0.11 GGGAGTTCACCAGCRGAGTCAGACCCCGG . . Other 5′UTR . CNPEX2 1171 T 0.92 A 0.08 0.14 AACATCCCAGCCTCWGACATTGACAGTCA . . Other 3′UTR . CNPEX2 139 G 0.96 A 0.04 0.08 GGACACCAAGTCGCRGGCAGCGTGGGCTC CGG CAG Nonsynonymous Arg Gln CNPEX2 357 A 0.95 G 0.05 0.10 GCCCGCCGCCCAGCCRGCCTTCGGAGGCGC . . Other 3′UTR . CNPEX2 41 T 0.98 C 0.02 0.03 GCTGCGGGCGGCGGYCAGAAGAAGGGCGA GGT GGC Synonymous Gly Gly COX1 1063 A 0.99 G 0.01 0.02 TTTCCTGCAGCTGARATTTGACCCAGAGC AAA AGA Nonsynonymous Lys Arg COX1 1314 A 0.99 G 0.01 0.02 ACATGGACCACCACRTCCTGCATGTGGCT ATC GTC Nonsynonymous Ile Val COX1 1386 A 0.99 G 0.01 0.02 TCAATGAGTACCGCRAGAGGTTTGGCATG AAG GAG Nonsynonymous Lys Glu COX1 1428 G 0.98 A 0.02 0.03 CCTTCCAGGAGCTCRTAGGAGAGAAGGAG GTA ATA Nonsynonymous Val Ile COX1 1906 T 0.96 C 0.04 0.08 GGTGAGTGTTGGGGYTGACATTTAGAACT . . Other 3′UTR . COX1 1948 T 0.99 C 0.01 0.02 ATTATCTGGAATATYGTGATTCTGTTTAT . . Other 3′UTR . COX1 2037 T 0.99 G 0.01 0.02 GTCTGCCAGAATACKGGGTTCTTAGTTGA . . Other 3′UTR . COX1 310 G 0.99 A 0.01 0.02 TGCCACCTTCATCCRAGAGATGCTCATGC CGA CAA Nonsynonymous Arg Gln COX1 626 C 0.91 A 0.09 0.16 TTCAAAACTTCTGGMAAGATGGGTCCTGG GGC GGA Synonymous Gly Gly COX1 696 C 0.98 A 0.02 0.03 TTTATGGAGACAATMTGGAGCGTCAGTAT CTG ATG Nonsynonymous Leu Met COX1 938 T 0.98 C 0.02 0.04 GACCTGCTGAAGGCYGAGCACCCCACCTG GCT GCC Synonymous Ala Ala COX2EX1 186 C 0.84 G 0.16 0.27 CGATTTTCTCATTTSCGTGGGTAAAAAAC . . Other Promoter . COX2EX1 358 T 0.84 G 0.16 0.27 GCGACCAATTGTCAKACGACTTGCAGTGA . . Other Promoter COX2EX10 156 T 0.94 C 0.06 0.12 AACCATGGTAGAAGYTGGAGCACCATTCT GTT GCT Nonsynonymous Val Ala COX2EX10 379 C 0.98 A 0.03 0.05 GCAAGTTCTTCCCGMTCCGGACTAGATGA CGC CGA Synonymous Arg Arg COX2EX10 866 T 0.51 C 0.49 0.50 AAAGTACTTTTGGTYATTTTTCTGTCATC . . Other 3′UTR . COX2EX10 87 A 0.99 G 0.01 0.02 CATCGATGCTGTGGRGCTGTATCCTGCCC GAG GGG Nonsynonymous Glu Gly COX2EX10 937 G 083 A 0.17 0.28 ATTAGACATTACCARTAATTTCATGTCTA . . Other 3′UTR . COX2EX3 166 G 0.93 C 0.07 0.13 ATTATGAGTTATGTSTTGACATGTAAGTA GTG GTC Synonymous Val Val COX2EX7 206 T 096 C 0.04 0.07 AACAGAGTATGCGAYGTGCTTAAACAGGA GAT GAC Synonymous Asp Asp COX2EX8 268 T 0.95 C 0.05 0.10 ATATTGCTGGAACAYGGAATTACCCAGTT CAT CAC Synonymous His His CYPIIB1EX1 351 T 0.97 C 0.03 0.06 TGACGTGATCCCTCYCGAAGGCAAGGCAC . . Other Promoter . CYPIIB1EX1 525 C 0.99 G 0.01 0.03 AGGACAGTGCTGCCSTTTGAAGCCATGCC CCC CCG Synonymous Pro Pro CYPIIB1EX1 542 G 0.97 A 0.03 0.06 TGAAGCCATGCCCCRGCGTCCAGGCAACA CGG CAG Nonsynonymous Arg Gln CYPIIB1EX1 601 G 0.97 C 0.03 0.06 AGCAGGGTTATGAGSACCTGCACCTGGAA GAC CAC Nonsynonymous Asp His CYPIIB1EX2 184 C 0.99 T 0.01 0.03 GTGGCGTGTTCTTGYTGTAAGCGGCGAGC CTG TTG Synonymous Leu Leu CYPIIB1EX2 188 A 0.96 G 0.04 0.07 CGTGTTCTTGCTGTRAGCGGCGAGCTGAG . . Other Intron . CYPIIB1EX2 36 T 0.46 C 0.54 0.50 CCCCACAGGTACGAYTTGGGAGGAGCAGG GAT GAC Synonymous Asp Asp CYPIIB1EX2 78 C 0.96 T 0.04 0.08 ATGCTGCCGGAGGAYGTGGAGAAGCTGCA GAC GAT Synonymous Asp Asp CYPIIB1EX3 114 G 0.99 C 0.01 0.02 AGGTTCCTCCCGATSGTGGATGCAGTGGC ATG ATC Nonsynonymous Met Ile CYPIIB1EX4 177 C 0.98 T 0.02 0.04 CCTGTCTCGCTGGAYCAGCCCCAAGGTGT ACC ATC Nonsynonymous Thr Ile CYPIIB1EX4 205 T 0.92 G 0.08 0.15 TGGAAGGAGCACTTKGAGGCCTGGGACTG TTT TTG Nonsynonymous Phe Leu CYPIIB1EX4 247 C 0.91 G 0.09 0.16 GGTGAGGCCAGGGASCCGGGCAGTGCTAT . . CYPIIB1EX5 103 G 0.97 A 0.03 0.06 ACCAGCATCGTGGCRGAGCTCCTGTTGAA GCG GCA Synonymous Ala Ala CYPIIB1EX5 107 C 0.84 G 0.16 0.26 GCATCGTGGCGGAGSTCCTGTTGAATGCG CTC GTC Nonsynonymous Leu Val CYPIIB1EX5 16 C 0.58 T 0.42 0.49 TGAGGGCTGCCTCCYGCTCCCCGGATAGG . . Other Intron . CYPIIB1EX5 55 T 0.97 C 0.03 0.06 ATCCAGAAAATCTAYCAGGAACTGGCCTT TAT TAC Synonymous Tyr Tyr CYPIIB1EX5 72 G 0.99 A 0.01 0.03 GGAACTGGCCTTCARCCGCCCTCAACAGT AGC AAC Nonsynonymous Ser Asn CYPIIB1EX7 52 C 0.99 T 0.01 0.03 CTGTGGGTCTGTTTYTGGAGCGAGTGGCG CTG TTG Synonymous Leu Leu CYPIIBlEX8 144 T 0.96 C 0.04 0.08 CCGGCAGGAACTTCYACCACGTGCCCTTT TAC CAC Nonsynonymous Tyr His CYPIIB1EX9 16 G 0.96 C 0.04 0.07 CCAGATGGAAACCCSGCTTCTGTCCTAGG . . Other Intron . CYPIIB1EX9 274 T 0.91 C 0.09 0.16 AGCCCCAGCACAAAYGGAACTCCCGAGGG . . Other 3′UTR . CYPIIB1EX9 350 T 0.88 G 0.12 0.21 GCTGGGGAAGATCTKGCTGACCTTGTCCC . . Other 3′UTR . CYPIIB1EX9 459 G 0.72 A 0.28 0.40 CCTCGTGTGGCCATRCAAGGGTGCTGTGG . Other 3′UTR . CYPIIB1EX9 592 A 0.93 C 0.07 0.13 TCTAGAGTCCAGTCMAGTTCCCTCCTGCA . . Other 3′UTR . CYPIIBiEX9 62 C 0.99 7 0.01 0.03 GTGGAGACACTAACYCAAGAGGACATAAA ACC ACT Synonymous Thr Thr CYPIIB1EX9 657 G 0.66 A 0.34 0.45 CTCTGAAAGTTGTCRCCCTGGAATAGGGT . . Other 3′UTR . CYPIIB1EX9 786 A 0.87 G 0.13 0.22 ATCGTGTCAGCCTCRTGCCCCTGGCCTCA . . Other 3′UTR . CYPIIB1EX9 835 C 0.77 T 0.23 0.35 GTTCCAGGAGTGGGYGTTGGGTCCTCTGC . . Other 3′UTR . CYPIIB1EX9 879 A 0.68 G 0.32 0.44 CTGGGGAAGGTCCCRAGGATGCTGTCAGG . . Other 3′UTR . CYPIIB2EX1 163 A 0.97 G 0.03 0.06 TCCTGGGTGAGATARAAGGATTTGGGCTG . . Other Promoter . CYPIIB2EX3 138 C 0.66 T 0.34 0.45 GTGGCCAGGGACTTYTCCCAGGCCCTGAA TTC TTT Synonymous Phe Phe CYPIIB2EX3 152 A 0.71 G 0.29 0.41 CTCCCAGGCCCTGARGAAGAAGGTTGCTGC AAG AGG Nonsynonymous Lys Arg CYPIIB2EX3 20 G 0.98 C 0.03 0.05 CAAGCTCTGCCCTGSCCTCTGTAGGAATG . . Other Intron . CYPIII32EX3 243 G 0.97 A 0.03 0.06 GGTGTGGGCCATGCRGGAAGGTCCAGCCC . . Other Intron . CYPIIB2EX4 177 T 0.96 C 0.04 0.07 CCTGTCTCGCTGGAYCAGCCCCAAGGTGT ATC ACC Nonsynonymous Ile Thr CYPIIB2EX4 250 G 0.98 A 0.02 0.04 GAGGCCAGGGACCCRGGCAGTGCTATGGG . . Other Intron . CYPIIB2EX4 99 A 0.94 C 0.06 012 TTCTGCCAGCCTGAMCTTCCTCCATGCCC AAC ACC Nonsynonymous Asn Thr CYPIIB2EX5 103 G 0.05 A 0.95 0.10 ACAGGCATCGTGGCRGAGCTCCTGTTGAA GCG GCA Synonymous Ala Ala CYPIIB2EX5 121 G 0.78 A 0.23 0.35 CTCCTGTTGAAGGCRGAACTGTCACTAGA GCG GCA Synonymous Ala Ala CYPIIB2EX5 55 C 0.99 T 0.01 0.02 ATCCAGAAAATCTAYCAGGAACTGGCCTT TAG TAT Synonymous Tyr Tyr CYPIIB2EX5 72 A 0.99 G 0.01 0.02 GGAACTGGCCTTCARCCGCCCTCAACACT AAC AGC Nonsynonymous Asn Ser CYPIIB2EX6 195 A 0.84 C 0.16 0.27 TCAAGGAGACCTTGMGGTGGGTGCTGGCT AGG CGG Synonymous Arg Arg CYPIIB2EX6 91 T 0.38 C 0.63 0.47 CGACGTGCAGCAGAYCCTGCGCCAGGAGA ATC ACC Nonsynonymous Ile Thr CYPIIB2EX7 52 T 0.99 C 0.01 0.03 CTGTGGGTCTGTTTYTGGAGCGAGTGGTG TTG CTG Synonymous Leu Leu CYPIIB2EX7 56 A 0.97 T 0.03 0.06 GGGTCTGTTTTTGGWGCGAGTGGTGAGCT GAG GTG Nonsynonymous Glu Val CYPIIB2EX7 65 T 0.91 C 0.09 0.17 TTTGGAGCGAGTGGYGAGCTCAGACTTGG GTG GCG Nonsynonymous Val Ala CYPIIB2EX7 78 G 0.82 A 0.18 0.30 GTGAGCTCAGACTTRGTGCTTCAGAACTA TTG TTA Synonymous Leu Leu CYPIIB2EX8 132 G 0.97 A 0.03 0.06 ACATCAGGGGCTCCRGCAGGAACTTCCAC GGC AGC Nonsynonymous Gly Ser CYPIIB2EX8 18 C 0.99 T 0.01 0.02 TGATCCCTGCTCTGYACCGTCCGCAGACA . . Other Intron . CYPIIB2EX8 182 C 0.98 T 0.02 0.04 ATGCGCCAGTGCCTYGGGCGGCGCCTGGC CTC CTT Synonymous Leu Leu CYPIIB2EX8 37 T 0.99 A 0.01 0.02 TCCGCAGACATTGGWACAGGTTTTCCTCT GTA GAA Nonsynonymous Val Glu CYPIIB2EX9 224 G 0.89 A 0.11 0.20 GTCTTCTCTCCCACRTGCACAGCTTCCTG . . Other 3′UTR . CYPIIB2EX9 90 T 0.99 G 0.01 0.03 AGATGGTCTACAGCKTCATATTGAGGCCT TTC GTC Nonsynonymous Phe Val DBHEX1 152 G 0.99 A 0.01 0.02 GGGCCAGCCTGCCCRGCCCCAGCATGCGG . . Other 5′UTR . DBHEX3 153 G 0.92 A 0.08 0.14 AGTTGCCCTCAGACRCGTGCACCATGGAG GCG ACG Nonsynonymous Ala Thr DBHEX3 239 G 0.97 C 0.03 0.06 AAGGAGCTTCCAAASGGCTTCTCTCGGCA AAG AAC Nonsynonymous Lys. Asn DBHEX3 257 C 0.98 T 0.03 0.05 TTCTCTCGGCACCAYATTATCAAGGTACG CAC CAT Synonymous His His DBHEX3 63 G 0.96 C 0.04 0.08 CGTTCCGGTCACTGSAGGCCATCAACGGC GAG CAG Nonsynonymous Glu Gly DBHEX4 12 G 0.96 C 0.04 0.08 CCTCCTCACAGTACSAGCCCATCGTCACC GAG CAG Nonsynonymous Glu Gln DBHEX4 132 G 0.94 A 0.06 0.11 CCAAGATGAAACCCRACCGCCTCAACTAC GAC AAC Nonsynonymous Asp Asn DBHEX5 37 T 0.94 C 0.06 0.11 AGAGGAAGCCGGCCYTGCCTTCGGGGGTC CTT CCT Nonsynonymous Leu Pro DBHEX5 39 G 0.94 T 0.06 0.11 AGGAAGCCGGCCTTKCCTTCGGGGGTCCA GCC TCC Nonsynonymous Ala Ser DDIR 122 A 0.84 G 0.16 0.27 CCTATTCCCTGCTTRGGAACTTGAGGGGT . . Other Promoter . DDIR 1521 G 0.96 A 0.04 0.08 CTGAACTCGCAGATRAATCCTGCCACACA . . Other 3′UTR . DDIR 278 A 0.96 C 0.04 0.08 TGCTCATCCTGTCCMCGCTCCTGGGGAAC ACG CCG Nonsynonymous Thr Pro DDIR 279 C 0.99 G 0.01 0.02 GCTCATCCTGTCCASGCTCCTGGGGAACA ACG AGG Nonsynonymous Thr Arg DDIR 310 C 0.98 G 0.02 0.04 CTGGTCTGTGCTGCSGTTATCAGGTTCCG GCC GCG Synonymous Ala Ala DDIR 319 G 0.99 T 0.01 0.02 GCTGCCGTTATCAGKTTCCGACACCTGCG AGG AGT Nonsynonymous Arg Ser DDIR 76 G 0.98 A 0.03 0.05 GCAAAGTGCTGCCTRGTGGGGAGGACTCC . . Other Promoter . DDIR 764 T 0.98 G 0.03 0.05 ATGCCATCTCATCCKCTGTAATAAGCTTT TCT GCT Nonsynonymous Ser Ala EDNRAEX6 124 A 0.28 G 0.72 0.40 ACTGTGTATAACGARATGGACAAGAACCG GAA GAG Synonymous Glu Glu EDNRAEX6 88 C 0.31 T 0.69 0.43 TGGTTCCCTCTTCAYTTAAGCCGTATATT CAC CAT Synonymous His His EDNRAEX8 1157 G 0.66 A 0.34 0.45 TTTTCAGATGATTCRGAAATTTTCATTCA . . Other 3′UTR . EDNRAEX8 1380 C 0.52 T 0.48 0.50 ACGATTCTTCACTTYTTGGGGTTTTCAGT . . Other 3′UTR . EDNRAEX8 1687 A 0.83 G 0.17 0.28 TTGTGCCAAAGTGCRTAGTCTGAGCTAAA . . Other 3′UTR . EDNRAEX8 228 C 0.47 G 0.53 0.50 CAAGGCAACTGTGASTCCGGGAATCTCTT . . Other 3′UTR . EDNRAEX8 295 A 0.99 G 0.0 0.02 AAGAAATGCTTTCCRAAACCGCAAGGTAG . . Other 3′UTR . EDNRAEX8 622 G 0.38 A 0.62 0.47 ACAATATGGGCTCARGTCACTTTTATTTG . . Other 3′UTR . EDNRAEX8 655 G 0.99 A 0.01 0.03 GTCATTTGGTGCCARTATTTTTTAACTGC . . Other 3′UTR . EDNRAEX8 788 A 0.88 G 0.12 0.21 CTATTTATTTTTTTRAAACACAAATTCTA . . Other 3′UTR . EDNRAEX8 950 T 0.96 C 0.04 0.08 GAACATGTTTTGTAYGTTAAAFICAAAAG . . Other 3′UTR . EDNRAEX8 985 T 0.97 C 0.03 0.06 TTCAATCAGATAGTYCTTTTTCACAAGTT . . Other 3′UTR . EDNRBEX1 33 T 0.98 A 0.03 0.05 GCCGCCTCCAAGTCWGTGCGGACGCGCCC CTG CAG Nonsynonymous Leu Gln EDNRBEX1 347 T 0.99 G 0.01 0.02 TGTCCTGCCTTGTGKTCGTGCTGGGGATC TTC GTC Nonsynonymous Phe Val EDNRBEX1 62 C 0.99 T 0.01 0.02 TGGTTGCGCTGGTTYTTGCCTGCGGCCTG CTT TTT Nonsynonymous Leu Phe EDNRBEX2 78 C 0.95 T 0.05 0.10 ATACAGAAAGCCTCY0T000AATCACT0T TCC TCT Synonymous Ser Ser EDNRBEX2 87 C 0.99 T 0.01 0.03 GCCTCCGTGGGAATYACTGTGCTGAGTCT ATC ATT Synonymous Ile Ile EDNRBEX3 144 C 0.94 T 0.06 0.11 TTTTGATATAATTAYGATGGACTACAAAG ACG ATG Nonsynonymous Thr Met EDNRBEX4 122 G 0.99 A 0.01 0.03 GTTGAGAAAGAAAARTGGCATGCAGATTG AGT AAT Nonsynonymous Ser Asn EDNRBEX4 39 G 0.82 A 0.18 0.29 AAAGATTGGTGGCTRTTCAGTTTCTAflT CTG CTA Synonymous Leu Leu ELAMIEX1 143 A 0.93 G 0.07 0.13 TCTTTGACCTAAATRATGAAAGTCTTAAA . . Other Promoter . ELAMIEX1 209 T 0.97 G 0.03 0.06 TTATTGCACTAGTOKCCTTTGCCCAAAAT . . Other Promoter . ELAMIEX10 107 C 0.91 T 0.09 0.16 CATTAGCACCATTTYTCCTCTGGCTTCGG CTC TTC Nonsynonymous Leu Phe ELAMIEX12 54 T 0.96 C 0.04 0.08 AGCCTTGAATCAGAYGGAAGCTACCAAAA GAT GAG Synonymous Asp Asp ELAMIEX13 1004 T 0.98 G 0.02 0.04 CAGAAATATGTGGTKTCCACGATGAAAAA . . Other 3′UTR . ELAMIEX13 1158 6 0.18 A 0.82 0.29 GATGTTTGTCAGATRTGATATGTAAACAT . . Other 3′UTR . ELAM1EX13 1549 G 0.39 A 0.61 0.47 TGAACACTGGCAACRACAAAGCCAACAGT . . Other 3′UTR . ELAM1EX13 967 T 0.97 C 0.03 0.06 ACTGAATGGAAGGTYTGTATATTGTCAGA . . Other 3′UTR . ELAM1EX2 382 C 0.98 G 0.02 0.04 AATGATGAGAGGTOSAGCAAGAAGAAGCT TGC TGG Nonsynonymous Cys Trp ELAMIEX3 152 T 0.95 C 0.05 0.10 GTAAGTCTGGTTCTYGCCTCTTTCTTCAC . . Other Intron . ELAMIEX3 53 A 0.97 C 0.03 0.06 CCAATACATCCTGCMGTGGCCACGGTGAA AGT CGT Nonsynonymous Ser Arg ELAMIEX5 197 G 0.95 A 0.05 0.10 GGAATTGGGACAACRAGAAGCCAACGTGT GAG AAG Nonsynonymous Glu Lys ELAMIEX5 55 T 0.97 C 0.03 0.06 GATGCTGTGACAAAYCCAGCCAATGGGTT AAT AAC Synonymous Asn Asn ELAMIEX7 199 C 0.94 T 0.06 0.12 GGGGAGTGGGACAAYGAGAAGCCCACATG AAC AAT Synonymous Asn Asn ELAM1EX7 200 G 0.94 C 0.06 0.11 GGGAGTGGGACAACSAGAAGCCCACATGT GAG CAG Nonsynonymous Gln Gln ELAM1EX8 152 C 0.96 T 0.04 0.08 AGGGATTTGAATTAYATGGATCAACTCAA CAT TAT Nonsynonymous His Tyr ELAMIEX8 22 T 0.91 C 0.09 0.16 AGTGCTCTCTCGTOYGTTCCAGCTGTGAG . . Other Intron . . ENDGTHELIN2 440 T 0.97 C 0.03 0.07 CCCCTGCAGACGTGYTCCAGACTGGCAAG TTC CTC Nonsynonymous Phe Leu ENDGTHELIN2 556 G 0.99 A 0.01 0.02 ATGCGGGAGCCTCGRTCCACACATTCCAG CGG CGA Synonymous Arg Arg ENDGTHELIN2 976 A 0.84 G 0.16 0.27 AGCCAGCCCTGGAGRCTGGATGGCTCCCC . . Other 3′UTR . ET1EX3 114 G 0.88 A 0.12 0.21 GCAACAGACCGTGARAATAGATGCCAATG GAG GAA Synonymous Glu Glu ETTEX5 90 G 0.69 T 0.31 0.43 AAGCTGAAAGGCAAKCCCTCCAGAGAGCG AAG AAT Nonsynonymous Lys Asn GALNREX1 1052 G 0.94 T 0.06 0.11 CTGCCCACCTGGGTKCTGGGCGCCTTCAT GTG GTT Synonymous Val Val GALNREX1 325 C 0.98 G 0.02 0.04 GGTGCAGCACGCAGSCGCTCCGGGAGCCA . . Other Promoter . GALNREX1 327 G 0.81 C 0.19 0.30 TGCAGCACGCAGCCSCTCCGGGAGCCAGG . . GALNREX1 553 G 049 C 0.51 0.50 TCTCTCAGAAGGTCSCGGCGCAAAGACGG . . Other Promoter . GALNREX1 887 C 0.49 T 0.51 0.50 ATCTTCGCGCTGGGYGTGCTGGGCAACAG GGC GGT Synonymous Gly Gly GALNREX3 298 A 0.68 G 0.32 0.43 TGATACTAAAGAAARTAAAAGTCGAATAG AAT AGT Nonsynonymous Asn Ser GALNREX3 322 C 0.98 T 0.02 0.04 AATAGACACCCCACYATCAACCAATTGTA CCA CTA Nonsynonymous Pro Leu GALNREX3 388 T 0.98 C 0.02 0.04 AGTTTCCATATAAGYGGACCAGACACAGA . Other 3′UTR . GALNREX3 418 C 0.97 G 0.03 0.06 ACAAACAGAATGAGSTAGTAAGCGATGCT . . Other 3′UTR . GALNREX3 523 G 0.98 T 0.02 0.04 TAGGAAATTCCTAGKTCTAGTGAGAATTA . . Other 3′UTR . GALNREX3 650 C 0.94 T 0.06 0.11 TCCATATATATGTTYAACTCTTCATAGAT . . Other 3′UTR . GALNREX3 799 A 0.84 G 0.16 0.26 ATGTATTTTAAAATRTGATCATGGACACA . . Other 3′UTR . GGREX1 125 G 0.98 A 0.02 0.04 CTGCTGTTGCTGCTRCTGCTGGCCTGCCA CTG CTA Synonymous Leu Leu GGREX11 57 C 0.91 T 0.09 0.16 CACGAAGTGGTCTTYGCCTTCGTGACGGA TTC TTT Synonymous Phe Phe GGREX4 68 C 0.98 G 0.02 0.05 GACCCCGGGGGCAGSCTTGGCGTGATGCC CCT GCT Nonsynonymous Pro Ala GGREX5 71 C 0.83 G 0.17 0.28 CTGTCCCTGGGGGCSCTGCTCCTCGCCTT GCC GCG Synonymous Ala Ala GGREX9 29 T 0.93 G 0.07 0.12 TGACAACATGGGCTKCTGGTGGATCCTGC TTC TGC Nonsynonymous Phe Cys GHA1EX4 144 G 0.98 A 0.02 0.03 CCTCTGACAGCAACRTCTATGACCTCCTA GTC ATC Nonsynonymous Val Ile GH2EX3 126 A 0.94 T 0.06 0.12 CAACACCTTCCAACWGGGTGAAAACGCAG AGG TGG Nonsynonymous Arg Trp GHREX2 72 C 0.93 G 0.08 0.14 CTTCGCCGCCCTCASGATGACTACCTCTC . . Other 5′UTR . GIPREX7 51 C 0.79 T 0.21 0.33 CATTGCACTAGAAAYTATATCCACATCAA AAC AAT Synonymous Asn Asn GIPREX8 180 C 0.98 G 0.03 0.05 GCTACTACCTGCTCSTCGGCTGGGGTCAG CTC GTC Nonsynonymous Leu Val GLUT2EX1 137 C 0.32 A 0.68 0.44 CCACAGCACTAATTMTCTGTGGAGCAGAG . . Other Promoter . GLUT2EX1 164 T 0.31 C 0.69 0.43 AGTGCAGTGTGCCTYCCATGCTCCACAGC . . Other Promoter . GLUT2EX1 237 T 0.96 C 0.04 0.07 AAAGATTTCTCTTTYCACCGGCTCCCAAT . . Other Promoter . GLUT2EX1 242 G 0.34 A 0.66 0.45 TTTCTCTTTTCACCRGCTCCCAATTACTG . . Other Promoter . GLUT2EX10 161 G 0.99 A 0.01 0.02 GAATTCCAAAAGAARAGTGGCTCAGCCCA AAG AAA Synonymous Lys Lys GLUT2EX10 87 C 0.99 G 0.01 0.03 TCCTGGCCTTTACCSTGTTTACATTTTTT CTG GTG Nonsynonymous Leu Val GLUT2EX10 92 T 0.35 C 0.65 0.46 GCCTTTACCCTGTTYACATTTTTTAAAGTT TTT TTC Synonymous Phe Phe GLUT2EX3 250 C 0.87 T 0.13 0.23 AGTTGGTGGAATGAYTGCATCATTCTTTG ACT ATT Nonsynonymous Thr Ile GLUT2EX4A 153 T 0.96 C 0.04 0.08 TCAGGACTATATTGYGGTAAGTCTCACAC TGT TGC Synonymous Cys Cys GLUT2EX4A 162 T 0.83 A 0.17 0.28 TATTGTGGTAAGTCWCACACACACACACA . . Other Intron . GLUT2EX4A 164 A 0.94 T 0.06 0.11 TTGTGGTAAGTCTCWCACACACACACACA . . Other Intron . GLUT2EX4B 127 A 0.28 G 0.72 0.40 CTGGCCATCGTCACRGGCATTCTTATTAG ACA ACG Synonymous Thr Thr GLUT2EX5 78 C 0.93 T 0.08 0.14 ATCTGTGGCACATCYTGCTTGGCCTGTCT CTG TTG Synonymous Leu Leu GLUT2EX6 15 T 0.10 C 0.90 0.18 TGTTTCAACCTGATYATTTTCTTGGACAG .. . Other Intron . GLUT2EX8 21 T 0.88 C 0.12 0.21 TAATTTCTTTAAAAYTGTCCTAGGTATTC . . Other Intron . GLUT2EX8 38 T 0.95 C 0.05 0.10 TCCTAGGTATTCCTYGTGGAGAAGGCAGG CTT CTC Synonymous Leu Leu GLUT4EX1 1002 A 0.99 C 0.01 0.02 CGTTGTGGGAACGGMATTTCCTGGCCCCC . . Other Promoter . GLUT4EX1 1051 C 0.74 T 0.26 0.38 AGCATGTCGCGGACYCTTTAAGGCGTCAT . . Other Promoter . GLUT4EX1 1228 A 0.86 T 0.14 0.24 TCTCAGGCCGCTGGWGTTTCCCCGGGGCA . . Other Promoter . GLUT4EX1 1632 A 0.71 C 0.29 0.42 CAGCCCCGCTCCACMAGATCCCCGGGAGC . . Other 5′UTR . GLUT4EX1 1662 A 0.64 G 0.36 0.46 CCACTGCTCTCCGGRTCCTTGGCTTGTGG . . Other 5′UTR . GLUT4EX1 1683 G 0.98 C 0.02 0.05 GCTTGTGGCTGTGGSTCCCATCGGGCCCG . . Other 5′UTR . GLUT4EX1 1691 G 0.94 A 0.06 0.11 CTGTGGGTCCCATCRGGCCCGCCCTCGCA . . Other 5′UTR . GLUT4EX1 368 G 0.96 A 0.04 0.07 ACAGGAGGAATCGARCCTGACTTCTACCA . . Other Promoter . GLUT4EX1 560 A 0.90 G 0.10 0.19 GCGGAAAGGCGAGARATAGTGGGTTGAGA . . Other Promoter . GLUT4EX1 615 G 0.93 A 0.07 0.14 TCGCTCGCCCTCCARGTGGCAGCACAACC . . Other Promoter . GLUT4EX1 91 C 0.95 T 0.05 0.10 CAGGAGGTTTTGTTYACTCTGAAAAGGGA . . Other Promoter . GLUT4EX1 966 C 0.95 A 0.05 0.10 CTGAAAGACAGGACMAAGCAGCCCGGCCA . . Other Promoter . GLUT4EX10 19 C 0.94 G 0.06 0.11 TCCACCCTCCCTGTSTGGCCCCTAGGAGC . . Other Intron . GLUT4EX11 1005 G 0.83 A 0.17 0.28 GTGCTGGGATTACARGCGTGAGCCACCGC . . Other 3′UTR . GLUT4EX11 1099 A 0.95 C 0.05 0.10 GAAAGTATGTGCCCMTGTGTGGCAAGATG . . Other 3′UTR . GLUT4EX11 791 T 0.93 C 0.07 0.14 CGAGTGCAGTGGCGYGATCTTGCTTCACT . . Other 3′UTR . GLUT4EX11 827 C 0.90 T 0.10 0.18 GTCTCCCAGGTTCAYGCCATTCTCCTGCC . . Other 3′UTR . GLUT4EX11 872 G 0.79 A 0.21 0.33 CTGGGACTACAGGCRCATGCCACCACACC . . Other 3′UTR . GLUT4EX11 874 A 0.92 C 0.08 0.15 GGGACTACAGGCGCMTGCCACCACACCTG . . Other 3′UTR . GLUT4EX11 884 A 0.73 G 0.27 0.40 GCGCATGCCACCACRCCTGGCTAATTTAT . . Other 3′UTR . GLUT4EX11 897 A 0.89 T 0.11 0.20 CACCTGGCTAATTTWTTTTGTATTTTTAG . . Other 3′UTR . GLUT4EX11 930 A 0.88 G 0.13 0.22 TACGCGGTTTCACCRTGTTAGCCAGAATG . . Other 3′UTR . GLUT4EX11 935 A 0.86 G 0.14 0.24 GGTTTCACCATGTTRGCCAGAATGGTCTC . . Other 3′UTR . GLUT4EX11 941 A 0.49 G 0.51 0.50 ACCATGTTAGCCAGRATGGTCTCGATCTC . . Other 3′UTR . GLUT4EX11 963 C 0.96 T 0.04 0.07 CGATCTCCTGACCTYGTGATCTGCCTGCC . . Other 3′UTR . GLUT4EX3 112 C 0.90 G 0.10 0.17 TCCAGGCACCCTCASCACCCTCTGGGCCC ACC AGC Nonsynonymous Thr Ser GLUT4EX4 96 C 0.71 T 0.29 0.42 ATGGGCCTGGCCAAYGCTGCTGCCTCCTA AAC AAT Synonymous Asn Asn GLUT4EX7 19 C 0.95 T 0.05 0.09 TCAGGCCTGACCTTYCCTTCTCCAGGTCT . . Other Intron . GLUT4EX7 227 G 0.99 C 0.01 0.02 ATGCTGTATGTGTGSAGCAGCCTCCAGGC . . Other Intron . GLUT5EX1 184 G 0.95 A 0.05 0.10 AAAAGGAGGTCAGCRGCACTCTGCCCTTC . . Other 5′UTR . GNB3EX1 184 A 0.89 C 0.11 0.20 GACAGATGGGGAACMCTGTGCCTCCCTGA . . Other Promoter . GNB3EX1 201 A 0.63 G 0.37 0.47 GTGCCTCCCTGAACRGAAATGGCAGGGGA . Other Promoter . GNB3EX1 328 A 063 G 0.37 0.47 GCCAGGGGCCAGTCRAGTGTATCACAGAT . . Other Promoter . GNB3EX10 144 G 0.93 A 0.07 0.13 AGAGCATCATCTGCRGCATCACGTCCGTG GGC AGC Nonsynonymous Gly Ser GNB3EX10 155 C 061 T 0.39 0.48 TGCGGCATCACGTCYGTGGCCTTCTCCCT TCC TCT Synonymous Ser Ser GNB3EX11 129 G 0.97 T 0.03 0.06 CTTCCTCAAAATCTKGAACTGAGGAGGCT TGG TTG Nonsynonymous Trp Leu GNB3EX11 254 C 0.75 T 0.25 0.38 CCACTAAGCTTTCTYCTTTGAGGGCAGTG . . Other 3′UTR . GNB3EX11 536 C 0.60 T 0.40 0.48 TATGGCTCTGGCACYACTAGGGTCCTGGC . . Other 3′UTR . GSY1EX10 46 A 0.99 G 0.01 0.02 GGAGCCTTCCGGACRTGAACAAGATGCTG ATG GTG Nonsynonymous Met Val GSY1EX12 152 A 0.95 G 0.05 00.1 GCCTTGGGGCTACACRCCGGGTGAGTGTAG ACA AGG Synonymous Thr Thr GSY1X12 163 G 0.95 A 0.05 0.09 GAGAGCGGGTGAGTRTAGTGGGGAGGGGA . . Other intron GSY1EX15 75 G 0.96 C 0.04 0.07 GCAAGGGCTTTCCASAGGACTTCAGGTAG GAG CAG Nonsynonymous Glu Gln OSY1EX16 152 C 0.99 T 0.01 0.02 CCGCTGGAGGAAGAYGGGGAGGGGTAGGA GAG GAT Synonymous Asp Asp GSY1EX16 210 C 0.94 G 0.06 0.11 GCAACATCCGTGCASGAGAGTGGCCGCGG CCA GCA Nonsynonymous Pro Ala GSY1EX16 65 G 0.94 A 0.06 0.11 GGGCGAGGGTCGGTRCCAGGGTCGCGCTG GTG GTA Synonymous Val Val GSY1EX2 219 G 0.99 A 0.01 0.03 GTGCAAGGTGGGAGRTGGGGGAGGGGAGG . . Other Intron . GSY1EX3 117 A 0.95 G 0.05 0.10 GGCTGGAGCGGTGGRAGGGAGAGGTCTGG AAG GAG Nonsyrtonymous Lys Glu OSY1EX3 134 T 0.96 C 0.04 0.08 GGAGAGGTGTGGGAYACGTGCAACATGGG GAT GAG Synonymous Asp Asp OSY1EX3 149 A 0.95 G 0.05 0.01 CAGCTGGAAGATGGGRGTGCGGTGGTACGA GGA GGG Synonymous Gly Gly GSYlEX3 53 C 0.99 G 0.01 0.03 GGGCGCTGGGTGATSGAGGGAGGGCCTGT ATC ATG Nonsynonymous Ile Met GSY1EX4 16 C 0.93 T 0.07 0.12 ACAGTGGGGCTGTGYGTGTTGGCGACAGT . . Other Intron . OSY1EX5 44 G 0.96 A 0.04 0.08 TTCAAGGTGGACAARGAAGGAGGGGAGAG AAG AAA Synonymous Lys Lys GSY1EX6 54 A 0.99 G 0.01 0.03 CGGGAATGGGGTGARTGTGAAGAAGTTTT AAT AGT Nonsynonymous Asn Ser GSY1EX7 114 C 0.71 T 0.29 0.42 GGTGGTGAGGTGTTYCTGGAGGCATTGGG TTC TTT Synonymous Phe Phe OSY1EX7 16 T 0.98 G 0.02 0.04 GCTTTAGGGTGCGTKGTGGGTTCTTTAGG . . Other Intron . OSY1EX7 17 G 0.99 C 0.01 0.02 GTTTACGGTGGCTTSTGGGTTCTTTAGGC . . Other Intron . OSY1EX8 43 A 0.94 G 0.06 0.11 GGTGAACGGCAGCGRGCAGACAGTGGTTG GAG GGG Nonsynonymous Glu Gly HAPTEX1 135 T 0.97 C 0.03 0.06 GATAAAGAGACAGAYTGATGGTTCCTGCC . . Other 5′UTR . HAPTEX1 188 C 0.90 T 0.10 0.18 GATTTGAGGAAATAYTTTGGGAGGTTTGT . . Other 5′UTR . HAPTEX1 239 T 0.95 G 0.05 0.09 CTTGGGATTTGTAAKAGAACATGAGAAGA . . Other 5′UTR . HAPTEX1 326 T 0.45 A 0.55 0.50 ACTGGAAAAGATAGWGAGCTTAGCAGGGC . . Other 5′UTR . HAPTEX1 329 C 0.76 G 0.24 0.37 GGAAAAGATAGTGASCTTAGCAGGGGCAA . . Other 5′UTR . HAPTEX1 369 A 0.88 C 0.12 0.21 ACAGGAATTAGGAAMTGGAGAAGGGGGAG . . Other 5′UTR . HAPTEX1 375 A 0.89 G 0.11 0.19 ATTACGAAATGGAGRAGGGGGAGAAGTGA . . Other 5′UTR . HAPTEX4 34 A 0.53 G 0.47 0.50 TTTGTTTCAGGAGTRTACACCTTAAATGA GTA GTG Synonymous Val Val HAPTEX6 34 G 0.66 A 0.34 0.45 TTTGTTTCAGGAGTRTACACCTTAAACAA GTA GTG Synonymous Val Val HAPTEX7 1331 C 0.98 T 0.02 0.03 CATGCTGTTGCCTCYTCAAAGTGAATTAG . . Other 3′UTR . HAPTEX7 367 G 0.98 A 0.02 0.03 GTGTCTGTTAATGARAGAGTGATGCCCAT GAG GAA Synonymous Glu Glu HAPTEX7 610 T 0.98 C 0.02 0.04 CACACCTTCTGTGCYGGCATGTCTAAGTA GCT GCC Synonymous Ala Ala HAPTEX7 673 C 0.98 T 0.02 0.03 GCCTTTGCCGTTCAYGACCTGGAGGAGGA CAC CAT Synonymous His His HSD11KEX2 232 C 0.95 A 0.05 010 ACCAAGGCCCACACMACCAGCACCGGTCA ACC ACA Synonymous Thr Thr HSD11KEX3 139 G 0.83 A 0.18 0.29 AATTTCTTTGGCGCRCTCGAGCTGACCAA GCG GCA Synonymous Ala Ala HSD11KEX 5951 T 0.96 A 0.04 0.08 ACTGTACTTCCCAAWTGCCACATTHAAA . . Other 3′UTR . HSTSCGENE 1392 C 0.97 T 0.03 0.06 ATCTTCGGGGCCACYCTCTCCTCTGCCCT ACC ACT Synonymous Thr Thr HSTSCGENE 1881 G 0.98 A 0.02 0.03 GCCCTCAGCTACTCRGTGGGCCTCAATGA TCG TCA Synonymous Ser Ser HSTSCGENE 2139 C 0.88 T 0.13 0.22 TCGGATGTCATTGCYGAGGACCTCCGCAG GCC GCT Synonymous Ala Ala HSTSCGENE 2595 C 0.90 T 0.10 0.18 CGTGTGTTCGTAGGYGGCCAGATTAACAG GGC GGT Synonymous Gly Gly HSTSCGENE 3269 G 0.81 A 0.19 0.30 GGTCTTGTGTTTATRGGCTAGAGAAATAG . . Other 3′UTR . HSTSCGENE 3660 C 0.94 T 0.06 0.11 CTGCAACCTCCTCCYGGGTTCAAGCATTT . Other 3′UTR . HSTSCGENE 3710 G 0.98 C 0.02 0.03 TAGCTGGGATTACASGCACCTGCCATCAC . Other 3′UTR . HSTSCGENE 3727 C 0.69 G 0.31 0.43 ACCTGCCATCACACSAGCTAATTTTTGTA . Other 3′UTR . HSTSCGENE 3838 G 0.90 A 0.10 0.18 CCCAAAGTGCTGGGRTTACAGGCCTGAGC . Other 3′UTR . HUMAPNH1A 3057 T 0.92 C 0.08 0.15 AGGGCATCTCTGAGYGTCTCTGCCTGGAG . . Other 3′UTR . HUMOFAT 2930 T 0.65 G 0.35 0.45 ATCTCCTAAAAGTGKTTTTTATTTCCTTG . Other 3′UTR . HUMGLUTRN 2110 G 0.94 C 0.06 0.12 GGCTATGGCCACCCSTTCTGCTGGCCTGG . Other 3′UTR . HUMGLUTRN 933 A 0.99 C 0.01 0.02 GATGATGCGGGAGAMGAAGGTCACCATCC AAG ACG Nonsynonymous Lys Thr HUMGUANCYC 2388 C 0.93 T 0.07 0.14 ATTGTCACTGAATAYTGTCCTCGTGGGAG TAC TAT Synonymous Tyr Tyr HUMGUANCYC 2571 A 0.86 G 0.14 0.24 CGTTTTGTGCTCAARATCACAGACTATGG AAA AGA Nonsynonymous Lys Arg HUMGUANCYC 2643 G 0.93 A 0.07 0.14 GCCCTCTATGCCAARAAGCTGTGGACTGC AAG AAA Synonymous Lys Lys HUMGUANCYC 2787 C 0.93 G 0.07 0.13 GAGGGCCTGGACCTSAGCCCCAAAGAGAT CTC CTG Synonymous Leu Leu HUMGUANCYC 2905 C 0.97 G 0.03 0.07 AGCGATGTTGGGCTSAGGACCCAGCTGAG CAG GAG Nonsynonymous Gln Glu HUMGUANCYC 3300 C 0.81 G 0 19 0.31 GACAACTTTGATGTSTACAAGGTGGAGAC GTC GTG Synonymous Val Val HUMGUANCYC 3663 G 0.96 A 0.04 0.08 CTTCGGGGGGATGTRGAAATGAAGGGAAA GTG GTA Synonymous Val Val IAPPEX1-2 199 T 0.97 C 0.03 0.06 TTTATTTAGAGAAAYGCACACTTGGTGTT . . Other Intron . IAPPEX1-2 358 A 0.99 C 0.01 0.02 GACTGTATCAATAAMAATTTTGATCCTTG . . Other Intron . IAPPEX3 1050 T 0.83 C 0.18 0.29 TAAAGTCTATTGTTYGTTGTGCTTGCTGG . . Other 3′UTR . IAPPEX3 1076 T 0.75 A 0.25 0.38 TGGTACTAAGAGGCWATTTAAAAGTATAA . . Other 3′UTR . IAPPEX3 1184 A 0.66 C 0.34 0.45 TTTAAGTGGCTTTCMGCAAACCTCAGTCA . . Other 3′UTR . IAPPEX3 296 C 0.85 T 0.15 0.26 TGCCCTTTTCATCTYCAGTGTGAATATAT . . Other 3′UTR . IAPPEX3 848 G 0.11 A 0.89 0.19 CTCCAGCCTGGGTGRCAGAGTGAGACTCG . . Other 3′UTR . IAPPEX3 959 A 0.93 G 0.07 0.13 TTCCTTTTTGCAGTRTATTTCTGAAATGA . . Other 3′UTR . ICAM1EX1 683 A 0.66 C 0.34 0.45 AGAGTTGCAACCTCMGCCTCGCTATGGCT . . Other Promoter . ICAM1EX2 115 A 0.70 T 0.30 0.42 CTGTGACCAGCCCAWGTTGTTGGGCATAG AAG ATG Nonsynonymous Lys Met ICAM1EX3 151 G 0.99 C 0.01 0.02 CTCCGTGGGGAGAASGAGCTGAAACGGGA AAG AAC Nonsynonymous Lys Asn ICAM1EX4 115 C 0.92 T 0.08 0.15 TGTTCCCTGGACGGKCTGTTCCCAGTCTC GGG GGT Synonymous Gly Gly ICAM1EX4 238 C 0.95 T 0.05 0.10 GTGACCGCAGAGGAYGAGGGCACCCAGCG GAC GAT Synonymous Asp Asp ICAM1EXS 47 G 0.99 A 0.01 0.02 TTCCGGCGCCCAACRTGATTCTGACGAAG GTG ATG Nonsynonymous Val Met ICAM1EX6 18 G 0.94 A 0.06 0.12 CATGTCATCTCATCRTGTTTTTCCAGATG . . Other Intron . ICAM1EX6 254 G 0.45 A 0.55 0.50 GGGAGGTCACCCGCRAGGTGACCGTGAAT GAG AAG Nonsynonymous Glu Lys ICAM1EX6 39 G 0.95 A 0.05 0.10 TCCAGATGGCCCCCRACTGGACGAGAGGG CGA CAA Nonsynonymous Arg Gln 1CAM1EX7 304 C 0.99 T 0.01 0.03 GCAGCTACACCTACYGGCCCTGGGACGCC . . Other 3′UTR . ICAM1EX7 869 A 0.99 G 0.01 0.03 TGGCAAAAAGATCARATGGGGCTGGGACT . . Other 3′UTR . ICAM1EX7 929 T 0.96 C 0.04 0.07 GAGTGATTTTTCTAYCGGCACAAAAGCAC . . Other 3′UTR. ICAM2EX1 300 C 0.99 T 0.01 0.02 GAGATGTCCTCTTTYGGTTACAGGACCCT TTC TTT Synonymous Phe Phe ICAM2EX2 63 G 0.93 A 0.07 0.13 GGCCAAAGAAGCTGRCGGTTGAGCCCAAA GCG ACG Nonsynonymous Ala Thr ICAM2EX3 281 G 0.98 A 0.03 0.05 GGACTTGATGTCTCRCGGTGGCAACATCT CGC CAC Nonsynonymous Arg His INSEX1 233 T 0.39 A 0.61 0.48 CAGCCCTGCCTGTCWCCCAGATCACTGTC . . Other 5′UTR . INSEX1 247 C 0.97 T 0.03 0.06 TCCCAGATCACTGTYCTTCTGCCATGGCC . . Other 5′UTR . INSEX1 453 C 0.78 T 0.22 0.34 CAGGGTGAGCCAACYGCCCATTGCTGCCC . . Other Intron . INSEX2 14 C 0.99 T 0.01 0.02 GAACCTGCTCTGCGYGGCACGTCCTGGCA . . Other Intron . KALSTEX1 133 G 0.88 T 0.12 0.21 CTGCTCCTCCTGCTKGTTGGACTACTGGC CTG CTT Synonymous Leu Leu KALSTEX1 511 A 0.89 G 0.11 0.19 CATGGGCTGGAAACRCGCGTGGGCAGTGC ACA ACG Synonymous Thr Thr KALSTEX2 318 A 0.67 T 0.33 0.44 GTAATCAGTGTGCTWTGGGGGCTGAATCT . . Other Intron . KALSTEX2 79 C 0.72 T 0.28 0.40 ACTCCCAAAGACTTYTATGTTGATGAGAA TTC TTT Synonymous Phe Phe KALSTEX3 17 A 0.98 G 0.02 0.05 AATGTTCTAACTCARTGCCCCTTTCAGGA . . Other Intron . KALSTEX3 91 T 0.97 C 0.03 0.07 CTGGCTCCTATGTAYTAGATCAGATTTTG TTA CTA Synonymous Leu Leu KLKEX1 105 G 0.98 T 0.02 0.03 AGGGCATTCTGAAGKCCAAGGCTTATATT . . Other 5′UTR . KLKEX3 253 C 0.68 G 0.32 0.44 TGGAGTTGCCCACCSAGGAACCCGAAGTG CAG GAG Nonsynonymous Gln Glu KLKEX3 50 G 0.98 A 0.02 0.03 GCTCTGGCTGGGTCRCCACAACTTGTTTG CGC CAC Nonsynonymous Arg His KLKEX4 110 T 0.97 A 0.03 0.07 CCACGTCCAGAAGGWGACAGACTTCATGC GTG GAG Nonsynonymous Val Glu KLKEX4 88 A 0.66 G 0.34 0.45 CTAATGATGAGTGCRAAAAAGCCCACGTC AAA GAA Nonsynonymous Lys Glu KLKEX5 318 A 0.75 G 025 0.38 CCCCAGCTGTGTCARTCTCATGGCCTGGA . . Other 5′UTR . MRLEX1B 156 T 0.46 C 0.54 0.50 GCCGATCAGCCAATAYTGGACTTGCTGGTG . . Other 5′UTR . MRLEX1B 16 G 0.90 C 0.10 0.18 GGGCGGGTGCCCGCSTCCCCCTCTGCGCG . . Other 5′UTR . MRLEX2 1338 A 0.97 C 0.03 0.05 CTCTTTTAAAGGGAMTCCAACAGTAAACC AAT ACT Nonsynonymous Asn Thr MRLEX2 1405 T 0.99 C 0.01 0.03 GATGATAAAGACTAYTATTCCCTATCAGG TAT TAC Synonymous Tyr Tyr MRLEX2 1617 G 0.99 A 0.01 0.03 AATATCTTTATCACRATCGGCTAGAGACC CGA CAA Nonsynonymous Arg Gln MRLEX2 1668 A 0.97 G 0.03 0.05 CTTTCCTCCTGTCARTACTTTAGTGGAGT AAT AGT Nonsynonymous Asn Ser MRLEX2 1696 C 0.97 T 0.03 0.06 TCATGGAAATCACAYGGCGACCTGTCGTC CAC CAT Synonymous His His MRLEX2 1720 T 0.50 C 0.50 0.50 TCGTCTAGAAGAAGYGATGGGTATCCGGT AGT AGC Synonymous Ser Ser MRLEX9 1326 C 0.99 T 0.01 0.03 GGAATGACACACTGYGGTGTCTGCAGCTC . . Other 3′UTR . MRLEX9 1572 A 0.43 G 0.57 0.49 GTTAAAGATCAGCTRTTCCCTTCTGATCT . . Other 3′UTR . MRLEX9 1670 A 0.88 G 0.13 0.22 GGCCCATCTTGGCARGGTTCAGTCTGAAT . . Other 3′UTR . MRLEX9 1964 G 0.86 A 0.14 0.24 AATCTTTTAAAAATRATGATAATCATCAG . . Other 3′UTR . MRLEX9 247 T 0.97 C 0.03 0.06 ACCTGTTTTTAACAYGTGATGGTTGATTC . . Other 3′UTR . MRLEX9 2551 T 0.88 C 0.13 0.22 CCAAATTGTCTGTCYGCTCTTATTTTTGT . . Other 3′UTR . MRLEX9 2635 G 0.36 A 0.64 0.46 TCATATAATTTAAARAAACACTAAATTAG . . Other 3′UTR . MRLEX9 869 C 0.99 G 0.01 0.02 TTTGCTGTGCTGTASATTACTGTATGTAT . . Other 3′UTR . MRLEX9 916 A 0.83 C 0.18 0.29 AATAAGGTATAAGGMTCTTTTGTAAATGA . . Other 3′UTR . NCX1EX12 1135 A 0.57 G 0.43 0.49 AGATTCCCAGGAACRTGCAAAATCCTTTC . . Other 3′UTR . NCX1EX12 1190 C 0.80 T 0.20 0.32 TGATTGGCAAGGTCYTTCTTCCAGCATTC . . Other 3′UTR . NCX1EX12 1298 A 0.99 G 0.01 0.03 ATAACCCCATTCAARAAGCACATCATCGT . . Other 3′UTR . NCX1EX12 1366 G 0.99 C 0.01 0.03 CGTTGCTTGGGATTSTCTGTCAGTTTTAT . . Other 3′UTR . NCX1EX12 1407 A 0.84 G 0.16 0.26 CCATGGCTTGCACARTCCTGTTCCAGTCA . . Other 3′UTR . NCX1EX12 1841 G 0.97 C 0.03 0.06 ACCCATTAATTCAGSAAGGCCAAGGAGAA . . Other 3′UTR . NCX1EX12 2099 T 0.94 C 0.06 0.11 GAAAGAAGCCAGGGYGACCAACGGGCCTT . . Other 3′UTR . NCX1EX12 2123 T 0.70 Del 0.30 0.42 GCCTTTAAAAGTGTTGTCTCCTCTACTTA . . Other 3′UTR . NCX1EX12 2614 T 0.96 C 0.04 0.08 TGTGATTACTATTTYCATGAGTAAAAGTG . . Other 3′UTR . NCX1EX12 2810 G 0.67 A 0.33 0.44 TTTATCTTTGACCGRCTTGCAGATAAATA . . Other 3′UTR . NCX1EX12 2832 C 0.99 G 0.01 0.03 ATAAATATATCTCTSCATTTTAAACCAAG . . Other 3′UTR . NCX1EX12 3079 A 0.66 C 0.34 0.45 TAAACATTAGAAAAMTTTTTGCACTCATT . . Other 3′UTR . NCX1EX12 3193 G 0.99 C 0.01 0.03 TTGAAAGCTTTTTGSTTTGTTTGCTTTTT . . Other 3′UTR . NCX1EX12 664 T 0.99 C 0.01 0.03 TCTCTCCAGGTTGAYAAATCCTTAAGGCT . . Other 3′UTR . NCX1EX12 709 A 0.94 G 0.06 0.10 TTGGTTTTGTTTTCRGTGGAGCTGGGGAG . . Other 3′UTR . NCX1EX12 948 G 0.89 A 0.11 0.20 AGCATGCTTCATCRTATTACCAAAGTTC . . Other 3′UTR . NCX1EX4 59 G 0.99 A 0.01 0.03 TAGAATATTTGACCRTGAGGAATATGAGA CGT CAT Nonsynonymous Arg His NCX1EX9 66 A 0.97 T 0.03 0.06 ACTGACCAGCAAAGWGGAAGAGGAGAGGC . . Other Intron . NETEX11 123 T 0.86 G 0.14 0.24 CGTCAGTCCTGCCTKCCTCCTGGTGTGTA TTC TGC Nonsynonymous Phe Cys NETEX12 81 T 0.93 C 0.07 0.13 TCACCTACGACGACYACATCTTCCCGCCC TAC CAC Nonsynonymous Tyr His NETEX13 50 G 0.93 A 0.07 0.12 GCCTATGGCATCACRCCAGAGAACGAGCA ACG ACA Synonymous Thr Thr NETEX14 29 G 0.93 C 0.07 0.14 TGTCTTTCTCTGCASTTGCAACACTGGCT . . Other Intron . NETEX5 121 A 0.93 C 0.07 0.12 CTCCAATGGCATCAMTGCCTACCTGCACA AAT ACT Nonsynonymous Asn Thr NETEX5 175 A 0.96 G 0.04 0.07 CACGGTCAGTGCTCRGTGACCACCAAGCC . . Other Intron . NETEX5 83 C 0.95 G 0.05 0.10 TTCGTGCTCCTGGTSCATGGCGTCACGCT GTC GTG Synonymous Val Val NETEX7 112 G 0.92 C 0.08 0.15 TCCTTGGTTACATGSCCCATGAACACAAG GCC CCC Nonsynonymous Ala Pro NETEX7 131 A 0.93 G 0.07 0.14 TGAACACAAGGTCARCATTGAGGATGTGG AAC AGC Nonsynonymous Asn Ser NETEX7 73 G 0.94 C 0.06 0.11 GTATCACCAGCTTCSTCTCTGGGTTCGCC GTC CTC Nonsynonymous Val Leu NETEX8 17 C 0.55 A 0.45 0.49 TGATGAGGTCCTTGMTGTTTCTTACAGGA . Other Intron . NETEX9 157 A 0.91 G 0.09 0.16 GTTCTGCATAACCARGGTGAGTAG0GGCT AAG AGG Nonsynonymous Lys Arg NETEX9 56 G 0.96 A 0.04 0.07 GAGGCTGTCATCACRGGCCTGGCAGATGA ACG ACA Synonymous Thr Thr NPYEX1 112 G 0.97 A 0.03 0.06 GCGCTGGCCGAGGCRTACCCCTCCAAGCC GCG GCA Synonymous Ala Ala NPYEX1 178 A 0.90 G 0.10 0.18 GCCAGATACTACTCRGCGCTGGGACACTA TCA TCG Synonymous Ser Ser NPYEX1 92 C 0.95 A 0.05 0.10 GCCCTGCTCGTGTGCMTGGGTGCGCTGGCC CTG ATG Nonsynonymous Leu Met NPYEX2 45 T 0.40 C 0.60 0.48 TATGGAAAACGATCYAGCCCAGAGACACT TCT TCC Synonymous Ser Ser NPYEX3 100 A 0.96 G 0.04 0.08 CCTATTTTCAGCCCRTATTTCATCGTGTA . . Other 3′UTR . NPYEX3 78 G 0.91 T 0.09 0.16 GAGACTTGCTCTCTKGCCTTTTCCTATTT . . Other 3′UTR . NPYR1EX2 144 T 0.94 G 0.06 0.12 AACATACTGTCCATKTGTCTAAAATAATC . . Other 5′UTR . NPYR1EX3 451 A 0.94 C 0.06 0.12 AGTCGCATTTAAAAMAATCAACAACAATG AAA ACA Nonsynonymous Lys Thr PG1SEX1 196 C 0.99 A 0.01 0.03 GCATATAATCTCTTMCTTCCTGTAAATCC . . Other Promoter . PG1SEX1 396 T 0.82 G 0.18 0.30 TGCGGGGAGCAGGGKTTCTCCCAGAGCGC . . Other Promoter . PG1SEX1 419 G 0.95 A 0.05 0.09 GAGCGCCCCGGTCCRACCCCTGCGGACCT . . Other Promoter . PG1SEX1 568 C 0.93 T 0.07 0.12 CCCCGCCAGCCCCGYCAGCCCCGCCAGCC . . Other 5′UTR . PG1SEX1 636 C 0.98 T 0.02 0.04 CACTGTTGCTGCTGYTGCTACTGAGCCGC CTG TTG Synonymous Leu Leu PG1SEX10 1255 C 0.95 T 0.05 0.09 TTCTGCATTCACAGYGSCTCCTGGRCCTG . . Other 3′UTR . PG1SEX10 149 C 0.99 T 0.01 0.03 GCTACCGCATCCGCYCATGACACAGGGAG CCA TCA Nonsynonymous Pro Ser PG1SEX10 1500 C 0.84 T 0.16 0.28 CCTGGCCAACATGGYGAAACCCCGTCTCT . . Other 3′UTR . PG1SEX10 1505 C 0.97 T 0.03 0.06 CCAACATGGCGAAAYCCCGTCTCTACTAA . . Other 3′UTR . PG1SEX10 1521 C 0.94 A 0.06 0.11 CCGTCTCTACTAAAMATAAAAAAATTAGT . . Other 3′UTR . PG1SEX10 1525 A 0.66 C 0.34 0.45 CTCTACTAAACATAMAAAAATTAGTCAGG . . Other 3′UTR . PG1SEX10 1544 G 0.65 C 0.35 0.45 ATTAGTCAGGTGTGSCGGTGCCGTGCCTG . . Other 3′UTR . PG1SEX10 1760 T 0.99 G 0.01 0.02 TTATGATGCTATTTKTATTAATATAAAGT . . Other 3′UTR . PG1SEX10 1776 C 0.99 T 0.01 0.02 ATTAATATAAAGTCYTGTTTATTGAGACC . . Other 3′UTR . PG1SEX10 1852 A 0.91 G 0.09 0.16 CAGCATCTCTATGARGAGAAGGAGGGTTG . . Other 3′UTR . PG1SEX10 2474 C 0.90 T 0.10 0.19 CGCAGGCTGCAACCYTGGTGTGCTGGGCG . . Other 3′UTR . PG1SEX10 2636 T 0.48 C 0.52 0.50 ACTCAAGGAAAAGAYGTGCTCCCACCAGG . . Other 3′UTR . PG1SEX10 270 T 0.99 C 0.01 0.03 GCTAGCATTACCACYTCCCTGCTTTTCTC . . Other 3′UTR . PG1SEX10 2967 C 0.98 T 0.02 0.04 TTGAGATGGAGTCTYGCTCTGCTGCCCAG . . Other 3′UTR . PG1SEX10 2974 C 0.52 T 0.48 0.50 GGAGTCTCGCTCTGYTGCCCAGGCTAGAG . . Other 3′UTR . PG1SEX10 3009 T 0.91 C 0.09 0.17 GGCGTGATCTCGGCYCACTGCAAGCTCTG . . Other 3′UTR . PG1SEX10 3022 T 0.77 C 0.23 0.35 CTCACTGCAAGCTCYGCCTCCCGTGTTCA . . Other 3′UTR . PG1SEX10 3061 T 0.69 C 0.31 0.43 CTGCCTCAGCCTCCYGAGTAGCTGGGACT . . Other 3′UTR . PG1SEX10 308 G 0.95 T 0.05 0.10 TGGGTCCAGGGGAGKGAAAAGCTAAGAGG . . Other 3′UTR . PG1SEX10 3082 A 0.88 G 0.12 0.21 CTGGGACTACAGGCRCCCGCCACCACACC . . Other 3′UTR . PG1SEX10 3139 A 0.88 G 0.13 0.22 TGGGATTTCACCGTRTTAGCCAGGATGGT . . Other 3′UTR . PG1SEX10 3140 T 0.82 C 0.18 0.30 GGGATTTCACCGTAYTAGCCAGGATGGTC . . Other 3′UTR . PG1SEX10 3186 C 0.90 T 0.10 0.17 TGATCTGCCCGCCTYGGCCTCCCAAAGTG . . Other 3′UTR . PG1SEX10 3214 T 0.88 C 0.12 0.21 GCTGGGATTACAGGYGTGAGCCACCGC0C . . Other 3′UTR . PG1SEX10 3217 G 0.88 A 0.12 0.20 GGGATTACAGGTGTRAGCCACCGCGCCCA . . Other 3′UTR . PG1SEX10 3244 A 0.98 C 0.02 0.04 CAGCCAAGAATAAAMTACTCTTAAGTTGA . . Other 3′UTR . PG1SEX10 3339 C 0.99 T 0.01 0.03 GTTTACCAAATATTYTCCTTTAAACAGAC . . Other 3′UTR . PG1SEX10 3419 G 0.95 A 0.05 0.10 GCCCAGGCTGGAGTRCAATGGCACGA1CI . . Other 3′UTR . PG1SEX10 3540 A 0.98 T 0.02 0.04 CAACTGGTTTTTGTWTTTTTAGTAGAGAC . . Other 3′UTR . PG1SEX10 3651 G 0.91 A 0.09 0.16 GATTACAGGCATGARCCACCATGCCCGGC . . Other 3′UTR PG1SEX10 3663 G 0.94 A 0.06 0.11 GAGCCACCATGCCCRGCCTAAACTTTGTT . . Other 3′UTR . PG1SEX10 3774 C 0.85 T 0.15 0.26 ATGAAAAATAAATTYGCTGGGGAAGGGGG . . Other 3′UTR . PG1SEX10 3840 C 0.73 T 0.27 0.40 TCTCTGTTACAAAAYGAGATAAGCAAGTR . . Other 3′UTR . PG1SEX10 400 C 0.98 T 0.02 0.05 TCAGGCTFFGTCTGYTCCCAAITCACCTC . . Other 3′UTR PGISEX10 4074 A 0.96 G 0.04 0.07 GATTTTAATGATTARAAAGAAIAAACACA . . Other 3′UTR . PG1SEX10 454 T 0.98 C 0.02 0.04 AAATGCTATTCAGAYAAGGCAGAACTAGG . . Other 3′UTR . PG1SEX10 573 G 0.99 T 0.01 0.02 GGATGCTGGCCACAKAAAGGCCACTCAGG . . Other 3′UTR . PG1SEX10 578 G 0.99 A 0.01 0.02 CTGGCCACAGAAAGRCCACTCAGGATGTC . . Other 3′UTR . PG1SEX10 948 C 0.99 A 0.01 0.02 CTCCTTAGACTGATMAAGCCAAAAAAGAA . . Other 3′UTR . PG1SEX3 165 T 0.98 A 0.02 0.05 CATTACAGCCCCAGWGATGAAAAGGCCAG AGT AGA Nonsynonymous Ser Arg PG1SEX3 69 6 0.98 T 0.02 0.05 TCCTACGACGCGGTKGTGTGGGAGCCTCG GTG GTT Synonymous Val Val PG1SEX4 143 T 0.96 C 0.04 0.07 ACTTCTCCIACAGCYICCTGCTCAGGTGA TTC CTC Nonsynonymous Phe Leu PG1SEX4 93 A 0.99 C 0.01 0.02 GGGCGATGCTACAGMAGCAGGCAGTGGCT GAA GCA Nonsynonymous Glu Ala PG1SEX5 79 C 0.99 T 0.01 0.02 CAGGCCCAGGACCGYGTCCACTCAGCTGA CGC CGT Synonymous Arg Arg PG1SEX6 35 C 0.98 T 0.02 0.05 GCAGTGTCAAAAGTYGCCTGTGGAAGCTG CGC TGC Nonsynonymous Arg Cys PG1SEX6 52 A 0.98 G 0.02 0.05 CTGTGGAAGCTGCTRTCCCCAGCCAGGCT CTA CTG Synonymous Leu Leu PG1SEX6 97 G 0.90 A 0.10 0.18 CGGAGCAAATGGCTRGAGAGTTACCTGCT CTG CTA Synonymous Leu Leu PG1SEX8 102 A 0.26 C 0.74 0.38 CCATGGCAGACGGGMGAGAATTCAACCTG AGA CGA Synonymous Arg Arg PG1SEX9 42 C 0.99 T 0.01 0.02 TTCCTGAACCCTGAYGGATCAGAGAAGAA GAC GAT Synonymous Asp Asp PLA2AEX1 302 T 0.96 A 0.04 0.07 CCCCGCAGTCTCAAWTCGAGGTTCCCAGT . . Other Intron . PLA2AEX2 118 C 0.95 T 0.05 0.10 GGGAGTGACCCCTTYTTGGAATACAACAA TTC TTT Synonymous Phe Phe PLA2AEX2 42 A 0.95 C 0.05 0.10 CAGTGGCCGCCGCCGMCAGCGGCATCAGCC GAC GCC Nonsynonymous Asp Ala PLA2AEX3 103 A 0.95 C 0.05 0.10 ATTTCTGCTGGACAMCCCGTACACCCACA AAC ACC Nonsynonymous Asn Thr PLA2AEX3 104 C 0.89 A 0.11 0.20 TTTCTGCTGGACAAMCCGTACACCCACAC AAC AAA Nonsynonymous Asn Lys PLA2AEX3 131 G 0.91 A 0.09 0.17 ACCTATTCATACTCRTGCTCTGGCTCGGC TCG TCA Synonymous Ser Ser PLA2AEX3 59 C 0.60 T 0.40 0.48CATGACAACTGCTAYGACCAGGCCAAGAA TAC TAT Synonymous Tyr Tyr PNMTEX3 181 A 0.89 T0 11 0.19 GCTTGGAGGCTGTOWOCCCAGATCTTGCC AGC TGC Nonsynonymous Ser Cys PNMTEX3 251 T 0.89 A 0.11 0.19 GCCTGGGGGGCACCWCCTCCTCATCGGGG CTC CAC Nonsynonymous Leu His PNMTEX3 269 T 0.93 A 0.08 0.14 CCTCATCGGGGCCCWGGAGGAGTCGTGGT CTG CAG Nonsynonymous Leu Gln PNMTEX3 380 G 0.96 A 0.04 0.08 GGTCCGGGACCTCCRCACCTATATCATGC CGC CAC Nonsynonymous Arg His PNMTEX3 445 T 0.96 A 0.04 0.08 GCGTCTTCTTCGCCWGGGCTCAGAAGGTT TGG AGG Nonsynonymous Trp Arg PNMTEX3 554 C 0.88 T 0.13 0.22 AAATAATACCCTGCYGCTGCGGTCAGTGC . . Other 3′UTR . PNMTEX3 75 A 0.96 G 0.04 0.08 CGAGCCAGGGTGAARCGGGTCCTGCCCAT AAA AAG Synonymous Lys Lys PPGLGCEX1 133 G 0.98 A 0.02 0.05 CAGGTATTAAATCCRTAGTCTCGAACTAA . . Other Intron . PPGLGCEX1 44 C 0.99 T 0.01 0.03 ATGAAAAGCATTTAYTTTGTGGCTGGATT TAC TAT Synonymous Tyr Tyr PPGLGCEX1 560 C 0.99 T 0.01 0.03 AAGTACTCAAAATTYCTCTGTCCAAAGAA . . Other Intron . PPGLGCEX1 635 T 0.92 A 0.08 0.15 ACGTAAACTGTACAWAAATATCTCTTGGC . . Other Intron . PPGLGCEX2 196 G 0.93 A 0.07 0.14 AGAGGAACAGGTAARAGTCTAAGCCTGGC . . Other Intron . PPGLGCEX3 119 C 0.99 T 0.01 0.02 TTTGGAAGGCCAAGYTGCCAAGGAATTCA GAT GTT Nonsynonymous Ala Val PPGLGCEX4 447 A 0.99 T 0.01 0.02 AAATGAAACATGGGWAATGTTACATCATT . . Other 3′UTR . PPGLGCEX4 571 C 0.96 T 0.04 0.07 TAGTGAGAACTGGAYACCGAAAAATACTT . . Other 3′UTR . PPGLGCEX4 615 T 0.70 C 0.30 0.42 GATTTTTTAATAATYATTCATAATTGTTT . . Other 3′UTR . PPGLGCEX4 672 T 0.98 C 0.02 0.04 AAATAATCTTTAAAYGAAAATATTTTAAG . . Other 3′UTR . PPTHREX1 106 C 0.96 G 0.04 0.08 CCCCGGATCCCGGASCCATCCTGTGGAGC . . Other 5′UTR . PPTHREX1 36 G 0.99 C 0.01 0.02 AGAGGGCTCGCCAGSCGCCCGGGGTCCTC . . Other 5′UTR . PPTHREX2 19 G 0.95 A 0.05 0.09 AACCCAGACGCCGCRATGCCCGGCCCTTG . . Other 5′UTR . PPTHREX2 41 C 0.96 G 0.04 0.08 GCCCTTGGTTGCTGSTCGCTCTGGCTTTG CTC GTC Nonsynonymous Leu Val PPTHREX2 79 C 0.99 G 0.01 0.02 CTGACCGGTGTCCCSOOCGGCCGTGCTCA CCC CCG Synonymous Pro Pro PPTHREX3 1234 C 0.97 G 0.03 0.06 TAATGATAATAAAASCTGCATCCAGATAA . . Other 3′UTR . . PPTHREX3 185 T 0.91 C 0.09 0.16T CATGGTCAGTCGAYGTAACCCAGCACAA GAT GAC Synonymous Asp Asp PPTHREX3 401 G 0.95 A 0.05 0.09 CCCTGTGGGCCCCARGGAGCCTATGGTCA CAG CAA Synonymous Gln Gln PPTHREX3 425 C 0.90 T 0.10 0.18 GGTCAAGCGGGCCTYCTGCTGGGGCTCCT CTC CTT Synonymous Leu Leu PPTHREX3 512 G 0.90 A 0.10 0.19 GCAGCCTGGGTCAGRGAGCCCCTGGAGGA AGG AGA Synonymous Arg Arg PPTHREX3 576 A 0.91 G 0.09 0.16 CTAAGGATGTCTTGRGCCCTGTGTGCCCC . . Other 3′UTR . PPTHREX3 895 C 0.99 A 0.01 0.03 AGCCCCTGGGAGGGMAGCCAGTGAGGGTG . . Other 3′UTR . PPTHREX3 963 G 0.98 C 0.02 0.05 CCCCTCCCCAACCTSGCAGGATTCTCCAT . . Other 3′UTR . PTGER3EX1 232 C 0.96 T 0.04 0.08 TGCGGCTCTCTGGAYGCCATCCCCTCCTC . . Other 5′UTR . PTGER3EX1 371 C 0.96 G 0.04 0.07 GCGCGGGGCAACCTSACGCGCCCTCCAGG CTC CTG Synonymous Leu Leu PTGER3EX1 765 A 0.98 T 0.02 0.04 GGTATGCGAGCCACWTGAAGACGCGTGCC ATG TTG Nonsynonymous Met Leu PTGER3EX1 878 G 0.90 T 0.10 0.18 CAGTGGCCCGGGACKTGGTGCTTCATCAG ACG ACT Synonymous Thr Thr PTGER3EX10 206 T 0.98 C 0.03 0.05 ACATGTTTTTGTACYTTTACTATATCTAC . . Other 3′UTR . PTGER3EX10 281 A 0.85 G 0.15 0.26 GCGTATACATTATCRTATGTAAAATTTGC . . Other 3′UTR . PTOER3EX2 1293 T 0.38 C 0.62 047 ACTAAAATGTTTTTYCTACAGTCTACATG . . Other Intron . PTGER3EX2 1295 T 0.86 C 0.14 0.23 TAAAATGTTTTTTCYACAGTCTACATGAA . . Other Intron . PTGER3EX2 1393 T 0.84 C 0.16 0.27 GCACTTCTTAAAAAYGTCTCCCCACCAAA . . Other Intron . PTGER3EX2 1403 C 0.98 A 0.03 0.05 AAAATGTCTCCCCAMCAAACATAGTAATC . . Other Intron . PTGER3EX2 1614 T 0.94 C 0.06 0.11 TAAAGAATTAATTTYGATAGGTACAATAT . . Other Intron . PTGER3EX2 1719 G 0.98 C 0.03 0.05 TGGAGACAAAATCTSTTGAGAGTGCTTAT . . Other Intron . PTGER3EX2 2153 A 0.99 G 0.01 0.03 AGTCCATCAGGCTGRTAAAGTGAATTATT . . Other Intron . PTGER3EX2 2517 T 0.92 C 0.08 0.15 TAGGCATTCGTTAGYATGGGGAAACCTGA . . Other Intron . PTOER3EX2 3069 T 0.93 C 0.08 0.14 TAGTGCTGTATATAYCCCAAGATATTTTA . . Other Intron . PTGER3EX2 3101 A 0.91 G 0.09 0.17 AAATGTAAGTGTTTRATCATGCCAGATTT . . Other Intron . PTGER3EX2 326 T 0.91 A 0.09 0.17 ATATCGCTAAACCTWACTGTGAATTTAGG . . Other Intron . PTGER3EX2 3282 A 0.98 G 0.03 0.05 ACTAAAAACTGGCARACAGTATTTTAATA . . Other Intron . PTGER3EX2 3382 T 0.63 C 0.37 0.47 TTTTTATAATTTTGYTCTTTTTGACTCCA . . Other Intron . PTGER3EX2 557 G 0.99 T 0.01 0.03 TATAAATGATCTTGKTCTATTGGGGAGCG . . Other Intron . PTGER3EX2 628 T 0.83 C 0.17 0.28 AACCACATACATCAYTGAAGACAAGGGAT . . Other Intron . PTGER3EX2 769 T 0.91 A 0.09 0.17 GTATAATGTATTTAWAATATTCATCGATA . . Other Intron . PTGER3EX2 787 T 0.94 G 0.06 0.12 ATTCATCGATACCAKTATTCAAATATTGC . . Other Intron . PTGER3EX2 805 A 0.91 C 0.09 0.16 TCAAATATTGCTCAMTACAGCAAATTAGC . . Other Intron . PTGER3EX2 850 G 0.98 A 0.02 0.04 TTTAAGTTTACTTGRATTGATAATTAGGT . . Other Intron . PTGER3EX2 852 T 0.62 A 0.38 0.47 TAAGTTTACTTGGAWTGATAATTAGGTTT . . Other Intron . PTGER3EX2 855 A 0.98 T 0.02 0.04 GTTTACTTGGATTGWTAATTAGGTTTACT . . Other Intron . PTGER3EX3 76 C 0.94 T 0.06 0.12 CTCCACCTCCTTACYCTGCCAGT0TTCCT CCC CTC Nonsynonymous Pro Leu PTGER3EX3 80 C 0.93 T 0.07 0.13 ACCTCCTTACCCTGYCAGTGTTCCTCAAC TGC TGT Synonymous Cys Cys PTGER3EX4 719 G 0.84 T 0.16 0.27 TCTAAGCYTTTGATKACAAAGGAGTGATG . . Other 3′UTR . PTGER3EX4 94 C 0.98 T 0.03 0.05 TTTGCATATTTCTTYCCACCTGAGAAGGA . . Other 3′UTR . PTGER3EX6 197 A 0.98 G 0.03 0.05 GAGTGCTGTGTTTTRAAAAAGCAAGCTCC . . Other 3′UTR . PTGER3EX6 300 G 0.91 A 0.09 0.16 GAGATTACCAGCAARCCAGGTCATTTCCG . . Other 3′UTR . PTGER3EX6 387 T 0.98 A 0.03 0.05 CCAATTTAGACTTAWAGTAAGAATAGCAC . . Other 3′UTR . PIGER3EX7 85 A 0.98 G 0.02 0.04 TTGGTGCAGTTCTCRTGATAGTGAGTGAG CAT CGT Nonsynonymous His Arg PTGER3EX8 116 C 0.83 T 0.17 0.28 GATTTGTCCTTTCCYGCCATGTCTTCATC CCC CCT Synonymous Pro Pro PTGER3EX9 16 T 0.94 C 0.06 0.12 TGCCTATCACATAAYAGGAGAACCCTGCA . . Other Intron . RENEX1 80 A T GGAAGCATGGATGGWTGGAGAAGGATGCC GGA GGT Synonymous Gly Gly RENEX2 135 A 0.76 C 0.24 0.37 ATGAAGAGGCTGACMCTTGGCAACACCAC ACA ACC Synonymous Thr Thr RENEX4 151 A 0.97 G 0.03 0.05 GACATCATCACCGTRAGTTGGGCCGCCCT . . Other Intron . RENEX4 165 T 0.66 G 0.34 0.45 AAGTTGGGCCGCCCKAGGTCATCTGCCCC . . Other Intron . RENEX9 138 G 0.99 A 0.01 0.03 TTCAGGTGAGGTTCRAGTCGGCCCCCTCG . . Other Intron . SAEX1 167 T 0.91 C 0.09 0.17 GTTTTGGGCCAGTCYTGCTCCTCCGGATT Other Promoter . SAEX1 76 G 0.98 T 0.03 0.05 ATTACCTGTAAGAGKAACCGCTGGGAGTC . . Synonymous Other Promoter SAEX11 143 C 0.99 T 0.01 0.02 AGAGCAGATGATGTYATATTATCCTCTGG GTC GTT Synonymous Val Val SAEX2 54 T 0.94 C 0.06 0.12 CTCTGTGCAAATCCYGAGTGCTAAAGCTT . . Other 5′UTR . SAEX3 109 T 0.99 C 0.01 0.03 GAGTTTTGAGGAACYGGGATCTCTGTCCA CTG CCG Nonsynonymous Leu Pro SAEX4 187 T 0.82 C 0.18 0.30 CACTCCAAGCTGATYGTATCAGAGAACTC ATT ATC Synonymous Val Val SAEX5 182 T 0.14 C 0.86 0.24 TGGAAGGTATACTTYCACAAAAGTGCAGC . . Other Intron . SAEX8 111 G 0.97 C 0.03 0.06 AAATGGAGAAACAASACGGGCCTGGATAT AAG AAC Nonsynonymous Lys Asn SAEX9 101 C 0.98 T 0.03 0.05 CCTTCTCCTGCTTTYGATGTTAAGGTTTG TTC TTT Synonymous Phe Phe SCNN1GEX1 167 G 0.48 A 0.52 0.50 GGTGGCCCAGGAAGRCGCAGCGCGGCCGG . . Other Promoter . SCNN1GEX1 236 G 0.81 T 0.19 0.30 TGAAGTCGTGGCCCKCTCCGGGCGGTCTC . . Other Promoter . . SCNN1GEX1 498 G 0.99 A 0.01 0.02 TGGAGCGGATGCCGRGCGCCAGGGCGTCG . . Other Intron . . SCNN1GEX1 552 C 0.70 G 0.30 0.42 GAGCCAGCATCAGCSGGTGGCGGCTTCCC . . Other Intron . SCNN1GEX1 553 G 0.99 A 0.01 0.02 AGCCAGCATCAGCCRGTGGCGGCTTCCCG . . Other Intron . SCNN1GEX12 1016 T 0.80 A 0.20 0.32 AGATCAGAGTGCCGWGGTGGAGGTCTGGG . . Other 3′UTR . SCNN1GEX12 1085 A 0.75 G 0.25 0.38 CAGGAGATGGATTTRGTTATTCAATTTTG . . Other 3′UTR . SCNN1GEX12 407 C 0.78 G 0.22 0.34 ATGCTGGATGAGCTSTGAGGCAGGGTTGA CTC CTG Synonymous Leu Leu SCNN1GEX12 454 G 0.99 T 0.01 0.02 GACCACCAGCCATGKTCTAAGGACATGGA . . Other 3′UTR . SCNN1GEX12 485 G 0.99 A 0.01 0.02 GGGTGCCCCCAGACRTGTGCACAGGGGAC . . Other 3′UTR . SCNN10EX12 569 T 0.86 G 0.14 0.24 CGCAAGATGGGGCCKGGGCATGCGCAGGA . . Other 3′UTR . SCNNIGEX12 646 C 0.80 T 0.20 0.32 ATAAATCCCGGGACYTGAACTATTAGCAC . . Other 3′UTR . SCNN1GEX12 678 G 0.80 A 0.20 0.32 ACTAGAGACTGGGARCCGAGGCAGTGGTG . . Other 3′UTR . SCNN1GEX12 982 A 0.76 G 0.24 0.37 GAGAACTGGCCCAGRGCCCTTGGAGTGTT . . Other 3′UTR . SCNN1GEX2 219 G 0.92 T 0.08 0.14 TCGTGGTGTCCCGCKGCCGTCTGCGCCGC GGC TGC Nonsynonymous Gly Cys SCNN1GEX2 26 G 0.16 C 0.84 0.27 TCTTCTTTGCCCCTSCAGCACGCCCGTCC . . Other Intron . SCNN1GEX2 43 G 0.36 A 0.64 0.46 GCACGCCCGTCCTCRGAGTCCCGTCCTCA . . Other 5′UTR SCNN1GEX3 186 T 0.79 C 0.21 0.34 TTCTCCCACCGGATYCCGCTGCTGATCTT ATT ATC Synonymous Ile Ile SCNN1GEX3 259 G 0.94 A 0.06 0.12 GGAAGCGGAAAGTCRGCGGTAGCATCATT GGC AGC Nonsynonymous Gly Ser SCNN1GEX3 261 C 0.91 T 0.09 0.16 AAGCGGAAAGTCGGYGGTAGCATCATTCA GGC GGT Synonymous Gly Gly SCNN1GEX3 301 G 0.97 A 0.03 0.06 ATGTCATGCACATCRAGTCCAAGCAAGTG GAG AAG Nonsynonymous Glu Lys SCNN1GEX3 99 T 0.73 C 0.27 0.40 CTGAAGTCCCTGTAYGGCTTTCCAGAGTC TAT TAC Synonymous Tyr Tyr SCNN1GEX4 47 C 0.96 T 0.04 0.07 TCAAATGACACCTCYGACTGTGCCACCTA TCC TCT Synonymous Ser Ser SCNN1GEX7 142 G 0.70 A 0.30 0.42 GGTAACAGATTGGCRGGGGCACCCAGCCC . . Other Intron . TBXA2REX1 518 T 0.89 A 0.11 0.20 GCTGGGCCCGCCCCWGGTCACAGCCAGAC . . Other 5′UTR . TBXA2REX1B 130 T 0.80 C 0.20 0.32 CTCAGCCTCCCGAGYAGCTGGGATTACAG . . Other 5′UTR . TBXA2REX2 292 T 0.98 A 0.02 0.04 TCCTCACCTTCCTCWGCGGCCTCGTCCTC TGC AGC Nonsynonymous Cys Ser TBXA2REX2 329 T 0.98 A 0.03 0.05 CCTGGGGCTGCTGGWGACCGGTACCATCG GTG GAG Nonsynonymous Val Glu TBXA2REX2 333 C 0.96 T 0.04 0.08 GGGCTGCTGGTGACYGGTACCATCGTGGT ACC ACT Synonymous Thr Thr TBXA2REX2 371 A 0.99 T 0.01 0.03 CGCCGCGCTCITCGWGTGGCACGCCGTGG GAG GTG Nonsynonymous Glu Val TBXA2REX2 390 T 0.94 A 0.06 0 12 CACGCCGTGGACCCWGGCTGCCGTCTCTG CCT CCA Synonymous Pro Pro TBXA2REX2 525 G 0.95 A 0.05 0.10 CCGGCGGTCGCCTCRCAGCGCCGCGCCTG TCG TCA Synonymous Ser Ser TBXA2REX2 568 G 0.99 A 0.01 0.02 TGGTGTGGGCGGCCRCGCTGGCGCTGGGC GCG ACG Nonsynonymous Ala Thr TBXA2REX2 617 T 0.98 A 0.03 0.05 GGGTCGCTACACCGWGCAATACCCGGGGT GTG GAG Nonsynonymous Val Glu TBXA2REX2 739 G 0.96 A 0.04 0.07 TCCTGCTGAACACGRTCAGCGTGGCCACC GTC ATC Nonsynonymous Val Ile TBXA2REX2 852 C 0.98 A 0.02 0.04 ATCATGGTGGTGGCMAGCGTGTGTTGGCT GCC GCA Synonymous Ala Ala TBXA2REX3 145 T 0.36 C 0.64 0.46 GACCCCTGGGTGTAYATCCTGTTCCGCCG TAT TAC Synonymous Tyr Tyr TBXA2REX3 358 A 0.93 G 0.07 0.13 GGGGTGCTGGATGGRCAGTGGGCATCAGC . . Other 3′UTR . TBXA2REX3 528 A 0.89 G 0.11 0.19 AAGGGCATGCAGACRTTGGAAGAGGGTCT . . Other 3′UTR . TBXA2REX3 599 C 0.89 T 0.11 0.20 CCCAGGCTGGAGTGYAGTGGCGCAATCTC . . Other 3′UTR . TBXA2REX3 701 C 0.86 T 0.14 0.24 GGCGCGCGCCACCAYGCCCGGCTAATTTT . . Other 3′UTR . TBXA2REX3 904 A 0.70 G 0.30 0.42 TGGAGTACAGTGGCRCGATCTCGGCTCAC . . Other 3′UTR . TBXA2REX3 906 G 0.53 A 0.47 0.50 GAGTACAGTGGCACRATCTCGGCTCACTG . . Other 3′UTR . TBXA2REX3 953 G 0.39 C 0.61 0.47 TTCAAGCGATTCTCSTGCCTCAGCCTCCC . . Other 3′UTR . TBXASEX10 61 G 0.97 T 0.03 0.06 CAGCCTCGAGGAAGKCCTGCCCTATCTGG GGC GTC Nonsynonymous Gly Val TBXASEX10 98 G 0.93 A 0.07 0.14 ATTGCAGAGACGCTRAGGATGTACCCGCC CTG CTA Synonymous Leu Leu TBXASEX11 105 C 0.91 T 0.09 0.16 GTGCTAGAGATGGCYGTGGGTGCCCTGCA GCC GCT Synonymous Ala Ala TBXASEX11 152 C 0.99 A 0.01 0.03 GCCAAGCCCGGAGAMCTTCAACCCTGAAA ACC AAC Nonsynonymous Thr Asn TBXASEX11 49 C 0.98 G 0.02 0.05 CACGGGAGGCAGCTSAGGACTGCGAGGTG CAG GAG Synonymous Gln Glu TBXASEX11 73 C 0.99 T 0.01 0.02 AGGTGCTGGGGCAGYGCATCCCCGCAGGC CGC TGC Nonsynonymous Arg Cys TBXASEX11 88 G 0.90 A 0.10 0.18 GCATCCCCGCAGGCRCTGTGCTAGAGATG GCT ACT Nonsynonymous Ala Thr TBXASEX12 46 C 0.98 A 0.02 0.04 TCACGGCTGAGGCCMGGCAGCAGCACCGG CGG AGG Synonymous Arg Arg TBXASEX13 226 A 0.99 G 0.01 0.02 CCTGGCATGCAAGGRTAAGAGGTTCTTTT . . Other 3′UTR . TBXASEX4 130 C 0.99 T 0.01 0.03 CCAACAGAATGGTAYGTAGTTTTCTTTCC . . Other Intron . TBXASEX5 15 G 0.99 A 0.01 0.02 CTGACCCTCTGCTTRTTACTTCCCAACAG . . Other Intron . TBXASEX6 59 C 0.98 A 0.02 0.04 AGCCAAGCCTGCGAMCTTCTCCTGGCTCA GAC GAA Synonymous Asp Asp TBXASEX8 110 A 0.89 G 0.11 0.20 ATGGCTTTTTTAACRAACTCATTAGGAAT AAA GAA Nonsynonymous Lys Asp TBXASEX8 119 A 0.99 G 0.01 0.03 TTAACAAACTCATTRGGAATGTGATTGCC AGG GGG Nonsynonymous Arg Gly TBXASEX9 156 C 0.96 A 0.04 0.07 CGAACCCTTCCCGGMAACACCAGCCCAGC CAA AAA Nonsynonymous Gln Lys TBXASEX9 276 C 0.88 G 0.12 0.21 CTTTTGCCACCTACSTACTGGCCACCAAC CTA GTA Nonsynonymous Leu Val TRHREX1 56 G 0.44 C 0.56 0.49 TTCTGCAGAACTTASATGATAAGCAACGA . . Other Promoter . TRHREX1 84 T 0.98 C 0.02 0.04 ACAAAGCCAGCTGCYTCTAGACCCCTGGC . . Other Promoter . TRHREX2 147 C 0.99 A 0.01 0.03 GTCAGTGAACTGAAMCAAACACAGCTTCA AAC AAA Nonsynonymous Asn. Lys TRHREX2 240 A 0.99 G 0.01 0.03 GGCCTGGGCATTGTRGGCAACATCATGGT GTA GTG Synonymous Val Val TRHREX3 1161 T 0.58 C 0.42 0.49 TCCCACATGATGGGYGGAAAAAGGCAAAA . . Other 3′UTR . TRHREX3 1231 T 0.98 C 0.03 0.05 TTAAATTTGAAAAGYATAGTCAAGACAAA . . Other 3′UTR . TRHREX3 1540 T 0.97 A 0.03 0.06 TTCTTTTTTTGTTTWTCTCAAATGCTAGT . . Other 3′UTR . TRHREX3 1786 A 0.99 T 0.01 0.03 GAATCTCCGAGGGCWAAAATTGCCCTTGG . . Other 3′UTR . TRHREX3 1846 T 0.94 C 0.06 0.12 GTAGATCAAAAAAGYACCCATACCTTTAC . . Other 3′UTR . TRHREX3 2046 G 0.98 A 0.02 0.04 CCTCATTCTAGAGTRCGCTTTTTTTTTTT . . Other 3′UTR . TRHREX3 2175 A 0.97 G 0.03 0.06 ACCTGCATGACAGTRAGCAATCTATGTTA . . Other 3′GlR TRHREX3 2283 G 0.95 A 0.05 0.10 ACAAGCACATGTGTRTTTATAAACACATA . . Other 3′UTR . TRHREX3 377 T 0.95 C 0.05 0.10 GCCACAAAAGTGTCYTTTGATGACACCTG TCT TCC Synonymous Ser Ser TRHREX3 960 T 0.96 C 0.04 0.07 TAAGATTTTAGACAYACATGTTAACTGTA . . Other 3′UTR .

[0116] 2 TABLE 2 Base Ref Alt Heterozygosity Ref Alt Type of amino Ref amino Alt amino Gene/ExOn Position Allele Freq (P) Allele Freq (Q) (H) Sequence Tag Codon Codon acid change acid acid ACEEX13 138 C 0.81 T 0.19 0.30 CCTCTGCTGGTCCCYAGCCAGGAGGCATC CCC CCT Synonymous Pro Pro ACEEX17 52 A 0.20 G 0.80 0.32 AATGTGATGGCCACRTCCCGGAAATATGA ACA ACG Synonymous Thr Thr ADRB3EX1 416 T 0.90 C 0.10 0.18 TCGTGGCCATCGCCYGGACTCCGAGACTC TGG CGC Nonsynonymous Trp Arg AGTEX2 644 C 0.86 T 0.14 0.24 GCTGCTGCTGTCCAYGGTGGTGGGCGTGT ACG ATG Nonsynonymous Thr Met AGTEX2 827 T 0.10 C 0.90 0.18 TGGCTGCTCCCTGAYGGGAGCCAGTGTGG ATG ACT Nonsynonymous Mer Thr AGTEXP1 173 C 0.71 T 0.29 0.41 TGCTTGTGTGTTTTYCCCAGTGTCTATTA . . Other Promoter . AGTEXP2 203 G 0.86 A 0.14 0.24 CTCGACCCTGCACCRGCTCACTCTGTTCA . . Other Promoter . AGTEXP3 144 C 0.24 A 0.76 0.37 GCTATAAATAGGGCMTCGTGACCCGGCCA . . Other Promoter . ANPEX3 120 T 0.91 C 0.09 0.16 GTCTCTGCTGCATTYGTGTCATCTTGTTG . . Other 3′UTR . ANPEX3 33 T 0.80 C 0.20 0.32 TCTCTTTGCAGTACYGAAGATAACAGCCA TGA AGA Nonsynonymous Stop Arg ATIEX5 1138 A 0.93 G 0.07 0.13 AAGAAGCCTGCACCRTGTTTTGAGGTTGA CCA CCG Synonymous Pro Pro ATIEX5 1593 G 0.88 T 0.12 0.21 AAAGTTTTCGTGCCKGTTTTCAGCTATTA . . Other 3′UTR . ATIEX5 649 T 0.61 C 0.39 0.47 CAAAATTCAACCCTYCCGATAGGGCTGGG CTT CTC Synonymous Leu Leu MRLEX2 1504 C 0.89 T 0.11 0.20 CAAGAACCAGATGAYGGGAGCTATTACCC GAC GAT Synonymous Asp Asp MRLEX2 545 A 0.81 G 0.19 0.30 GCGTCATGCGCGCCRTTGTTAAAAGCCCT ATT GTT Nonsynonymous Ile Val NCXIEX12 3101 A 0.16 T 0.84 0.26 ACTCATTTTTTAGCWGTATTAGGAATGTC . . Other 3′UTR .

[0117] 3 TABLE 3 Gene/Exon Gene Name Table 1 AADD Alpha-Adducin ACE Angiotensin Converting Enzyme ADDB Beta Adducin ADDG Gamma Adducin ADORA2A A2a Adenosine Receptor ADRB3 Beta-3-Adrenergic Receptor ADROM (prepro)Adrenomedullin AEI Anion Exchanger AGT Angiotensinogen ALDRED Aldose Reductase ANPEX1 Atrial Natriuretic Factor APOA1 Apolipoprotein A-I APOA2 Apolipoprotein A-II APOA4 Apolipoprotein A-IV APOC1EX1 Apolipoprotein C-I APOC2 Apolipoprotein C-II APOC3 Apolipoprotein C-III APOC4 Apolipoprotein C-IV APOER2 Apolipoprotein E Receptor 2 AT1 Angiotensin II Receptor Type-1 AT2 Angiotensin II Receptor Type 2 AVP Arginine Vasopressin AVPR2 Arginine Vasopressin Receptor Type II BIR Beta Inward Rectifier Subunit (Pancreatic K Channel) BKRB2 B2-Bradykinin Receptor BNP Brain Natriuretic Protein BRS3 Bombesin Receptor Subtype-3 CAL/CGRP Calcitonin/Calcitonin Gene Related Peptide CHY Chymase CLCNKB Chloride Channel (Human Kidney - B) CNP C-Type Natriuretic Peptide COX1 Cyclooxygenase-1 COX2 Cyclooxygenase-2 CYP11B1 Cytochrome P-450 11 Beta 1 CYP11B2 Cytochrome P-450 11 Beta 2 DBH Dopamine Beta-Hydroxylase DD1R Dopamine D1 Receptor EDNRA Endothelin Receptor Subtype A EDNRB Endothelin Receptor Subtype B ELAM1 Endothelial Leukocyte Adhesion Molecule 1 ENDOTHEL Endothelin-2 ET1 Endothelin-1 GALNR Galanin Receptor GGR Glucagon Receptor GH1 Growth Hormone 1 GH2 Growth Hormone 2 GIPR Glucose Insulinotropic Peptide Receptor or Gastric Inhibitory Polypeptide Receptor GLUT2 Glucose Transporter 2 GLUT4 Glucose Transporter 4 GLUT5 Glucose Transport-Like 5 GNB3 G-Protein Beta-3 Chain GSY1 Glycogen Synthetase HAPT Haptoglobin HSD11K Hydroxysteroid Dehydrogenase 11 Beta Kidney Isozyme HSTSCGENE Homo sapiens Thiazide-Sensitive Cotransporter HUMAPNH1A Human Na/H Antiporter HUMGFAT Human Glutamine:Fructose-6-Phosphate Amidotransferase HUMGLTRN Human Glucose Transporter HUMGUANCYC Human Guanylate Cyclase IAPP Islet Amyloid Polypepode ICAM1 Intercellular Adhesion Molecule 1 ICAM2 Intercellular Adhesion Molecule 2 INS Insulin KALST Kallistatin KLK Kallilrein MRL Mineralocorticoid Receptor NCX1 Sodium-Calcium Exchanger NET Norepinephrine Transporter NPY Neuropeptide Y NPYR1 Neuropeptide Y Y1 Receptor PGIS Prostacyclin Synthase PLA2A Pancreatic Phospholipase A-2 PNMT Phenylethanolamine N-Methyltransferase PPGLUC Preproglucagon PPTHR Preprothyrotropin-Releasing Hormone PTGER3 Prostaglandin E Receptor EP3 Subtype REN Renin SA SA Gene Acetyl-CoA Synthetase Homologue ?? (a candidate gene for genetic hypertension SCNNIG Amiloride-Sensitive Epithelial Sodium Channel Gamma Subunit TBXA2R Thromboxane A2 Receptor TBXASO Thromboxane Synthase TRHR Thyrotropin-Releasing Hormone Receptor Table 2 ACE Angiotensin Converting Enzyme ADRB3 Beta-3-Adrenergic Receptor AGT Angiotensinogen ANP Atrial Natriuretic Factor AT1 Angiotensin II Receptor Type-1 MRL Mineralocorticoid Receptor NCX1 Sodium-Calcium Exchanger

Claims

1. A nucleic acid of between 10 and 100 bases comprising at least 10 contiguous nucleotides including a polymorphic site from a sequence shown in Table 1, column 8 or the complement thereof.

2. The nucleic acid of claim 1 that is DNA.

3. The nucleic acid of claim 1 that is RNA.

4. The nucleic acid of claim 1 that is less than 50 bases.

5. The nucleic acid of claim 1 that is less than 20 bases.

6. The nucleic acid of claim 1, wherein the polymorphic form occupying the polymorphic site is a reference base shown in Table 1, column 3.

7. The nucleic acid of claim 1, wherein the polymorphic form occupying the polymorphic site is an alternative base shown in Table 1, column 5.

8. The nucleic acid of claim 7, wherein the alternative base correlates with hypertension or susceptibility thereto.

9. The nucleic acid of claim 1, wherein the polymorphic site is one for which reference and alternative bases shown in columns 3 and 5 of Table 1 are respectively components of different codons encoding different amino acids.

10. The nucleic acid of claim 1, which is from a gene encoding a human angiotensin I receptor.

11. The nucleic acid of claim 1, which is from a gene encoding an angiotensin II receptor.

12. The nucleic acid of claim 1, which is from a gene encoding an atrial natriuretic peptide.

13. The nucleic acid of claim 1, which is from a gene encoding a &bgr;-3-adrenergic receptor.

14. The nucleic acid of claim 1, which is from a gene encoding a bradykinin receptor B2.

15. The nucleic acid of claim 1, which is from a gene encoding a mineralocorticoid receptor

16. The nucleic acid of claim 1, which is from a gene encoding a renin protein.

17. The nucleic acid of claim 1, which from a gene encoding an angiotensinogen protein.

18. The nucleic acid of claim 1, which from a gene encoding a sodium calcium ion channel.

19. The nucleic acid of claim 1, which is from a gene encoding an angiotensin converting protein.

20. The nucleic acid of claim 1, which is from a gene encoding an angiotensin converting protein.

21. Allele-specific oligonucleotide that hybridizes to a sequence including a polymorphic site shown in Table 1 or the complement thereof.

22. The allele-specific oligonucleotide of claim 21 that is a probe.

23. An isolated nucleic acid comprising a sequence of Table 1, column 8 or the complement thereof, wherein the polymorphic site within the sequence or its complement is occupied by a base other than the reference base show in Table 1, column 3.

24. A method of analyzing a nucleic acid, comprising:

obtaining the nucleic acid from an individual; and

determining a base occupying any one of the polymorphic sites shown in Table 1 or other polymorphic sites in equilibrium dislinkage therewith.

25. The method of claim 24, wherein the determining comprises determining a set of bases occupying a set of the polymorphic sites shown in Table 1.

26. The method of claim 25, wherein the nucleic acid is obtained from a plurality of individuals, and a base occupying one of the polymorphic positions is determined in each of the individuals, and the method further comprising testing each individual for the presence of a disease phenotype, and correlating the presence of the disease phenotype with the base.

27. The method of claim 24, wherein the determined base is correlated with susceptibility to hypertension.

28. A method of diagnosing a phenotype comprising:

determining which polymorphic form(s) are present in a sample from a subject at one or more polymorphic sites shown in Table 1;

diagnosing the presence of a phenotype correlated with the form(s) in the subject.

29. The method of claim 28, wherein the phenotype is hypertension.

30. A method of screening for a polymorphic site suitable for diagnosing a phenotype, comprising:

identifying a polymorphic site linked to a polymorphic site shown in Table 1, wherein a polymorphic form of the polymorphic site shown in Table 1 has been correlated with a phenotype; and

determining haplotypes in a population of individuals to indicate whether the linked polymorphic site has a polymorphic form in equlibrium dislinkage with the polymorphic form correlated with the phenotype.

31. The method of claim 30, wherein the polymorphic form of the polymorphic site shown in Table I has been correlated with hypertension.

32. The method of claim 30, wherein the linked polymorphic site and the polymorphic site shown in Table 1 are from the same gene.

33. A computer-readable storage medium for storing data for access by an application program being executed on a data processing system, comprising:

a data structure stored in the computer-readable storage medium, the data structure including information resident in a database used by the application program and including:

a plurality of records, each record of the plurality comprising information identifying a polymorphisms shown in Table 1.

34. The computer-readable storage medium of claim 33, wherein each record has a field identifying a base occupying a polymorphic site and a location of the polymorphic site.

35. The computer-readable storage medium of claim 33, wherein each record identifies a nucleic acid segment of between 10 and 100 bases from a fragment shown in Table 1 including a polymorphic site, or the complement of the segment.

36. The computer-readable storage medium of claim 33, comprising at least 10 records, each record comprising information identifying a different polymorphism shown in Table 1.

37. The computer-readable storage medium of claim 33, comprising at least 10 records, each record comprising information identifying a different polymorphism shown in Table 1.

38. A signal carrying data for access by an application program being executed on a data processing system, comprising:

a data structure encoded in the signal, said data structure including information resident in a database used by the application program and including:

a plurality of records, each record of the plurality comprising information identifying a polymorphism shown in Table 1