Human single nucleotide polymorphisms

Abstract

The invention provides nucleic acid segments of the human genome, particularly nucleic acid segments from genes including polymorphic sites. Allele-specific primers and probes hybridizing to regions flanking or containing these sites are also provided. The nucleic acids, primers and probes are used in applications such as phenotype correlations, forensics, paternity testing, medicine and genetic analysis.

Description

BACKGROUND OF THE INVENTION

[0002] The genomes of all organisms undergo spontaneous mutation in the course of their continuing evolution, generating variant forms of progenitor nucleic acid sequences (Gusella, Ann. Rev. Biochem. 55, 831-854 (1986)). The variant form may confer an evolutionary advantage or disadvantage relative to a progenitor form, or may be neutral. In some instances, a variant form confers a lethal disadvantage and is not transmitted to subsequent generations of the organism. In other instances, a variant form confers an evolutionary advantage to the species and is eventually incorporated into the DNA of many or most members of the species and effectively becomes the progenitor form. In many instances, both progenitor and variant form(s) survive and coexist in a species population. The coexistence of multiple forms of a sequence gives rise to polymorphisms.

[0003] Several different types of polymorphism have been reported. A restriction fragment length polymorphism (RFLP) is a variation in DNA sequence that alters the length of a restriction fragment (Botstein et al., Am. J. Hum. Genet. 32, 314-331 (1980)). The restriction fragment length polymorphism may create or delete a restriction site, thus changing the length of the restriction fragment. RFLPs have been widely used in human and animal genetic analyses (see WO 90/13668; WO 90/11369; Donis-Keller, Cell 51, 319-337 (1987); Lander et al., Genetics 121, 85-99 (1989)). When a heritable trait can be linked to a particular RFLP, the presence of the RFLP in an individual can be used to predict the likelihood that the animal will also exhibit the trait.

[0004] Other polymorphisms take the form of short tandem repeats (STRs) that include tandem di-, tri- and tetra-nucleotide repeated motifs. These tandem repeats are also referred to as variable number tandem repeat (VNTR) polymorphisms. VNTRs have been used in identity and paternity analysis (U.S. Pat. No. 5,075,217; Armour et al., FEBS Lett. 307, 113-115 (1992); Horn et al., WO 91/14003; Jeffreys, EP 370,719), and in a large number of genetic mapping studies.

[0005] Other polymorphisms take the form of single nucleotide variations between individuals of the same species. Such polymorphisms are far more frequent than RFLPs, STRs and VNTRs. Some single nucleotide polymorphisms (SNP) occur in protein-coding nucleic acid sequences (coding sequence SNP (cSNP)), in which case, one of the polymorphic forms may give rise to the expression of a defective or otherwise variant protein and, potentially, a genetic disease. Examples of genes in which polymorphisms within coding sequences give rise to genetic disease include β-globin (sickle cell anemia), apoE4 (Alzheimer's Disease), Factor V Leiden (thrombosis), and CFTR (cystic fibrosis). cSNPs can alter the codon sequence of the gene and therefore specify an alternative amino acid. Such changes are called “missense” when another amino acid is substituted, and “nonsense” when the alternative codon specifies a stop signal in protein translation. When the cSNP does not alter the amino acid specified the cSNP is called “silent”.

[0006] Other single nucleotide polymorphisms occur in noncoding regions. Some of these polymorphisms may also result in defective protein expression (e.g., as a result of defective splicing). Other single nucleotide polymorphisms have no phenotypic effects.

[0007] Single nucleotide polymorphisms can be used in the same manner as RFLPs and VNTRs, but offer several advantages. Single nucleotide polymorphisms occur with greater frequency and are spaced more uniformly throughout the genome than other forms of polymorphism. The greater frequency and uniformity of single nucleotide polymorphisms means that there is a greater probability that such a polymorphism will be found in close proximity to a genetic locus of interest than would be the case for other polymorphisms. The different forms of characterized single nucleotide polymorphisms are often easier to distinguish than other types of polymorphism (e.g., by use of assays employing allele-specific hybridization probes or primers).

[0008] Only a small percentage of the total repository of polymorphisms in humans and other organisms has been identified. The limited number of polymorphisms identified to date 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 DNA 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

[0009] Work described herein pertains to the identification of polymorphisms which can predispose individuals to disease, by resequencing large numbers of genes in a large number of individuals. Various genes from a number of individuals have been resequenced as described herein, and SNPs in these genes have been discovered (see the Table). Some of these SNPs are cSNPs which specify a different amino acid sequence (shown as mutation type “M” in the Table), some of the SNPs are silent cSNPs (shown as mutation type “S” in the Table), and some of these cSNPs specify a stop signal in protein translation (shown as an “N” in the “Mutation Type” column and an asterisk in the “Alt AA” column in the Table). Some of the identified SNPs were located in non-coding regions (indicated with a dash in the “Mutation Type” column in the Table).

[0010] The invention relates to a nucleic acid molecule which comprises a single nucleotide polymorphism at a specific location. In a particular embodiment the invention relates to the variant allele of a gene having a single nucleotide polymorphism, which variant allele differs from a reference allele by one nucleotide at the site(s) identified in the Table. Complements of these nucleic acid segments are also included. The segments can be DNA or RNA, and can be double- or single-stranded. Segments can be, for example, 5-10, 5-15, 10-20, 5-25, 10-30, 10-50 or 10-100 bases long.

[0011] The invention further provides allele-specific oligonucleotides that hybridize to a nucleic acid molecule comprising a single nucleotide polymorphism or to the complement of the nucleic acid molecule. These oligonucleotides can be probes or primers.

[0012] The invention further provides a method of analyzing a nucleic acid from an individual. The method allows the determination of whether the reference or variant base is present at any one of the polymorphic sites shown in the Table. Optionally, a set of bases occupying a set of the polymorphic sites shown in the Table is determined. This type of analysis can be performed on a number of individuals, who are also tested (previously, concurrently or subsequently) for the presence of a disease phenotype. The presence or absence of disease phenotype is then correlated with a base or set of bases present at the polymorphic site or sites in the individuals tested.

[0013] Thus, the invention further relates to a method of predicting the presence, absence, likelihood of the presence or absence, or severity of a particular phenotype or disorder associated with a particular genotype. The method comprises obtaining a nucleic acid sample from an individual and determining the identity of one or more bases (nucleotides) at specific (e.g., polymorphic) sites of nucleic acid molecules described herein, wherein the presence of a particular base at that site is correlated with a specified phenotype or disorder, thereby predicting the presence, absence, likelihood of the presence or absence, or severity of the phenotype or disorder in the individual.

DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention relates to a nucleic acid molecule which comprises a single nucleotide polymorphism (SNP) at a specific location. The nucleic acid molecule, e.g., a gene, which includes the SNP has at least two alleles, referred to herein as the reference allele and the variant allele. The reference allele (prototypical or wild type allele) has been designated arbitrarily and typically corresponds to the nucleotide sequence of the nucleic acid molecule which has been deposited with GenBank or TIGR under a given Accession number. The variant allele differs from the reference allele by one nucleotide at the site(s) identified in the Table. The present invention also relates to variant alleles of the described genes and to complements of the variant alleles. The invention further relates to portions of the variant alleles and portions of complements of the variant alleles which comprise (encompass) the site of the SNP and are at least 5 nucleotides in length. Portions can be, for example, 5-10, 5-15, 10-20, 5-25, 10-30, 10-50 or 10-100 bases long. For example, a portion of a variant allele which is 21 nucleotides in length includes the single nucleotide polymorphism (the nucleotide which differs from the reference allele at that site) and twenty additional nucleotides which flank the site in the variant allele. These additional nucleotides can be on one or both sides of the polymorphism. Polymorphisms which are the subject of this invention are defined in the Table with respect to the reference sequence deposited in GenBank or TIGR under the Accession number indicated.

[0015] For example, the invention relates to a portion of a gene (e.g., phosphatidylinositol 4-kinase (catalytic alpha peptide) (PIK4CA)) having a nucleotide sequence as deposited in GenBank or TIGR (e.g., under Accession No. L36151) comprising a single nucleotide polymorphism at a specific position (e.g., nucleotide 2749). The reference nucleotide for this polymorphic form of PIK4CA is shown in column 8 of the Table, and the variant nucleotide is shown in column 9 of the Table. In a preferred embodiment, the nucleic acid molecule of the invention comprises the variant (alternate) nucleotide at the polymorphic position. For example, the invention relates to a nucleic acid molecule which comprises the nucleic acid sequence shown in row 1, column 6, of the Table having an “A” at nucleotide position 2749. The nucleotide sequences of the invention can be double- or single-stranded.

[0016] The invention further provides allele-specific oligonucleotides that hybridize to a gene comprising a single nucleotide polymorphism or to the complement of the gene. Such oligonucleotides will hybridize to one polymorphic form of the nucleic acid molecules described herein but not to the other polymorphic form(s) of the sequence. Thus, such oligonucleotides can be used to determine the presence or absence of particular alleles of the polymorphic sequences described herein. These oligonucleotides can be probes or primers.

[0017] The invention further provides a method of analyzing a nucleic acid from an individual. The method determines which base is present at any one of the polymorphic sites shown in the Table. Optionally, a set of bases occupying a set of the polymorphic sites shown in the Table is determined. This type of analysis can be performed on a number of individuals, who are also tested (previously, concurrently or subsequently) for the presence of a disease phenotype. The presence or absence of disease phenotype is then correlated with a base or set of bases present at the polymorphic site or sites in the individuals tested.

[0018] Thus, the invention further relates to a method of predicting the presence, absence, likelihood of the presence or absence, or severity of a particular phenotype or disorder associated with a particular genotype. The method comprises obtaining a nucleic acid sample from an individual and determining the identity of one or more bases (nucleotides) at polymorphic sites of nucleic acid molecules described herein, wherein the presence of a particular base is correlated with a specified phenotype or disorder, thereby predicting the presence, absence, likelihood of the presence or absence, or severity of the phenotype or disorder in the individual. The correlation between a particular polymorphic form of a gene and a phenotype can thus be used in methods of diagnosis of that phenotype, as well as in the development of treatments for the phenotype.

DEFINITIONS

[0019] An oligonucleotide 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 oligonucleotides of the invention include segments of DNA, or their complements, which include any one of the polymorphic sites shown in the Table. The segments can be between 5 and 250 bases, and, in specific embodiments, are between 5-10, 5-20, 10-20, 10-50, 20-50 or 10-100 bases. For example, the segment can be 21 bases. 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 the Table.

[0020] As used herein, the terms “nucleotide”, “base” and “nucleic acid” are intended to be equivalent. The terms “nucleotide sequence”, “nucleic acid sequence”, “nucleic acid molecule” and “segment” are intended to be equivalent.

[0021] Hybridization probes are oligonucleotides which bind in a base-specific manner to a complementary strand of nucleic acid. Such probes include peptide nucleic acids, as described in Nielsen et al., Science 254, 1497-1500 (1991). Probes can be any length suitable for specific hybridization to the target nucleic acid sequence. The most appropriate length of the probe may vary depending upon the hybridization method in which it is being used; for example, particular lengths may be more appropriate for use in microfabricated arrays, while other lengths may be more suitable for use in classical hybridization methods. Such optimizations are known to the skilled artisan. Suitable probes and primers can range from about 5 nucleotides to about 30 nucleotides in length. For example, probes and primers can be 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 25, 26, 28 or 30 nucleotides in length. The probe or primer preferably overlaps at least one polymorphic site occupied by any of the possible variant nucleotides. The nucleotide sequence can correspond to the coding sequence of the allele or to the complement of the coding sequence of the allele.

[0022] As used herein, the term “primer” refers to a single-stranded oligonucleotide which acts as a point of initiation of template-directed DNA synthesis under appropriate conditions (e.g., 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 refers to 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.

[0023] As used herein, 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. It can be measured by percent recombination between the two genes, alleles, loci or genetic markers.

[0024] As used herein, 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 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 diallelic or biallelic polymorphism has two forms. A triallelic polymorphism has three forms.

[0025] Work described herein pertains to the resequencing of large numbers of genes in a large number of individuals to identify polymorphisms which can predispose individuals to disease. For example, polymorphisms in genes which are expressed in liver may predispose individuals to disorders of the liver.

[0026] By altering amino acid sequence, SNPs may alter the function of the encoded proteins. The discovery of the SNP facilitates biochemical analysis of the variants and the development of assays to characterize the variants and to screen for pharmaceutical that would interact directly with on or another form of the protein. SNPs (including silent SNPs) may also alter the regulation of the gene at the transcriptional or post-transcriptional level. SNPs (including silent SNPs) also enable the development of specific DNA, RNA, or protein-based diagnostics that detect the presence or absence of the polymorphism in particular conditions.

[0027] 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).

[0028] 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. Typically the polymorphic site is occupied by a base other than the reference base. For example, where the reference allele contains the base “T” at the polymorphic site, the altered allele can contain a “C”, “G” or “A” at the polymorphic site.

[0029] 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 NaPhosphate, 5 mM EDTA, pH 7.4) and a temperature of 25-30° C., or equivalent conditions, are suitable for allele-specific probe hybridizations. Equivalent conditions can be determined by varying one or more of the parameters given as an example, as known in the art, while maintaining a similar degree of identity or similarity between the target nucleotide sequence and the primer or probe used.

[0030] The term “isolated” is used herein to indicate that the material in question exists in a physical milieu distinct from that in which it occurs in nature. For example, an isolated nucleic acid of the invention may be substantially isolated with respect to the complex cellular milieu in which it naturally occurs. In some instances, the isolated material will form part of a composition (for example, a crude extract containing other substances), buffer system or reagent mix. In other circumstance, the material may be purified to essential homogeneity, for example as determined by PAGE or column chromatography such as HPLC. Preferably, an isolated nucleic acid comprises at least about 50, 80 or 90 percent (on a molar basis) of all macromolecular species present.

[0031] I. Novel Polymorphisms of the Invention

[0032] The novel polymorphisms of the invention are shown in the Table. Columns one and two show designations for the indicated polymorphism. Column three shows the Genbank or TIGR Accession number for the wild type (or reference) allele. Column four shows the location (nucleotide position) of the polymorphic site in the nucleic acid sequence with reference to the Genbank or TIGR sequence shown in column three. Column five shows common names for the gene in which the polymorphism is located. Column six shows the polymorphism and a portion of the 3′ and 5′ flanking sequence of the gene. Column seven shows the type of mutation; N, non-sense; S, silent; and M, missense. Columns eight and nine show the reference and alternate nucleotides, respectively, at the polymorphic site. Columns ten and eleven show the reference and alternate amino acids, respectively, encoded by the reference and variant, respectively, alleles.

[0033] II. Analysis of Polymorphisms

[0034] A. Preparation of Samples

[0035] 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. For example, if the target nucleic acid is a cytochrome P450, the liver is a suitable source.

[0036] 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.

[0037] 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.

[0038] B. Detection of Polymorphisms in Target DNA

[0039] There are two distinct types of analysis of target DNA for detecting polymorphisms. The first type of analysis, sometimes referred to as de novo characterization, is carried out to identify polymorphic sites not previously characterized (i.e., to identify new polymorphisms). This analysis compares target sequences in different individuals to identify points of variation, i.e., polymorphic sites. By analyzing groups of individuals representing the greatest ethnic diversity among humans and greatest breed and species variety in plants and animals, patterns characteristic of the most common alleles/haplotypes of the locus can be identified, and the frequencies of such alleles/haplotypes in the population can be determined. Additional allelic frequencies can be determined for subpopulations characterized by criteria such as geography, race, or gender. The de novo identification of polymorphisms of the invention is described in the Examples section.

[0040] The second type of analysis determines which form(s) of a characterized (known) polymorphism are present in individuals under test. There are a variety of suitable procedures, which are discussed in turn.

[0041] 1. Allele-Specific Probes

[0042] 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.

[0043] 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.

[0044] 2. Tiling Arrays

[0045] The polymorphisms can also be identified by hybridization to nucleic acid arrays, some examples of which are described in WO 95/11995. The same arrays or different arrays can be used for analysis of characterized polymorphisms. WO 95/11995 also describes subarrays that are optimized for detection of a variant form 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, except that the probes exhibit complementarity to the second reference sequence. The inclusion of a second group (or further groups) can be particularly 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 (e.g., two or more mutations within 9 to 21 bases).

[0046] 3. Allele-Specific Primers

[0047] 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 complementarity. 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, resulting in a detectable product which indicates 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 complementarity 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).

[0048] 4. Direct-Sequencing

[0049] 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)).

[0050] 5. Denaturing Gradient Gel Electrophoresis

[0051] 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.

[0052] 6. Single-Strand Conformation Polymorphism Analysis

[0053] 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 differences between alleles of target sequences.

[0054] 7. Single Base Extension

[0055] An alternative method for identifying and analyzing polymorphisms is based on single-base extension (SBE) of a fluorescently-labeled primer coupled with fluorescence resonance energy transfer (FRET) between the label of the added base and the label of the primer. Typically, the method, such as that described by Chen et al., (PNAS 94:10756-61 (1997)), uses a locus-specific oligonucleotide primer labeled on the 5′ terminus with 5-carboxyfluorescein (FAM). This labeled primer is designed so that the 3′ end is immediately adjacent to the polymorphic site of interest. The labeled primer is hybridized to the locus, and single base extension of the labeled primer is performed with fluorescently-labeled dideoxyribonucleotides (ddNTPs) in dye-terminator sequencing fashion. An increase in fluorescence of the added ddNTP in response to excitation at the wavelength of the labeled primer is used to infer the identity of the added nucleotide.

[0056] III. Methods of Use

[0057] The determination of the polymorphic form(s) present in an individual at one or more polymorphic sites defined herein can be used in a number of methods.

[0058] A. Forensics

[0059] 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 biallelic 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.

[0060] 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.

[0061] p(ID) is the probability that two random individuals have the same polymorphic or allelic form at a given polymorphic site. In biallelic 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 is (see WO 95/12607):

[0062] Homozygote: p(AA)=x2

[0063] Homozygote: p(BB)=y2=(1−x)2

[0064] Single Heterozygote: p(AB)=p(BA)=xy=x(1−x)

[0065] Both Heterozygotes: p(AB+BA)=2xy=2x(1−x)

[0066] 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.

[0067] 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

[0068] In a locus of n alleles, the appropriate binomial expansion is used to calculate p(ID) and p(exc).

[0069] 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)

[0070] 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).

[0071] 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.

[0072] B. Paternity Testing

[0073] 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.

[0074] If the set of polymorphisms in the child attributable to the father does not match the set of polymorphisms of 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.

[0075] 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)

[0076] where x and y are the population frequencies of alleles A and B of a biallelic polymorphic site.

[0077] (At a triallelic site p(exc)=xy(1−xy)+yz(1−yz)+xz(1−xz)+3xyz(1−xyz))), where x, y and z and the respective population frequencies of alleles A, B and C).

[0078] The probability of non-exclusion is

p (non-exc)=1-p(exc)

[0079] 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)

[0080] 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).

[0081] 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.

[0082] C. Correlation of Polymorphisms with Phenotypic Traits

[0083] 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. For example, 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.

[0084] Phenotypic traits include diseases that have known but hitherto unmapped genetic components (e.g., agammaglobulimenia, 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 hemorrhagic 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.

[0085] The correlation of one or more polymorphisms with phenotypic traits can be facilitated by knowledge of the gene product of the wild type (reference) gene. The genes in which SNPs of the present invention have been identified are genes which have been previously sequenced and characterized in one of their allelic forms. Thus, the SNPs of the invention can be used to identify correlations between one or another allelic form of the gene with a disorder with which the gene is associated, thereby identifying causative or predictive allelic forms of the gene.

[0086] Correlation is performed for a population of individuals who have been tested for the presence or absence of a phenotypic trait of interest and for polymorphic markers sets. To perform such analysis, the presence or absence of a set of polymorphisms (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 κ-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 heart disease. 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 milk production of a farm animal.

[0087] 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.

[0088] For animals and plants, correlations between characteristics and phenotype are useful for breeding for desired characteristics. For example, Beitz et al., U.S. Pat. No. 5,292,639 discuss use of bovine mitochondrial polymorphisms in a breeding program to improve milk production in cows. To evaluate the effect of mtDNA D-loop sequence polymorphism on milk production, each cow was assigned a value of 1 if variant or 0 if wildtype with respect to a prototypical mitochondrial DNA sequence at each of 17 locations considered. Each production trait was analyzed individually with the following animal model:

Y 1jknp =μYS i +P j +X k +β1+. . . +β17+PEn+an+ep

[0089] where Y1jknp is the milk, fat, fat percentage, SNF, SNF percentage, energy concentration, or lactation energy record; μ is an overall mean; YS1 is the effect common to all cows calving in year-season; Xk is the effect common to cows in either the high or average selection line; μ1 to μ17 are the binomial regressions of production record on mtDNA D-loop sequence polymorphisms; PEn is permanent environmental effect common to all records of cow n; an is effect of animal n and is composed of the additive genetic contribution of sire and dam breeding values and a Mendelian sampling effect; and ep is a random residual. It was found that eleven of seventeen polymorphisms tested influenced at least one production trait. Bovines having the best polymorphic forms for milk production at these eleven loci are used as parents for breeding the next generation of the herd.

[0090] D. Genetic Mapping of Phenotypic Traits

[0091] The previous section concerns identifying correlations between phenotypic traits and polymorphisms that directly or indirectly contribute to those traits. The present section describes identification of a 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).

[0092] 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).

[0093] 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 θ, 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 (θ), ranging from θ=0.0 (coincident loci) to θ=0.50 (unlinked). Thus, the likelihood at a given value of θ is: probability of data if loci linked at θ 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 0 (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 θ at which the lod score is the highest is considered to be the best estimate of the recombination fraction.

[0094] Positive lod score values suggest that the two loci are linked, whereas negative values suggest that linkage is less likely (at that value of θ) 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.

[0095] IV. Modified Polypeptides and Gene Sequences

[0096] The invention further provides variant forms of nucleic acids and corresponding proteins. The nucleic acids comprise one of the sequences described in the Table, column 5, in which the polymorphic position is occupied by one of the alternative bases for that position. Some nucleic acids encode full-length variant forms of proteins. Similarly, variant proteins have the prototypical amino acid sequences encoded by nucleic acid sequences shown in the Table, column 6, (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 variant or alternative amino acid shown in the Table.

[0097] 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.

[0098] 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. As used herein, “gene product” includes mRNA, peptide and protein products.

[0099] 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.

[0100] 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.

[0101] 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.

[0102] 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.

[0103] V. Kits

[0104] The invention further provides kits comprising at least one agent for identifying which alleleic form of the SNPs identified herein is present in a sample. For example, suitable kits can comprise at least one antibody specific for a particular protein or peptide encoded by one alleleic form of the gene, or allele-specific oligonucleotide as described herein. 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 the Table. 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.

[0105] The following Examples are offered for the purpose of illustrating the present invention and are not to be construed to limit the scope of this invention. The teachings of all references cited herein are hereby incorporated herein by reference.

EXAMPLES

[0106] The polymorphisms shown in the Table were identified by resequencing of target sequences from individuals of diverse ethnic and geographic backgrounds by hybridization to probes immobilized to microfabricated arrays. The strategy and principles for design and use of such arrays are generally described in WO 95/11995.

[0107] 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. In the present analysis, probes were 25 nucleotides long. Arrays tiled for multiple different references sequences were included on the same substrate.

[0108] Publicly available sequences for a given gene were assembled into Gap4 (http://www.biozentrum.unibas.ch/˜biocomp/staden/Overview.html). PCR primers covering each exon were designed using Primer 3 (http://www-genome.wi.mit.edu/cgi-bin/primer/primer3.cgi). Primers were not designed in regions where there were sequence discrepancies between reads. Genomic DNA was amplified in at least 50 individuals using 2.5 pmol each primer, 1.5 mM MgCl2, 100 μM dNTPs, 0.75 μM AmpliTaq GOLD polymerase, and 19 ng DNA in a 15 μl reaction. Reactions were assembled using a PACKARD MultiPROBE robotic pipetting station and then put in MJ 96-well tetrad thermocyclers (96° C. for 10 minutes, followed by 35 cycles of 96° C. for 30 seconds, 59° C. for 2 minutes, and 72° C. for 2 minutes). A subset of the PCR assays for each individual were run on 3% NuSieve gels in 0.5×TBE to confirm that the reaction worked.

[0109] For a given DNA, 5 μl (about 50 ng) of each PCR or RT-PCR product were pooled (Final volume=150-200 μl). The products were purified using QiaQuick PCR purification from Qiagen. The samples were eluted once in 35 μl sterile water and 4 μl 10×X One-Phor-All buffer (Pharmacia). The pooled samples were digested with 0.2μ DNaseI (Promega)for 10 minutes at 37° C. and then labeled with 0.5 nmols biotin-N6-ddATP and 15μ Terminal Transferase (GibcoBRL Life Technology) for 60 minutes at 37° C. Both fragmentation and labeling reactions were terminated by incubating the pooled sample for 15 minutes at 100° C.

[0110] Low-density DNA chips (Affymetrix, Calif.) were hybridized following the manufacturer's instructions. Briefly, the hybridization cocktail consisted of 3M TMACl, 10 mM Tris pH 7.8, 0.01% Triton X-100, 100 mg/ml herring sperm DNA (Gibco BRL), 200 pM control biotin-labeled oligo. The processed PCR products were denatured for 7 minutes at 100° C. and then added to prewarmed (37° C.) hybridization solution. The chips were hybridized overnight at 44° C. Chips were washed in 1×SSPET and 6× SSPET followed by staining with 2 μg/ml SARPE and 0.5 mg/ml acetylated BSA in 200 μl of 6×SSPET for 8 minutes at room temperature. Chips were scanned using a Molecular Dynamics scanner.

[0111] Chip image files were analyzed using Ulysses (Affymetrix, Calif.) which uses four algorithms to identify potential polymorphisms. Candidate polymorphisms were visually inspected and assigned a confidence value: high confidence candidates displayed all three genotypes, while likely candidates showed only two genotypes (homozygous for reference sequence and heterozygous for reference and variant). Some of the candidate polymorphisms were confirmed by ABI sequencing. Identified polymorphisms were compared to several databases to determine if they were novel. Results are shown in the Table.

				Gene De-	Flank-	Mutat-	Ref	Alt	Ref	Alt
Poly ID	WIAF ID	Genbank or TIGR Accession Number	Position in Sequence	scription	ing Seq	ion Type	NT	NT	AA	AA
G1004a5	WIAF-15233	L36151	2749	PIK4CA,	TGGAGCCCTG[C/A]GACCTCCCTG	—	C	A	—	—
				phosphatidylinositol 4—
				kinase, catalytic, alpha
				polypeptide
G1011a8	WIAF-15444	X07876	1501	WNT2, wingless-type MMTV	TATCTCAACG[C/A]AAGCCCCCTC	—	G	A	—	—
				integration site family
				member 2
G1023a3	WIAF-15252	D89722	606	ARNTL, aryl hydrocarbon	GACTACCTCC[A/C]TCCTAAAGAT	M	A	C	H	P
				receptor nuclear
				translocator-like
G1027a3	WIAF-15253	L47647	662	CKB, creatine kinase,	GGCCTCGGGC[A/C]Tc3cACCCCCGA	M	A	C	M	L
				brain
G1027a4	WIAF-15254	L47647	761	CKB, creatine kinase,	GGTCATCTCC[A/C]TGCAGAAGGG	M	A	C	M	L
				brain
G1034a8	WIAF-15255	J03544	669	PYGB, phosphorylase,	CGGCCTGAST[A/C]TATGCTTCCC	M	A	C	Y	S
				glycogen; brain
G1034a9	WIAF-15256	J03544	986	PYGB, phosphorylase,	CGTGCTCGGC[G/T]CCACGCTCCA	M	G	T	A	S
				glycogen; brain
G1034a10	WIAF-15257	J03544	1538	PYGB, phosphorylase,	GACCAATGGC[A/C]TCACCCCCCG	H	A	C	I	L
				glycogen; brain
G1034a11	WIAF-15258	J03544	1681	PYGB, phosphorylase,	TCATCAGGSA[C/T]GTGGCCAAGS	S	C	T	D	D
				glycogen; brain
G1034a12	WIAF-15259	J03544	2569	PYGB, phosphorylase,
				glycogen; brain	GTGTGGAGCC[C/T]TCCGACCTGC	S	C	T	P	p
G1036a2	WIAF-15260	D88460	877	WASL, Wiskott-Aldrich	ACACCAAGCA[A/T]TTTCCAGCAC	M	A	T	N	I
				syndrome-like
G1036a3	WIAF-15261	D88460	986	WASL, Wiskott-Aldrich	TCTTAGAGGC[A/G]CAACTTAAAG	S	A	S	A	A
				syndrome-like
G1517a10	WIAF-1521E3	HT1132	3858	ERBB3, v-erb-b2 avian	CCTTGAGGAG[C/T]TGGGTTATGA	S	C	T	L	L
				erythroblastic leukemia
				viral oncogene homolog 3
G1517a11	WIAF-15216	HT1132	3899	ERBB3, v-erb-b2 avian	CTCAGTGCCT[C/T]TCTSSGCASC	M	C	T	S	F
				erythroblastic leukemia
				viral oncogene homolog 3
G1517a12	WIAF-15217	HT1132	4013	ER8B3, v-erb--b2 avian	SGAGGTSGTC[C/T]TGGGCGTGAT	M	C	T	P	L
				erythroblastic leukemia
				viral oncogene homolog 3
G1528a5	WIAF-15448	HT1811	773	CSTM3, glutathione S-	AATAGCACTT[A/C]TGTTACTCGT	—	A	C	—	—
				transferase M3 (brain)
G1530a6	WIAF-15453	NT3010	597	GSTM5, glutathione S-	CCTTCCTAAA[C/T]TTGAACGACT	S	C	T	N	N
				transferase M5
G1530a7	WIAF-15454	HT3010	598	GSTMS, glutathione S-	CTTCCTAAAC[T/C]TGAAGCACTT	S	T	C	L	L
				transferase M5
G1653a6	WIAF-15232	L07868	3971	ERBB4, v-erb-a avian	GCTCAGTTGT[G/A]GTTTTTTAGG	—	G	A	—	—
				erythroblastic leukemia
				viral oncogene homolog-like
				4
G185a8	WIAF-15190	X77533	904	ACVR2S, activin A	GCCTCTCATA[C/T]CTGCATGAGG	S	C	T	Y	Y
				receptor, type IIB
G185a7	WIAF-15191	X77533	1462	ACVR2B, activin A	CCTCGGTCAA[C/T]GGCACTACCT	S	C	T	N	N
				receptor, type IIB
G185a8	WIAF-15192	X77533	1536	ACVR2B, activin A	AAAGACTCAA[G/T]CATCTAAGCC	M	C	T	S	I
				receptor, type IIB
G185a9	WIAF-15193	X77533	1059	ACVR2B, activin A	GCCAAACCTC[C/T]ACCGCACACC	M	C	T	P	L
				receptor, type IIB
G185a10	WIAF-15194	X77533	1249	ACVR2B, activin A	TGCCCTTTGA[G/C]CAAGACATTC	M	G	C	E	D
				receptor, type IIB
G185a11	WIAF-15195	X77533	1525	ACVR2B, activin A	ACCTCCCCCC[T/C]AAAGAGTCAA	S	T	C	P	P
				receptor, type IIB
G185a12	WIAF-15196	X77533	1464	ACVR2B, activin A	TCCCTCAACCE[G/A]CACTACCTCG	M	G	A	G	D
				receptor, type IIB
G214a2	WIAF-15320	M27533	981	CD80, CD80 antigen (CD28	CAAGTATCCA[C/T]ATTTAAGAGT	M	C	T	H	Y
				antigen ligand 1, B7-1
				antigen)
				CD80, CD80 antigen (CD28
G214a3	WIAF-15399	M27533	1107	antigen ligand 1, 137-1	ATGCTCCCTC[A/G]CCTACTCCTT	M	A	C	T	A
				antigen)
G2363a4	WIAF-15321	B37435	1328	CSF1, colony stimulating	ATCTCATCAC[T/C]CCGCCCCCAG	M	T	C	L	P
				factor 1 (macrophage)
G2363a5	WIAF-15322	M37435	1417	CSF1, colony stimulating	CCTCCCCCTT[C/A]CCCACCTCCA	M	G	A	G	R
				factor 1 (macrophage)
G244a2	WIAF-15262	X60592	200	TNFRSF5, tumor necrosis	TCACTCACTG[C/A]ACACAGTTCA	—	C	A	C	*
				factor receptor
				superfamily, member 5
G244a3	WIAF-15263	X60592	381	TNFPSF5, tumor necrosis	CTCCCACTCT[A/C]CCACTCAGCC	M	A	C	T	A
				factor receptor
				superfamily, member 5
G277a4	WIAF-15305	D10232	858	RENBP, renin-binding	TTCACAACTT[C/G]CTATTCTTCC	M	C	G	F	L
				protein
G277a5	WIAF-15306	D10232	959	RENBP, renin-binding	CACTCCCCCA[T/C]CAACCTCTCC	M	T	C	M	T
				protein
G277a8	WIAF-15348	D10232	506	RENBP, renin-binding	CACTCCGTCC[A/C]CCACGACCCC M	A	G	Q	R
				protein
G303a24	WIAF-15271	X13916	739	LRP1, low density	TCTCCCGCCT[C/T]TCCAATCCGC	S	C	T	L	L
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a25	WIAF-15272	X13916	826	LRP1, low density	GCCTCCGCTG[C/T]CACCACCATT	S	C	T	C	C
				lipoprotein-related protein
				1 (alpha-2-macroglobulim
				receptor)
G303a26	WIAF-15273	X13916	862	LRP1, low density	ATGGGCCCAC[C/T]TGCTACTGCA	S	C	T	T	T
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a27	WIAF-15274	X13916	1486	LRP1, low density	TGTTTTTCAC[T/C]GACTATGGGC	S	T	C	T	T
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a28	WIAF-15275	X13916	1519	LRP1, low density	TGGAACGCTG[T/C]GACATGGATG	S	T	C	C	C
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a29	WIAF-15276	X13916	1675	LRP1, low density	GCCGCCAGAC[C/T]ATCATCCACG	S	C	T	T	T
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a30	WIAF-15277	X13916	2097	LRP1, low density	ATGGATATGG[G/A]GGCCAAGGTC	M	G	A	G	E
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a31	WIAF-15278	X13916	2352	LRP1, low density	ACAATCACCG[T/C]CGCCACGCTC	M	T	C	V	A
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a32	WIAF-15279	X13916	3083	LRP1, low density	CCCCTCGAAC[T/C]CTGACCGAGA	M	T	C	C	R
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a33	WIAF-15280	X13916	3115	LRP1, low density	TGGACAACAC[T/A]CATGAGCCCC	M	T	A	S	R
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a34	WIAF-16281	X13916	3664	LRP1, low density	ACACTCATGA [A/T]TTCCAGTGCC	M	G	T	E	D
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a35	WIAF-15282	X13916	6043	LRP1, low density	ACTGCTCCCA[G/T]CTCTGCCTGC	M	G	T	Q	H
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a36	WIAF-15283	X13916	6641	LRP1, low density	CGGCATCTCA[G/T]TGGACTACCA	M	G	T	V	L
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a37	WIAF-15284	X13916	6706	LRP1, low density	AACGCATCCA[C/T]CTGCAGACAG	S	C	T	D	D
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a38	WIAF-15285	X13916	7550	LRP1, low density	CATGCCCCCG[C/T]CCCTCTCCGC	M	G	T	A	S
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a39	WIAF-15286	X13916	7552	LRP1, low density	TGCGGGCGGC[G/A]CTCTCGGGAG	S	G	A	A	A
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a40	WIAF-15287	X13916	8013	LRP1, low density	GATGACCTCA[C/T]CTGCCGAGCG	M	C	T	T	I
				lipoprotein-related protein
				1(alpha-2-macroglobulin
				receptor)
G303a41	WIAF-15288	X13916	8100	LRP1, low density	CTAACCTACC[A/T]CAACATCCCC	M	A	T	D	V
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a42	WIAF-15289	X13918	9022	LRP1, low density	AGTCCCCCGA[G/C]TGTGAGTACC	M	G	C	E	D
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a43	WIAF-15290	X13916	9081	LRP1, low density	CCCTCTCTGA[C/T]CTCCCGCCAC	M	G	T	S	T
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a44	WIAF-15291	X13916	9725	LRP1, low density	CCCAAGCATC[C/T]ACCTTAACCC	M	C	T	H	Y
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a45	WIAF-15292	X13910	10400	LRP1, low density	CCCCGCCGCA[G/T]GCCACAAATG	M	G	T	G	W
				lipoprotein-releted protein
				1 (alpha-2-macroglobulin
				receptor)
G303a4G	WIAF-15293	X13916	10994	LRP1, low density	CTCCATCCCA[G/T]CCCCTTCGGAA	M	G	T	A	S
				lipoprotein related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a47	WIAF 15294	X13916	11044	LRP1, low density	GCTCCGATCA[G/T]CCCAACGAAG	M	G	T	E	D
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a48	WTAF-15295	X13916	11605	LRP1, low density	TCTGCATCCC[G/A]CGCCAATGCG	S	G	A	C	C
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a49	WIAF-15296	X13916	12473	LRP1, low density	GATTCACCAG[C/T]CCCACCCCAT	N	C	T	P	S
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a50	WIAF-15297	X13916	13175	LRP1 low density	GGACCAGTGC[T/C]CCCAGCACTG	M	T	C	W	R
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a51	WIAF-15298	X13916	13228	LRP1, low density	CTCCCATGCC[C/T]ACCTCCCGGT	S	C	T	P	P
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a52	WIAF-15299	X13916	13364	LRP1, low density	CCGCTTCCTG[C/A]GCCACCCCTG	M	C	A	G	S
				lipoprotein-related protein
				1 (alpha 2-macroglobulin
				receptor)
G303a53	WIAF-15300	X13916	13412	LRP1, low density	TCAGAACTTT[C/A]CCACATCCCA	M	G	A	G	S
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a54	WIAF-15324	X13916	1057	LRP1, low density	CAGTACACCG[C/C]CCCCCTGTCC	S	G	C	R	R
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a55	WIAF-15325	X13916	1993	LRP1, low density	GCCGTTCCCC[C/T]TTCAGCcTCS	S	C	T	G	G
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a56	WIAF-15326	X13916	1998	LRP1, low density	TCCCGCTTCA[G/A]CCTCCGCACT	M	G	A	S	N
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303557	WIAF-15327	X13916	2764	LRP1, low density	CCACTGTCTA[C/T]CGCTTCCAAC	S	C	T	Y	Y
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
6303a58	WIAF-15328	X13916	4646	LRP1, low density	GGCAATCGCA[C/T]TGGATCCCCG	S	C	T	L	L
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a59	WIAF-15329	X13916	4909	LRP1, low density	TGTCGCACCC[C/A]TTTGCAGTGA	S	G	A	P	P
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
5303a60	WIAP-15330	X13916	5474	LRP1, low density	CTGGGTCTCC[C/T]GAAACCTGTT	—	C	T	R	*
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a61	WIAF-15331	X13916	5552	LRP1, low density	CTTCAACAAC[C/A]CAGTGGTGCA	M	G	A	A	T
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
6303a62	WIAF-15332	X13916	6201	LRP1, low density	AATGACAAGT[C/T]AGATGCCCTC	M	C	T	S	L
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a63	WIAF-15333	X13916	6104	LRP1, low density	CTATAGCCTC[C/T]GGAGTGGCCA	M	C	T	R	W
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a64	WIAF-15334	X13916	7002	LRP1, low density	GGGCAGCGCC [C/T]CTGCGCCTGT	M	C	T	A	V
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
6303a65	WIAF-15335	X13916	7051	LRP1, low density	CATCGTGCCG[C/T]GAGTATGCCG	S	C	T	R	R
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a66	WIAF-15336	X13916	7744	LRP1, low density	TCGGCCTGGC[C/T]GTGTATGGGG	S	C	T	A	A
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a67	WIAF-15337	X13916	7782	LRP1, low density	GACTCGGTCC [G/A]CCGGGCAGTG	M	C	A	R	Q
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a68	WIAF-15338	X13916	8392	LRP1, low density	CCAGTCCCAC[C/T]GACTGCACCA	S	C	T	T	T
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a69	WIAF-15339	X13916	8574	LRP1, low density	TACTTCGCCT[G/A]CCCTAGTCCC	M	G	A	C	Y
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a70	WIAF-15340	X13916	8608	LRP1, low density	TCACCTCCAC[G/A]TCTGACAAG	S	G	A	T	T
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a71	WIAF-15341	X13916	9204	LRP1, low density	TTCCTCTGCA [C/A]CAGTCCGCGC	M	G	A	S	N
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a72	WIAF-15342	X13916	9469	LRP1, low density	ACACCCATCC[C/T]ACCTATAAGT	S	C	T	G	G
				lipoprotein-related protein
				1 (alpha-2-mecroglobulin
				receptor)
G303a73	WIAF-15343	X13916	11403	LRP1, low density	CACCAGGACC[C/G]CGTCGGCACT	M	C	G	A	G
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a74	WIAF-15344	X13916	12042	LRP1, low density protein	ACGCACAACA[C/T]CTGCAAGGCC	M	C	T	T	I
				1 (alpha-2-macroglobulin
				receptor)
G303a75	WIAF-15345	X13916	11950	LRP1, low density	TCAACGAGTG[C/T]CTGCCCTTCG	S	C	T	C	C
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G303a76	WIAF-15346	X13916	13599	LRP1, low density	CTGACCTGCG[T/C]CGGCCACTGC	M	T	C	V	A
				lipoprotein-related protein
				1 (alpha-2-macroglobulin
				receptor)
G309a1	WIAF-15318	HT0259	246	MVK, mevalonate kinase	GTCGACCTCA [G/A]CTTACCCAAC	M	G	A	S	N
				(mevalonic aciduria)
G309a2	WIAF-15319	HT0259	257	MVK, mevalonate kinase	CTTACCCAAC[A/T]TTGCTATC~	M	A	T	I	F
				(mevalonic aciduria)
G326a4	WIAF-15301	HT1009	988	KLKB1, kallikrein B	AATTTACCCG[G/T]CAGTTCACTT	—	G	T	G	*
				plasma, (Fletcher factor) 1
G326a5	WIAF-15302	HT1009	1102	KLKB1, kallikrein B	TTCTTTACTC[C/T]CACAAGACTG	M	C	T	P	S
				plasma, (Fletcher factor) 1
G326a5	WIAF-15303	HT1009	1724	KLKB1, kallikrein B	CCTTTGCTAA[C/T]ATCAAGAA	M	C	T	T	I
				plasma, (Fletcher factor) 1
G326a7	WIAF-15304	HT1009	1772	KLKB1, kallikrein B	ATAACCCAAC[A/C]GATGGTCTGT	M	A	C	R	Q
				plasma, (Fletcher factor) 1
G326a8	WIAF-15347	HT1009	1286	KLKB1, kallikrein B	ACAAACTCTT[C/T]TTCGGCACAG	M	C	T	S	F
				plasma, (Fletcher factor) 1
G33a7	WIAF-15107	X82540	176	INHBC, inhibin, beta C	TCCAACCACA[G/A]TGGCCACTCC	M	G	A	V	M
G334a8	WIAF-15307	HT1220	205	THBS1, thrombospondin 1	CAGCCTGTTT[C/A]ACATCTTTCA	M	G	A	D	N
G334a9	WIAF-15308	HT1220	1055	THBS1, thrombospondin 1	CTGAGGCGGC[C/T]TCCCCTATGC	M	C	T	P	L
G334a10	WIAF-15309	HT1220	1142	THBS1, thrombospondin 1	TGTCAGAACT[C/T]ACTTACCATC	M	C	T	S	L
G334a11	WIAF-15310	HT1220	1288	THBS1, thrombospondin 1	CTCCTGTTCT[A/G]CGAGCTGTGG	M	A	G	T	A
G334a12	WIAF-15311	HT1220	961	THBS1, thrombospondin 1	GGTCCTCGAA[C/T]TCAGGGGCCT	M	C	T	L	F
G334a13	WIAF-15312	HT1220	1678	THBS1, thrombospondin 1	CAACAACCCC[A/C]CACCCCAGTT	M	A	G	A	T
G334a14	WIAF-15349	HT1220	812	THBS1, thrombospondin 1	GGCTCCTCCA[G/C]CTCTACCAGT	M	G	C	S	T
G334a15	WIAF-15350	HT1220	914	THBS1, thrombospondin 1	CACTTCCAAG[C/T]CATCTGCCGC	M	C	T	A	V
G334a16	WIAF-15351	HT1220	1401	THBS1, thrombospondin 1	AGTGTCACAA[A/C]AGATTTAAAC	S	A	G	K	K
G334a17	WIAF-15352	HT1220	2438	THBS1, thrombospondin 1	CCCTCTCACA[A/C]CTCTCCCTAC	M	A	G	N	S
G334a18	WIAF-15353	HT1220	3703	THBS1, thrombospondin 1	CTTCAGAAAA[C/T]CCCCAGGATC	—	C	T	—	—
G337a3	WIAF-15370	HT1259	286	EDNRB, endothelin receptor	TGCCCTCCTT[C/T]TTCCCTGCGG	M	C	T	L	F
				type B
G337a4	WIAF-15371	HT1259	1068	EDNRB, endothelin receptor	ATTGGTGGCT[C/A]TTCACTTTCT	S	G	A	L	L
				type B
G344a1	WIAF-15369	HT1679	1220	EDNRA, endothelin receptor	TAAAACCTCT[A/C]TCCTCAATCC	M	A	C	M	L
				type A
G344a2	WIAF-15387	HT1679	1856	EDNRA, endothelin receptor	CCAACTGTCA [C/G]TCCGGCAATC	—	C	G	—	—
				type A
G357a4	WIAF-15361	HT2244	2642	C4B, complement component	TCTCAGCCTC[C/T]ACGTCTCCCC	M	C	T	H	Y
				4B
G357a5	WIAF-15362	HT2244	2411	C4B, complement component	AACACTCCAC[C/T]GCTTTCAAAT	M	C	T	R	C
				4B
G357a6	WIAF-15363	HT2244	3258	C4B, complement component	TTCTCACCCC[A/G]CACCACCACC	M	A	G	D	G
				4B
G357a7	WIAF-15364	HT2244	3399	C4B, complement component	TTCCACCACC[C/T]CTCTCCACTC	M	C	T	P	L
				4B
G357a8	WIAF-15365	HT2244	3410	C4B, complement component	CTCTCCACTG[T/A]TACACACCAC	M	T	A	L	I
				4B
G357a9	WIAF-15366	HT2244	3413	C4B, complement component	TCCAGTCTTA[G/C]ACAGCACCAT	M	G	C	D	H
				4B
G357a10	WIAF-15367	HT2244	3415	C4B, complement component	CAGTGTTAGA[C/T]AGGAGCATGC	S	C	T	D	D
				4B
G357a11	WIAF-15368	HT2244	4035	C4B, complement component	GTGACTCTCA[C/T]CTCCACAGGC	M	G	T	S	I
				4B
G357a12	WIAF-15384	HT2244	3655	C4B, complement component	TGACCAAGCC[G/C]CCTGTGGACC	S	G	C	A	A
				4B
G357a13	WIAF-15385	HT2244	3660	C45, complement component	AAGGCGCCTG[T/C]CGACCTGCTC M	T	C	V	A
				4B
G357a14	WIAF-15386	HT2244	3766	C4B, complement component	ATCCCGTGTC[G/A]CCCACCCCGG	S	G	A	S	S
				4B
G357a15	WIAF-15502	HT2244	1080	C4B, complement component	ATCATTGACT[C/A]TCCAGCTGGC	M	C	A	S	Y
				4B
G357a16	WIAF-15503	HT2244	1102	C4B, complement component	ACATGCAGGA[G/T]GCAGAGCTCA	M	C	T	E	D
				4B
G357a17	WIAF-15504	HT2244	1771	C4B, complement component	CCCTGGACGG[T/A]CCCAAGCACT	S	T	A	G	G
				4B
G357a18	WIAF-15505	HT2244	1829	C4B, complement component	CGACTCCCTA[C/T]CCCTCCTCCC	M	G	T	A	S
				4B
G357a19	WIAF-15506	HT2244	1686	C4B, complement component	TTCTACTACC[A/C]TCCACACCAC	M	A	C	H	P
				4B
G367a2	WIAF-15100	HT27685	1021	ACACA, acetyl-Coenzyme A	TCAACCTCAA[G/A]TTCCTCCATC	M	G	A	V	I
				carboxylase alpha
C367a3	WIAF-15101	HT27685	1812	ACACA, acetyl-Coenzyme A	AAAGCTTTCA[A/C]ATCAACACAA	S	A	C	Q	Q
				carboxylase alpha
G367a4	WIAF-15102	HT27685	1698	ACACA, acetyl-Coenzyme A	GGGGACAAAA[C/A]ACAGAAGAAC	M	C	A	S	R
				carboxylase alpha
G391a23	WIAF-15313	HT3630	1951	VWF, von Willebrend factor	ACCACCACAG[C/G]GATCCCTGCC	M	C	G	S	R
G391a24	WIAF-15314	HT3630	1798	VWF, von Willebrand factor	CCCCCGTCTA[C/T]GCCCGGAAGA	S	C	T	Y	Y
G391a25	WIAF-15315	HT3630	2805	VWF, von Willebrand factor	TCTGTCTGTC[C/A]GGACCCCAAG	M	G	A	R	Q
G391a26	WIAF-15316	HT3630	3233	VWF, von Willebrand factor	AGTGTCTCCC[C/T]TCTGTCGCAA	S	C	T	L	L
G391a27	WIAF-15317	HT3630	5028	VWF, von Willebrand factor	TTCTTCCTCA[C/A]CCAGGCTGAC	M	C	A	S	N
G391a28	WIAF-15354	HT3630	3130	VWF, von Willebrand factor	ACTCTGCCCG[C/A]TACATCATTC	S	G	A	R	R
G391a29	WIAF-15355	HT3630	4391	VWF, von Willebrand factor	CTCCCGCATC[G/A]CCCTGCTCCT	M	G	A	A	T
G391a30	WIAF-15356	HT3630	5131	VWF, von Willebrand factor	AGCTGGTGCC[C/T]ATTCGAGTCG	S	C	T	P	P
G391a31	WIAF-15357	HT3630	5356	VWF, von Willebrand factor	CCTCCAGTTT[C/T]CCAGCTTCTT	S	C	T	F	F
G391a32	WIAF-15358	HT3630	6094	VWF, von Willebrand factor	CCTGCCCCTG[C/T]GTGTGCACAG	S	C	T	C	C
G391a33	WIAF-15359	HT3630	6733	VWF, von Willebrand factor	CATTCTATGC[C/T]ATCTGCCAGC	S	C	T	A	A
G391a34	WIAF-15360	HT3630	8247	VWF, von Willebrand factor	CGTGATSAGA[C/T]GCTCCAGGAT	M	C	T	T	M
G395a6	WIAF-15372	HT4158	358	ECE1, endothelin	CCTGCCATGA[C/T]TTCTTCAGCT	S	C	T	D	D
				converting enzyme 1
G395a7	WIAF-15373	HT4158	401	ECE1, endothelin	GCCCAACCCA[G/T]TCCCTGATGG	M	G	T	V	F
				converting enzyme 1
G395a8	WIAF-15374	HT4158	1008	ECE1, endothelin	GAGCTGCAGAEC/T]CTTCCCACCC	M	C	T	T	I
				converting enzyme 1
G395a9	WIAF-15375	HT4158	1141	ECE1, endothelin	TCAACACCAC[C/T]GACAGATGCC	S	C	T	T	T
				converting enzyme 1
G395a10	WIAF-15376	HT4158	1874	ECE1, endothelin	CCGGCCATGG[T/A]GGAACAACTC	M	T	A	W	R
				converting enzyme 1
G4125a1	WIAF-14995	HT1492	227	PRG1, proteoglycan 1,	AACAAGATCC[C/S]CCGTCTGAGG	M	C	G	P	R
				secretory granule
G4l25a2	WIAF-14996	HT1492	324	PRG1, proteoglycan 1,	GCTTCGGCTC[C/T]CGCTCCGGCT	S	C	T	S	S
				secretory granule
G4125a3	WIAF-14997	HT1492	325	PRG1, proteoglycan 1,	CTTCGGCTCC[G/C]GCTCCGGCTC	M	G	C	G	R
				secretory granule
G4125a4	WIAF-14998	HT1492	116	PRG1, proteoglycan 1,	TATCCTACCC [A/C]GACACCCACC	M	A	G	Q	R
				secretory granule
G421a1	WIAF-15214	M25650	383	AVP, arginine vasopressin	AACCCACCTT[C/T]TCCCACCGCT	S	C	T	F	F
				(neurophysin II,
				antidiuretic hormone,
				diabetes insipidus,
				neurohypophyseal)
G4591a1	WIAF-14992	HT97307	614	BCAT2, branched chain	TCCCTCCTCG[C/C]CGAACCAACC	M	C	G	A	G
				aminotransferase 2,
				mitochondrial
G4591a2	WIAF-14983	HT97307	634	BCAT2, branched chain	CTTCATCCGG[G/T]CCTGCGTTGG	M	G	T	A	S
				aminotransferase 2,
				mitochondrial
G4591a3	WIAF-14984	HT97307	669	BCAT2, branched chain	ACAAGTTAGG[T/C]GGGAATTATG	S	T	C	G	G
				aninotransferase 2,
				mitochondrial
G4615a1	WIAF-14981	HT2833	171	calcium-binding protein	AATCCCAACT[C/G]AAGCACCTCA	S	C	G	L	L
				S100P
G4615a2	WIAF-14982	HT2833	388	calcium-binding protein	GTAACAGAGA[C/T]GGTCATGCAA	—	C	T	—	—
				S100P
G4643a1	WIAF-14883	HT2439	107	CNR2, cannabinoid receptor	CTCCCTCCCT[C/T]ACTGGAAGAA	M	C	T	H	Y
				2 (macrophage)
G4643a2	WIAF-14984	HT2439	1125	CNR2, cannabinoid receptor	AACAACCCCC[C/A]ACATCCTCAG	S	G	A	P	P
				2 (macrophage)
G4G43a3	WIAF-14985	HT2439	1140	CNR2, cannabinoid receptor	CCTCACTCAC[C/G]CAGACAGAGG	S	C	G	T	T
				2 (macrophage)
G4643a4	WIAF-14586	HT2439	123	CNR2, cannabinoid receptor	CCAATTTAAA[C/G]AACTCAAGTC	—	C	G	—	—
				2 (macrophage)
G4643a5	WIAF-14987	HT2439	1251	CNR2, cannabinoid receptor	TCAGAAATCA[G/A]TTCACTCCCT	—	G	A	—	—
				2 (macrophage)
G4643a6	WIAF-14988	HT2439	1265	CNR2, cannabinoid receptor	ACTCCCTCGA[A/G]GAGACACACC	—	A	G	—	—
				2 (macrophage)
G4643a7	WIAF-14989	HT2439	1313	CNR2, cannabinoid receptor	CCAGTCCCAC[A/G]CACCTAGACA	—	A	G	—	—
				2 (macrophage)
C4643a8	WIAF-14990	HT2439	1331	CNR2, cannabinoid receptor	ACACGCACCC[C/G]TTTTTCCTCA	—	C	C	—	—
				2 (macrophage)
G478a1	WIAF-15168	J03810	632	SLC2A2, solute carrier	CCATCCTCAC[C/A]GCCATTCTTA	S	C	A	T	T
				family 2 (facilitated
				glucose transporter),
				member 2
G478a2	WIAF 15169	J03810	1249	SLC2A2, solute carrier	ATGATACCCA[T/C]CTTCCTCTTT	M	T	C	I	T
				family 2 (facilitated
				glucose transporter)
				member 2
G2478a3	WIAF-15170	J03810	1475	SLC2A2, solute carrier	TTACCCTGTT[C/T]ACATTTTTTA	S	C	T	F	F
				family 2 (facilitated
				glucose transporter)
				member 2
G482a3	WIAF-15171	J04501	685	GYS1, glycogen synthase 1	AGCCACATGT[G/C]GTTGCTCACT	S	G	C	V	V
				(muscle)
G482a4	WIAF-15172	J04501	715	GYS1, glycogen synthase 1	GGTTGCCAGG[C/T]GTTGGACTCT	S	C	T	G	G
				(muscle)
G491a1	WIAF-15197	U40002	2182	LIPE, lipase, hormone-	AGCTCTGCCC [C/A]CCCCCCCACC	S	G	A	P	P
				sensitive
G491a2	WIAF-15198	U40002	2686	LIPE, lipase, hormone-	ACAAACCCCT [C/T]CGCATCATCC	S	C	T	L	L
				sensitive
C500a4	WIAF-15000	X99101	1434	ESR1, estrogen receptor 1	ACGGCTCCCA[C/T]AACCCACACT	M	G	T	Q	H
C500a5	WIAF-15001	X99101	1096	ESR1, estrogen receptor 1	TATCTACCCT[C/C]TCCTCACACC	M	C	G	L	V
C505a5	WIAF-15382	HT1113	1849	PRLR, prolactin receptor	CGTCCATTAT[C/G]ATTCCTACCA	—	C	G	S	*
G510a2	WIAF-15063	U17280	315	STAR, steroidogenic acute	GTTCTCCCCT[C/A]CAAGACACTC	S	G	A	L	L
				regulatory protein
G524a2	WIAF-15123	L05144	1230	PCK1, phosphoenolpyruvate	CGCCTTTACT[C/C]GCAACCCATT	M	G	C	W	S
				carboxykinase 1 (soluble)
G524a3	WIAF-15124	L05144	1257	PCK1, phosphoenolpyruvate	CCGCTAGCTT [C/T]ACCCGTCACC	M	C	T	S	L
				carboxykinase 1 (soluble)
G524a4	WIAF-15125	L05144	1261	PCK1, phosphoenolpyruvate	TACCTTCACG[C/T]GTCACCATCA	S	C	T	C	G
				carboxykinase 1 (soluble)
G524a5	WIAF-15126	L05144	1253	PCK1, phosphoenolpyruvate	GCTTCAGGCG[T/C]CACCATCACG	M	T	C	V	A
				carboxykinase 1 (soluble)
G524a6	WIAF-15127	L05144	1298	PCK1, phosphoenolpyruvate	GGAGTGGAGC[T/C]CAGAGGATGG	M	T	C	S	P
				carboxykanase 1 (soluble)
G524a7	WIAF-15128	L05144	1308	PCK1, phosphoenolpyruvate	TCAGAGGATC[G/A]cGAACCTTCT M	G	A	G	E
				carboxykinase 1 (soluble)
G525a1	WIAF-15129	X92720	158	PCK2, phosphoenolpyruvate	CACACCCTGC [G/A]ACTCCTTACT	M	G	A	R	Q
				carboxykinase 2
				(mitochondrial)
G525a2	WIAF-15130	X92720	230	PCK2, phosphoenolpyruvate	GCCCGCCTTGT[G/A]CCAACCAGAG	M	G	A	C	Y
				carboxykinase 2
				(mitochondrial)
0525a3	WIAF-15131	X92720	438	PCK2, phosphoenolpyruvate	CACTCCCGCC[T/C]GGTGGGCCCT	S	T	C	P	P
				carboxykinase 2
				(mitochondrial)
G528a2	WIAF-15439	V00572	1282	PGK1, phosphoglycerate	CCAGTTTGGA[G/A]CTCCTGGAAG	S	G	A	E	E
				kinase 1
G536a6	WIAF-15199	M20747	992	SLC2A4, solute carrier	GGGCAACCGT[A/T]CCCACCAGCA	M	A	T	T	S
				family 2 (facilitated
				glucose transporter),
				member 4
C53Ga7	WIAF-15200	M20747	655	SLC2A4, solute carrier	ACCTCCAGGC[C/T]GCCCTGCAGA	S	C	T	A	A
				family 2 (facilitated
				glucose transporter),
				member 4
G536a8	WIAF-15201	M20747	1806	SLC2A4, solute carrier	CCCTGGTAGA[A/T]TTGGGAACCT	—	A	T	—	—
				family 2 (facilitated
				glucose transporter)
				member 4
G538a4	WIAF-15433	M55531	434	SLC2A5, solute carrier	GGATGCAGCA [G/C]AGTCCCCACA	M	G	C	R	T
				family 2 (facilitated
				glucose transporter)
				member 5
G538a5	WIAF-15434	M55531	515	SLC2A5, solute carrier	AACGTGGTCC[A/G]CATGTACTTA	M	A	G	P	R
				family 2 (facilitated
				glucose transporter)
				member 5
G528a6	WIAF-15435	M55531	1237	SLC2A5, solute carrier	CATAGCACAT[G/T]CCCTCGGCCC	M	G	T	A	S
				family 2 (facilitated
				glucose transporter)
				member 5
G538a7	WIAF-15450	M55531	822	SLC2A5, solute carrier	AGGTGGCCGA[G/C]ATCCGGCACC	M	G	C	E	D
				family 2 (facilitated
				glucose transporter)
				member 5
G538a8	WIAF-1545l	M55531	957	SLC2A5, solute carrier	CGCCCCTCAA[C/T]GCTATCTACT	S	C	T	N	N
				family 2 (facilitated
				glucose transporter)
				member 5
G538a9	WIAF-15452	M55531	1655	SLC2A5, solute carrier	ACTTCTACCT[G/T]TCTGTGAATA	—	G	T	—	—
				family 2 (facilitated
				glucose transporter)
				member 5
C540a9	WIAF-15166	HT960	2997	SOS1	CCATGCCAAA[T/C]AGCATCCAGA	S	T	C	N	N
				TKT, transketolase
C546a3	WIAF-14936	HT225	1223	(Wernicke-Korsakoff	AAGTCTCCGG[C/T]GGCCCTCTCA	?	C	T	—	—
				syndrome)
C546a4	WIAF-15202	HT225	645	TRT, transketolase
				(Wernicke-Korsakoff	CTATGTTTCG[G/T]TCAGTCCCCA	S	G	T	R
				syndrome)
G546a5	WIAF-15203	HT225	646	TKT, traneketolase	TATGTTTCGG[T/C]CAGTCCCCAC	M	T	C	S	P
				(Wernicke-Korsakoff
				Syndrome)
G2546a6	WIAF-15204	HT225	672	TKT, tranaketolase	CCCTCTTTTA[C/G]CCAAGTcAATG	—	C	G	Y	*
				(Wernicke-Korsakoff
				syndrome)
G546a7	WIAF-15205	HT225	790	TKT, transketolase	CAATGACCAC[T/C]TCCACCTCGG	M	T	C	F	L
				(Wernicke-Korsakoff
				syndrome)
G546a8	WIAF-15206	HT225	869	TKT, transketolase	CTGACCCTGC[A/C]CCAGGCCTTG	M	A	G	H	R
				(Wernicke-Korsakoff
				syndrome)
G546a9	WIAF-15207	HT225	535	TKT, transketolase	CCACATTCCC [A/T]TCGCCGCCAT	M	A	T	M	L
				(Wernicke-Korsakoff
				syndrome)
G556a5	WIAF-15457	AF001787	813	UCP2, uncoupling protein 2	TCCTGGACTA[C/T]CACCTGCTCA	S	C	T	Y	Y
				(mitochondrial proton
				carrier)
G574a2	WIAF-15471	NT4058	1094	SSTRS, somatostatin	ACCCCACCCC [C/A]CCCGCCCACC	S	G	A	P	P
				receptor 5
G592a8	WIAF-15459	X96586	1101	NSMAF, neutral	GTAACCCAGT[A/G]CCGGCCCTAA	S	A	G	V	V
				sphingomyelinase (N-SMase)
				activation associated
				factor
G596a4	WIAF-15099	HT3537	1298	PC, pyruvate carboxylase	TCATCTCCCC [C/T]CACTACCACT	S	C	T	P	P
G596a5	WIAF-15103	HT3537	897	PC, pyruvate carboxylase	CGACCCCCAC [C/T]TTCCCACTCC	M	C	T	L	F
G596a6	WIAF-15104	HT3537	2657	PC, pyruvate carboxylase	AGTACACCAA[C/T]CTCCACTTCC	S	C	T	N	N
G596a7	WIAF-15105	HT3537	3588	PC, pyruvate carboxylase	TTCCCCCACA[C/T]CGCCAGCCTC	—	C	T	—	—
598a40	WIAF-15186	HT48666	11262	HERC1, hect (homologous to	GATGGTGGGA[C/G]CAGGAATCAA	M	C	G	B	E
				the E6-AP (UBE3A) carboxyl
				terminus) domain and RCC1
				(CHC1)-like domain (RLD) 1
G598a41	WIAF-15187	HT48666	10876	HERC1, hect (homologous to	GTTCAGTGAA[G/A]ACAGACCATT	M	G	A	D	N
				the E6-AP (UBE3A) carboxyl
				terminus) domain and RCC1
				(CHC1)-like domain (RLD) 1
G612a2	WIAF-15221	HT1436	1247	RAF1, v-ref-1 murine	GCAGATGTTG[C/G]AGTAAAGATC	M	C	G	A	G
				leukemia viral oncogene
				homolog 1
G625a3	WIAF-15189	HT1961	462	PPP2R2A, protein	ATAAAACAAT[A/T]AAATTATGGA	S	A	T	I	I
				phosphatase 2 (formerly
				2A), regulatory subunit B
				(PR 52), alpha isoform
G630a13	WIAF-15188	HT5086	3326	protein phosphatase 2A, 130	AGCATATTCT[C/T]TGGTGCACTA	M	C	T	S	F
				kDa regulatory subunit
G634a12	WIAF-15002	X04434	1355	IGFIR, insulin-like growth
				factor 1 receptor	TGc3CACCACC [C/A]CAACCTGACC	M	G	A	R	M
C634a13	WIAF-15003	X04434	1387	IGF1R, insulin-like growth	CAAAATCTAC [T/C]TTGCTTTCAA	M	I	C	F	L
				factor 1 receptor
G634a14	WIAF-15004	X04434	1520	IGF1R, insulin-like growth	CAAACTCACC[TIC]CCTCCATTTC	M	T	C	V	A
				factor 1 receptor
G639a1	WIAF-15381	M62403	224	ICFBP4, insulin-like	CCCACCACCT[G/A]GTCCCACAGC	S	C	A	L	L
				growth factor-binding
				protein 4
G649a1	WIAF-15482	HT1376	1402	RARG, retinoic acid	TTACTCTCAA[G/A]ATCCACATTC	S	G	A	K	K
				receptor, gamma
G649a2	WIAF-15483	HT1376	1479	RARG, retinoic acid	CATGACTCCT[C/T]GCACCCTCGT	M	C	T	S	L
				receptor, gamma
G658a5	WIAF-15380	J02943	810	CBG, corticosteroid	GAACTACGTGTG/T]CCAATGCCAC	M	G	T	G	C
				binding globulin
G658a8	WIAE-15396	J02943	1199	CBG, corticosteroid	TCATGATCTT[C/A]CACCACTTCA	M	C	A	F	L
				binding globulin
G688a3	WIAF-15228	Z48923	1759	BMPR2, bone morphogenetic	AAAACACAGA[C/G]CCAAGTTCCC	M	C	G	P	A
				protein receptor, type II
				(serine/threonine kinase)
G686a4	WIAF-15229	Z48923	1862	BMPR2, bone morphogenetic	CGGCTTACTC[C/T]ACAGTGTCCT	M	C	V	A	V
				protein receptor, type II
				(serine/threonine kinase)
G688a1	WIAF-15230	HT0639	937	CALB2, calbindin 2, (29kD,	AGACTCACAC[A/G]CCGTGACCGC	—	A	G	—	—
				calretinin)
G696a16	WIAF-15378	HT27700	516	calcium-sensing receptor	ACCACCCAGC[C/G]CAAAACAAGC	S	C	G	A	A
G696a17	WIAF-15379	HT27700	2712	calcium-sensing receptor	CCCCCCCCCC[C/G]TCAACCTACC	S	C	G	P	P
G696a18	WIAE-15388	HT27700	944	calcium-sensing receptor	AGTTATCCCTTC/T]CTCCACCAGA	M	C	V	S	F
G696a19	WIAF-15389	HT27700	1038	calcium-sensing receptor	TCCCAGACAT[C/T]ATCGAGTATT	S	C	T	I	I
G696a20	WIAF-15390	HT27700	1178	calcium-sensing receptor	TCCCACTACT[C/G]TCATGAGCAA	M	C	G	S	G
G696a21	WIAF-15391	HT27700	1787	calcium-sensing receptor	CCCTCCTCTC[C/C]AGACATCAAC	M	C	G	A	G
G698a22	WIAF-15392	HT27700	2577	calcium-sensing receptor	ACCGTCTCCT[C/T]CTCCTCTTTG	S	C	T	L	L
G696a23	WIAF-15393	HT27700	2595	calcium-sensing receptor	TTCACGCCAA[C/A]ATCCCCACCA	S	G	A	K	K
G696a24	WIAF-15394	HT27700	3180	calcium-sensing receptor	GCCTTCGACG[C/A]TCCACCGCAT	S	C	A	G	G
G698a25	WIAF-15395	HT27700	3325	calcium-sensing receptor	CCTCCCACAG[C/G]AGCAACGATC	M	C	G	Q	E
G708a16	WIAF-15234	U73778	754	COL12A1, collagen, type	CCATATAAAC[G/A]TCGCAACACA	M	G	A	G	D
				XII, alpha 1
G708a17	WIAF-15235	P73778	947	COL12A1, collagen, type	CCATTAAAGC[T/G]GCACATCCAA	S	T	C	A	A
				XII, alpba 1
G708a18	WIAF-15236	U73778	3149	COL12A1, collagen, type	AAAACACAAT[G/A]AGAGTTACAT	M	G	A	M	I
				XII, alpha 1
G708a19	WIAF-15237	U73778	6059	COL12A1, collagen, type	CTATAGTAGT[G/A]CCAGGAAACA	S	G	A	V	V
				XII, alpha 1
G708a20	WIAE-15498	D73778	2969	COL12A1, collagen, type	GAGAGAAAAA[T/C]CTSCCTGAAG	S	T	C	N	N
				XII, alpha 1
G710a3	WIAF-15238	D38163	740	COL19A1, collagen, type	TTCCATGGAC[G/A]GACAGTTATT	M	G	A	R	Q
				XIX, alpha 1
G710a4	WIAF-15239	D38163	2403	COL19A1, collagen, type	GGGAGAAAGG[T/C]GATGAGGGTC	S	T	C	G	G
				XIX, alpha 1
G710a5	WIAF-15240	D38163	2403	COL19A1, collagen, type	AGGCATTCCA[G/T]GTGCTCCAGG	M	G	T	G	C
				XIX, alpha 1
G710a6	WIAF-15241	D38163	2437	COL19A1, collagen, type	TGGGAAACCC[G/T]GACCACCTGG	—	G	T	G	*
				XIX, alpha 1
G710a7	WIAF-15242	D38163	3295	COL19A1, collagen, type	TGGGCCACCA[G/A]GGAAGGATGG	M	G	A	G	R
				XIX, alpha 1
G710a8	WIAF-15243	D38163	3354	COL19A1, collagen, type	ACAGAGGACA[G/A]AAGGGAGAAA	S	G	A	Q	Q
				XIX, alpha 1
G710a9	WIAF-15244	D38163	3456	COL19A1, collagen, type	CCCCAGGCCC[C/A]CAGGGCCCCC	S	C	A	P	P
				XIX, alpha 1
G710a10	WIAF 15245	D38163	3566	COL19A1, collagen, type	AAGAAGACTT[A/G]GTTCCTGGTA	—	A	G	—	—
				XIX, alpha 1
G710a11	WIAF-15499	D38163	451	COL19A1, collagen, type	ACGAAGAAAC[G/A]CCAAAAAGGA	M	G	A	A	T
				XIX, alpha 1
G711a8	WIAF-15246	L25286	1525	COL15A1, collagen, type	GAGGAAGCCA[G/A]TGGGGTCCCC	M	G	A	S	N
				XV, alpha 1
G711a9	WIAF-15247	L25286	1600	COL15A1, collagen, type	TCTGGTCCTC[G/T]TGATGAAGAA	M	G	T	G	V
				XV, alpha 1
G711a10	WIAF-15248	L25286	1681	COL15A1, collagen, type	AGCCCTCCCC[C/G]TGATGGGCCA	M	C	G	P	R
				XV, alpha 1
G711a11	WIAF-15249	L25286	1826	COL15A1, collagen, type	GCCCTCCTGA[A/T]CCTTCTGGGC	M	A	T	E	D
				XV, alpha 1
G711a12	WIAF-15250	L25286	2527	COL15A1, collagen, type	CATGGATTCA[T/G ]GAATTTCTCG	M	T	G	M	R
				XV, alpha 1
G711a13	WIAF-15251	L25286	2647	COL15A1, collagen, type	GGCTTTCCAG[G/]ACTAAAAGGA	M	G	A	G	E
				XV, alpha 1
G711a14	WIAF-15500	L25286	1178	COL15A1, collagen, type	CAGCAGCGGG[G/A]CTGGCCGAGG	S	G	A	G	G
				XV, alpha 1
G711a15	WIAF-15501	L25286	1328	COL15A1, collagen, type	CAACAGCAGC[A/G]GGGGAGGCCG	S	A	G	A	A
				XV, alpha 1
G729a23	WIAF-15403	L02870	1540	COL7A1, collagen, type	GGTCTCCAGC[C/T]GGGCACTGAG	M	C	T	P	L
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a24	WIAF-15404	L02870	2359	COL7A1, collagen, type	GATACTGAGT[A/T]TACGGTCCAT	M	A	T	Y	F
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a25	WIAF-15405	L02870	2150	COL7A1, collagen, type	CTGCAGTCAT[C/T]GTGGCTCGAA	S	C	T	I	I
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a26	WIAF-15406	L02870	3261	COL7A1. collagen, type	AGTGTGCCCC[C/T]GTGCCCTGGC	M	C	T	R	C
				VII, alpha 1 (epidernolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a27	WIAF-15407	L02870	3732	COL7A1, collagen, type	GGCGCCGGGT[A/C]TGGACTCTGT	M	A	C	M	L
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a28	WIAF-15408	L02870	3749	COL7A1, collagen, type	CTGTCCAGAC/T]TTCTTCGCCG	S	C	T	T	T
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a29	WIAF-15409	L02870	3936	COL7A1, collagen, type	TGGCGACCCT[G/A]GCCTCCCGGG	M	G	A	G	S
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a30	WIAF-15410	L02870	3943	COL7A1, collagen, type	CCTGGCCTCC[C/T]GGGCAGGACC	M	C	T	P	L
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a31	WIAF-15411	L02870	5199	COL7A1, collagen, type	CAAGCGTGAC[C/T]GTGGCGAGCC	M	C	T	R	C
				VII, alpha 1 (epidernolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a32	WIAF-15412	L02870	6036	COL7A1, collagen, type	GCCTGTGCCC[G/A]AACGGCGTCG	M	G	A	E	K
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a33	WIAF-15413	L02870	7399	COL7A1, collagen, type	CTGGCAGGCC[C/T]CCCAGGGAGA	M	C	T	P	L
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a34	WIAF-15414	L02870	7987	COL7A1, collagen, type	CGGGGCCTCA[A/T]GOGTGAACGG	M	A	T	K	M
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a35	WIAF-15415	L02870	8102	COL7A1, collagen, type	ACATGGGGGA[G/C]CCTGGTGTCC	M	G	C	E	D
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a36	WIAF-154161	L02870	8104	COL7A1, collagen, type	ATGGGGGAGC[C/T]TGGTGTGCCG	M	C	T	P	L
				VII, alpha 1 (epidernolysis
				bullosa, dystrophic,
				dominant and recessive)
G729a37	WIAF-15417	L02870	7938	COL7A1, collagen, type	AGTCCCTGGT[A/C]TCCGACGAGA	M	A	C	I	L
				VII, alpha 1 (epidermolysis
				bullosa, dystrophic,
				dominant and recessive)
G749a1G	WIAF-15402	HT3734	673	osteopontin, alt.	GAGGACATCA[C/T]CTCACACATG	M	C	T	T	I
				transcript 1
G765a38	WIAF-15264	HT2456	328	DCP1, dipeptidyl	AGAAGGCCAA[G/A]CACCTGTATG	S	G	A	K	K
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G765a39	WIAF-15265	HT2456	355	DCP1, dipeptidyl	TCTGGCAGAA[C/T]TTCACGGACC	S	C	T	N	N
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G765a40	WIAF-15266	HT2456	364	DCP1, dipeptidyl	ACTTCACCCA[C/T]CCCCAGCTGC	S	C	T	D	D
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G765a41	WIAF-15267	HT2456	530	DCP1, dipeptidyl	GTCCCTCGAC[C/T]CAGATCTCAC	M	C	T	P	S
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G765a42	WIAF-15268	HT2456	1032	DCPl, dipeptidyl	CAGCTCTCCCEC/T]CATGCCTCCC	M	C	T	P	L
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G765a43	WIAF-15269	HT2456	1074	DCP1, dipeptidyl	CTGGAGAAGCEC/T]CGCCGACGGG	M	C	T	P	L
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G765a44	WIAF-15270	HT2456	3346	DCP1, dipeptidyl	CCAGGACTCA[A/T]GCTGACTTTG	M	A	T	Q	H
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G765a45	WIAF-15323	HT2456	906	DCP1, dipeptidyl	AACATCTACG[A/G]CATGGTGTTCC	M	A	G	D	G
				carboxypeptidase 1
				(anglotensin I converting
				enzyme)
G776a4	WIAF-15383	U66088	1208	SLC5A5, solute carrier	TCAACCAGCT[C/T]CGCCTGTTCC	S	C	T	V	V
				family 5 (sodium iodide
				symporter), member 5
G776a5	WIAF-15400	U66088	2127	SLC5A5, solute carrier	TCCTGAACAA[C/T]TCCCCACTCG	M	C	T	L	F
				family 5 (sodium iodide
				symporter), member S
G776a6	WIAF-15401	U66088	2348	SLC5A5, solute carrier	CAGACAACGG(G/CICCCATCGCCT	—	G	C	—	—
				family S (sodium iodide
				symporter), member 5
G797a7	WIAF-15082	HT3919	2658	glutamate receptor 3, flip	CTTTAACCCT[G/T]CTCCTGCCAC	M	G	T	A	S
				isoform
G797a8	WIAF-15083	HT3919	2661	glutamate receptor 3, flip	TAACCCTCCT[C/T]CTGCCACCAA	M	C	T	P	S
				isoform
G797a9	WIAF-15089	HT3919	743	glutamate receptor 3, flip	ACACAATTTT[C/T]CAACACGTTC	M	G	T	L	F
				isoform
G797a10	WIAF-15090	HT3919	1428	glutamate receptor 3, flip	TCTACACCTA [C/A]CCTATCAAAT	M	G	A	A	T
				isoform
G797a11	WIAF-15091	HT3919	1316	glutamate receptor 3, flip	CATCCTCAGA[G/A]AATCCCACCA	S	G	A	E	E
				isoform
G797a12	WIAF-15092	HT3919	1993	glutamate receptor 3, flip	ATAATTTCTT[C/T]CTATACTGCC	M	C	T	S	F
				isoform
G798a8	WIAF-15418	X77748	1521	GRM3, glutamate receptor,	ATGCTATGAA[C/A]ATCCTGGATG	S	G	A	K	K
				metabotropic 3
G798a9	WIAF-15419	X77748	2303	GRM3, glutamate receptor,	AAATTCATCA[G/A]CCCCAGTTCT	M	G	A	S	N
				metabotropic 3
G798a10	WIAF-15420	X77748	2082	GRM3, glutamate receptor,	TCAAAGCATC[G/C]GGCCGAGAAC	S	G	C	S	S
				metabotropic 3
G799a6	WIAF-15067	M81883	710	GAD1, glutamate	CTTGCAAACG [A/T]CCAACAGCCT	M	A	T	T	S
				decarboxylase 1 (brain,
				67 kD)
G799a7	WIAF-15058	M81883	1523	GAD1, glutamate	AGCTGATTTT[G/T]AGGCAAAAAT	—	G	T	E	*
				decarboxylase 1 (brain,
				67 kD)
G799a8	WIAF-15059	M8lS83	1613	GAD1, glutamate	AGCTTTTCAT[C/T]CGATACAAGA	M	C	T	P	S
				decarboxylase 1 (brain,
				67 kD)
G799a9	WIAF-15070	M81883	1435	GAD1, glutamate	ATTCCATAAA[G/A]AAAGCTGGGC	S	G	A	K	K
				decarboxylase 1 (brain,
				G7kD)
G790a10	WIAF-15084	M81883	2277	GAD1, glutamate	CCAGCCGCTA[C/A]CCAGTCTCAC	M	C	A	T	N
				decarboxylase 1 (brain,
				67 kD)
G799a11	WIAF-15085	M81883	2351	CAD1, glutamate	CTTCCCACAA[C/T]ATGAGTTTAT	—	C	T	—	—
				decarboxylase 1 (brain,
				67 kD)
G799a12	WIAF-15086	M81883	2145	GAD1, glutamate	CCTCAACCAC[G/A]CGAAAACCTA	m	G	A	R	Q
				decarboxylase 1 (brain,
				67 kD)
G801a2	WIAF-15074	D49394	1002	HTR3, 5-hydroxytryptamine	TCATCGACAT[C/T]CTCGGCTTCT	S	C	T	I	I
				(serotonin) receptor 3
G804a8	WIAF-15421	Z26653	7652	LAMA2, laminin, alpha 2	TCCTAACCCT[G/T]GTTTTGTGGA	M	G	T	G	C
				(merosin, congenital
				muscular dystrophy)
G804a9	WIAF-15422	Z26653	9050	LAMA2, laminin, alpha 2	CATGTTTCAT[C/A]TCGACAATCG	M	G	A	V	M
				(merosin, congenital
				muscular dystrophy)
G804a10	WIAF-15423	Z26653	9052	LAMA2, laminin, alpha 2	TGTTTCATGT[G/C]GACAATCGTG	S	C	C	V	V
				(merosin, congenital
				muscular dystrophy)
G805a4	WIAF-15071	U14755	556	LHX1 , LIM homeobox protein	GACCCAGAAC[T/C]GCTTCTCCAC	M	T	C	C	R
				1
G805a5	WIAF-15072	U14755	6511	LHX1, LIM homeobox protein	TCTCCCCTAG[C/T]GACCTCCTCC	S	C	T	S	S
				1
G805a6	WIAF-15073	U14755	4871	LHX1,LIM homeobox protein	TCTCTTCAAC[G/A]TGCTCGACAG	M	G	A	V	M
				1
G806a13	WIAF-15397	AF026547	328	CSPG3, chondroitin sulfate	CCTCCCACGC[A/G]CCACTCTCAC	S	A	G	G	G
				proteoglycan 3 (neurocan)
G806a14	WIAF-15424	AF026547	704	CSPC3, chondroitin sulfate	TAGCACCCTT[C/G]CACCCGTTCC	M	C	G	P	A
				proteoglycan 3 (neurocan)
G810a13	WIAF-15075	X98248	1217	SORT1, sortilin 1	ACTACCACAC[G/T]CGCACAGACG	M	G	T	G	V
G810a14	WIAF-15076	X98248	1031	SORT1, sortilin 1	CGCGACACAT[G/A]CAGCATCCCC	—	G	A	W	*
G810a15	WIAF-15093	X98248	1564	SORT1, sortilin 1	GGGTTACTCC[T/G]CCACAAACAT	M	T	G	W	G
G811a7	WIAF-15077	HT3676	129	synapsin I, alt. transcript	CCGGAGCCAC[G/T]CCCCCTCCCG	S	G	T	T	T
G811a8	WIAF-15078	HT3676	258	synapsin I, alt. transcript	CCCTCAACCA [C/A]ACCACGCCCC	S	G	A	Q	Q
G811a9	WIAF-15079	HT3676	312	synapsin I, alt, transcript	GCGGCTCTCG [C/A]GCCGCACCCC	S	G	A	G	C
G811a10	WIAF-15080	HT3676	912	synapsin I, alt, transcript	ATCCCACTCC [C/T]CAGCCCTTCA	S	C	T	A	A
G811a11	WIAF-15094	HT3676	765	synapsin I, alt. transcript	TTCTTCCGAA [T/C]CCCGTCAAGC	S	T	C	N	N
G811a12	WIAF-15095	HT3676	438	synapsin I, alt. transcript	ACCCCAATCA[C/T]AAACAAATCC	S	C	T	H	H
G811a13	WIAF-15096	HT3676	1316	synapsin I, alt. transcript	TAGACCAGCC[C/T]CAATTCTCTG	S	C	T	A	A
G811a14	WIAF-15097	HT3676	1316	synapsin I, alt, transcript	ACTCCGTCCC[C/T]AGGGGCCCTG	M	C	T	P	L
G811a15	WIAF-15098	HT3676	1353	synapsin I, alt, transcript	CCTCCCAGCA[G/C]CCCGCAGCCC	M	G	C	Q	M
G812a3	WIAF-15081	HT4564	109	STX1A, syntaxin 1A (brain)	TCGCAGAGAA[C/T]GTGGAGGAGG	S	C	T	N	N
G813a3	WIAF-15398	U72508	239	Human 57 mRNA, complete	CCCTGAGCAA[T/G]GGCTGCCCAC	M	T	G	W	G
				cds.
G813a4	WIAF-15425	U72508	566	Human 57 nRNA, complete	CACTGAAGGC[A/C]TCTCTCATCC	M	A	C	I	L
				cds.
G813a5	WIAF-15426	U72508	611	Human B7 mRNA, complete	ACCGAACAGC[A/C]TCCACATCGT	M	A	C	I	L
				cds.
G813a6	WIAF-15427	U72508	621	Human 57 mRNA, complete	ATCCACATGD[T/A]CACAGGTCTG	M	T	A	V	E
				cds.
G813a7	WIAF-15428	U72508	483	Human B7 mRNA, complete	CATGCCAATC[G/T]CCTCCGAACT	M	G	T	R	L
				cds.
G830a1	WIAF-15163	X74142	1186	FKHL1, forkhead	TCCCCCTACC[C/T]CAGCCACCCC	M	C	T	P	L
				(Drosophila)-like 1
G830a2	WIAF-15164	X74l42	1217	EKELl, forkhead	CCTCCCTGTT[G/A]ACTCAAAACT	S	G	A	L	L
				(Drosophila)-like 1
G830a3	WIAF-15173	X74142	1556	FKHL1, forkhead	CTTTAACACC[C/T]TCTTTCCAA	S	C	T	P	P
				(Drosophila)-like 1
G830a4	WIAF-15174	X74142	1688	FKHLl, forkhead	AACGTTTTAC[A/G]CACATTTGCA	—	A	G	—	—
				(Drosophila)-like 1
G830a5	WIAF-15175	X74142	1487	FKHL1, forkhead	CGTCCATCAG[C/T]CCCAGGGCCG	S	C	T	S	S
				(Drosopbila)-like 1
G831a1	WIAF-15176	X74143	1353	FKHL2, forkhead	TCAACCCCTC[C/T]TCCCTCAACC	S	C	T	C	C
				(Drosophila)-like 2
G831a2	WIAF-15177	X74143	1440	FKHL2, forkhead	CCACCTCCAT[G/T]AGCCCCACGC	M	G	T	M	I
				(Drosophila)-like 2
G831a3	WIAF-15178	X74143	1443	FKHL2, forkhead	CGTCCATCAC[C/T]GCCACCCCCC	S	C	T	S	S
				(Drosophila)-like 2
G836a3	WIAF-15113	U28369	505	SEMA3B, sema domain,	CCAACAACCT[G/A]GCCTCGCCCC	S	G	A	L	L
				immunoglobulin domain (Ig)
				short basic domain,
				secreted, 3B
G836a4	WIAF-15114	U28369	549	SEMA3B, sema domain,	TCCAACTGCG[C/T]ACGCAACGAC	M	C	T	A	V
				immunoglobulin domain (Ig),
				short basic domain,
				secreted, 3B
G836a5	WIAF-15115	U28369	1159	SEMA3B, sema domain,	ATCACCTCCA[G/A]GATGTCTTTC	S	G	A	Q	Q
				imnunoglobulin domain (Ig),
				short basic domain,
				secreted, 3B
G838a3	WIAF-15429	U72671	1676	ICAM5, intercellular	CCGTCATCCA[G/A]GGCCTGTTGC	S	G	A	E	E
				adhesion molecule 5,
				telencephalen
G841a4	WIAF-15165	HT97420	1475	SMOH, smoothened	CTATGTCAGC[C/T]CAATGTGACC	H	C	T	A	V
				(Drosophila)homolog
G841a5	WIAF-15167	HT97420	2085	SMOH,smoothened	ACCCCCCTGC[C/T]CCTGCCCCCA	S	C	T	A	A
				(Drosophila)homolog
G841a6	WIAF-15179	HT97420	808	SMOH,smoothened	TCTCTTCTAC [D/A]TCAATGCGTC	M	C	A	V	I
				(Drosophila)homolog
G841a7	WIAF-15180	HT97420	1749	SMOH, smoothened	TGCACAACCC[A/G]GDCCAGGAGC	S	A	G	P	P
				(Drosophila) homolog
G841a8	WIAF-15181	HT97420	1774	SMOH, smoothened	CTTCACCATC[C/T]ACACTCTGTC	M	C	T	H	Y
				(Drosophila) homolog
G841a9	WIAF-15182	HT97420	1905	SMOH, smoothened	TACTCCCCCA[G/A]GATATTTCTC	S	G	A	Q	Q
				(Drosophila) homolog
G841a10	WIAF-15183	HT97420	1934	SMOH, smoothened	CTCCCAACTC[C/G]AGTCCCCCCA	M	C	G	P	R
				(Drosophila) homolog
G841a11	WIAF-15184	HT97420	1936	SMOH, smoothened	CCCAACTCCA[G/C]TGCCCCCAGA	M	C	C	V	L
				(Drosophila) homolog
G841a12	WIAF-15185	HT97420	1938	SMOH, smoothened	CAACTCCAGT[G/A]CCCCCACAGC	S	G	A	V	V
				(Drosophila) homolog
G845a1	WIAF-15132	J04076	1223	ECR2, early growth	CCCATATCCC[C/A]ACCCACACCG	S	C	A	R	R
				response 2 (Krox-20
				(Drosophila) homolog)
G847a4	WIAF-15133	L41939	3089	EPHB2, EphB2	CCTCCCCTCA[C/T]CTCTTCCTCC	—	C	T	—	—
G847a5	WIAF-15134	L41939	3126	EPHB2, EphB2	CCCCCACGTC [C/T]CCCCCCTCCT	—	C	T	—	—
G847a6	WIAF-15136	L41939	1481	EPHB2, EphB2	CCTCCCAGCC[A/G]GACCAGCCCA	S	A	G	P	P
G847a7	WIAF-18137	L41939	2514	EPHE2, EphB2	GTACCGGAAG [T/C]TCACCTCGGC	M	T	C	F	L
G848a3	WIAF-15116	L40636	1426	EPHE1, EphB1	ACACCCCCTA [C/G]ACCTTTGACA	—	C	C	Y	*
G848a4	WIAF-15117	L40636	2351	EPHB1, EphB1	TTTCCTCACG[C/G]AAAATCACGG	M	C	G	Q	E
G848a5	WIAF-18118	L40636	2363	EPHB1, EphB1	AAATCACCCC[C/A]ACTTCACCGT	M	C	A	Q	K
G848a6	WIAF-15138	L40636	1657	EPHB1, EphB1	ACAATCACTT[C/T]AACTCCTCCA	S	C	T	F	F
G848a7	WIAF-15139	L40636	1600	EPHB1, EphB1	CGGAGCACCC[C/T]AATCCACATCA	S	C	T	P	P
G848a8	WIAF-15140	L40636	2598	EPHE1, EphB1	TGGACAGCTC[C/T]ACACGCCATC	M	C	T	P	L
G848a9	WIAF-15141	L40636	2718	EPHB1, EphB1	AACCAAGATG[T/C]CATCAATACC	M	T	C	V	A
G848a10	WIAF-15142	L40636	2822	EPHB1, EphB1	CCCGAACAGC[C/A]GGCCCCGGTT	S	C	A	R	R
G849a11	WIAF-15064	D83492	2523	EPHB6, EphB6	CCCAGCTTCC[G/A]GAAACACTCT	S	G	A	P	P
G849a12	WIAF-15065	D83492	2640	EPHB6, EphB6	CTGGCTACAC[G/A]GAGCAGCTGC	S	G	A	T	T
G849a13	WIAF-15066	D83492	2390	EPHB6, EphB6	AACACTGCCA[C/T]CGTCACACAG	M	C	T	T	I
G849a14	WIAF-15087	D83492	1246	EPHB6, EphB6	CGAGAGCTTT[C/T]CCTCCTCCTC	M	C	T	P	S
G849a15	WIAF-15088	D83492	2792	EPHB6, EphB6	GGGACAGCCT[C/T]TTTTCCAGAA	M	C	T	S	F
G855a1	WIAF-15210	D26309	1046	LIMK1, LIM domain kinase 1	AGCGCAAGGA[C/A]CTCGCTCGCT	M	C	A	D	E
G856a2	WIAF-15119	D45906	1256	LINK2, LIM domain kinase 2	AAACTCATCC[G/A]CAGCCTCAGAC	M	G	A	R	H
G856a3	WIAF-15120	D45906	1047	LINK2, LIM domain kinase 2	ACATCAGCCG[C/T]TCACAATCCC	S	C	T	R	R
G856a4	WIAF-15135	D45906	2157	LINK2, LIM domain kinase 2	AGCAGAACAA[G/A]CCATTCCTAT	—	G	A	—	—
G856a5	WIAF-15143	D45906	751	LINK2, LIM domain kinase 2	GACCCCCCTC[C/T]GCACACTTCG	M	C	T	R	C
G857a1	WIAF-15430	D58496	2209	DYRK1, dua1-specificity	TTTTCTGCTA[A/C]TACAGSTCCT	M	A	C	N	T
				tyrosine-(Y)-
				phosphorylation regulated
				kinase 1
G859a1	WIAF-15431	HT97433	798	metrin-2	CCACGACAGC[A/G]GCCCCCCAGG	M	A	G	S	G
G859a2	WIAF-15432	HT97433	893	metrin-2	CTAGCACGCC[A/G]GGTCACCCCA	S	A	G	A	A
G865a2	WIAF-15144	HT3917	847	glutamate receptor 2, alt.	TTCCAAAACA[C/T]CTTAAAGCCT	S	C	T	H	H
				transcript 1, flop
G866a3	WIAF-15121	HT0101	1175	glutamate receptor	TACACGCTCC[A/T]CGTCATTGAA	M	A	T	H	L
				(GE:M64752)
G3866a4	WIAF-15122	HT0101	1280	glutamate receptor	GGCGATAATT[C/T]AAGTGTTCAG	M	C	T	S	L
				(GB:M64752)
G870a6	WIAF-15218	HT4468	246	SLC1A1, solute carrier	CCGTGGCCGC[G/C]GTGGTGCTAG	S	G	C	A	A
				family 1
				(neuronal/epithelial high
				affinity glutamate
				transporter, system Xag),
				member 1
G871a7	WIAF-15440	HT3187	1840	SLC1A3, solute carrier	TTGAGCACCA[G/A]GTGTTAAAAA	—	G	A	—	—
				family 1 (glial high
				affinity glutamate
				transporter), member 3
G871a8	WIAF-15441	HT3187	1940	SLC1A3, solute carrier	ACACTGGAAA[A/G]TAGTCCTCCA	—	A	G	—	—
				family 1 (glial high
				affinity glutamate
				transporter), member 3
G871a9	WIAF-1544S	HT3187	645	SLC1A3, solute carrier	CAAAACATGC[A/G]CAGAGAAGCC	M	A	G	H	R
				family 1 (glial high
				affinity glutamate
				transporter), member 3
G871a10	WIAF-15446	HT3187	1590	SLC1A3, solute carrier	ATCATCGCCG[T/A]GCACTCGTTC	M	T	A	V	E
				family 1 (glial high
				affinity glutamate
				transporter), member 3
G871a11	WIAF-15447	HT3187	1066	SLC1A3, solute carrier	TTGTCGAGCA[C/T]TTGTCACGAC	S	C	T	H	H
				family 1 (glial high
				affinity glutamate
				transporter), member 3
G876a1	WIAF-15449	U16127	1467	GRIK3, glutamate receptor,	CCTATCACAT [C/T]CCCCTGCTCC	S	C	T	I	I
				ionotropic, kainate 3
G879a8	WIAF-15455	HT28317	1545	GRM2, glutamate receptor,	TGTGCACCCC[G/A]CCCAAGTCTC	M	G	A	G	S
				metabotropic 2
G879a9	WIAF-15456	HT28317	2474	CRM2, glutamate receptor,	CGCACAACAA[C/T]CTGGTTACCC	S	C	T	N	N
				metabotropic 2
G880a7	WIAF-15436	HT33719	2052	GRM4, glutamate receptor,	ACTGACCTAC[G/A]TGCTGCTGCC	M	G	A	V	M
				metabotropic 4
G880a8	WIAF-15437	HT33719	2079	CRM4, glutamate receptor,	CTTCCTGTGC[T/G]ATCCCACCAC	M	T	G	Y	D
				metabotropic 4
G880a9	WIAF-15438	HT33719	2129	CRM4, glutamate receptor,	CCACCTGCTC[G/A]CTCCCCCGG	S	G	A	S	S
				metabotropic 4
G880a10	WIAF-15442	HT33719	3060	CRM4, glutamate receptor,	CCCCCCACCC[A/G]TCACTCCTCG	—	A	G	—	—
				metabotropic 4
G885a4	WIAF-1521l	AF002700	113	GFRA2, GDNF family	CTTCCTCCCT [C/T]CAGCCCCCCG	S	G	T	L	L
				receptor alpha 2
G885a5	WIAF-15443	AF002700	1420	GFRA2, CDNF family	ATCCTCAAAC[A/T]GCCCTTCTAG	M	A	T	Q	L
				receptor alpha 2
G892a27	WIAF-15145	U12140	418	NTRK2, neurotrophic	CTGCCTGCTT[G/T]TGCCCTTCTG	M	G	T	V	L
				tyrosine kinase, receptor,
				type 2
G892e28	WIAF-15146	U12140	433	NTRK2, neurotrophic	CTTCTCGACC[G/A]CCCCTTTCCC	M	G	A	A	T
				tyrosine kinase, receptor,
				type 2
G892a29	WIAF-15147	U12140	631	NTRK2, neurotrophic	TCTCCCACTC[A/T]CAAATCTCAC	—	A	T	R	*
				tyrosine kinase, receptor,
				type 2
G892a30	WIAF-15148	U12140	1201	NTRK2, neurotrophic	CCTCACTCTC[C/G]ATTTTCCACC	M	C	G	H	D
				tyrosine kinase, receptor,
				type 2
G892a31	WIAF-15149	U12140	2127	NTRK2, neurotrophic	CCCACCTCCT[G/A]ACCAACCTCC	S	G	A	L	L
				tyrosine kinase, receptor,
				type 2
15892a32	WIAF-15150	U12140	2866	NTRK2, neurotrophic	TCCTCAGACG [G/T]GCTGAGAGGA	—	G	T	—	—
				tyrosine kinase, receptor,
				type 2
G892a33	WIAF-15151	U12140	2899	NTRK2, neurotrophic	AACTGCCGCT[G/A]GAGGCCACCA	—	G	A	—	—
				tyrosine kinase, receptor,
				type 2
G892a34	WIAF-15152	U12140	740	NTRK2, neurotrophic	CTGACGAGTT[T/A]GTCTA15GAAA	—	T	A	L	*
				tyrosine kinase, receptor,
				type 2
G892a35	WIAF-15153	U12140	1428	NTRK2, neurotrophic	ATGGGGACTA[C/T]ACTCTAATAG	S	C	T	Y	Y
				tyrosine kinase, receptor,
				type 2
G892a36	WIAF-15154	U12140	1440	NTRK2, neurotrophic	CTCTAATAGC[C/G]AAGAATGACT	S	C	G	A	A
				tyrosine kinase, receptor,
				type 2
G5893a4	WIAF-15212	U05012	482	NTRK3, neurotrophic	AAAAGCTGAC[C/T]ATCAAGAACT	S	C	T	T	T
				tyrosine kinase, receptor,
				type 3
G5893a5	WIAF-15458	U05012	728	NTRK3, neurotrophic	ACTGCATCAA[C/T]GCTGATGGCT	S	C	T	N	N
				tyrosine kinase, receptor,
				type 3
G895a2	WIAF-15475	HT48617	1593	SYN2, synapsin II	GGTGCCSTTG[C/T]TGCGTTCTTT	—	C	T	—	—
G895a3	WIAF-15476	HT48617	1597	SYN2, synapsin II	CCGTTGCTGC[G/T]TTCTTTCAAT	—	G	T	—	—
G897a1	WIAF-15470	HT1165	1101	SYNT1, synaptotagmin 1	AAGTGCAGGT[G/T]GTCGTAACTG	S	G	T	V	V
G90a5	WIAF-15110	HT1847	1063	INHA, inhibin, alpha	ATCTAAGGGT[G/T]GGGGGTCTTC	—	G	T	—	—
G90a6	WIAF-15111	HT1847	636	INHA, inhibin, alpha	ACCCAGTGGA[G/A]GGGAGAGAGC	S	G	A	E	E
G5900a2	WIAF-15477	HT3470	714	STX4A, syntaxin 4A	TTGAACGCAG[T/C]ATTCGTGAGC	S	T	C	S	S
				(placental)
G901a9	WIAF-15478	HT27792	694	STX3A, syntaxin 3A	ATGGACATCG[C/T]CATCCTGGTG	M	C	T	A	V
G5917a8	WIAF-15460	U79734	394	HIP1, huntingtin	TGGACGAGCC[T/C]GGAGAAAGTG	S	T	C	A	A
				interacting protein 1
G5917a9	WIAF-15479	U79734	2665	HIP1, huntingtin	AGGACAGCCC[C/T]AACCTAGCCC	S	C	T	P	P
				interacting protein 1
G917a10	WIAF-15480	U79734	2724	HIP1, huntingtin	GCCGGCGTTG[T/C]GGCCTCAACC	M	T	C	V	A
				interacting protein 1
G920a10	WIAF-15461	X78520	869	CLCN3, chloride channel 3	ATGCGTGGTC[A/T]GGATGGCTAC	S	A	T	S	S
G920a1l	WIAF-15462	X78520	1495	CLCN3, chloride channel 3	GTTCTTTTTA[G/C]CCTGGAAGAG	M	G	C	S	T
G920a12	WIAF-15463	X78520	1520	CLCN3, chloride channel 3	GCTATTATTT[T/C]CCTCTCAAAA	S	T	C	F	F
G920a13	WIAF-15464	X78520	1598	CLCN3, chloride channel 3	ATCCATTTCG[T/C]AACAGCCGTC	S	T	C	G	G
G923a4	WIAF-15465	M19650	405	Human 2′,3′-cyclic	GTGGAGCCCA[A/G]GACGGCGTGG	M	A	G	K	R
				nucleotide 3′-
				phosphodiesterase mRNA,
				complete cds.
5923a5	WIAF-15472	M19650	1048	Human 2′,3′-cyclic	ACGACGTGCC[C/T]GAGCTAACCC	S	C	T	G	G
				nucleotide 3′-
				phosphodiesterase mRNA,
				complete cds.
G923a6	WIAF-15473	M19650	1246	Human 2′,3′-cyclic	TTATCCCCCT[A/G]CAACGGAAGC	—	A	G	—	—
				nucleotide 3′-
				phosphodiesterase mRNA,
				complete cds.
G924a1	WIAF-15474	D85758	141	ERH, enhancer of	TGCTCACTAC[G/A]AATCTCTCAA	M	G	A	E	K
				rudimentary (Drosophila)
				homolog
G925a7	WIAF-15219	L11315	2916	CAK, cell adhesion kinase	CCTCACCCAG[C/T]GATCCAGCGC	—	C	T	—	—
G925a8	WIAF-15466	L11315	396	CAK, cell adhesion kinase	ACCAGGACCA[G/C]TACTTCCACG	M	G	C	E	D
G925a9	WIAF-15467	L11315	423	CAK, cell adhesion kinase	TACAACCACT[C/C]CACCTCCTCG	S	G	C	V	V
G925a10	WIAF-15468	L11315	2187	CAK, cell adhesion kinase	TCAACCACCC[A/C]AACATCATTC	S	A	C	P	P
G926a16	WIAF-15469	AF018956	2106	NRD1, neuropilin 1	AAAATCAGAA[G/A]GCCAAAGTGC	S	G	A	K	K
G927a14	WIAF-15155	AF022860	159	NRP2, neuropilin 2	CCTCCCACCA[G/A]AACTCCGACT	S	G	A	Q	Q
G927a15	WIAF-15156	AF022860	183	NRP2, neuropilin 2	TTCTTTACCC[C/A]CCCGAACCCA	S	C	A	A	A
G927a16	WIAF-15157	AF022860	254	NRP2, neuropilin 2	CACTGCAACT[A/G]TGACTTTATC	M	A	G	Y	C
G927a17	WIAF-15158	AF022860	99	NRP2, neuropilin 2	GTCGTTTCAA[T/C]TCCAAAGATC	S	T	C	N	N
G927a18	WIAF-15150	AF022860	1208	NRP2, neuropilin 2	GCTCCACTCC[T/C]GACAACGTTT	M	T	C	L	P
G927a19	WIAF-15180	AF022880	1298	NRP2, neuropilin 2	TCACAGATGC[T/C]CCCTGCTCCA	S	T	C	A	A
G927a20	WIAF-15181	AF022880	1404	NRP2, neuropilin 2	CCCGCCTGGT[C/T]AGCAGCCGCT	S	C	T	V	V
G927a21	WIAF-15162	AF022860	833	NRP2, neuropilin 2	TTTCAGTGCA[A/T]TGTTCCTCTG	M	A	T	N	I
G936a6	WIAF-15220	HT3432	381	GABRB2, gamma-amino-	GAGACCAGAT[T/C]TTGCAGGTCC	M	T	C	F	L
				butyric acid (GABA)
				A receptor, beta 2
G947a1	WIAF-15484	U20350	832	CX3CR1, chenokine (C-X3-C)	ACCCTACAAC[G/A]TTATCATTTT	M	G	A	V	I
				receptor 1
G947a2	WIAF-15485	U20350	928	CX3CR1, chemokine (C-X3-C)	GTGACTGAGA[C/T]GGTTGCATTT	M	C	T	T	N
				receptor 1
G953a4	WIAF-14838	HT0310	7245	CACNA1B, calcium channel,	CACCGGGCAG[T/C]CGGCCCTCSG	—	T	C	—	—
				voltage-dependent, L type,
				alpha 1B subunit
G957a13	WIAF-15222	HT4229	1258	calcium channel, voltage-	GGAGAACCGA[A/G]GGGCTTTCAT	M	A	G	R	G
				gated, alpha 1E subunit,
				alt. transcript 2
G957a14	WIAF-15223	HT4229	2878	calcium channel, voltage	CGCAGCCCGC[A/C]TCGCCGCGTC	M	A	C	H	P
				gated, alpha 1E subunit,
				alt. transcript 2
G957a15	WIAF-15224	HT4229	2991	calcium channel, voltage-	AGGACCATGA[G/A]CTCAGGGCCA	S	G	A	E	E
				gated, alpha 1E subunit,
				alt. transcript 2
G957a18	WIAF-15225	HT4229	3139	calcium channel, voltage-	CCTGCCCCAT[C/T]CTCACCTCGA	M	C	T	P	S
				gated, alpha 1E subunit,
				alt, transcript 2
G957a17	WIAF-15481	HT4229	4889	calcium channel, voltage-	TATACCATAC[G/T]CATTTTGCTG	M	G	T	R	L
				gated, alpha 1E subunit,
				alt. transcript 2
0957a18	WIAF-15486	HT4229	3528	calcium channel, voltage-	GCACCACCAA[C/A]CCGATCCGGA	M	C	A	N	K
				gated, alpha 1E subunit,
				alt. transcript 2
G957a19	WIAF-15487	HT4229	5270	calcium channel, voltage	TTTGTGGCCG[T/A]CATCATGGAC	M	T	A	V	D
				gated, alpha IE subunit,
				alt. transcript 2
G957a20	WIAF-15488	HT4229	5952	calcium channel, voltage-	ATATATTCCA[G/A]TTGGCTTGTA	S	G	A	Q	Q
				gated, alpha IE subunit,
				alt. transcript 2
G957a21	WIAF-15489	HT4229	5962	calcium channel, voltage-	GTTGGCTTGT[A/C]TGGACCCCGC	M	A	C	M	L
				gated, alpha IE subunit,
				alt. transcript 2
G957a22	WIAF-15490	HT4229	6862	calcium channel, voltage-	TGGGCCAGGC[A/C]TGATGTGTGG	M	A	C	M	L
				gated, alpha 15 subunit,
				alt. transcript 2
G955a4	WIAE-15491	HT2200	3332	CACNA2D1, calcium channel,	CCAAATCTGC[A/C]TAGTTAAACT	—	A	C	—	—
				voltage-dependent, alpha
				2/delta subunit 1
G958a5	WIAS-15492	HT2200	3246	CACNA2D1, calcium channel,	TCCCTGTGGT[A/C]TATCATTGGA	M	A	C	Y	S
				voltage-dependent, alpha
				2/delta subunit 1
G960a5	WIAF-15493	HT3336	621	CACNB3, calcium channel,	GGTCACAGAC [A/C]TGATGCAGAA	M	A	C	M	L
				voltage-dependent, beta 3
				subunit
G961a3	WIAF-15494	U95019	2130	CACNB2, calcium channel,	ACGGGAGCAG[T/C]GACCACAGAC	S	T	C	S	S
				voltage-dependent, beta 2
				subunit
5974a3	WIAF-15226	HT4527	1757	SLC18A3, solute carrier	GCTTCGSAAG[C/T]CTAGTGGCCC	S	C	T	S	S
				family 18 (vesicular
				acetylcholine), member 3
G974a4	WIAF-15227	HT4527	1811	SLC18A3, solute carrier	GCAAGCGCGT[G/A]CCCTTCTTGG	S	G	A	V	V
				family 18 (vesicular
				acetylcholine), member 3
G974a5	WIAF-15495	HT4527	1194	SLC18A3, solute carrier	GGTGCTTGTT[A/C]TCGTCTGCGT	M	A	C	I	L
				family 18 (vesicular
				acetylcholine), member 3
G974a6	WIAF-15496	HT4527	1337	SLC18A3, solute carrier	TGCCGCTGCC[C/A]ACTCCGGCCA	S	C	A	P	P
				family 18 (vesicular
				acetylcholine), member 3
G974a7	WIAF-15497	HT4527	1372	SLC18A3, solute carrier	ACGGCCAACA[C/A]CTCCCCGTCC	M	C	A	T	N
				family 18 (vesicular
				acetylcholine), member 3
G989a4	WIAF-15231	D86519	934	NPY6R, neuropeptide Y	CCTTCTGCTG[T/C]CTATTCCCTT	M	T	C	S	P
				receptor Y6
G990a13	WIAF-15213	N73980	852	NOTCH1, Notch (Drosophila)	GCCCGTGCCC[G/A]CCAGAGTGGA	S	G	A	P	P
				homolog 1 (translocation-
				associated)

[0112] 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, such as cancer, inflammation, heart disease, diseases of the cardiovascular system, and infection by microorganisms. 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.

[0113] While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Claims

1. A nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of the nucleic acid sequences listed in the Table, wherein said nucleic acid sequence is at least 10 nucleotides in length and comprises a polymorphic site identified in the Table, and wherein the nucleotide at the polymorphic site is different from a nucleotide at the polymorphic site in a corresponding reference allele.

2. A nucleic acid molecule according to claim 1, wherein said nucleic acid sequence is at least 15 nucleotides in length.

3. A nucleic acid molecule according to claim 1, wherein said nucleic acid sequence is at least 20 nucleotides in length.

4. A nucleic acid molecule according to claim 1, wherein the nucleotide at the polymorphic site is the variant nucleotide for the nucleic acid sequence listed in the Table.

5. An allele-specific oligonucleotide that hybridizes to a portion of a nucleic acid sequence selected from the group consisting of the nucleic acid sequences listed in the Table, wherein said portion is at least 10 nucleotides in length and comprises a polymorphic site identified in the Table, and wherein the nucleotide at the polymorphic site is different from a nucleotide at the polymorphic site in a corresponding reference allele.

6. An allele-specific oligonucleotide according to claim 5 that is a probe.

7. An allele-specific oligonucleotide according to claim 5, wherein a central position of the probe aligns with the polymorphic site of the portion.

8. An allele-specific oligonucleotide according to claim 5 that is a primer.

9. An allele-specific oligonucleotide according to claim 8, wherein the 3′ end of the primer aligns with the polymorphic site of the portion.

10. An isolated gene product encoded by a nucleic acid molecule according to claim 1.

11. A method of analyzing a nucleic acid sample, comprising obtaining the nucleic acid sample from an individual; and determining a base occupying any one of the polymorphic sites shown in the Table.

12. A method according to claim 11, wherein the nucleic acid sample is obtained from a plurality of individuals, and a base occupying one of the polymorphic positions is determined in each of the individuals, and wherein 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.