WO2003014319A2 - Polymorphisms associated with multiple sclerosis - Google Patents

Abstract

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

Description

POLYMORPHISMS ASSOCIATED WITH MULTIPLE SCLEROSIS

FIELD OF THE INVENTION The present invention resides in the field of polymorphisms in genes associated with multiple sclerosis.

BACKGROUND OF THE INVENTION

Multiple sclerosis is an inflammatory, autoimmune, demyelinating disorder of the central nervous system. It has a relatively late age of onset, usually arising in the second to fourth decade of life. It is approximately twice as common in women as in men. The first detailed description of the disease was given by Charcot in the 1860s and many other reports quickly followed. Multiple sclerosis has a widely variable phenotype with symptoms including weakness of the limbs, temporary blindness, lack of co-ordination and many others. Currently there is no satisfactory test for multiple sclerosis and diagnosis is based on clinical criteria. This results in early cases often being misdiagnosed due to the lack of sufficiently characteristic clinical features. Additionally, individuals with unrelated conditions that have a similar clinical appearance have been misdiagnosed with multiple sclerosis. Furthermore, different clinicians still use different criteria in evaluating and diagnosing patients. Thus, there exits a need for a more definitive method of diagnosis of multiple sclerosis based on something other than observed symptomatology.

The population prevalence of multiple sclerosis in Western countries is approximately 0.1% and the lifetime incidence of multiple sclerosis is 0.2-0.3%. However, the lifetime risk of the disease in the siblings of affected individuals is much higher at 3-5%. Notably, the recurrence risk in rriono-zygotic (identical) twins is between 20% and 30% whereas in di-zygotic (non-identical) twins it is only 3-4%, comparable to the recurrence risk for pairs of siblings. It has also been observed that the risk to offspring when both parents have the disease is considerably higher (10-12%) than when only one parent is affected (2%). Finally, there is no increase in the incidence of disease in non- biological relatives of affected individuals adopted at an age before their affection status was known. This incidence data indicates that genetic, rather than environmental, factors are important in transmission of multiple sclerosis, and suggests that it may be possible to identify genetic mutations useful in diagnosing and developing treatments for multiple sclerosis.

SUMMARY OF THE INVENTION The invention provides isolated polynucleotides comprising a nucleic acid having at least 15 contiguous nucleotides of the variant nucleic acid sequences shown in Table 4. Additionally, the invention provides a nucleic acid sequence that is fully complementary to the variant nucleic acid sequences shown in Table 4. These polynucleotides may be nucleic acid probes for the detection of loci associated with multiple sclerosis. These probes may be conjugated to a detectable marker.

Another embodiment of the invention provides an array of polynucleotides having two or more isolated polynucleotides, at least one of which is variant nucleic acid sequences shown in Table 4.

The invention also provides a method for detecting in an individual a polynucleotide containing a variant sequence associated with multiple sclerosis in which a nucleic acid sample from an individual is contacted with a polynucleotide probe that contains a nucleic acid sequence from one of the variant sequences of Table 4 or the complement thereof and detecting the specific hybridization between said polynucleotide probe and said nucleic acid sample. The detection of such hybridization is indicative of the presence of a multiple sclerosis polynucleotide in the nucleic acid sample.

The method of the present invention may be conducted with an array of polynucleotides having at least one polynucleotide probe from the variant sequences of Table 4.

The invention also provides a computer-readable storage medium for storing data for access by an application program being executed on a data processing system, having a data structure stored in the computer-readable storage medium, the data structure including information resident in a database used by the application program including a plurality of records, each record of the plurality comprising information identifying a variant sequence shown in Table 4.

Another embodiment of the invention provides a signal carrying data for access by an application program being executed on a data processing system having a data structure encoded in the signal. The data structure includes information resident in a database used by the application program including a plurality of records, each record of the plurality comprising information identifying a polymorphism shown in Table 4.

DETAILED DESCRIPTION OF THE INVENTION The invention provides a collection of novel polymorphisms in genes encoding products known or suspected to affect the susceptibility to, course or outcome of multiple sclerosis. Detection of polymorphisms in such genes is useful in designing and performing diagnostic assays for evaluation of genetic risks for multiple sclerosis and other related conditions. Analysis of polymorphisms is also useful in designing prophylactic and therapeutic regimes customized to underlying abnormalities. Detection of polymorphisms is also useful for conducting clinical trials of drugs for treatment of these diseases and the underlying biological abnormalities. A drug or pharmaceutical agent means any substance used in the prevention, diagnosis, alleviation, treatment or cure of a disease. These terms include a vaccine, for example. The present invention also includes nucleic acid molecules that are oligonucleotides capable of hybridizing, under stringent hybridization conditions, with complementary regions of a gene associated with multiple sclerosis containing a polymorphism of the present invention. A nucleic acid can be DNA or RNA, and single- or double-stranded. Oligonucleotides can be naturally occurring or synthetic, but are typically prepared by synthetic means. Preferred oligonucleotides of the invention include segments of DNA, or their complements including any one of the polymorphic sites shown in Table 4. The segments are usually between 5 and 100 contiguous bases, and often range from 5, 10, 12, 15, 20, or 25 nucleotides to 10, 15, 30, 25, 20, 50 or 100 nucleotides. Nucleic acids between 5-10, 5- 20, 10-20, 12-30, 15-30, 10-50, 20-50 or 20-100 bases are common. The polymorphic site can occur within any position of the segment. The segments can be from any of the allelic forms of DNA shown in Table 4. For brevity in Table 4, the symbol T is used to represent both thymidine in DNA and uracil in RNA. Thus, in RNA oligonucleotides, the symbol T should be construed to indicate a uracil residue. Oligonucleotides of the present invention can be RNA, DNA, or derivatives of either. The minimum size of such oligonucleotides is the size required for formation of a stable hybrid between an oligonucleotide and a complementary sequence on a nucleic acid molecule of the present invention. The present invention includes oligonucleotides that can be used as, for example, probes to identify nucleic acid molecules or primers to produce nucleic acid molecules. Also provided are oligonucleotides that can be used as primers to amplify DNA. Preferred oligonucleotide probes or primers include a single base change of a polymorphism of the present invention or the wildtype nucleotide that is located at the same position. Preferably the nucleotide of interest occupies a central position of a probe. Preferably the nucleotide of interest occupies a 3* position of a primer. In another embodiment of the present invention, an array of oligonucleotides are provided, where discrete positions on the array are complementary to one or more of the provided polymorphic sequences, e.g. oligonucleotides of at least 12 nucleotides, frequently 20 nucleotides or larger and including the sequence flanking the polymorphic position. Such an array may comprise a series of oligonucleotides, each of which can specifically hybridize to a different polymorphism. For examples of arrays, see Hacia et al., 1996, Nat. Genet., vol. 14, pages 441-447 and DeRisi et al., 1996, Nat. Genet., vol. 14, pages 457-460. Arrays of interest may further comprise sequences, including polymorphisms, of other genetic sequences, particularly other sequences of interest for pharmacogenetic screening. As with other human polymorphisms, the polymorphisms of the invention also have more general applications, such as forensics, paternity testing, linkage analysis and positional cloning.

Polymorphism refers to the occurrence of two or more genetically determined alternative sequences or alleles in a population. A polymoφhic marker or site is the locus at which divergence occurs. Preferred markers have at least two alleles, each occurring at a 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 polymorphism has two forms. A triallelic polymorphism has three forms. A single nucleotide polymorphism (SNP) 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 1/100 or 1/1000 members of the population).

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. A set of polymorphisms means at least 2, and sometimes 5, or more of the polymorphisms shown in Table 4.

The present application provides 100 polymorphisms in 15 genes that may play a significant role in the incidence, detection or treatment of multiple sclerosis. Table 1 lists these genes, their chromosomal location, and related GenBank accession numbers.

The estrogen receptor gene, referred to as ESR1, has been localized to chromosome 6q25.1. This gene has a suspected link to multiple sclerosis as the disease state occurs predominately in females of reproductive age.

The interleukin-12p35 gene, referred to as IL12A, has been localized to chromosome 3pl2-ql3.2. This gene has a suspected link to multiple sclerosis because it is necessary for Thl responses. The interleukin-12p40 gene, referred to as EL12B, has been localized to chromosome 5q33. This gene has a suspected link to multiple sclerosis because IL-12 treatment exacerbates disease in EAE while anti-IL-12 blocks disease development and progression in EAE. Additionally IFN-β treatment decreases IL-12 production by human dendritic cells and monocytes. Further, an increase in 11-12 p40 expression correlates with acute formation of MS plaques.

The monocyte chemoattractant protein 1 gene, referred to as MCP1, has been localized to chromosome 17qll-12. This gene has a suspected link to multiple sclerosis because knockout mice failed to mount a Th2 response indicating that monocyte chemoattractant protein is involved in T cell polarization. Additionally, the protein stimulates production of IL-4 and EL- 10, and the protein is found in brain lesions in astrocytes and glia cells.

The homo sapiens small inducible cytokine subfamily B (Cys-X-Cys), member 10 gene, referred to as IP- 10, has been localized to chromosome 4q21. This gene has a suspected link to multiple sclerosis because it is expressed in brain lesions caused by astrocytes and macrophages while the IP- 10 receptor (CXCR3) is expressed within the plaques by T cells and astrocytes. Additionally, the expression of the gene is stimulated by EFN-gamma while antisense molecules directed against the RNA protects animals from EAE. Further, the protein stimulates migration of T cells, monocytes and NK cells while modulating adhesion molecule expression.

The interleukin-6 gene, referred to as EL6, has been localized to chromosome 7pl4-p21. This gene has a suspected link to multiple sclerosis because it is a mediator of inflammatory responses and shows increased expression in the CNS of MS patients.

The interferon receptor 1 gene, referred to as IFNAR1, has been localized to chromosome 21. This gene has a suspected link to multiple sclerosis because it is a receptor for type I interferons including INF alpha, beta and omega, inducing a signal through Jak/STAT and the IRS pathways.

The interferon receptor 2 gene, referred to as EFNAR2, has been localized to chromosome 21q22.1-q22.2. This gene has a suspected link to multiple sclerosis because it too is a receptor for type I interferons including INF alpha, beta and omega, inducing a signal through Jak/STAT and the IRS pathway.

The chemokine receptor type 3 gene, referred to as CXCR3, has been localized to the X chromosome at ql3. This gene has a suspected link to multiple sclerosis because the protein is involved in leukocyte trafficking including integrin activation, cytoskeleton changes and chemotactic migration and forms the receptor for IP 10, MIG and I-TAC. Additionally, the protein is preferentially expressed on Thl cells with CCR5 and by T cells and astrocytes in MS plaques.

The interferon gamma receptor 1 gene, referred to as INFGR1, has been localized to chromosome 6q23-24. This gene has a suspected link to multiple sclerosis because it participates in the receptor complex for type 2 interferon and is involved in ligand binding.

The interferon gamma receptor 2 gene, referred to as INFGR2, has been localized to chromosome 21q22.1-22.2. This gene has a suspected link to multiple sclerosis because it participates in the receptor for type 2 interferon and is involved in signal transduction.

The tumor necrosis factor alpha gene, referred to as TNFα, has been localized to chromosome 6q21.3. This gene has a suspected link to multiple sclerosis because it is mostly produced by macrophages and monocytes and has a dual role in EAE including inflammation and immunosuppression. Additionally, an innate low EL- 10 level with a high innate TNFα level has been linked to increased risk for developing MS.

The myelin-associated glycoprotein gene, referred to as MAG, has been localized to chromosome 19ql3.1. This gene has a suspected link to multiple sclerosis because the protein may play a role in myelination and it is a putative autoantigen in MS as both T cells and antibodies specific for MAG have been detected in the CSF of MS patients.

The myeloperoxidase gene, referred to as MPO, has been localized to chromosome 17q23.1. This gene has a suspected link to multiple sclerosis because the protein is a major component of neutrophile azurophilic granules and is present in invading macrophages in the CNS of MS patients. Additionally, knockout mice show increased susceptibility to EAE. Further, the protein plays a role in processing of light and heavy chain proteins and produces hypohalous acids central to the anti-microbial activity of neutrophiles.

The interleukin 3 gene, referred to as EL3, has been localized to chromosome

5q31.1. This gene has a suspected link to multiple sclerosis because transgenic mice expressing EL-3 in the brain develop a MS-like disease. Additionally, the protein activates macrophages and microglia and shows decreased production by PBMC in MS patients.

The nucleotide-binding oligomerization domain 2 gene, referred to as NOD2, has been localized to chromosome 16ql2. This gene has a suspected link to multiple sclerosis because it is associated with inflammatory bowel disease.

Three tables describe these new polymoφhisms and how they were identified; Table 1 summarizes information about the 15 genes analyzed. Table 2 shows the manner in which each gene was divided into sub-regions for analysis, including information about the primers for PCR amplification. Table 3 shows the base occupying the polymoφhic sites, the observed frequency of the alleles in the study population, data on whether the polymoφhism is in the coding region of the gene or not and the number of observation in the study population of each genotype. Table 4 describes the polymoφhisms that were detected. A study population can consist of any number of individuals, subjects or biological samples that may come from human or non-human organisms. The study population in which the polymoφhisms described below were identified consisted of 176 multiple sclerosis patients from the USA. The demographics of this population were typical of a cohort of multiple sclerosis patients (e.g. >90% Caucasian, 2:1 female to male ratio). Table 4 shows the reference or variant base occupying the polymoφhic sites and the nucleotides observed on either side of the polymoφhic site. Column 5 of Table 4 shows the two bases that can occupy each polymoφhic site. The first base was observed more frequently in the study population and is therefore designated as being a wildtype or reference base. The second base is designated as an alternative or variant base. These polymorphisms were identified by direct-sequencing of PCR products amplified from genomic DNA from the study population. TABLE 1 : Genes referenced in this a lication

of t gene, PRO = promoter sequence, UTR = untranslated region. Where the sequence was amplified in segments, letters denote the particul segment, e.g. Ex-4A represents the first segment (A) of the fourth exon (4) of a gene. Segments are labeled alphabetically A-Z) 2. Primers can be located in the sequences given in Appendix A.

1. Gene symbols are defined in Table 1.

2. Gene Regions are defined in Table 2.

3. The polymoφhism in exon 11 of the NOD2 gene is an insertion of a nucleotide. This is referenced as "INS C" in the table and as [ in the sequence.

4. One of the polymoφhisms in the exon2 region of the MCP1 gene is a 14 base pair deletion. This is referenced as "DEL (14)" in t table and the deleted sequences are enclosed by brackets.

5. Counts of genotypes and allele frequencies were calculated using data from the study population.

6. Polymoφhisms are marked as [X Y] where X is the more common of the nucleotides (reference allele) and Y is the rarer of t nucleotides at that position (alternative or variant allele).

7. Flanking sequences can be used to identify the location of the polymoφhisms in the reference sequences in the Sequence Listing.

Table 4

ANALYSIS OF POLYMORPHISMS

Polymoφhisms 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. Tissue means any sample taken from any subject, preferably a human. For example, convenient tissue samples include whole blood, semen, saliva, tears, urine, fecal material, sweat, buccal epithelium, 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.

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, NY, 1992); PCR Protocols: A Guide to Methods and Applications (eds. Innis, et al., Academic Press, San Diego, CA, 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. Patent 4,683,202 (each of which is incorporated herein in its entirety by this reference for all purposes).

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)), 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. The term "patient" refers to both human and veterinary subjects. The term

"subject" or "individual" typically refers to humans, but also to mammals and other animals, multicellular organisms such as plants, and single-celled organisms or viruses. The identity of bases occupying the polymorphic sites shown in Table 4 can be determined in an individual (e.g., a patient being analyzed) by several methods, which are described as follows: 1. Single Base Extension Methods

Single base extension methods are described by e.g., US 5,846,710, US 6,004,744, US 5,888,819 and US 5,856,092. In brief, the methods work by hybridizing a primer that is complementary to a target sequence such that the 3' end of the primer is immediately adjacent to, but does not span a site of, potential variation in the target sequence. That is, the primer comprises a subsequence from the complement of a target polynucleotide terminating at the base that is immediately adjacent and 5' to the polymorphic site. The term primer refers to a single-stranded oligonucleotide capable of acting as a point of initiation of template-directed DNA synthesis under appropriate conditions (i.e., in the presence of four different nucleoside triphosphates and an agent for polymerization, such as DNA or RNA polymerase or reverse transcriptase) in an appropriate buffer and at a suitable temperature. The appropriate length of a primer depends on the intended use of the primer but typically ranges from 15 to 40 nucleotides. Short primer molecules generally require cooler temperatures to form sufficiently stable hybrid complexes with the template. A primer need not reflect the exact sequence of the template but must be sufficiently complementary to hybridize with a template. The term primer site refers to the area of the target DNA to which a primer hybridizes. The term primer pair means a set of primers including a 5' upstream primer that hybridizes with the 5' end of the DNA sequence to be amplified and a 3', downstream primer that hybridizes with the complement of the 3' end of the sequence to be amplified. Hybridization probes are capable of binding in a base-specific manner to a complementary strand of nucleic acid. Such probes include nucleic acids and peptide nucleic acids as described in Nielsen et al., Science 254, 1497-1500 (1991). A probe primer can be labeled, if desired, by incorporating a label detectable by spectroscopic, photochemical, biochemical, immunochemical, or chemical means. For example, useful labels include 32P, fluorescent dyes, electron dense reagents, enzymes (as commonly used in an ELISA), biotin, or haptens and proteins for which antisera or monoclonal antibodies are available. A label can also be used to "capture" the primer, so as to facilitate the immobilization of either the primer or a primer extension product, such as amplified DNA, on a solid support. The hybridization is performed in the presence of one or more labeled nucleotides complementary to base(s) that may occupy the site of potential variation. For example, for biallelic polymoφhisms, two differentially labeled nucleotides can be used. For tetraallelic polymorphisms, four differentially-labeled nucleotides can be used. In some methods, particularly methods employing multiple differentially labeled nucleotides, the nucleotides are dideoxynucleotides. Hybridization is performed under conditions permitting primer extension if a nucleotide complementary to a base occupying the site of variation if the target sequence is present. Extension incoφorates a labeled nucleotide thereby generating a labeled extended primer. If multiple differentially-labeled nucleotides are used and the target is heterozygous then multiple differentially-labeled extended primers can be obtained. Extended primers are detected providing an indication of which base(s) occupy the site of variation in the target polynucleotide. 2. Allele-Specific Probes

The design and use of allele-specifϊc probes for analyzing polymoφhisras 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 polymoφhic forms in the respective segments from the two individuals. Hybridization conditions should be sufficiently stringent such 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. Hybridizations are usually performed under stringent conditions that allow for specific binding between an oligonucleotide and a target DNA containing one of the polymoφhic sites shown in Table 4. Stringent conditions are defined as any suitable buffer concentrations and temperatures that allow specific hybridization of the oligonucleotide to highly homologous sequences spanning at least one of the polymoφhic sites shown in Table 4 and any washing conditions that remove non-specific binding of the oligonucleotide. For example, conditions of 5X SSPE (750 mM NaCl, 50 mM Na Phosphate, 5 mM EDTA, pH 7.4) and a temperature of 25- 30°C are suitable for allele-specific probe hybridizations. The washing conditions usually range from room temperature to 60°C. Some probes are designed to hybridize to a segment of target DNA such that the polymoφhic 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 probe design achieves good discrimination in hybridization between different allelic forms. 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 polymoφhisms within the same target sequence. The polymoφhisms can also be identified by hybridization to nucleic acid arrays, some examples of which are described by WO 95/11995 (incoφorated by this reference in its entirety for all puφoses).

3. Allele-Specific Amplification Methods

An allele-specific primer hybridizes to a site on target DNA overlapping a polymorphism and only primes amplification of an allelic form to which the primer exhibits perfect complementarily. See Gibbs, Nucleic Acid Res. 17, 2427-2448 (1989). This primer is used in conjunction with a second primer that hybridizes at a distal site. Amplification proceeds from the two primers leading to a detectable product signifying that 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 polymoφhic site and the other of which exhibits perfect complementarily to a distal site. The single-base mismatch prevents amplification and no detectable product is formed. In some methods, the mismatch is included in the 3'-most position of the oligonucleotide aligned with the polymoφhism because this position is most destabilizing to elongation from the primer. See, e.g., WO 93/22456. h other methods, a double-base mismatch is used in which the first mismatch is included in the 3'-most position of the oligonucleotide aligned with the polymoφhism and a second mismatch is positioned at the immediately adjacent base (the pen-ultimate 3' position). This double mismatch further prevents amplification in instances in which there is no match between the 3' position of the primer and the polymoφhism. 4. Direct-Sequencing The direct analysis of the sequence of polymoφhisms 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)).

5. Denaturing Gradient Gel Electrophoresis

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.

6. Single-Strand Conformation Polymoφhism Analysis

Alleles of target sequences can be differentiated using single-strand conformation polymoφhism 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 that are partially dependent upon the base sequence. The different electrophoretic mobilities of single- stranded amplification products can be related to base-sequence differences between alleles of target sequences. METHODS OF USE

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

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

The polymoφhisms shown in Table 4 can be analyzed for a correlation with multiple sclerosis or specific sub-phenotypes associated with multiple sclerosis including, but not limited to, relapsing remitting, primary progressive, secondary progressive and progressive relapsing multiple sclerosis as well as with response to drugs used to treat these diseases.

Correlation is performed for a population of individuals who have been tested for the presence or absence of multiple sclerosis or an intermediate phenotype and for one or more polymoφhic markers. To perform such analysis, the presence or absence of a set of polymoφhic forms (i.e. a polymoφhic 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 polymoφhism 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 including, but not limited to, chi-squared test, Analysis of Variance, parametric linkage analysis, non-parametric linkage analysis, etc. and statistically significant correlations between polymoφhic form(s) and phenotypic characteristics are noted. For example, it might be found that the presence of allele Al at polymoφhism A correlates with multiple sclerosis or a sub- phenotype including relapsing remitting, primary progressive, secondary progressive and progressive relapsing multiple sclerosis , measured either as a dichotomous or continuous trait. As a further example, it might be found that the combined presence of allele Al at polymoφhism A and allele Bl at polymoφhism B correlates with multiple sclerosis or a sub-phenotype.

Polymoφhic forms that correlate with multiple sclerosis or sub-phenotypes are also useful in diagnosing multiple sclerosis or susceptibility thereto. Combined detection

\ of several such polymoφhic forms typically increases the probability of an accurate diagnosis. For example, the presence of a single polymoφhic form known to correlate with multiple sclerosis might indicate a probability of 20% that an individual has or is susceptible to multiple sclerosis, whereas detection of five polymoφhic forms, each of which correlates with less than 20% probability, might indicate a probability up to 80% that an individual has or is susceptible to multiple sclerosis. Analysis of the polymoφhisms of the invention can be combined with that of other polymoφhisms or other risk factors of multiple sclerosis, such as family history. Polymoφhisms can be used to diagnose multiple sclerosis or sub-phenotypes of multiple sclerosis at the pre- symptomatic stage, as a method of post-symptomatic diagnosis, as a method of confirmation of diagnosis or as a post-mortem diagnosis.

Patients diagnosed with multiple sclerosis can be treated with conventional therapies and/or can be counseled to avoid environmental factors that exacerbate the condition or trigger episodes. Conventional therapies for multiple sclerosis include, but are not limited to, the use of steroids, beta-interferon, physiotherapy and immune suppressor therapies. Patients diagnosed with multiple sclerosis may also be counseled about the risk of genetically transmitting the disease to offspring, or counseled about the risk of family members sharing genetic variation(s) relevant to multiple sclerosis.

The polymoφhism(s) showing the strongest correlation with multiple sclerosis within a given gene are likely either to have a causative role in the manifestation of the phenotype or to be in linkage disequilibrium with the causative variants. Such a role can be confirmed by in vitro gene expression of the variant gene or by producing a transgenic animal expressing a human gene bearing such a polymoφhism and determining whether the animal develops insulin resistance. Polymoφhisms in coding regions that result in amino acid changes usually cause multiple sclerosis by decreasing, increasing or otherwise altering the activity of the protein encoded by the gene in which the polymoφhism occurs. Polymoφhisms in coding regions that introduce stop codons usually cause multiple sclerosis by reducing (heterozygote) or eliminating (homozygote) functional protein produced by the gene. Occasionally, stop codons result in production of a truncated peptide with aberrant activities relative to the full-length protein. Polymoφhisms in regulatory regions typically cause multiple sclerosis by causing increased or decreased expression of the protein encoded by the gene in which the polymoφhism occurs. Polymoφhisms in intronic or untranslated sequences can cause multiple sclerosis either through the same mechanism as polymoφhisms in regulatory sequences or by causing altered splicing patterns resulting in an altered protein.

The precise role of polymoφhisms in the genes shown in Table 4 can be elucidated by several means. Alterations in expression levels of a protein can be determined by measuring protein levels in sample groups of persons characterized as having or not having multiple sclerosis (or intermediate phenotypes). Alterations in enzyme activity can similarly be detected by assaying for enzyme activity in samples from the above groups of persons. Alterations in receptor-transducing activity can be detected by comparing receptor ligand binding, either in vitro or in a cellular expression system.

Having identified certain polymoφhisms as having causative roles in multiple sclerosis, and having elucidated, at least in general terms, whether such polymoφhisms increase or decrease the activity or expression level of associated proteins, customized therapies can be devised for classes of patients with different genetic subtypes of metabolic diseases. For example, if a polymoφhism in a given protein causes multiple sclerosis by increasing the expression level or activity of the protein, the diseases associated with the polymoφhism can be treated by administering an antagonist of the protein. If a polymoφhism in a given protein causes insulin resistance by decreasing the expression level or activity of a protein, the form of multiple sclerosis associated with the polymoφhism can be treated by administering the protein itself, a nucleic acid encoding the protein that can be expressed in a patient, or an analog or agonist of the protein. Agonists can be obtained by producing and screening large combinatorial libraries. Combinatorial libraries can be produced for many types of compounds that can be synthesized in a step by step fashion. Such compounds include polypeptides, beta-turn mimetics, polysaccharides, phospholipids, hormones, prostaglandins, steroids, aromatic compounds, heterocyclic compounds, benzodiazepines, oligomeric N-substituted glycines and oligocarbamates. Large combinatorial libraries of the compounds can be constructed by the encoded synthetic libraries (ESL) method described in Affymax, WO 95/12608, Affymax, WO 93/06121, Columbia University, WO 94/08051, Pharmacopeia, WO 95/35503 and Scripps, WO 95/30642 (each of which is incoφorated herein by this reference for all puφoses). Peptide libraries can also be generated by phage display methods. See, e.g., Devlin, W0 91/18980. The libraries of compounds can be initially screened for specific binding to the protein for which agonists or antagonists are to be identified, or to its natural binding ligand. Preferred agents bind with a Kd < 1 μM. For example, for receptor ligand combinations, the assay can be performed using a cloned receptor immobilized to a support such as a microtiter well and binding of compounds can be measured in competition with ligand to the receptor. Agonist or antagonist activity can then be assayed using a cellular reporter system or a transgenic animal model.

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

Furthermore, the polymoφhisms of the invention may be used after the completion of a clinical trial to elucidate differences in response to a given treatment. For example, the set of polymoφhisms may be used to stratify the enrolled patients into disease sub-types or classes. It may further be possible to use the polymoφhisms to identify subsets of patients with similar polymoφhic profiles who have unusual (high or low) response to treatment or who do not respond at all (non-responders). In this way, information about the underlying genetic factors influencing response to treatment can be used in many aspects of the development of treatments (these range from the identification of new targets, through the design of new trials to product labeling and patient targeting). Additionally, the polymoφhisms may be used to identify the genetic factors involved in adverse response to treatment (adverse events). For example, patients who show adverse response may have more similar polymoφhic profiles than would be expected by chance. This would allow the early identification and exclusion of such individuals from treatment. It would also provide information that might be used to understand the biological causes of adverse events and to modify the treatment to avoid such outcomes.

In addition to multiple sclerosis, the polymoφhisms in Table 4 can also be tested for association with other diseases in which auto immunity or demyelination are a common feature but the underlying genetic defects are poorly understood. These include: systemic lupus erythematosus, type I diabetes (IDDM), rheumatoid arthritis, inflammatory bowel disease, scleroderma, thyroid diseases, Graves disease, psoriasis and other conditions. The polymoφhic DNA sequences of the present invention listed in Table 4 can also be used to prepare probes or as primers for detection of the presence of the genes listed in Table 2. In this manner, the presence of these genes can be detected from biological samples isolated from an individual of interest. This allows the presence of these genes to be assayed in selected patients. Additionally, the sequences listed in Tables 3 and 4 that have been found to reside within the coding regions of these genes can be used to assay a biological sample from an individual for the presence of gene expression by detection of the corresponding mRNA transcript. Using detection means known to those of skill in the art, these sequences of the present invention can also be used to evaluate quantitative expression of these genes as it may differ between individuals or within different tissues in the same individual.

The reported polymoφhisms may also be in linkage disequilibrium with nearby genes (within 30 kb or greater) that are not related to multiple sclerosis, but contribute to phenotypes such as autoimmune diseases, inflammation, cancer, diseases of the nervous system, and infection by pathogenic microorganisms. 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. Such correlations can be exploited in several ways. In the case of a strong correlation between a set of one or more polymoφhic forms and a disease for which treatment is available, detection of the polymoφhic 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 polymoφhic 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 polymoφhism from her husband to her offspring. In the case of a weaker, but still statistically significant correlation between a polymoφhic 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 polymoφhic 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.

Determination of which polymoφhic forms occupy a set of polymoφhic sites in an individual identifies a set of polymoφhic 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 polymoφhic forms in one individual is the same as that in an unrelated individual. Preferably, if multiple sites are analyzed, the sites are unlinked. Thus, polymoφhisms of the invention are often used in conjunction with polymoφhisms in distal genes. Preferred polymoφhisms for use in forensics are diallelic because the population frequencies of two polymoφhic forms can usually be determined with greater accuracy than those of multiple polymoφhic forms at multi-allelic loci.

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 polymoφhic forms occupying selected polymoφhic sites is the same in the suspect and the sample. If the set of polymoφhic 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 polymoφhic 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. p(ID) is the probability that two random individuals have the same polymoφhic or allelic form at a given polymoφhic site. The term genotype as used herein broadly refers to the genetic composition of an organism, including, for example, whether a diploid organism is heterozygous or homozygous for one or more alleles of interest. In diallelic loci, four genotypes are possible: AA, AB, BA, and BB. If alleles A and B occur in a haploid genome of the organism with frequencies x and y, the probability of each genotype in a diploid organism can be calculated as described in International Publication WO 95/12607 which is incoφorated herein by this reference in its entirety. These calculations can be extended for any number of polymoφhic forms at a given locus. For example, in a locus of n alleles, the appropriate binomial expansion is used to calculate p(ID) and ρ(exc).

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

The probability of parentage exclusion (representing the probability that a random male will have a polymoφhic form at a given polymoφhic site that makes him incompatible as the father) can be calculated as described in International Publication WO 95/12607 which is incoφorated herein by this reference in its entirety. If several polymoφhic 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 polymoφhic marker set matches the child's polymoφhic marker set attributable to his/her father.

Linkage describes the tendency of genes, alleles, loci or genetic markers to be inherited together as a result of their location on the same chromosome, and can be measured by percent recombination between the two genes, alleles, loci or genetic markers that are physically-linked on the same chromosome. Loci occurring within 50 centimorgan of each other are linked. Some linked markers occur within the same gene or gene cluster. Linkage disequilibrium (LD) or allelic association means the preferential association of a particular allele or genetic marker with a specific allele, or genetic marker at a nearby chromosomal location more frequently than expected by chance for any particular allele frequency in the population. For example, if locus X has alleles a and b, which occur with equal frequency, and linked locus Y has alleles c and d, which occur with equal frequency, one would expect the haplotype ac to occur with a frequency of 0.25 in a population of individuals. If ac occurs more frequently, then alleles a and c are considered in linkage disequilibrium. Linkage disequilibrium may result from natural selection of a certain combination of alleles or because an allele has been introduced into a population too recently to have reached equilibrium (random association) between linked alleles. A marker in linkage disequilibrium with disease predisposing variants can be particularly useful in detecting susceptibility to disease (or association with sub-clinical phenotypes) notwithstanding that the marker does not cause the disease. For example, a marker (X) that is not itself a causative element of a disease, but which is in linkage disequilibrium with a gene (including regulatory sequences) (Y) that is a causative element of a phenotype, can be used to indicate susceptibility to the disease in circumstances in which the gene Y may not have been identified or may not be readily detectable. Younger alleles (i.e., those arising from mutation relatively late in evolution) are expected to have a larger genomic segment in linkage disequilibrium. The age of an allele can be determined from whether the allele is shared among different human ethnic groups and/or between humans and related species.

The polymoφhisms shown in Table 4 can also be used to establish physical linkage between a genetic locus associated with a trait of interest and polymoφhic 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 Landau et al., Proc. Natl. Acad. Sci. (USA) 83, 7353-7357 (1986); Landau et al., Proc. Natl. Acad. Sci. (USA) 84, 2363- 2367 (1987); Donis-Keller et al., Cell 51, 319-337 (1987); Landau et al., Genetics 121, 185-199 (1989)). Genes localized by linkage can be cloned by a process known as directional cloning. See Wainwright, Med. J. Australia 159, 170-174 (1993); Collins, Nature Genetics 1, 3-6 (1992) (each of which is incoφorated herein by this reference in its entirety for all puφoses).

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 polymoφhic markers. The distribution of polymoφhic markers in an informative meiosis is then analyzed to determine which polymoφhic 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). 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 loglO 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 θ (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. 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. MODIFIED POLYPEPTIDES AND GENE SEQUENCES

The invention further provides variant forms of nucleic acids and corresponding proteins. The nucleic acids comprise one of the sequences described in Table 4 in which the polymoφhic position is occupied by an alternative base for that position. Some nucleic acids encode full-length variant forms of proteins. Similarly, variant proteins have the prototypical amino acid sequences encoded by a nucleic acid sequence shown in Table 4 (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 polymoφhic positions shown in the Table. That position is occupied by the amino acid coded by the corresponding codon in the alternative forms shown in Table 4.

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 that is recognized by the host. The selection of an appropriate promoter, for example tφ, 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.

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.

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. 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 drag screening systems.

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 that simulate the interactions of the peptides. Biologically active fragments include any portion of the full-length polypeptide that 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.

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. KITS The invention further provides kits comprising at least one allele-specific oligonucleotide as described above. Often, the kits contain one or more pairs of allele- specific oligonucleotides hybridizing to different forms of a polymoφhism. 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 any or all of the polymoφhisms shown in Table 4. 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.

COMPUTER SYSTEMS FOR STORING POLYMORPHISM DATA

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

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

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

Information identifying polymoφhisms shown in Table 4 is represented in records, which optionally, are subdivided into fields. Each record stores information relating to a different polymoφhisms in Table 4. Collectively, the records can store information relating to all of the polymoφhisms in Table 4, or any subset thereof, such as 5, 10, 50, or 100 polymoφhisms from Table 4. In some databases, the information identifies a base occupying a polymoφhic position and the location of the polymoφhic position. The base can be represented as a single letter code (i.e., A, C, G or T/U) present in a polymoφhic form other than that in the reference allele. Alternatively, the base occupying a polymoφhic site can be represented in TUPAC ambiguity code as shown in Table 4. The location of a polymoφhic site can be identified as its position within one of the sequences shown in Table 4. For example, in the first sequence shown in Table 4, the polymoφhic site occupies the A or C base. The position can also be identified by reference to, for example, a chromosome, and distance from known markers within the chromosome, h other databases, information identifying a polymoφhism contains sequences of 10-100 bases shown in Table 4 or the complements thereof, including a polymoφhic site. Preferably, such information records at least 10, 15, 20, or 30 contiguous bases of sequences including a polymoφhic site. From the foregoing, it is apparent that the invention includes a number of general uses that can be expressed concisely as follows. The invention provides for the use of any of the nucleic acid segments described above in the diagnosis or monitoring of diseases, particularly insulin resistance and related metabolic syndrome. 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.

All publications and patent applications cited above are incoφorated by reference in their entirety for all puφoses to the same extent as if each individual publication or patent application were specifically and individually indicated to be so incoφorated by reference. Although the present invention has been described in some detail by way of illustration and example for puφoses of clarity and understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims.

1. Appendix A. Location of the polymoφhisms in the gene sequences

2. In Table 3 of Section I, the genomic sequence flanking all of the polymoφhisms is given. Complete genomic sequence for all the exons and promoter regions are given below with the polymoφhisms described in Tables 3 indicated as [X/Y] where X is the nucleotide in the consensus genomic sequence and Y is the novel nucleotide. Intronic sequence flanking the exons is also given and some the primers given in Table 2 lie in these intronic segments. The beginning of each exon or promoter is marked by "[" and the end of each exon or promoter is marked by "]".

3. >ESR1_01 CCAGGGTCATCCTATGTACACACTACGTATTTCTAGCCAACGAGGAGGGGGAATCAAACAGA AAGAGAGACAAACAGAGATATATCGGAGTCTGGCACGGGGCACATAAGGCAGCACATTAGA GAAAGCCGGCCCCTGGATCCGTCTTTCGCGTTTATTTTAAGCCCAGTCTTCCCTGGGCCACC TTTAGCAGATCCTCGTGCGCCCCCGCCCCCTGGCCGTGAAACTCAGCCTCTATCCAGCAGC GACGACAAGTAAAGTAAAGTTCAGGGAAGCTGCTCTTTGGGATCGCTCCAAATC[GAGTTGT GCCTGGAGTGATGTTTAAGCCAATGTCAGGGCAAGGCAACAGTCCCTGGCCGTCCTCCAGC ACCTTTGTAATGCATATGAGCTCGGGAGACCAGTACTTAAAGTTGGAGGCCCGGGAGCCCA GGAGCTGGCGGAGGGCGTTCGTCCTGGGACTGCACTTGCTCCCGTCGGGTCGCCCGGCTT CAC[C/T]GGACCCGCAGGCTCCCGGGGCAGGGCCGGGGCCAGAGCTCGCGTGTCGGCGGG ACATGCGCTGCGTCGCCTCTAACCTCGGGCTGTGCTCTTTTTCCAGGTGGCCCGCCGGTTT CTGAGCCTTCTGCCCTGCGGGGACACGGTCTGCACCCTGCCCGCGGCCACGGACCATGAC CATGACCCTCCACACCAAAGCATCTGGGATGGCCCTACTGCATCAGATCCAAGGGAACGAG CTGGAGCCCCTGAACCGTCCGCAGCTCAAGATCCCCCTGGAGCGGCCCCTGGGCGAGGTG TACCTGGACAGCAGCAAGCCCGCCGTGTACAACTACCCCGAGGGCGCCGCCTACGAGTTCA ACGCCGCGGCCGCCGCCAACGCGCAGGTCTACGGTCAGACCGGCCTCCCCTACGGCCCCG GGTCTGAGGCTGCGGCGTTCGGCTCCAACGGCCTGGGGGGTTTCCCCCCACTCAACAGCG TGTCTCCGAGCCCGCTGATGCTACTGCACCCGCCGCCGCAGCTGTCGCCTTTCCTGCAGCC CCACGGCCAGCAGGTGCCCTACTACCTGGAGAACGAGCCCAGCGGCTACACGGTGCGCGA GGCCGGCCCGCCGGCATTCTACAGGTACCCGCGC]CCGCGCCGCCCGTCGGGGTGGCCGC CGCGCCCGGCAGGAGGGAGGGAGGGAGGGAGGGAGAAGGGAGAGCCTAGGGAGCTGCG GGAGCCGCGGGACGCGCGACCCGAGGGTGCGCGCAGGGAGCCCGGGGCGCGCGGCCCA GCCCGGGGGTTCTGCGTGCAGCCCGCGCTGCGTTCAGAGTCAAGTTCTCTCGCCGGGCAG CTGAAAAAAACGTACTCTCCACCCACTTACCGTCCGTGCGAGAGGCAGACCCGAAAGCCCG GGCTTCCTAACAAA

4. >ESR1_02 CATTGGTCTCTAATGGTTCTGAAATAATTGTATATTCCTGCAAAAACATTAAGTCTATTAGAAA CCAGCTAATTTCATTTTGTCATTTTTATAGGTAACATATTCTGGTGCAGGTAGTATGTTTTTAA AACAAGTTTGCAATAAACAATTTCCCCTCAAGGTTAATATAATAGGCAACACCTTTTGCTGCAA CAGACGGCAAGAGGTAATGAAAGATTAGCTTACATTATGATTCATTATTTCAAAATGTCAGGA TAAAGTGGATCTGCTGCATCTCCCAGAGAGTGCATGTTTTGCTTT[TCTAATGTTAATGGATTT ACTGTTTTTTTCCCCCCAGGCCAAATTCAGATAATCGACGCCAGGGTGGCAGAGAAAGATTG GCCAGTACCAATGACAAGGGAAGTATGGCTATGGAATCTGCCAAGGAGACTCGCTACTGTG CAGTGTGCAATGACTATGCTTCAGGCTACCATTATGGAGTCTGGTCCTGTGAGGGCTGCAAG GCCTTCTTCAAGAGAAGTATTCAAGGTAATAGTGTGTTGAAAACGACTTCTATTTTTGATCCTA TGAGCAGATCCTA]AGAGCCAAAGCGACTGAGGAAGGAAGACATAGAATCAGCCATTTGTAC AAAACATGAATCCCTAGTAGGTCCACTAGTATCTTTGGTAGAAACATGGAGAAGAGACAGGA TCTCAGGAGAAGGAGTTGACACATGGCAGGGCAGCTGAGGCTGAGTAATTCCGCTTCCTTC CTTTGGCAAGACTCAATCAGTCTTGAGCAACTCTACAGAAGAATTCCACTAGCTGGATCTCTG AGGAAAAAAGAAATGTTGTCTGTGCCCTGACTGGGG

5. >ESR1_03

GGATTACAGGTGTACACCACCATACCCAGGTTTTTTTTGTATTTTTAGTAGAGACGGGGTTTC ACCATGTTGGTCAGGCTGGTCTTGAACTCCTGACGTCGTGATCCACCTGCCTCGGCCTCCCA AAGTTCTGGGATTACAGGCATGAGCCACCGTGCCCGGCCCATGAGAGGTTTTGTTTGCACTT CAAGAAGGACAGAAAAAGGCAGGCAGGCTGGGAGCAACATAGTAAGGCTGAGGAAGTGATA GGAAAACAGCCTCCAAAAGGTTTCCCTGTAGA[TTCTGACTGGCTAAGTTTCCTGAAATAATAT TAATTCTGTCCTCTTGCTTTTAATAGGACATAACGACTATATGTGTCCAGCCACCAACCAGTG CACCATTGATAAAAACAGGAGGAAGAGCTGCCAGGCCTGCCGGCTCCGTAAATGCTACGAA GTGGGAATGATGAAAGGTGGTAGGTACATCTCTCCCAGGGGCCCTTGGGGGATGGCCCTG GCCACCGCCCAGTGCJTGGCTCTACCCATTGGAATAACACCATGGGAATTTTGTGTTTTTTTC TTTTAATTGTTTTTTTTCTATTCTTATTTTTCTTTGCAACAAAAGTATTTTCATAATCCATTTTATT TTAAAAAGGTGGAAGTGTCTGGAACTGGAAATTCTAACATGGCATTTTGTGTTTTGGATTTTC AATGTAAATAATTATATTTTAAATCAAAGGTGTGTGGGAGGCGGTGATGGAAGGAAACGAAG AGTGCTTAGTAAATTATTCTAGAAATATTTTTCAGTTACTGTTTATGTTGC

6. >ESR1_04

CACAGGTTACTATTATAGCTGTCTAAGTAGAAGGCACACAAGTTTTCACACTGAGTATAACAC TTTATAGAAAGCTAAGTGTGTTGCTCAAGTTGGTACATTTCTGTAGATGTGACACTATGGCAC TAAGAAACTTAATGCCACATTGAAATTCATTGAGATAGCTAGACTTTAAAAATAATTACTTGAC TTCACTATAAAGTATGTTCGTATTGCATTTACTCCATCTAGTAGAAAATAGACCTTGTCAGTTC AAATCCCTGTTGCATT[AATTTCACCAGTAATGAGTCTTTTTCATTTGAGTCAGCAGGGTTTTT CTTGCTTGTTTTCAGGCTTTGTGGATTTGACCCTCCATGATCAGGTCCACCTTCTAGAATGTG CCTGGCTAGAGATCCTGATGATTGGTCTCGTCTGGCGCTCCATGGAGCACCCAGGGAAGCT ACTGTTTGCTCCTAACTTGCTCTTGGACAGGTAAGTGACCTGGCTGTAGCTTAGGAGTAGCA TGTTCTTTACGATCATAGTTCATTCAT]GAAACTATTTTATTCATCTCTCGGTGAAGCTTCAGAG AACTTTATTAGGTATGTTTACTTAACAAAAGAGTGCATTGGGGGTGATGAAGCCTAGTCAAAT TCACAGAAAGCTAAGGATAACTTTCTGCTAGACATTACCTCAGAAGAATTCTATTATTTCTAAT ACACACACACACACACACACACACACACACTCACACTCTCTCTCTCTCTCTCTCTGTCATTAT GAATGGTAATTTTCTAACTCCATCTTCAACTTGTATCATATAA

7. >ESR1_05

ACCCAGATCTTGATCATTTTCAATTACCCATAGGTTGAAGAACTCCATATTTAACATGGCAGA CTTGAGGACTGAACTACCTACCTCTTCTAAGAAGTTGAAATGAGAATGTTTTATTGATGGGAA ATTATTTTTTTGTTTTGCCTTCTAGAATTCAAATGAATGTTCATATTCCATGAAGACAATGGCT GATAGTTTTTTGTTAAAGATTTAGAACCAGTGGATTTTTATGAATGTGAACCCTTTCATGTCTT GTGGAA[GATTTTCTGTTTTTTAATCTTTTTATTTATTTATTTATTTTTGCTATGTTTTCATAGGAA CCAGGGAAAATGTGTAGAGGGCATGGTGGAGATCTTCGACATGCTGCTGGCTACATCATCTC GGTTCCGCATGATGAATCTGCAGGGAGAGGAGTTTGTGTGCCTCAAATCTATTATTTTGCTTA ATTCTGGTGAGTTGATAACACAAGATAACTCAATGCTGGATGAAATGTTTATTTGTA[G/T]TTTT CAA]CCAGATACGATCTACCCACTCCAAAGGCATAATGTCATAAATAGAAAGAAACTACTGAC ACACGTTTTAAAATAACCTACCAACATTGCAGATTCCTTATAAAGGTAGAACCATGCTAGCCA AATAGACACATGAAAAATTGTAATTTGGCATTGAATCAAATGGCCTTTGAGCTAAAATTTTTGT ATGCTTTCACAGATAGGATGTTTTTATTCAAATGGTACATGTATATAGACATATGTTAGTTGAT AGTTATATTATGTCTGAAAATAAGTAGACCAAGTAATTCT

8. >ESR1_06

ATGATGGTGTCAGACCTGTCTGAGAAAAGGTGGCCCATGTTACCATGACAGGCCCCAAGGC TAACAGCCCCTTTCTGGGTCATGGCTCATACAAAGGAGCCCTCCTTGGTTTGCTGGTGCTCT GAGACTTGCAAATGCATTAGGAATTTTACACTGTAACCCGGTTTTAAATGGGTCCAGAGCATC CCCATTGCTAGACTACTGTGCTGAGGAAGGGCACTGGCTCATTGTTACATCCCATGAACACT CTGGGTCTCCTAGACCTCATCCTCTTTGAGCTTCTCTCTCTC[ACTCTCTCTCTGCGCATTCAG GAGTGTACACATTTCTGTCCAGCACCCTGAAGTCTCTGGAAGAGAAGGACCATATCCACCGA GTCCTGGACAAGATCACAGACACTTTGATCCACCTGATGGCCAAGGCAGGCCTGACCCTGC AGCAGCAGCACCAGCGGCTGGCCCAGCTCCTCCTCATCCTCTCCCACATCAGGCACATGAG GTGAGGCATCTGTGGGCTTCCTACA]GGAGAGACATAAAGAAAACATGCCCCCAAACCTATG TGACAGCTGGCCGGGAAGGACTGGTGCCTGCATATGGAGAGTGCACTTGTGACAGTTCCTG GCATAGAATAAGCATAAATGCTATAGGAGGACAGAAGAGAGAGGTTTTAAATCTGCGAGGGT CACAGGGCAAGTGTCAGAGAAGGCATAGAGGAAGCGATACTTACGCTTGGTTTAAAGCATGT GCTTTGGGGCAGTGGTTTAGAGATTGGGTGCAGTGTGCAAATAGGAGGAGGGGGCCAAT

9. >ESR1_07

GCCACGGAGGTCCATGGAAGTCACCTGCATAGCAAATACCCTGAAAGTGGCTGCAGGGAGA GTGTGAGGGTGGGACCGCCCTGGTAGGAGGTGGAAAATGAAAAACACACGGCCATGAGTTC CAGATTAGGGCTTCTGAAAGCCCTCAGCTTTCCCAGCTCCCATCCTAAAGTGGGTCTTTAAA CAGG AAG AAAG AAAG ATTGCTAAGTGTCTTTGG AGTTCCTCTTCCTTCCCCTTCTAGGGATTT CAGCACTCCTGGGGCTCGGGTTGGCTCTAAAGTAGTCCTTTCTGTGTCTTC[CCACCTACAGT AACAAAGGCATGGAGCATCTGTACAGCATGAAGTGCAAGAACGTGGTGCCCCTCTATGACCT GCTGCTGGAGATGCTGGACGCCCACCGCCTACATGCGCCCACTAGCCGTGGAGGGGCATC CGTGGAGGAGACGGACCAAAGCCACTTGGCCACTGCGGGCTCTACTTCATCGCATTCCTTG CAAAAGTATTACATCACGGGGGAGGCAGAGGGTTTCCCTGCCACGGTCTGAGAGCTCCCTG GCTCCCACACGGTTCAGATAATCCCTGCTGCATTTTACCCTCATCATGCACCACTTTAGCCAA ATTCTGTCTCCTGCATACACTC[C/T]GGCATGCATCCAACACCAATGGCTTTCTAGATGAGTG GCCATTCATTTGCTTGCTCAGTTCTTAGTGGCACATCTTCTGTCTTCTGTTGGGAACAGCCAA AGGGATTCCAAGGCTAAATCTTTGTAACAGCTCTCTTTCCCCCTTGCTATGTTACTAAGCGTG AGGATTCCC[G/A]TAGCTCTTCACAGCTGAACTCAGTCT[A/G]TGGGTTGGGGCTCAGATAACT CTGTGCATTTAAGCTACTTGTAGAGACCCAGGCCTGGAGAGTAGACATTTTGCCTCTGATAA GCACTTTTTAAATGGCTCTAAGAATAAGCCACAGCAAAGAATTTAAAGTGGCTCCTTTAATTG GTGACTTGGAGAAAGCTAGGTCAAGGGTTTATTATAGCACCCTCTTGTATTCCTATGGCAATG CATCCTTTTATGAAAGTGGTACACCTTAAAGCTTTTATATGACTGTAGCAGAGTATCTGGTGA TTGTCAATTCATTCCCCCTATAGGAATACAAGGGGCACACAGGGAAGGCAGATCCCCTAGTT GGCAAGACTATTTTAACTTGATACACTGCAGATTCAGATGTGCTGAAAGCTCTGCCTCTGGCT TTCCGGTCATGGGTTCCAGTTAATTCATGCCTCCCATGGACCTATGGAGAGCAGCAAGTTGA TCTTAGTTAAGTCTCCCTATATGAGGGATAAGTTCCTGATTTTTGTTTTTATTTTTGTGTTACAA AAGAAAGCCCTCCCTCCCTGAACTTGCAGTAAGGTCAGCTTCAGGACCTGTTCCAGTGGGCA CTGTACTTGGATCTTCCCGGCGTGTGTGTGCCTTACACAGGGGTGAACTGTTCACTGTGGTG ATGCATGATGAGGGTAAATGGTAGTTGAAAGGAGCAGGGGCCCTGGTGTTGCATTTAGCCC TGGGGCATGGAGCTGAACAGTACTTGTGCAGGATTGTTGTGGCTACTAGAGAACAAGAGGG AAAGTAGGGCAGAAACTGGATACAGTTCTGAGGCACAGCCAGACTTGCTCAGGGTGGCCCT GCCACAGGCTGCAGCTACCTAGGAACATTCCTTGCAGACCCCGCATTGCCCTTTGGGGGTG CCCTGGGATCCCTGGGGTAGTCCAGCTCTTCTTCATTTCCCAGCGTGGCCCTGGTTGGAAG AAGCAGCTGTCACAGCTGCTGTAGACAGCTGTGTTCCTACAATTGGCCCAGCACCCTGGGG CACGGGAGAAGGGTGGGGACC[G/A]TTGCTGTCACTACTCAGGCTGACTGGGGCCTGGTCA GATTACGTATGCCCTTGGTGGTTTAGAGATAATCCAAAATCAGGGTTTGGTTTGGGGAAGAA AATCCTCCCCCTTCCTCCCCCGCCCCGTTCCCTACCGCCTCCACTCCTGCCAGCTCATTTCC TTCAATTTCCTTTGACCTATAGGCTAAAAAAGAAAGGCTCATTCCAGCCACAGGGCAGCCTTC CCTGGGCCTTTGCTTCTCTAGCACAATTATGGGTTACTTCCTTTTTCTTAACAAAAAAGAATGT TTGATTTCCTCTGGGTGACCTTATTGTCTGTAATTGAAACCCTATTGAGAGGTGATGTCTGTG TTAGCCAATGACCCAGGTGAGCTGCTCGGGCTTCTCTTGGTATGTCTTGTTTGGAAAAGTGG ATTTCATTCATTTCTGATTGTCCAGTTAAGTGATCACCAAAGGACTGAGAATCTGGGAGGGCA AAAAAAAAAAAAAAGTTTTTATGTGCACTTAAATTTGGGGACAATTTTATGTATCTGTGTTAAG GATATGTTTAAGAACATAATTCTTTTGTTGCTGTTTGTTTAAGAAGCACCTTAGTTTGTTTAAG AAGCACCTTATATAGTATAATATATATTTTTTTGAAATTACATTGCTTGTTTATCAGACAATTGA ATGTAGTAATTCTGTTCTGGATTTAATTTGACTGGGTTAACATGCAAAAACCAAGGAAAAATAT TTAGTTTTTTTTTTTTTTTTTGTATACTTTTCAAGCTACCTTGTCATGTATACAGTCATTTATGCC TAAAGCCTGGTGATTATTCATTTAAATGAAGATCACATTTCATATCAACTTTTGTATCCACAGT AGACAAAATAGCACTAATCCAGATGCCTATTGTTGGATACTGAATGACAGACAATCTTATGTA GCAAAGATTATGCCTGAAAAGGAAAATTATTCAGGGCAGCTAATTTTGCTTTTACCAAAATAT CAGTAGTAATATTTTTGGACAGTAGCTAATGGGTCAGTGGGTTCTTTTTAATGTTTATACTTAG ATTTTCTTTTAAAAAAATTAAAATAAAACAAAAAAAAA[T/A]TTCTAGGACTAGACGATGTAATAC CAGCTAAAGCCAAACAATTATACAGTGGAAGGTTTTACATTATTCATCCAATGTGTTTCTATTC ATGTTAAGATACTACTACATTTGAAGTGGGCAGAGAACATCAGATGATTGAAATGTTCGCCCA GGGGTCTCCAGCAACTTTGGAAATCTCTTTGTATTTTTACTTGAAGTGCCACTAATGGA[C/T]A GCAGATATTTTCTGGCTGATGTTGGTATTGGGTGTAGGAACATGATTTAAAAAAAAACTCTTG CCTCTGCTTTCCCCCACTCTGAGGCAAGTTAAAATGTAAAAGATGTGATTTATCTGGGGGGC TCAGGTATGGTGGGGAAGTGGATTCAGGAATCTGGGGAATG[G/A]CAAATATATTAAGAAGA GTATTGAAAGTATTTGGAGGAAAATGGTTAATTCTGGGTGTGCACCAGGGTTCAGTAGAGTC CACTTCTGCCCTGGAGACCACAAATCAACTAGCTCCATTTACAGCCATTTCTAAAATGGCAGC TTCAGTTCTAGAGAAGAAAGAACAACATCAGCAGTAAAGTCCATGGAATAGCTAGTGGTCTG TGTTTCTTTTCGCCATTGCC[T/C]AGCTTGCCGTAATGATTCTATAATGCCATCATGCAGCAAT TATGAG AGGCTAGGTCATCCAAAG AGAAGACCCTATCAATGTAGGTTGCAAAATCTAACCCC TAAGGAAGTGCAGTCTTTGATTTGATTTCCCTAGTAACCTTGCAGATATGTTTAACCAAGCCA TAGCCCATGCCTTTTGAGGGCTGAACAAATAAGGGACTTACTGATAATTTACTTTTGATCACA TTAAGGTGTTCTCACCTTGAAATCTTATACACTGAAATGGCCATTGATTTAGGCCACTGGCTT AGAGTACTCCTTCCCCTGCATGACACTGATTACAAATACTTTCCTATTCATACTTTCCAATTAT GAGATGGACTGTGGGTACTGGGAGTGATCACTAACACCATAGTAATGTCTAATATTCACAGG CAGATCTGCTTGGGGAAGCTAGTTATGTGAAAGGCAAATAGAGTCATACAGTAGCTCAAAAG GCAACCATAATTCTCTTTGGTGCAGGTCTTGGGAGCGTGATCTAGATTACACTGCACCATTC CCAAGTTAATCCCCTGAAAACTTACTCTCAACTGGAGCAAATGAACTTTGGTCCCAAATATCC ATCTTTTCAGTAGCGTTAATTATGCTCTGTTTCCAACTGCATTTCCTTTCCAATTGAATTAAAG TGTGGCCTCGTTTTTAGTCATTTAAAATTGTTTTCTAAGTAATTGCTGCCTCTATTATGGCACT TCAATTTTGCACTGTCTTTTGAGATTCAAGAAAAATTTCTATTCTTTTTTTTGCATCCAATTGTG CCTGAACTTTTAAAATATGTAAATGCTGCCATGTTCCAAACCCATCGTCAGTGTGTGTGTTTA GAGCTGTGCACCCTAGAAACAACATATTGTCCCATGAGCAGGTGCCTGAGACACAGACCCCT TTGCATTCACAGAGAGGTCATTGGTTATAGAGACTTGAATTAATAAGTGACATTATGCCAGTT TCTGTTCTCTCACAGGTGATAAAC[A G]ATGCTTTTTGTGCACTACATACTCTTCAGTGTAGAG CTCTTGTTTTATGGGAAAAGGCTCAAATGCCAAATTGTGTTTGATGGATTAATATGCCCTTTTG CCGATGCATACTATTACTGATGTGACTCGGTTTTGTCGCAGCTTTGCTTTGTTTAATGAAACA CACTTGTAAACCTCTTTTGCACTTTGAAAAAGAATCCAGCGGGATGCTCGAGCACCTGTAAAC AATTTTCTCAACCTATTTGATGTTCAAATAAAGAATTAAACTAAAGACAACG]AGTTTGTTTTTT GTAAGCTCCACTTCTTGCTAGCAGTTCACCACTGATCCTCTAAAATCAAAGTGGTTAAACGAT CTGTCACACACAGTGAGTCTGAATGCTAAAGCCTCTCCTCACCTCACTCCCTCTGCCCAACA CCCCCAGGTGTATCAGGAAGTGTGTGGACACTGTGGTCAGGCAGAACTGGCCTCAATTCTT GGCTTCACCACTTACAAATTTTATGATCATTGGCAGTTGATTTTTCAGAGTTTCGGCTTCCTTA TCAACAATATGATGATAAGTAATAACAC

10. >ΓFNARI_OI

CTCCCAACGCCACTGTCCAAGACTCTAGGGTCAGCAAGCGCCCCGGGCGGAGAAGGGCGA GGACGAAGAGCGCCGGGCCGCGACCAGGAGCCCACCCGCGCCCTCCGACTGCAGACATG GGGAAGAGACGCGGGAACTCCAAAGTCGCTGGGTCTGCGCAGGTGTGTGCCGCGATCCTG TGAAGGTCAAGGCCTCCTGTGAGGGGGAGTCGTCCTGGAATGCGATGGTGAAGTGCTCCAG ACCGGCCATAGGCCGGAAAGAGTGAGGAAGAAGAGAATGCAGGAGGCCTGCGATTTCTAAG GCGCGCGCGCACAGGGGTGCTGCAATTAGGATGGGGCAATGGGAGCTTG[GAGAAGGGGT GCTAGCTAGGAGGAAAGGCGCGTGCGTGGAGGAACGGCGCGTGCGCGGAGGGGCGGTGT GTGTGTCAGAAGAGGCGGCGCGTGCGTAGAGGGGCGGTGAGAGCTAAGAGGGGCAGCGC GTGTGCAGAGGGGCGGTGTGACTTAGGACGGGGCGATGGCGGCTGAGAGGAGCTGCGCG TGCGCGAACATGTAACTGGTGGGATCTGCGGCGGCTCCCAGATGATGGTCGTCCTCCTGGG CGCGACGACCCTAGTGCTCGTCGCCGTGGCGCCATGGGTGTTGTCCGCAGCCGCAGGTGA GAGGCGGGGAGGAGAGTCTTGGCGCAGGGCGGGAGGTAGGGC]ACGCAGCTGGGCTACG GGGGCGGCGATGCTGTTGGGGGCGACAGACGCCCAGTCTGGGAAACCTTCGGTCCACTTT GCCGCGCCAAAGATTAAACCCGACCTGGGCTCGCAAATCAACCAGGAGAAAGTGGTGTTCT GGGTCCTCTCTTGCCGCTTGCCTGTGGCCGTGTACGGGTCCTCGGGAGCGCCCGGGTCCC ACC 11. >IFNAR1_02

AGGCCATAAAACAGTTGAACCTCATCATAAGAGTGACTCATCGGTGTCACTTCTAAGACCAA GAAAAATTCTATTTTTATGCAGAGACCATTTGTTTTTTAATTAAAAGACAACTCTATTTCAAAGA GGAAAAAAAATCAACTCTTTTTTCAGCTCTCTCAGATGCAGAAATGTAATTATCAGCATCCCT GTGCTGGGAG[CAATCATTAGTTTTTTTAGATTTTTAAAATATACTTCATTATGTTTCACTGTAT TCATTCTTTAATCAGGGATGTGAGGGATAGAATAACATTTAGAATATCTGTACAGTTTGTATAT AATGTTCTTATTTCTTGTTGCTTTTATAGGTGGAAAAAATCTAAAATCTCCTCAAAAAGTAGAG GTCGACATCATAGATGACAACTTTATCCTGAGGTGGAACAGGAGCGATGAGTCTGTCGGGAA TGTGACTTTTTCATTCGATTATCAAAAGTATGTGACTCTACTTACTGATTTGTCAG]AATGACCT GAATAATTTTTACAAGTTTAACAACACCATAATTTTTAGATTTGGAAAGTGTTTGGTTTTTCTAT TTTTTAGAAATGTTACGCCTATTTTACATAATATTTTTAACTTTGTTTCTGTAGAGACTTAGTCA AATACATCTTTGGGTGTTGAAGCAAAAAATTGGGGATGAGGGTGGTAGACAGCGTCTCTAAC 12. >IFNAR1_03

TTTTACCTTATGGGTCATTTATTTCTCTGCTTCCTGAAGCAACCACCCACAAAATTATATAAAG AACTGTATTTTAAAATTCAGTTTCATAAGTAATAACTTGGCTTATATGCATTGAAAAAGAGTGG AAGGGTGTATGCTAAAATGTTAATAGGACATTAGCTCAAGTAGAAGAAATAACTCTTAAACCA AAAATAGAAATAACTCTTAAACAAGAGTTATTAAGAGTTAAGAAATAACTCTTATACCA[GTAAA TAGAAAGTATTTGACACTTACATTTATACATTTGCTCACTCATTCATTTGTTTTTTTTACTTTAAA GAACTGGGATGGATAATTGGATAAAATTGTCTGGGTGTCAGAATATTACTAGTACCAAATGCA ACTTTTCTTCACTCAAGCTGAATGTTTATGAAGAAATTAAATTGCGTATAAGAGCAGAAAAAGA AAACACTTCTTCATGGTATGAGGTTGACTCATTTACACCATTTCGCAAAGGTAAGAAAAAGTT GCTAGCTGAATTATATTCTTTAGTAAATATTACCAGAGCAGTTCACTTTCC]AAGCCATTCATTT GCATGATGCAAAATCTAACATCTTTTAAAAAGAACAAAAATTCCCTTAAACCTATATCTTCTTC CTGCTATGGCTCCATTTGTCCTACTTTCCCTGTAGTAGTGGTTCTCAAAGAGTGATCCTCAAG GCCCTTTCAGGGGGCTGTAAAGACAAAGCTATATTTATGACAAATCTAAGACTTAGTTGCCTT TTTAATTTTTGTTCTTTCTTGTATTCACAGTGGAG

13. >IFNAR1_4 TGCTCATTGATCGCTTCATCTTCCCAACTTTTCAGTGTTAGACTGCTGCTGGGCTCAGTCATT GAACCTCTTCTCTTTCTGTATCACTCCACTGGTGATCTTACAGCTTTCTATCCTATCTGTATGC TCTTAACTCCCAGAAGTGGCAGGCACATATTAAGTGCTCAGAATTATTTGTTGAATGAAGGTT TTGGCATTGTATTAATAAAGTTCCATAGTAATTGTTTTGATTTTTTTGCAG[CTCAGATTGGTCC TCCAGAAGTACATTTAGAAGCTGAAGATAAGGCAATAGTGATACACATCTCTCCTGGAACAAA AGATAGTGTTATGTGGGCTTTGGATGGTTTAAGCTTTACATATAGCTTA[G/C]TTATCTGGAAA AACTCTTCAGGTGTAGAAGTAAGCATTATTTTTACCTCTGTTTAATCGATGTGAGAGAAAAATT AGGCGAATTAATCCTAAAATTTGACTTTATACTTTTTTAAAGAACCAACTTATATTTGTGTTATA GGAAAGGATTGAAAATATTTATTCCAGACATAAAATTTATAAACTCTCACCAGAGACTACTTAT TGTCTAAAAGTTAAAGCAGCACTACTTACGTCATGGAAAATTGGTGTCTATAGTCCAGTACAT TGTATAAAGACCACAG]GTAAGGAAGATGTTTTGTTTTAGATTCAATAAATATATAAACAGATT GTCAATTTTGGCATCTTCCCCATATTGCTGAAGTTTACATGATAGGTCAATATATGTTAAAAAC ATTGTAACATTTACATAAGCAAAATAAATGTTACTTGGGATTTTTGTCTCAAATAGTAATGAAA ATTAATTCTACTTAAAAGTTCAGGC

14. >IFNAR1_06 GGGGTTTCACCATGTTGGCCAGGCGCGTCTCGAACTCCTGACCTCAGGTGATCCATCCACC TCAGCCTCCCAAAGTTCTGGGATTACAGGTGTGAGCCACTGCGCCCGGCCTGTAGTCTTTCA AATGGCTGCATAGTATTACATAGTGTGAATACAAACCATATTTAACTATTACCTTATAATGATA AAATGCGAGCCTT[TATCTTCTTGCCAGTTATCTCACTTGAGTAAAAATGTGTGCTTTTTTTtT/A] ATCTGTTCTTTGGCTTCTAGTTGAAAATGAACTACCTCCACCAGAAAATATAGAAGTCAGTGT CCAAAATCAGAACTATGTTCTTAAAGTGGGATAAAACATATGCAAACATGACCTTTCAAGTTC AGTGGCTCCAGTAAGTTCCATTCCATAAATTTCCTTTTGCCCAGTTTGTTTTGATTATGCTTCT TTTCG[C/T]TCTGC]ATCAGTCACCAGGTCCTTGCACACAGAATGACCGACTGGGAGGTGGGT ACGATATATTGGAAACGTGAGAAATCTCATTTCTAACCCCAGTTCTGCCAGTAACTAACTGGA TGACATTGAGCTAATCGCTTAACCTCCATGGGCCTCAATTTCTTCACTTGTAAAATAGATGGA TTCTAATATCTGGGGTTCTTACTGGC

15. >IFNAR1 7 ACCAGCTTGCAGCATTCCTGGAAATTCTAACTAACAGATGTTCTTGCATATTGATATGAGCCA CCTCCAGCAGAGCACAACATGACCACAGTCTGGAACAGTCTTTGGTTTTCTTTTATGTTAGAT GCATATCTCTTCCATTGTTTGTGAGTTTCCTGAGTGTGGATACTATTTATTTCTGTAACCTTAG CCCCTAACATAGTGTCTGGCAATTGTAAATACTTAATAAATATCTAATGAATTTAAAAAATATTT GTCTTAAAAG[CGCCTTTTTAAAAAGGAATCCTGGAAACCATTTGTATAAATGGAAACAAATAC CTGACTGTGAAAATGTCAAAACTACCCAGTGTGTCTTTCCTCAAAACGTTTTCCAAAAAGGAA TTTACCTTCTCCGCGTACAAGCATCTGATGGAAATAACACATCTTTTTGGTCTGAAGAGATAA AGTTTGATACTGAAATACAAGGTAAGGCAGTAGTTTTTACTGGAGATTGTAATTCTCTGGTGC AAGTTTTTAAAATTGTTTTTCTAATTGAACATTATTTCTTTACAAATTTTTTCTAGCTTTCCTACT TCCTCCAGTCTTTAACATTAGATCCCTTAGTGATTCATTCCATATCTATATCGGTGCTCCAAAA CAGTCTGGAAACACGCCTGTGATCCAGGATTATCCACTGATTTATGAAATTATTTTTTGGGAA AACACTTCAAATGCTGAG]GTAAAAAGACTGTATAGTATAATTTTGTAACTTAGAGTTATAATTA TGATTTGGGTAAATAAAGCTTGAATGTAAAATTTGGGGGAAATTTTTAAACTTTATGTGGGCT GGATGCAGTGGCCTGTAATCCCAGCACTTCAGGAGGCCAAGGCGAGAGGATCACTTGAGCC TAAGGGTTTGAGACCAGCCTGGGCAACATAGGGAGACCCTGTCTCAATAAAAATTTTAAAAA

16. >IFNAR1_09

ATCTGTAATCCCAACTACTCAGGAGGGTGAGGCAGGAGAATCGCTTGAACCCAGGAGGCAG AGATTGCAGTGAGCCCAGATTGCACCACTGCACTCTAGCCTGGGTGACAGAGCGAGACTGT CTCACAAAAAAAACAAAACAAAACAAAACAAAACAAAAAATACATACCAACTACGTGGGAGAG GCCAATGTTAGACTG[AACATAAAAAATTGAGAAAGCACATATTCCCTGATTTCTTGAGGTGAC TAAATTTTATCAGTGATTTAATTATATTTTCTAGAGAAAAATTATCGAGAAAAAAACTGA[T/C]GT TACAGTTCCTAATTTGAAACCACTGACTGTATATTGTGTGAAAGCCAGAGCACACACCA[T/G] GGATGAAAAGCTGAATAAAAGCAGTGTTTTTAGTGACGCTGTATGTGAGAAAACAAAACCAG GTCAGAATCTTTTATTGTCTTTTTTAAAAATGTAGCTAGACATAATAAAAGTAATTCTATACTGT AC]ATTGAAAATTGTAAAACATTTTCTCTTTACTGCAAAAAATATATAGAAAGAATGTTTTCTTC ATGAACTACATGAATCAAAAGTAGACTTTTTAGAAAATATTTGTAACGCTTAACTCTCAAGTCG GTGTTGTTGGATGCTTTATATTTCATCCAGTATCCCTATAATTAATTTCCTTAATGTATTTCTCT TTAACATTT

17. >IFNAR1_10 AGGATACTTGCATGTTTGGCCTGTATGTCAATATTGTATTTCTCCCTGAGGATCTCTTACTTCA GTTCCCACGCCAATCTTTAAATGTAAATGTCATTGCCTATGGTTGCTGTGGACTCAGTGCTGC CAGAAATATTTTTAAGAGTATTATTTAATAGATTTTATATTTCCTTTCATATGGCTAGTCTTTCA CACAGCTG[TCAGCACTGTTAAGGCATTTGTATGTCAAAATATATGCTAAATATCACGTATATC TTTTTAGGAAATACCTCTAAAATTTGGCTTATAGTTGGAATTTGTATTGCATTATTTGCTCTCC CGTTTGTCATTTATGCTGCGAAAGTCTTCTTGAGATGCATCAATTATGTCTTCTTTCCATCACT TAAACCTTCTTCCAGTATAGATGAGGTATGTTACTTTTTTTATTTTTTTGTCAACAGCTAGGTAA TGAACAGAAAATGTGTTTGATTTCAACAGGATATATGTAGGTTTTCTTGATA]TCCAGAAAATA ATAGAGACTGATTTGGGTATCTTCTTCAAAGCTTTAGTCAATTAACTTTAAAAACAGTAATTTC ATGTAATAACATAGCATGAGATAGTAATGATTGTCCTTAATTTCATATTTTTCTGGCAATTCCT AGATTCACTGtGGCATTTGTTTTACCGTTTAAAGCCTGTGATTCTTGGCCAAGCGTGGTGG

18. >ΓFNARI_Π

CTTTCTTAGGTACTCTTCAAAGACTCACCACAGAAGGTACTAAGATATGAGTGACCTCACTAA TGATGCTTTTAAACATTATAAGGCAATTAGTATGTTCTTAGGCGACTTTTTAATATGCATGCCA GAAGATAGGTTTTCTCAGTAATGGATGTAAGAAACTAAAGCTATTACAACTAGAAAAGGAATT TTTATTATTTTAAATAATTGATTTCTACTCTTTCCCTTTTTTTAAATTAG[TATTTCTCTGAACAGC CATTGAAGAATCTTCTGCTTTCAACTTCTGAGGAACAAATCGAAAAATGTTTCATAATTGAAAA TATAAGCACAATTGCTACAGTAGAAGAAACTAATCAAACTGATGAAGATCATAAAAAATACAG TTCCCAAACTAGCCAAGATTCAGGAAATTATTCTAATGAAGATGAAAGCGAAAGTAAAACAAG TGAAGAACTACAGCAGGACTTTGTATGACCAGAAATGAACTGTGTCAAGTATAAGGTTTTTCA GCAGGAGTTACACTGGGAGCCTGAGGTCCTCACCTTCCTCTCAGTAACTACAGAGAGGACG TTTCCCTGTTTAGGGAAAGAAAAAACATCTTCAGATCATAGGTCCTAAAAATACGGGCAAGCT CTTAACTATTTAAAAATGAAATTACAGGCCCGGGCACGGTGGCTCACACCTGTAATCCCAGC ACTTTGGGAGGCTGAGGCAGGCAGATCATG AGGTCAAGAGATCGAGACCAGCCTGGCCAAC GTGGTGAAACCCCATCTCTACTAAAAATACAAAAATTAGCCGGGTGTGGTGGCGCGCGCCTG TTGTCTTAGCTACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAAAACAGGAGGTGGAGGTT GCAGTGAGCCGAGATCACGCCACTGCACTCCAGCCTGGTGACAGCGTGAGACTCTTTAAAA AAAGAAATTAAAAGAGTTGAGACAAACGTTTCCTACATTCTTTTCCATGTGTAAAATCATGAAA AAGCCTGTCACCGGACTTGCATTGGATGAGATGAGTCAGACCAAAACAGTGGCCACCCGTC TTCCTCCTGTGAGCCTAAGTGCAGCCGTGCTAGCTGCGCACCGTGGCTAAGGATGACGTCT GTGTTCCTGTCCATCACTGATGCTGCTGGCTACTGCATGTGCCACACCTGTCTGTTCGCCAT TCCTAACATTCTGTTTCATTCTTCCTCGGGAGATATTTCAAACATTTGGTCTTTTCTTTTAACAC TGAGGGTAGGCCCTTAGGAAATTTATTTAGGAAAGTCTGAACACGTTATCACTTGGTTTTCTG GAAAGTAGCTTACCCTAGAAAACAGCTGCAAATGCCAGAAAGATGATCCCTAAAAATGTTGA GGGACTTCTGTTCATTCATCCCGAGAACATTGGCTTCCACATCACAGTATCTACCCTTACATG GTTTAGGATTAAAGCCAGGCAATCTTTTACTATG]CATTAAGACCTCTGATTCAAAACTTATTA GAACAGTAGCTTCTGCTGGAATTTGCAATCACTGAAGTCATAGAAAATAGGTAACTATCTAAT TAGAGAAATAATTGTTGTATTTTAAGATCTGAGAGTGTGTACAAGTTTTAGTATACATGCCATG CCAGAAGATAGTGTATGCAAGAAGTCTTGGGACCAGAAAATGGCAATGATAGGAGACTGACA TAGAAGAAGAATGCTTCCCTAGGAAAAAGGTCGCTGGCTTTGGTGCAAGAGGAAGAAGAATG TTCCACTGGAAGCCTGAGCACCTAATCAGCTCTCAGTGATCAACCCACTCTTGTTATGGGTG GTCTCTGTCACTTTGAATGCCAGGCTGGCTTCTCGTCTAGCAGTATTCAGATACCCCTTCTGC TCAGCCTGCTTGGCGTTAAAATACAAATCATTGAACTGAGGGGGAAAAATGTAACTAGGAAG AAAAACCCAATTTAAGAAATTACATAATGCTTT 19. >IFNAR2_01

AGCTTTCTCGGCGAAGGCGGGATTGGTTAGGAGCTGACAATCGGCAGCAGACGATTGTAAA TGACCGGACCTTTTTTCTATTCTCCTGCCCAGCCCCCGGCCCGGCCTCCGCCTCCGGCCCT GCTCCAGCCCCGCCAGCGGCCCAGGACCCGCCCCTGGCTCCGGCCCCGCCCCTGGCTCC GCCCCCGCCCCCGCGCCGGCGGCGGCGCG[GCGCCCGCGCTTCCGTATCGCTCCTCGTAG GCCGGGGCTCGGCGCGCGCACCCGCACTAAAGACGCTTCTTCCCGGCGGGTAGGAATCCC GCCGGCGAGCCGAACAGTTCCCCGAGCGCAGCCCGCGGACCACCACCCGGCCGCACGGG CCGCTTTTGTCCCCCGCCCGCCGCTTCTGTCCGAGAGGCCGCCCGCGAGGCGCATCCTGA CCGCGAGCGTCGGGTCCCAGAGCCGGGCGCGGCTGGGGCCCGAGGCTAGCATCTCTCGG GAGCCGCAAGGCGAGAGCTGCAAAGGTAACGCAGCGTGGCGGGGTCGCGGGAGCGGAGC GCGTGGCCAGCTGACTGGAGGGA]AAACGCCGCCTCCCTGCAGCGGTTCCCGGAATCCCCT CCGGTTCCCTCTCGCTCTCCCCGACTCCTCCTCCTCCTCCTGCCCTCCCTCTGCGTCTTGAG TATGCGGCTAGTGCGCCCTTCCTCTCTCCCGGGGCCGCACCTGCGACCCCAGGACCCCTCC CGGGCCCTGTCCTGCGCCCTCCACGCGTCGCCCCTGCTGG 20. >IFNAR2_02

GATGGGGAAATTAGGAATATGTATTTGTTTTTGCTTATGCATGAAGATACTCTGAAGGATTCA CAAAAGAAAAAAAAGTTTTCTAAAGGGAGCAAGACTTTTCACAATTTTTTTTTTGAATGCTTAA AATTGTTG AACCCAACGACTGTTGCCTGTTCAAAAGTTAAATTTAAAATTCCTCCCAGACTAG GTAGGGGATTGGGCCCAGAAGCTGAGACCAGGCTCACTTGAATAAATGGGGTAAATGACT[A GGAATTTTACTATTCCTTACAGGTCTCTCATTATCTTGTCTTTGCTCCCATTTTTATATTTGCAG TTTAATTAGACACTTCAGAATTTTGATCACCTAATGTTGATTTCAGATGTAAAAGTCAAGAGAA GACTCTAAAAATAGCAAAGATGCTTTTGAGCCAGAATGCCT[T/A]CATCT[T/G]CAGATCACTTA ATTTGGTTCTCATGGGTAAGTGCTGCTTTTTATCTTAGCTCTTATAGAAGCAAGCTGTGATGC CATCCTCA]CTGAGAGCACTGGCAGGAAGTCGCAAACTCATTTCCCTGACTAGAGGACCCAG TACCACCCTGCCTAGTGTCAGGAGTTAAGTGGAAAGCAAATAGGAAACCTACACTAGTAGTT TAGATTCAATGTAGATTCCTGTCCTGTTGTTAATTTTAGGAAAACAAATGAGTGACTTAAGGCA ATAATAATCAGGACTATCCTCGCCATAATTTGAAGAGTAATTTCTCCTAACACGCTTTCTT 21. >IFNAR2_03

CCACCCACCTCGGCCTCCCAAAGTGCTGGGATTACAGACGTGAGCCACGACGCCCGGCCC CAGATATATTTTTAAGTGGAAAAAGCAGGGCAGAACAGGGACCGTACATATTGTTGTTAGTGT CAGCTCCCAAATGGATCTTATTTTATCTCAGATCACAGTCCTTGCACCATGTGCTGCTGGCAC CAATGTAGAGTAAAAACCATCTATGTGGGCATTTTTTTGGCACAAGAAAAATCTCAATCTGAT A[CCAATAAATGTGTGTTAAAGAATGTCAGACTTAGAGTAATCATTGCAAGTTGAGCCCAGATA AAACTATTGCCTCTCTAATGTGTTTTCTTCCTTCTAGTGTATATCAGCCTCGTGTTTGGTATTT CATATGATTCGCCTGGTAAGAGATGTTTTTT[G/C]GCTTCACTAAATTTTGTATAAGAGTGAAA GTGTTGGGGCAACCATTCAGAGGTATAAAATGTGGGAGATTTGATTTCTGATTGTACATCTGT ]TGCCTGTTTTATTGGGATTCTTTCTCTG[T/C]AAAAGGAGCTAAAATGAGCTAACTCTGGTTTT TTG AG AG ATACAAAACTAGTCTAAG AAATG AAC ACTAG AGATCATTTTTAAACTTCTTTAAAGA ATATTCAAACTCTTAATAATCTCACTAATAAAAGAATGAGGAGACACAGACTGTGCCAAATAAA AAATGGCCCAGAAATATTTACTCTTTAATTTACATTCTTCCACCCTGATGATTCCAGACAA 22. >IFNAR2 04 GGCTGGGATGGCCTGGGTTATTTTGGTCCAGTGAACCATGGAGGGACAGTCCAAGGGCATC GGAGAAGCCCTTCTGTCCAGACTCTCCTTACACAGTGCACAGTCCCTGTTTCCCATGCTTGC CTGCCCTGACAATATGTTGCTCGTTAATTGACTTACTAATTTATTTCCCATGTCCTGTAGACTT CCTGTTTTCAAGACACCAGGGCTCTCTGGAGAGGTTATCTGCCAGAGGTGTGGGTTCTAGAT C[CCAAGAAATGACTGAACAGTGGCCAGAATACAACTGTGGGTTCCAAATTTCAATGCCCTTT TTCTTCTTCTCTTTAGATTACACAGATGAATCTTGCACTTTCAAGATATCATTGCGAAATTTCC GGTCCATCTTATCATGGGAATTAAAAAACCACTCCATTGTACCAACTCACTATACATTGCTGT ATACAATCATGAGGTTGGTTTGATATTTCATTTTCTCTTGGTAAACATATTATTGTTCTGTTATA TGGGGAGAGGTGATCTTTTCTCTCTCTCTGTCTCTCC]CTCTCCCTTTTCCTATCTACCTCTCC TTCTCTCTGCGTTTCTTATTCAG AGCCTTAAAAAGCCAAAG ACAAAACACCATCACACATCCA TTTTTAATTCAGTTGAATACTTTAATAATCCAAATCTATTTTGACAAAGCTTGTATGTGTCATCA AAGCCA

23. >IFNAR2_05

CCAAAGTCCCTGCCCTCCTGGAGCAGACATTATGTAAATGGAGACATCAGTAAACAAAGGTA TAATGTG ACAGGTGTGGGTAAATGCTACAATCAAGAAAAG AG AGGG ATTG AAAGTGCAGGG GTGGGGAGGGCATAAGATGTTCCATTTTCAATAAGATGGTTGGGGAAGATCACTTAATACAA TGATATTTGGGCAGAGCCCTAAAGGAAACAATGAAGTAAGGCGCC[CAAAAATAGACTCTCAT TACATCAATGCTAACAATTTCCTTTTTCCATTTTTTTCTTTCCAAAGTAAACCAGAAGATTTGAA GGTGGTTAAGAACTGTGCAAATACCACAAGATCATTTTGTGACCTCACAGATGAGTGGAGAA GCACACACGAGGCCTATGTCACCGTCCTAGAAGGATTCAGCGGGAACACAACGTTGTTCAG TTGCTCACACAATTTCTGGCTGGCCATAGACAGTGAGTTTTATCTCTGTTTCTCCACTTCGTC CCCATCATCAAGATCTTTATTATTTGCTATTC]CATGAAATAGGAGGTCTACAAAGGTGTTTTA GACCTGGGGCTGGGCTCACCTCTTGGCCCTGCCACTTCCTAGCTCTGTAACCGTGGACTGC TTTGCTTCTCTGAGCCTTGGTTTTCTAAATCTGAAAAGTGGAATGATAATTTGTACTTTGCAGA TTTGCCCCGTGCCTGTATAAGGCAGTAGGAACTGCTGTTTTCGGTTTTGCAGCCTGACAGGA AG

24. >IFNAR2_06

AAAGAAAGAAATTATTAAGGACAAATGCAAAAATTTAGTTCCAAGAATATCCCATGATACATTA AGTCTTTAATAAAAATCAGAGACAATTTAAATGTTCAAAACAGTGAATCAGTTAAATCATGATA CAGTCACTTAGTGGAATAGCATTAGCAATGAAAAATTATGATGTAAATCAGGACTTGGCAGAT TTTCTATACAGGGCCAGAG[AAGAACCACTTTAGACTTTGTGGGCCACATATGGTCTCTGTGA CATATTCCTGTCTGTTTTTGTTTTTTGCACAGTGTCTTTTGAACCACCAGAGTTTGAGATTGTT GGTTTTACCAACCACATTAATGTGATGGTGAAATTTCCATCTATTGTTGAGGAAGAATTACAG TTTGATTTATCTCTCGTCATTGAAGAACAGTCAGAGGGAATTGTTAAGAAGGTAAGTGGCTTC TCCTGTTAGGATCAAAACAGTTCTG AGTGGGCAATCAATGCACTTGACTGTCTCTTTTGAAAG GAAATTTGCAGTTGAACAATTAAAGCTAAAACGTCAGGCTTCAGTATGGTCCGA]CTTAGGGA AGAAGTCACTATGGTTCATTCACTATTGATCTAAACCTGCAGCACAGTGTTCTTTAAAAGAATA AGCCACGGCTGGGCCTGGTGGCTCACGCCTATAATCCCAGCACTTTGGGAGGCCGAGGCG GGCAGATC

25. >IFNAR2_07

AGAGACTTTTATTCCTCTTTGAAGACTTTTATCTCATTTGTAAAATGAAGGCGCTAGACTAGAT GTCATGGTTATAAAATATGTGTGTGTGCAGGTGTATATTAAAAGTGCATGTAGGTGTAGTTTT CTGATAAATTACTTGCTCCAGATGACTTATAAATCCTTTTTCTTACCAAGCCTGTGATAAATCT AACCCTGTTTGAGATTTGAAGACAAATCCCAAAAGAGAT[TAAGGCCTACCTCTAAATGAAATT CTCAGTCTTACTGATTTTTTGCTTATGTTTACAGCATAAACCCGAAATAAAAGGAAACATGAGT GGAAATTTCACCTATATCATTGACAAGTTAATTCCAAACACGAACTACTGTGTATCTGTTTATT TAGAGCACAGTG ATGAGCAAGCAGTAATAAAGTCTCCCTTAAAATGCACCCTCCTTCCACCT GGCCAGGAATCAGGTATGTTCATTTTTTTAAATTCATGTTTTGAGTATTCATGCTTTTACTCTG AG]GGCAAGCCTATTTAAAGAAAAGAATCTGAAAAGAATTCATGGAGCACTAAAGGTCTTTCTT CCAGTAAACACCTCACAGAGATGTTTTCTGTTGGTTCGTGTGTATGATCTGGTAGAGTCACTT TTATATTGTCATACCAAAAAACAATCAGATACTACTCGATGAGATCAGAAATCTTGAAATGGAA ACGCTTTTGTTTCAGGGAGTCAGGATTAAATTCAGCACTGTGTGCCCTTTGT

26. >IFNAR2_08

GCCAGCTGCAGCCAGTGGCTACTCCACTGTACAGTGCAGTTATAGAACATAAACTGAAGGAA ATTTTACTTTTAAAAGCTAAGTCTATTTTATTGTTTAAAAAATGCACACTTAGATAATTCTCCAG TCTCTGGTATTTCTCAATATAAAACTGTTTTTTCAAACCTTTGGTTTCTTGATCATCTTGTAACA CCAGGCCAATGTACATTTATTTCCATCT[GCAATTGTTTATTGCATTTTTTGAAATAAAGTCATT TAATTTTTCATCAACAGAATCAGCAGAATCTGCCAAAATAGGAGGAATAATTACTGTGTTTTTG ATAGCATTGGTCTTGACAAGCACCATAGTGACACTGAAATGGATTGGTTATATATGCTTAAGA AATAGCCTCCCCAAAGTCTTGGTAGGTAGTTTTTTTGTTTTGTTTTGTTTTTTCTATCTTTGTTT TTTATTTTAACηTAAGAATTTGTATTTATATAAATATTTTCACAGAAGAAAATCTCATTTTCTATA AACACCAAAATGCTTTCTCACTCTGAGTTCTTTTCCATATCTATAAATGTATATTTTGCAGGGT TTTTGTTTTGTTTTTGTTTTTATTATACTTTTAAGTTTTAGGGTACATGTGCACAGTGTGCAGGT TAGTTACATATATATACATGTGCAGTTGTAAGTGTATCTGTGCATCTGTGCATTTTA

27. >IFNAR2_09

GCATAGTGGCGGGCGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCAGAGAATTGCTTGA ACCTGGGAGGTGGAGGTTGCAGTGAGCCAAGACCGCACTACTGCACTCCAGCCTGGGCAA CAGAGCGAGACTCCCGTCTCAAAAAAAAAAAAAAAAAAAAATAGTAAGCATACCTCATAGAGC AGTTGCAAGGGAAAGGTAAATTATATATAAAGCACCAAGAGTCATGCCCAGCATATAGTAAG CATGGTGTAACTGTTAGCTGTTATTATTGCTGTCATCATCATCAACTGCATCATCATTCAATCT[ CATTAAGTTTATTTTTTATTTTTTTAGAGGCAAGGTCTCGCTAAGGGCTGGAATGCAGTGGCT ATTCACAGGTGCAGTCATAATGCACTACAGTCTGAAACTCCTGAGCTCAAACAGTCGTCCTG CCTAAGCTTCCCCAGTAGCTGGGATTACAAGCGTGCATCCCTGTGCCCCAGTGATTAAGTTT TATTATGTAGAAAATAAAGAGCAAACAGTACAGCTGATACGGACTCTCTCTCTCTTTTTTTTTT TTTTTAAGAATTTTCATAACTTTTTAGCCTGGCCATTTCCTAACCTGCCACCGTTGGAAGCCAT GGATATGGTGGAGGTCATTTACATCAACAGAAAGAAGAAAGTGTGGGATTATAATTATGATGA TGAAAGTGATAGCGATACTGAGGCAGCGCCCAGGACAAGTGGCGGTGGCTATACCATGCAT GGACTGACTGTCAGGCCTCTGGGTCAGGCCTCTGCCACCTCTACAGAATCCCAGTTGATAG ACCCGGAGTCCGAGGAGGAGCCTGACCTGCCTGAGGTTGATGTGGAGCTCCCCACGATGC CAAAGGACAGCCCTCAGCAGTTGGAACTCTTGAGTGGGCCCTGTGAGAGGAGAAAGAGTCC ACTCCAGGACCCTTTTCCCGAAGAGGACTACAGCTCCACGGAGGGGTCTGGGGGCAGAATT ACCTTCAATGTGGACTTAAACTCTGTGTTTTTGAGAGTTCTTGATGACGAGGACAGTGACGAC TTAGAAGCCCCTCTGATGCTATCGTCTCATCTGGAAGAGATGGTTGACCCAGAGGATCCTGA TAATGTGCAATCAAACCATTTGCTGGCCAGCGGGGAAGGGACACAGCCAACCTTTCCCAGC CCCTCTTCAGAGGGCCTGTGGTCCGAAGATGCTCCATCTGATCAAAGTGACACTTCTGAGTC AGATGTTGACCTTGGGGATGGTTATATAATGAGATGACTCCAAAACTATTGAATGAACTTGGA CAGACAAGCACCTACAGGGTTCTTTGTCTCTGCATCCTAACTTGCTGCCTTATCGTCTGCAAG TGTTCTCCAAGGGAAGGAGGAGGAAACTGTGGTGTTCCTTTCTTCCAGGTGACATCACCTAT GCACATTCCCAGTATGGGGACCATAGTATCATTCAGTGCATTGTTTACATATTCAAAGTGGTG CACTTTGAAGGAAGCACATGTGCACCTTTCCTTTACACTAATGCACTTAGGATGTTTCTGCAT CATGTCTACCAGGGAGCAGGGTTCCCCACAGTTTCAGAGGTGGTCCAGGACCCTATGATATT TCTCTTCTTTCGTTCTTTTTTTTTTTTTTTTTTGAGACAGAGTCTCGTTCTGTCGCCCAAGCTG GAGCGCAATGGTGTGATCTTGGCTCACTGCAACATCCGCCTCCCAGGTTCAAGTGATTCTCC TGCCTCAGCCTCCCTCGCAAGTAGCTGGGATTACAGGCGCCTGCCACCATGCCTAGCAAAT TTTTGTATTTTTAGTAGAGACAGGATTTTACCATGTTGGCCAGGCTGGTCTCAAACTCCTGAC CTCAAGTGATCTGCCCTCCTCAGCCTCGTAAAGTGCTGGGATTACAGGGGTGAGCCGCTGT GCCTGGCTGGCCCTGTGATATTTCTGTGAAATAAATTGGGCCAGGGTGGGAGCAGGGAAAG AAAAGGAAAATAGTAGCAAGAGCTGCAAAGCAGGCAGGAAGGGAGGAGGAGAGCCAGGTG AGCAGTGGAGAGAAGGGGGGCCCTGCACAAGGAAACAGGGAAGAGCCATCGAAGTTTCAG TCGGTGAGCCTTGGGCACCTCACCCATGTCACATCCTGTCTCCTGCAATTGGAATTCCACCT TGTCCAGCCCTCCCCAGTTAAAGTGGGGAAGACAGACTTTAGGATCACGTGTGTGACTAATA CAGAAAGGAAACATGGCGTCGGGGAGAGGGATAAAACCTGAATGCCATATTTTAAGTTAAAA AAAAAAAA]AGCAAACACAAAGATGCTTCAAGATCTTCAGGAGAAGTATGGTATACAAGTTTCA GGGACCCTATTTGACAATTTTCAGAGTGCTCTCTATGCTGATTCCGAGTCGAGTGTGTCAGC TGTGATTACAGTGCCTGTGGATCTAGGCCGGGTTGGGGGGGTGTGGGCGGGGGAAGGGAA GTCTGGCCCGGAGCAATTGCTCCTGCCGGTAACCCCAGCACTTTGGGATGCCTAAACAGGC GTATCGCTTGAGGCCAGTAATTCGAGACCAGCCTGGGCAACATGGCAAATCTGTCTCTACAA AACAAAATTAGAAAAATTAACTGGGCGTAGTGGCATGTGCCTGTTGTCC 28. >IFNGR1_01

AATGGCTTTTGAAGTCTCATTCTCTTCTAAAAATGTCAGGCTCCAAGACAACCAGGTGAAGTC CAAGAGTTAGTAAAATAAGGATTGTGGCTCGGCTGTGGCCTAATGCAAACTTGCACAACCCC AGGAAACCGAAAAAAACTGGAAGAAGAATTGCAGAATGGGGTGCCAGGTTGAAAGACCTTAA CCTTTGCACTCAAATTCCTCCCACACCCAGAAGTCCAGGTCCCGACCGCACGACGCCGTGC TC[ACTGCTGGGTGCTGCGCCTGAGTCCGCCTCCTGCGGCTTCCCGGACTTGACCCCGCCC ACGCCCTGGTCCCGCCTCCTGCCGACGCCGGCACAGACCCCGGTGACGGAAGTGACGTAA GGCCGGGGCTGGAGGGCAGTGCTGGGCTGGTCCCGCAGGCGCTCGGGGTTGGAGCCAGC GACCGTCGGTAGCAGCATGGCTCTCCTCTTTCTCCTACCCCTTGTCATGCAGGGTGTGAGCA GGGCTGAGATGGGCACCGCGGATCTGGGGCCGTCCTCAGGTACCGTCGTTCGCGGCAGG] GCTGCGGCCGGGTCGGGACGAGAGGGAGGGAGGGATCCGCCCCAGCCGGGAAGCCCCGC CCCGCTTCTCCGAGGTCGCCCTAGCCCGGGACCCCTGCGTCGGGCCCTGAGCGGGCGACG GGGACGCGAGGTGGGGTCGCGAGACTGGGGCTCCGTGGTTTGAACTCGTCGGTTGCCTTT CTCCTGCCTCTTCCCTGGTTGCCGCCACAACAAATCACGCCGCTTGTTTTTCCGACTCTTGTA ATCCACTTTT

29. >IFNGR1_02

AATTCTAGTGATGAAATGAGGATTATTAATTCAATAATCAGTGCATTTGATTATAAAACTTCTAT CATATTAAGGGAATTTATTGCTTCATGCTGTATTTGTGTTTCCTTTATATTGCAATGATGTTTCC ATAATTTAAAACGAATCAG AACTCTTCTATAGATTTTTCAATAAAATTAATTTCTAG ATGTCTAC TCTTCATTTAAATAATTTTGGTATCCTGGTGAATTCTACTTTTCTTCAAATATACATATCTGGGC AATGTGGCATCTTACAATAAGGCTTTCCAATAT[TAATGTTAGTTTCTTACAATTGTCCCTTTTA CTTTTTTATTTTCTTACAGTGCCTACACCAACTAATGTTACAATTGAATCCTATAACATGAACC CTATCGTATATTGGGAGTACCAGATCATGCCACAGGTCCCTGTTTTTACC[G/A]TAGAGGTAA AGAACTATGGGTGAGTGTCACTCTTTTATTTATCCTTTTTATTCCATTTTTGTTTAGGTC]CTTG GAAATTCCACAACTGTGTTCTTTCATCAGCCTTCCCACGTGGCAAAACATTCTAAACTGCTTA TAGAGGTCCAAAAGTACTAAAGATGCAAATTCTTTGCCAAATATTTCTTGCCTCTTATTTCCTC TTCCTTATCAGTATTGAAATAGAGAAGTATCACTAAACTTCTGAGATTAGCATGACAAATAAAG CTAATAGTTACTATGTCATCTTCCTGTAGTGTATTTTTAGTAGAACA 30. >IFNGR1_03

ACAGATTTTTAAAAAATTGAATGTGGAATGTGGCTTGCATAGGTCTTACATTTTGAATTGAGCC TCTTTACTGTAACAGAGTTTGTAGTTCTTCTAACTAAAGAGTAAGGGTTTCCTACTTTCTCTGG CGTCTCCATCCTATTCTTAGCTCTGCTCTTTCTACCGCTTTGTGCTGTGAATAAAAAGCAAAG CACAGACAGAAATGGTTTGAGTTTATTTAATAACAATAAAAGTT[ATCTTCGCATTTTTTTATTC TTTTTAGTGTTAAGAATTCAGAATGGATTGATGCCTGCATCAATATTTCTCATCATTATTGTAAT ATTTCTGATCATGTTGGTGATCCATCAAATTCTCTTTGGGTCAGAGTTAAAGCCAGGGTTGGA CAAAAAGAATCTGCCTATGCAAAGTCAGAAGAATTTGCTGTATGCCGAGATGGTGAGTAGAA TGTGTACACATGTAAAT]TTTAAATTGGAAAATATTTATACATGTCTTCTGTATGTTTGCTTTTAT TAGCAGTTGCTGAAAATTATCACAATGCTTAAGAAACACTTGGAGGAATTTAGAGTCAGTACA GGTTGAGCATCCCAAGTCTAGAAACCCAGAATGCTCCAAAATCTGAAACTTTTTGAGCGCCA GCATGGCACTCAAAGGAAATACTCATTGGAGCATTTTGGATGTTCAGATTTAGAATGTTCAAC TG

31. >IFNGR1 04 ATTTACAACTAGAAATGAAATTAAACTGCTAAATAGGCATTCAGATTAAATAAGAGTACTTCTT GCCTGAGATTTATGAAACATTTGTTTATTAAGGACCCCGAGACTATCTTCTAGATATTTGTGG AGTGGTTTAAATGTGGTCCTGCTTTAGAACAACCAGAACAAAAACAATAGGTTGATTGATAGA TTCTGGTAATTTTATGAAATGTACCATTTAGTTCCAAGGCCAGTATTTATTATACT[TCCTCCTC CTCCTTCCCCAGGAAAAATTGGACCACCTAAACTGGATATCAGAAAGGAGGAGAAGCAAATC ATGATTGACATATTTCACCCTTCAGTTTTTGTAAATGGAGACGAGCAGGAAGTCGATTATGAT CC[C/T]GAAACTACCTGTTACATTAGGGTGTACAATGTGTATGTGAGAATGAACGGAAGTGAG GTATGTGTTTCACATTTTTC]ATAATGGAAATTCTTGTGTAGCTAGCAAAAGTTGTTCCTTTCTG TAGTGTAATGAAAATAGGATGCTTATAAATATTCAAGCAAGACTCACAGATCATAGATTTGATA AGAAAAATATGTGAATGCTATTAAAGCAAAAATGATACAG AGTTAGTCACTAACACTGACCAT GTGAATACATTTAGTTTTTATTTGCTTCATTTAGCAGAATGGCTCTAATCTAGGATTTTTCCCA GTACAC

32. >IFNGR1_05

AATGAATAGGACAAATGAACATTTGTTAGTTTAACAACTAACAATAAACATTCCTGCAATTTGA GTTTTTAAATTTACCATTTTTATAAGGAATATAACAGATGCATAGTATCGTGCTGTGTTG AAGT AACAAATTGACTTATTGATAGTAAAGCTATTTTTAGACATGTTCAAGTCAATCATATATATTTCT TCAGTTGTTTGACCAGGACTAATATGGTGATTTTTTTTTTTTTTCAGATTAAAAGAAGCTGTGC ATTTT[CACTGTTTTCTTTTTTCATCTAGATCCAGTATAAAATACTCACGCAGAAGGAAGATGAT TGTGACGAGATTCAGTGCCAGTTAGCGATTCCAGTATCCTCACTGAATTCTCAGTACTGTGTT TCAGCAGAAGGAGTCTTACATGTGTGGGGTGTTACAACTGAAAAGTCAAAAGAAGTTTGTATT ACCATTTTCAATAGCAGTATAAAAGGTAAGTTCTTGCCATTTTTTTTCTA]AATATAGAGGGAG CAGTAACTAAAATAGGATCATGTGAGGAAAGCAAACTCATTTGCAGTTTCAAAAGATCTGTTT TAACAATATTCATTTGCATTAGTTCCATTCCTTAGAGAAGTTCAAAATTAAAAATAAAGCAGTTT CTCACACATTTAAAGATATAGAACAACTAATTTGGAAAGCCATGTGATGGCCCCTTGACCCAG GA GAAAAAATATATAATAAGTACATAAAACTACACAAATGTTTGCAT

33. >TFNGR1_06

ACCCTGGAAACACACTGTATGTAGGGCTGTAAGGAAATTATTGTAGAAAAGCTATTTTAACTA

TGTTGTGTCATAGTAGAATAGTCCCAGAAAGTTCTAGAATTGCAGAGCTGGGAAGAACCATAT

TGCTATCTAAGACAGATACCTAATTTTTTACTCAGATTTCCTAACTTCTGCTTCCTTCAGTGTT CTTTAAAACTCTGGCCCTATTCACTAATTTGTAAATCTATTCAAGAATGGCACTAAG ACTTTTT GATAGAT[AATAGCAGTATTCCATCTTAATTGTAACTTGTGATTTCTGCCTTTTTTAAGGTTCTC TTTGGATTCCAGTTGTTGCTGCTTTACTACTCTTTCTAGTGCTTAGCCTGGTATTCATCTGTTT TTATATTAAGAAAATTAATCCATTGAAGGAAAAAAGCATAATATTACCCAAGTCCTTGGTAATG TATTTAATTTTTTTATATACACTAAAAAGTTAACTTGAACCTTηTTTGATAGTTTCTTAAATTATG TTTTTAAAGTAGAATGATATTCAACAAGATGTCACCTGCCATCAATCAGTCAGTCTACCACAC ATGCAAAATCACATACTGTGTCTTTTGCTGTGCAGCAAGTATTTTGTTTTTTTTTTTATTCTCAG GGAAAAACACGGTGAGACAATTCTGTTAAAGATCTTAAAGTCTAGGGGGAAGAAAAGATAAA TATACATTGGCTATATAACGTGTGATAGATTCAAAGATTTATACCTGA 34. >IFNGR1_07

ATCCTTCAGTCCAATCAAGTTGACACTCAGTATTAACCATCACAGTAACGTACAAAAAGCAAC ATATATTAGTAAGATATCTGATGGCTTTTTAAAAATTCTAAAACTTTGTTTTTAATATTACTATG GGACCTTTCATTAAAAAGAAATGGCAACATCTGATTCACCCATTATCCTAAATGTGCCATTTG GTGGTCCATTACTTCAGACCTTTGTTTTTTTTGAGGGTAGGCACTTAAGCTTAACAATTTTTTA TCTTTAATCAATTTTT[CTCCCC[A/G]TAGATCTCTGTGGTAAGAAGTGCTACTTTAGAGACAAA ACCTGAATCAAAATATGTATCACTCATCACGTCATACCAGCCATTTTCCTTAGAAAAGGAGGT GGTCTGTGAAGAGCCGTTGTCTCCAGCAACAGTTCCAGGCATGCATACCGAAGACAATCCA GGAAAAGTGGAACATACAGAAGAACTTTC[T/G]AGTATAACAGAAGTGGTGACTACTGAAGAA AATATTCCTGACGTGGTCCCGGGCAGCCATCTGACTCCAATAGAGAGAGAGAGTTCTTCACC TTTAAGTAGTAACCAGTCTGAACCTGGCAGCATCGCTTTAAACTCGTATCACTCCAGAAATTG TTCTGAGAGTGATCACTCCAGAAATGGTTTTGATACTGATTCCAGCTGTCTGGAATCACATAG CTCCTTATCTGACTCAGAATTTCCCCCAAATAATAAAGGTGAAATAAAAACAGAAGGACAAGA GCTCATAACCGTAATAAAAGCCCCCACCTCCTTTGGTTATGATAAACCACATGTGCTAGTGGA TCTACTTGTGGATGATAGCGGTAAAGAGTCCTTGATTGGTTATAGACCAACAGAAGATTCCAA AGAATTTTCATGAGATCAGCTAAGTTGCACCAACTTTGAAGTCTGATTTTCCTGGACAGTTTT CTGCTTTAATTTCATGAAAAGATTATGATCTCAGAAATTGTATCTTAGTTGGTATCAACCAAAT GGAGTGACTTAGTGTACATGAAAGCGTAAAGAGGATGTGTGGCATTTTCACTTTTGGCTTGTA AAGTACAGACTTTTTTTTTTTTTTAAACAAAAAAAGCATTGTAACTTATGAACCTTTACATCCAG ATAGGTTACCAGTAACGGAACAGTATCCAGTACTCCTGGTTCCTAGGTGAGCAGGTGATGCC CCAGGGACCTTTGTAGCCACTTCACTTTTTTTCTTTTCTCTGCCTTGGTATAGCATATGTTTTT GTAAGTTTATGCATACAGTAATTTTAAGTAATTTCAGAAGAAATTCTGCAAGCTTTTCAAAATT GGACTTAAAATCTAATTCAAACTAATAGAATTAATGGAATATGTAAATAGAAACGTGTATATTT

TTTATGAAACATTACAGTTAGAGATTTTTAAATAAAGAATTTTAAAACTCGTTTTTGTAT]TCATT TATTCAAGCACTTAGGCAGTCTTTCATAGTTAAGCAGAATATTTTTATATCCACTGCTTGTTTC CATGCATTAATGCTATAGGATTATTTGCTAATTGTTCATATTTAATATTTAAAACAACCCTAAAA ATAATATTTTTAAATGGTCCTTATAGGTCTATATTTCAGTGCTTAACACCCAGTGTGCAGAACA CTGTTCTAAGTGGTTTGAGAAGAAAAGATTTAGCTGTAGAGCATGTGGATTGAGGA 35. >IFNGR2_01 AACAGGCGTCAAACGACATGGTGCAGGCTCGGGCTGGGGAGCGGGCCTGCGGCTGCCCAG CTGCTAAAGGACTTCCTACTCGTGCACCGCCGCCGGCTCCAGGGCAAACCCCACGCCATTT AGAAATGCTGGAAGTTTCTGTCTCTCCCTCCCCCTGCTCGGAGGCCATTCCCCCCACCCCCA GAGCCCCACCTCCTCCTTCACTGGGCCCTTTCTAACTCCTTCCCCTTAAAACCCTTT[TCAAAA TGGGGTTGACTGGAGGCGGAGGTTGCAGTGAGCCGAGATCGCCCCACTGCACTCCAGCCT GGTGACTCCGTCTCAAAAAAAAGGGGAGGGGGGCGGGGGAGAGTTGAAAGCTTAATATGTA CTTTGGGGGCTATTAAAGCAAACATTTCGACTAAAGGGGCGAATCCTCGAATTGTGCGATCA AGCACCCGAGAGGAGAGTTGGGGGGGGTCAGGAGGGGTGGGGGCTCCAGGGAAAGCCCG GGGGTCTGGGCCGGGGTCTCGCGGGGCCCTTCCGGAAGGATCGCGGCCCCCGAAGGTGG GCGTCCCGCGGGGCTCCAGTCTCCAGGACGTTCCGGGAGGCTCCGCGCTCTGGGAGGCC GGCTGCGTGGGGTCCCCGCGCTGCAGCCGCAGAGGCCCCCCAGGGCCGCGGTTCCCGGA GCGGGAAAGTCCCGCGCGGGGGCGGTGGCCTCGGGGGCGGGACGGGGCGGGGGCGGG GGCGCGGGCGGCCGAGCCGAATCCCCTCCACCGGGACGCCCCGCTGCTGCTCGGGAAGA GGCGGGCCCTGCGCGCCCTGCGCTCGCCATGGCGGTTTGGGCGGCGACGTGAGCGGCTC CGCGGACCCCGAGCGGGGCCCCGGCCGCGACCTGAGCCGCCGCCGAGCGCCCGGGGCC ATGCGACCGACGCTGCTGTGGTCGCTGCTGCTGCTGCTCGGAGTCTTCGCCGCCGCCGCC GCGGCCCCGCCAGGTGAGCCGGG]CCTGGGCCTCCGCGGCGGGACGCGGGCGCAGCCGC AGCATGTGGGGGCTGGGGGACTCCCGGATCGTGGGGTGGGGGGAATCTGCCGGGTGCTC AGAGTGGGTGGGAATCTGCGGGGTGCTCCTGGTGGGTGGGATATGCGGAGTGCTCAGATC AGGTGGGAACCTGCGGGTGCCCCAGGTGGGGGTCTTGCGGGGTGCCCAGGGCTAGAGGG GCCCGCTGGGAGCCCGCAGCGGGGCTGGGATGGGCGGCCAGGAGTTCCAGACAGGA

36. >IFNGR2_02

CCGGCCAGACTCCAGGGCCCAGGACCTGTTCGTAACAACTGGGACCTGCAGGTGGAAAGG CTGCCCCAGGCGCCTCTTTTCTTTTTGTGCTGCCTGTACCAGTAGGGCCATCTTTGTAGCCA AAAGTCGGGGGTGTGGGGCCATGCCCAGGGGGACCTGGTAATGCCATTTCTGCACTTTGAC AAAAACTGAGTTGTATGAATGACTTAGATAATGGACATTGAAACATTTTTGTAATTATTT[CCCT CTCTCTCCTCCCTTCCTCCCTCTTCTTTTTCTCTGTCCCCCTCAAGACCCTCTTTCCCAGCTG CCCGCTCCTCAGCACCCGAAGATTCGCCTGTACAACGCAGAGCAGGTCCTGAGTTGGGAGC CAGTGGCCCTGAGCAATAGCA[C/G]GAGGCCTGTTGTCTACC[A/G]AGTGCAGTTTAAATAGT AAGCCGGTATTTCTGTTGGATCCTTGCTGGGAGCTGTGGGGGCATCGηGCGGAACCCTGG GGCCACATACTAGTCCCTGCCTCTGTGCAGGGTTTGTTATCAAACCCGTGGGAAACACATCG TTCTTGGAGCTTGTAAAATCTCTGAGGACAGAGGTTTCACAGCCTCCCACTCATCTGAAGGC TTAAACTACACTGGCAGTCAGGACTCCGCTGTCTAACCACACGGGTTCTTGCTTTGGTGGAA AGTTCATTCTTTCGCTGGTTTCAGGA

37. >IFNGR2_03

GGTGGCTCACACCTGTAGTTCCAGCTACTCGGGAGGCTGAGGCACAAGAATCACTTGAACC

CAGGAGGTGGAGGTTGCTGTGAGCCAAGATTGCGCTACTGCACTCCAGCCTGGGTGACAGA

GCAAAACTCCATCTCAAAAAAAAAAAAAAAAAAAGCGGGGGGGAACTGTATGGTACATATAAA TTGTATCTCAATAAACCTGCGTTTTGAACAAAAGCTCTGGGGAAACTATTACACATGAAACAG AGAATTCTGTGAATTGAAATCCTTTTTT[CCTTCCCAGCACCGACAGTAAATGGTTCACGGCC GACATCATGTCCATAGGGGTGAATTGTACACAGATCACAGCAACAGAGTGTGACTTCACTGC CGCCAGTCCCTCAGCAGGCTTCCCAATGGATTTCAATGTCACTCTACGCCTTCGAGCTGAGC TGGGAGCACTCCATTCTGCCTGGGTGACAATGCCTTGGTTTCAACACTATCGGAATGGTAAG AGAAC]TTGAGTATAGAACTTCCTTTATACTTTCCAGGTTTTCTTCACTTGCGGTATCGACTCC ACACACCTCTGTCCTGCCTGTCACCCTAAATGACCAGCAGACAAATGGGTAGGACAGTCAAA CCCACACTCTGACCTTGGAGGCTGATGCTAAGGGAGTGTGATTTGCTAAACCAGGGGTTGG CCAACTACAGCCTGCAGGCCAAATCGGGCCCACCACTTGTTTTTGTAAATAAAGTTTTATTGG AACAC

38. >IFNGR2_04

TTGTAATCCCAGCTACTTGAGAGGCTGATGCAAGAGAATTGCTTGAGCCCGGGAGGTGGAG GTTGCAGTGAGCCGAGATCGCACAACTGCACTCTAGCCTGGGCGACAGAGCAAAACTGTCT CGAAAAAATAATAATAAATAAAGAGATAGATAAAAACGTGTGTGTATATATCTACACCCACTAT ATATATATATATACATATATATATAGCATTATATAATACATTGTATTATATCT[ATAATACATATGT GTATGTGTGTGGTTTTCTCTTTGTAATTCTTTTTCAGTGACTGTCGGGCCTCCAGAAAACATT GAGGTGACCCCAGGAGAAGGCTCCCTCATCATCAGGTTCTCCTCTCCCTTTGACATCGCTGA TACCTCCACGGCCTTTTTTTGTTATTATGTCCATTACTGGGAAAAAGGAGGAATCCAACAGGC AAGAGCATCTTTCTTTTTTGTTTGGATTTTCTTTTCTTTGCAGTTTCηGGCTTAGCAAAAGAAA GAAACCTTTAACATGGGCAAGAACAGGGTGTCTCCATGTCCCCGTGTCCCCATAGAGGCTGA GCCCTGAGCCTGTTTTCATTGTCCTCTTCAAGACCTGTTTTTCCACTCGGTTTGCTGAGACCT CCCTCCGCCAGGCTGATCTGAAGGGCCAGCCATCCTTTGATGTCACTCTGTGTCCCTTGTGT GGGGTTGAG

39. >IFNGR2_05

TTATCCTAGAAATTGGGATTTACTGAAGTCTAGTTACTACAATGGGCACTCTGAGACCTCACA GCCAGAAACACAGTTCTAAAGCTATCAGCCTCTTTGGCCACACAACACACCAATTTTCACACA TAAAATGTGTCCACTGCCAGCCAGTGACCCACTAAAAATGGCATCTTGTTCTTCTTTGGTTGT CGTGTTCACAGTGAATTTGAGGAAACATCAGAAAAGATGTAGGCAGCTTGGCCATGTTCATTT ACATGTGTGC[TTGTGATGTTTTTAAAACAGGTCAAAGGCCCTTTCAGAAGCAACTCCATTTCA TTGGATAACTTAAAACCCTCCAGAGTGTACTGTTTACAAGTCCAGGCACAACTGCTTTGGAAC AAAAGTAACATCTTTAGAGTCGGGCATTTAAGCAACATATCTTGCTACGAAACAATGGCAGAT GGTAAAATATACCTTCTTATG]TCCTTTCTGAACTGGGAAAAGAATACTCCTCCAATAGTGAAA TCGGGGAATGCTTATGAGGTCATGGGTGGTGGGAGTGGGGAGACCCAGTGAGAAGAGTGC TGAACTGCAGGAATAATGAGCTTGTGCTGAGATTTGCAGTAGTGGAGGCTACCAGACAGCTA CCACTTGCTTTATTTCATTACAGGATTGACTTTAGCTATTAATGTAAGCATACCAGGTGAGGG

TGGGGGGTAGA

40. >TFNGR2_06 AGTGAGAAGAGTGCTGAACTGCAGGAATAATGAGCTTGTGCTGAGATTTGCAGTAGTGGAG GCTACCAGACAGCTACCACTTGCTTTATTTCATTACAGGATTGACTTTAGCTATTAATGTAAGC ATACCAGGTGAGGGTGGGGGGTAGAGGGACTTGCCCATTTTACTAGGACAGGAATGCTCTT TAAGCAGCATGGATGGAACATTAACTGATGTTTGTGTTGTGCGTAGGAAGATCATTCTGTTCA [CTTTCGTGTCCTCTTTTTAGCCTCCACTGAGCTTCAGCAAGTCATCCTGATCTCCGTGGGAA CATTTTCGTTGCTGTCGGTGCTGGCAGGAGCCTGTTTCTTCCTGGTCCTGAAATATAGAGGC CTGATTAAATACTGGTTTCACACTCCACCAAGCATCCCATTACAGATAGAAGAGGTACGTGTG CACACATCTCηTTTTTTTTTTTTGAGACAGGGTCTTGCTCTGTTGCCCAGGCGGGAGTGTCAT GGTACAATCTCTGCTCACTGCAGCCTCCATCTCCCAGGTTCAAGCGATTCTCCTGCCTCAGC CTCCTGAGTAGCTGGTATTACAAGTGCTCACCACCATGGCCTGCTAATTTTTGTATTTTTGGT AGAAACAGGGTTTTGCTATGTTGGCCAGACTGGTCTCAAACTCCTGACCTCAAGTGATCCAC CCACCTCAGCCTCC 41. >IFNGR2_07

AAACCCTGTCTCTACTAAAAATACAAAATTAGCCAGGCAAGGTGGTGGGCACCTGTAGTCCC AGCTACTTGGAGGATTGAGGCAGGAGAATCGCTTGAACCTGGGAAGCAGAGGTTGCAGTGA GCTGAGATCACACCACTATACTCCAGCCTAGGCAAGAGTAAGACTCCATCTCAAAAAAAAAAT AAAAATAAAAATAAAATAAAAACAAAAACTAAAGTTAAAAGGTCTGGTATACTGAACTGGTAAA CTAATTACAATTTTGCTTTCCAA[CCTCCTCAAGTATTTAAAAG ACCCAACTCAGCCCATCTTA GAGGCCTTGGACAAGGACAGCTCACCAAAGGATGACGTCTGGGACTCTGTGTCCATTATCTC GTTTCCGGAAAAGGAGCAAGAAGATGTTCTCCAAACGCTTTGAACCAAAGCATGGGCCTAGC CCACTGGCTCCCTGGAAGAGATCAAGCCATCGGAGCTGCTAGAGTTCTGTCTGGACTTTCCA GAGACCAGTATTCCCTTTTGCTGCCTCTAAAAGGCCTGTCCCTGCAGACATGAGAGACAGCA GGTCTC ATGGGGGTG ACAAGCTTTTTTTTTTTTTCTTAAAGAATTTTCAAAATC AAATTCCAG A ATGATTTTACGGAGATATCCCAGGAAAATTAAGGCTTCTCTTAAACACTAAAAAGGCATGTAA TTGCTTGTTAGCAAAATGGATATGACACATCTCTGATACTTTTTTCATTATTGGTTGGGCTGAG CAGTCAGAAGACCTGGTCGTCGTCTTGACTTTGGCAAATGAGCCGGAGCCCCTTGGGCAGG TCACACAACCTGTCCCAGCGAGGGACACCGAGTGGCCCTTCATGTACATCCATGGTGTGCT GGCTTAAAATGTAATTAATCTTGTAAATATACTCCTAGTAATTTAAGATTTTGTTTTTAAACTGG AAATAAAAGATTGTATAGTGCATGTTTTTTAAAGTCTATG]TGAAGTGTTTTCTTTATTGTAGCC TATTTTCTGCAGAGTTTCAGCTTTCTAAAATTACTCAATCTAAACTTGTTTTTTCTTAAATAACA CCTGCTAGAGCTACTGAGGCCTCATGGGAACTCAGCAAACACTTCCTATGGATGTCACTTGA TCCTCCAAAGGTTATAAAGAAGGCCAGGGCCTAGTGCAGTGGCCCACGCCTATAATCCCAG CACTTTGGGAGGCTGAGGTGGGTGGATCACTTGAGGCCAGGAGTTCTAGACCCACCTGG 42. >IL3_pro

AGCGGCACCAAGAGATGTGCTTCTCAGAGCCTGAGGCTGAACGTGGATGTTTAGCAGCGTG ACCGGCTACCAGACAAACTCTCATCTGTTCCAGTGGCCTCCTGGCCACCCACCAGGACCAA GCAGGGCGGGCAGCAGAGGGCCAGGGTAGTCCAGGTGATGGCAGATGAGATCCCACTGGG CAGGAGGCCTCAGTGAGC[TGAGTCAGGCTTCCCCTTCCTGCCACAGGGGTCCTCTCACCTG CTGCCATGCTTCCCATCTCTCATCCTCCTTGACAAGATGAAGTGATAACGTTTAAGTAATCTT TTTTCTTGTTTCACTGATCTTGAGTACTAGAAAGTCATGGATGAATAATTACGTCTGTGGTTTT CTATGGAGGTTCCATGTCAGATAAAGATCCTTCCGACGCCTGCCCCACACCACCACCTCCCC CCGCCTTGCCCGGGGTTGTGGGCACCTTGCTGCTGCACATATAAGGCGGGAGGTTGTTGCC AACTCTηCAGAGCCCCACGAAGGACCAGAACAAGACAGAGTGCCTCCTGCCGATCCAAACA TGAGCCGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGTCCGCCCCGGACTCCAAGCTCC CATGACCCAGACAACGCCCTTGAAGACAAGCTGGGTTAACTGCTCTAACATGATCGATGAAA TTATAACACACTTAAAGCAGCCACCTTTGCCTTTGCTGGTGAGTAGCTTGGATAAGACTGGC CTGCAGCAGTG

43. >IL3_01

GGCCAGGGTAGTCCAGGTGATGGCAGATGAGATCCCACTGGGCAGGAGGCCTCAGTGAGC TGAGTCAGGCTTCCCCTTCCTGCCACAGGGGTCCTCTCACCTGCTGCCATGCTTCCCATCTC TCATCCTCCTTGACAAGATGAAGTGATAACGTTTAAGTAATCTTTTTTCTTGTTTCACTGATCT TGAGTACTAGAAAGTCATGGATGAATAATTACGTCTGTGGTTTTCTATGGAGGTTCCATGTCA GATAAAGATCCTTCCGACGCCTGCCCCACACCACCACCTCCCCCCGCCTTGCCCGGGGTTG TGGGCACCTTGCTGCTGCACATATAAGGCGGGAGGTTGTTGCCAACTCTT[CAGAGCCCCAC G AAGGACCAG AACAAG ACAGAGTGCCTCCTGCCGATCCAAACATGAGCCGCCTGCCCGTCC TGCTCCTGCTCCAACTCCTGGTCCGCCCCGGACTCCAAGCTCCCATGACCCAGACAACGCC CTTGAAGACAAGCTGGGTTAACTGCTCTAACATGATCGATGAAATTATAACACACTTAAAGCA GCCACCTTTGCCTTTGCTGGTGAGTAGCTTGGATAAGACTGGCCTGCAGCAGTGAGGGGTG GTGGCTGCCTAAGGCCAAAAGGCCTCATGGGCCTTTCTCTCCCTTCACCCCCACAGGACTTC AACAACCTCA[A/G]TGGGGAAGACCAAGACATTCTGATGGTAAGAGCTC]AGCCCGTGGATCC CGATCCACTTCCTGCCTGGGTGACTTCAGCCATGTCATTCCATCTTACCTAGCCTTGCTTTCT TCATCTGTAAAATAGGGTTAATAGCACCTATCTCAGTGGGATTGTTATGACAATCAAATGGCA CAATGTGCATGTTCTGGCCCAGCATCTGGCACTTAAGAGTTCAATACATGGCCACAGCCATG GCTATAATAATGAAAATGACTTTTAAATTAGAAA 44. >IL3_03

TGCCTGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCTTGAGCCACTGCGCCCAGCCCAC CTAGGCCCTTTATGTAGCTCAAATGGAGCCAGAGACTGGGGGCTTGAGGAAACCAGGTCCT GCCTGCCACTCACTTCTAGGCCTGTGCCCTTGGGCAGGGACCCACCTGAGGCAAGAACGG GACTAGGAGGGAACCCGAGGATGTTCCCAACAGTGGGCTTGGGAAACTGTGGGGGTGACTT CCACCTGCTTGTGGGAGGGATACTCTGTAACCTTTCCCCCTTAAGTG[TATTCTCTGCCCCGT TAGGAAAATAACCTTCGAAGGCCAAACCTGGAGGCATTCAACAGGGCTGTCAAGAGTTTACA GAACGCATCAGCAATTGAGAGCATTCTTAAAGTATGTGAAGCTGTTGAGGGTTTGGGATCCC TGTGTTGGCCCTGCCCTGCCTCTGGGGAGGAGAGCAGGGCCCACTCCCTTTCCAAGGGAAT CTCTGACCATCTGCTTTGGTCTCTTTCCACAGAATCTCCTGCCATGTCTGCCCCTGGCCA[C/T ]GGCCGCACCCACGGTAAGCTGTCCCCCAA]GATGCCCGTCATGGCTTGCTCCTCAGCTGGT CATCACCATTACAGCCTGGACTCACCTAATGCCACCTTCTTGGTTTCTTTATAGCGACATCCA ATCCATATCAAGGACGGTGACTGGAATGAATTCCGGAGGAAACTGACGTTCTATCTGAAAAC CCTTGAGAATGCGCAGGCTCAACAGACGACTTTGAGCCTCGCGATCTTTTGAGTCCAACGTC CAGCTCGTTCTCTGGGCCTTCTCACCACAGAGCCTCGGGACATCAAAAACAG 45. >IL3__05

ATGTGAAGCTGTTGAGGGTTTGGGATCCCTGTGTTGGCCCTGCCCTGCCTCTGGGGAGGAG AGCAGGGCCCACTCCCTTTCCAAGGGAATCTCTGACCATCTGCTTTGGTCTCTTTCCACAGA ATCTCCTGCCATGTCTGCCCCTGGCCA[C/T]GGCCGCACCCACGGTAAGCTGTCCCCCAAGA TGCCCGTCATGGCTTGCTCCTCAGCTGGTCATCACCATTACAGCCTGGACTCACCTAATGCC ACCTTCrrTGGTTTCTTTATAGCGACATCCAATCCATATCAAGGACGGTGACTGGAATGAATTC CGGAGGAAACTGACGTTCTATCTGAAAACCCTTGAGAATGCGCAGGCTCAACAGACGACTTT GAGCCTCGCGATCTTTTGAGTCCAACGTCCAGCTCGTTCTCTGGGCCTTCTCACCACAGAGC CTCGGGACATCAAAAACAGCAGAACTTCTGAAACCTCTGGGTCATCTCTCACACATTCCAGG ACCAGAAGCATTTCACCTTTTCCTGCGGCATCAGATGAATTGTTAATTATCTAATTTCTGAAAT GTGCAGCTCCCATTTGGCCTTGTGCGGTTGTGTTCTCATTTTTATCCCATTGAGACTATTTATT TATGTATGTATGTATTTATTTATTTATTGCCTGGAGTGTGAACTGTATTTATTTTAGCAGAGGA GCCATGTCCTGCTGCTTCTGCAAAAAACTACAGAGTGGGGTGGGGAGCATGTTCATTTGTAC CTCGAGTTTTAAACTGGTTCCTAGGGATGTGTGAGAATAAACTAGACTCTGAACAACTGCTTT G]TTACCAGTGTCTCAATTTGACTTGGGACTTAGTGACCATTTTAAGGGAGACTGGTGTGCCA CAAATCCTGGGTGGCTTGATCCTGCCACGTGGATGCTGTCTGGGTGAGCTTGTTCTCACACT GCCCTCCTGCCACCCCCATTTCCAGAAAGGTGATGATAACCCTAGCAATCTTGAAAATCCAC AGAACTGCTACCAGGTACCAGGAGCCGTTCTGAGCATTTTACCTATGCTATCTAACTTATTCC TCACCCCAACCAAGAGTATGTT 46. >IL6_ρro

ATAAACACAAACTCTGCAAGATGCCACAAGGTCCTCCTTTGACATCCCCAACAAAGAGGTGA GTAGTATTCTCCCCCTTTCTGCCCTGAACCAAGTGGGCTTCAGTAATTTCAGGGCTCCAGGA GACCTGGGGCCCATGCAGGTGCCCCAGTGAAACAGTGGTGAAGAGACTCAGTGGCAATGG GGAGAGCACTGGCAGCACAAGGCAAACCTCTGGCACAGAGAGCAAAGTCCTCACTGGGAG GATTCCCAAGGGGTCACTTGGGAGAGGGCAGGGCAGCAGCCAACCTCCTCTAAGTG[GGCT GAAGCAGGTGAAGAAAGTGGCAGAAGCCACGCGGTGGCAAAAAGGAGTCACACACTCCACC TGGAGACGCCTTGAAGTAACTGCACGAAATTTGAGGATGGCCAGGCAGTTCTACAACAGCC GCTCACAGGGAGAGCCAGAACACAGAAGAACTCAGATGACTGGTAGTATTACCTTCTTCATA ATCCCAGGCTTGGGGGGCTGCGATGGAGTCAGAGGAAACTCAGTTCAGAACATCTTTGGTTT TTACAAATACAAATTAACTGGAACGCTAAATTCTAGCCTGTTAATCTGGTCACTGAAAAAAAAT TTTTTTTTTTTCAAAAAACATAGCTTTAGCTTATTTTTTTTCTCTTTGTAAAACTTCGTGCATGAC TTCAGCTTTACTCTTTGTCAAGACATGCCAAAGTGCTGAGTCACTAATAAAAGAAAAAAAGAA AGTAAAGGAAGAGTGGTTCTGCTTCTTAGCGCTAGCCTCAATGACGACCTAAGCTGCACTTT TCCCCCTAGTTGTGTCTTGCCATGCTAAAGGACGTCACATTGCACAATCTTAATAAGGTTTCC AATCAGCCCCACCCGCTCTGGCCCCACCCTCACCCTCCAACAAAGATTTATCAAATGTGGGA TTTTCCCATGAGTCTCAATATTAGAGTCTCAACCCCCAATAAATATAGGACTGGAGATGTCTG AGGCTCA]TTCTGCCCTCGAGCCCACCGGGAACGAAAGAGAAGCTCTATCTCCCCTCCAGGA GCCCAGCTATGAACTCCTTCTCCACAAGTAAGTGCAGGAAATCCTTAGCCCTGG AACTGCCA GCGCGGTCGAGCCCTGTGTGAGGGAGGGGTGTGTGGCCCAGGGAGGGCTGGCGGGCGGC CACGAGCAGAGGCAGGCTCCCAGCTGTGCTGTCAGCTCACCCCTGCGCTCGCTCCCCTCC GGCACAGGCGCCTTC 47. >IL6_01

GAAGAGTGGTTCTGCTTCTTAGCGCTAGCCTCAATGACGACCTAAGCTGCACTTTTCCCCCT AGTTGTGTCTTGCCATGCTAAAGGACGTCACATTGCACAATCTTAATAAGGTTTCCAATCAGC CCCACCCGCTCTGGCCCCACCCTCACCCTCCAACAAAGATTTATCAAATGTGGGATTTTCCC ATGAGTCTCAATATTAGAGTCTCAACCCCCAATAAATATAGGACTGGAGATGTCTGAGGCTCA [TTCTGCCCTCGAGCCCACCGGGAACGAAAGAGAAGCTCTATCTCCCCTCCAGGAGCCCAGC TATGAACTCCTTCTCCACAAGTAAGTGCAGGAAATCCTTAGCCCTGGAACTGCCAGCGCGGT CGAGCCCTGTGTGAGGGAGGGGTGTGTGGCCCAGGGAGGGCTGGCGGGCGGCCACGAGC AGAGGCAGGCTCCCAGCTGTGCTGTCAGCTCACCCCTGCGCTCGCTCCCCTCCGGCACAG] GCGCCTTCGGTCCAGTTGCCTTCTCCCTGGGGCTGCTCCTGGTGTTGCCTGCTGCCTTCCC TGCCCCAGTACCCCCAGGAGAAGATTCCAAAGATGTAGCCGCCCCACACAGACAGCCACTC ACCTCTTCAGAACGAATTGACAAACAAATTCGGTACATCCTCGACGGCATCTCAGCCCTGAG AAAGGAGGTGGGTAGGCTTGGCGATGGGGTTGAAGGGCCCGGTGCGCATGCGTTCCCCTT

GCCCCTGCGTGTGG 48. >IL6_02

TTCTGCCCTCGAGCCCACCGGGAACGAAAGAGAAGCTCTATCTCCCCTCCAGGAGCCCAGC TATGAACTCCTTCTCCACAAGTAAGTGCAGGAAATCCTTAGCCCTGGAACTGCCAGCGCGGT CGAGCCCTGTGTGAGGGAGGGGTGTGTGGCCCAGGGAGGGCTGGCGGGCGGCCACGAGC AGAGGCAGGCTCCCAGCTGTGCTGTCAGCTCACCCCTGCGCTCGCTCCCCTCCGGCACAG[ GCGCCTTCGGTCCAGTTGCCTTCTCCCTGGGGCTGCTCCTGGTGTTGCCTGCTGCCTTCCC TGCCCCAGTACCCCCAGGAGAAGATTCCAAAGATGTAGCCGCCCCACACAGACAGCCACTC ACCTCTTCAGAACGAATTGACAAACAAATTCGGTACATCCTCGACGGCATCTCAGCCCTGAG AAAGGAGGTGGGTAGGCTTGGCGA]TGGGGTTGAAGGGCCCGGTGCGCATGCGTTCCCCTT GCCCCTGCGTGTGGCCGGGGGTGCCTGCATTAGGAGGTCTTTGCTGGGTTCTAGAGCACTG TAGATTTGAGGCCAACGGGGCGAACTAGACTGACTTCTGTATTTATCCTTTGCTGGTGTCAG GAAGTTCCTTTCCTTTCTGGAAAATGCAGAATGGGTCTGAA 49. >IL6_03

TAATTATTGTCAAAATTGCTGTTATTAAGTATCTACTGTGTGCCAGGCACTTTAAATAAATATT GTGTCTAATCTTCAAAACAAATTTGCAAGGAAGGTTTTTGGAGATAAGGAAACTGAGACTCAG GATTAAGTAACACACCTAAAGTCACAGGTGAGCTTGGAACTGAACCCAAGTGTGCCCCCACT CCACTGGAATTTGCTTGCCAGGATGCCAATGAGTTGTAGCTTCATTTTTCTTAGAGACTTTCC TGGCTGTGGTTGAACAATGAAAAG[G/T]CCCTCTAGTGGTGTTTGTTTTAG[GGACACTTAGGT GATAACAATTCTGGTATTCTTTCCCAGACATGTAACAAGAGTAACATGTGTGAAAGCAGCAAA GAGGCACTGGCAGAAAACAACCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATGCTTCCA ATCTGG ATTC AATG AGGTACCAACTTGTCGCACTCACTTTTCACTATTCCTTAGGCAAAACTT] CTCCCTCTTGCATGCAGTGCCTGTATACATATAGATCCAGGCAGCAACAAAAAGTGGGTAAA TGTAAAGAATGTTATGTAAATTTCATGAGGAGGCCAACTTCAAGCTTTTTTAAAGGCAGTTTAT TCTTGGACAGGTATGGCCAGAGATGGTGCCACTGTGGTGAGATTTTAACAACTGTCAAATGT TTAAAACTCCCACAGGTTTAATTAGTTCATCCTGGGAAAGGTACTCTCAGGGCCTTTTCCCTC TCTGGCTGCCCCTGGCAGGGTCCAGGTCTGCCCTCCCTCCCTGCCCAGCTCATTCTCCACA GTGAGATAACCTGCACTGTCTTCTGATTATTTTATAAA 50. >IL6_04

AGGAGGTTCCAGCCCAGCATTAACAAGGGCAAGAGTGCAGGAAGAACATCAAGGGGGACAA TTCAGAGAAGGATCCCCATTGCCACATTCTAGCATCTGTTGGGCTTTGGGATAAAACTAATTA CATGGGGCCTCTGATTGTCCAGTTATTTAAAATGGTGCTGTCCAATGTCCCAAAACATGCTGC CTAAGAGGTACTTGAAGTTCTCTAGAGGAGCAGAGGGAAAAGATGTCGAACTGTGGCAATTT T[AACTTTTCAAATTGATTCTATCTCCTGGCGATAACCAATTTTCCCACCATCTTTCCTCTTAGG AGACTTGCCTGGTGAAAATCATCACTGGTCTTTTGGAGTTTGAGGTATACCTAGAGTACCTCC AGAACAGATTTGAGAGTAGTGAGGAACAAGCCAGAGCTGTGCAGATGAGTACAAAAGTCCTG ATCCAGTTCCTGCAGAAAAAGGTGGGTGTGTCCTCATTCCCTCAACTTGGTGTGGGGGAAGA CAGGCTCAA]AGACAGTGTCCTGGACAACTCAGGGATGCAATGCCACTTCCAAAAGAGAAGG

GTTTGGTTGGTTGGCTCTCTTCTGCAAAGGACATCAATAACTGTATTTTAAACTATATATTAAC TGAGGTGGATTTTAACATCAATTTTTAATAGTGCAAGAGATTTAAAACCAAAGGCGGGGGGG CGGGCAGAAAAAAGTGCATCCAACTCCAGCCAGTGATCCACAGAAACA 51. >IL6_05 CACTTGAACCCAGGAGGCAGAGGTTGCTGTGCACCACTGCACTCCAGCCTGGGTGACAGAA CGAGACCTTGACTCAAAAAAAAAAAAAAGAAGTTTGTTGCTATGGAAGGGTCCTACTCAGAG CAGGCACCCCAGTTAATCTCATTCACCCCACATTTCACATTTGAACATCATCCCATAGCCCAG AGCATCCCTCCACTGCAAAGGATTTATTCAACATTTAAACAATCCTTTTTACTTTCATΓΓTTCCT TCAGGCAAAGAATCTAG[A/T][T/A]GCAATAACCACCCCTGACCCAACCACAAATGCCAGCCTG CTGACGAAGCTGCAGGCACAGAACCAGTGGCTGCAGGACATGACAACTCATCTCATTCTGC GCAGCTTTAAGGAGTT[C/T]CTGCAGTCCAGCCTGAGGGCTCTTCGGCAAATGTAGCATGGG CACCTCAGATTGTTGTTGTTAATGGGCATTCCTTCTTCTGGTCAGAAACCTGTCCACTGGGCA CAGAACTTATGTTGTTCTCTATGGAGAACTAAAAGTATGAGCGTTAGGACACTATTTTAATTAT TTTTAATTTATTAATATTTAAATATGTGAAGCTGAGTTAATTTATGTAAGTCATATTTATATTTTT AAG AAGTACCACTTG AAACATTTTATGTATTAGTTTTG AAATAATAATGG AAAGTGGCTATGCA GTTTGAATATCCTTTGTTTCAGAGCCAGATCATTTCTTGGAAAGTGTAGGCTTACCTCAAATAA ATGGCTAACTTATACATATTTTTAAAGAAATATTTATATTGTATTTATATAATGTATAAATGGTTT TTATACCAATAAATGGCATTTTAAAAAATTC]AGCAACTTTGAGTGTGTCACGTGAAGCTTAAT ATAAACAAGTTTCTTGTCACTGCCACCACCACGACCAAAAAAAGCTAATCAATCACTATATATA ATACATATATATACTATATATAATAAATATATATACTATATATAATACATATATACACTATATATA ATACATATATACTATATATACACATATATACTATATATACACATATATATTATGAATGTATATATA TAGTATATATAGTATATATACTATGTATGTATATATATAGTATATATAGTATATATACTATGTATG

TGTATA 52. >TNF_pro

ACTTCCCAGTCTATCTAAGGAATGGAGGGAGGGACAGAGGGCTCAAAGGGAGCAAGAGCTG TGGGGAGAACAAAAGGATAAGGGCTCAGAGAGCTTCAGGGATATGTGATGGACTCACCAGG TGAGGCCGCCAGACTGCTGCAGGGGAAGCAAAGGAGAAGCTGAGAAGATGAAGGAAAAGT CAGGGTCTGGAGGGGCGG[GGGTCAGGGAGCTCCTGGGAGATATGGCCACATGTAGCGGC TCTGAGGAATGGGTTACAGGAGACCTCTGGGGAGATGTGACCACAGCAATGGGTAGGAGAA TGTCCAGGGCTATGGAAGTCGAGTATGGGGACCCCC[C/A]CTTAA[C/T]GAAGACAGGGCCAT GTAGAGGGCCCCAGGGAGTGAAAGAGCCTCCAGGACCTCCAGGTATGGAATACAGGGGAC GTTTAAGAAGATATGGCCACACACTGGGGCCCTGAGAAGTGAGAGCTTCATGAAAAAAATCA GGGACCCCAGAGTTCCTTGGAAGCCAAGACTGAAACCAGCATTATGAGTCTCCGGGTCAGA ATGAAAGAAGAAGGCCTGCCCCAGTGGGGTCTGTGAATTCCCGGGGGTGATTTCACTCCCC GGGGCTGTCCCAGGCTTGTCCCTGCT[A/C]CCCCCACCCAGCCTTTCCTGAGGCCTCAAGCC TGCCACCAAGCCCCCAGCTCCTTCTCCCCGCAGGGACCCAAACACAGGCCTCAGGACTCAA CACAGCTTTTCCCTCCAACCCCGTTTTCTCTCCCTCAAGGACTCAGCTTTCTGAAGCCCCTCC CAGTTCTAGTTCTATCTTTTTCCTGCATCCTGTCTGGAA[G/A]TTAGAAGGAAACAGACCACAG ACCTGGTCCCCAAAAGAAATGGAGGCAATAGGTTTTGAGGGGCATG[G/A]GGACGGGGTTCA GCCTCCAGGGTCCTACACACAAATCAGTCAGTGGCCCAGAAGACCCCCCTCGGAATC[G/A]G AGCAGGGAGGATGGGGAGTGTGAGGGGTATCCTTGATGCTTGTGTGTCCCCAACTTTCCAA ATCCCCGCCCCCGCGATGGAGAAGAAACCGAGACAGAAGGTGCAGGGCCCACTACCGCTT CCTCCAGATGAGCTCATGGGTTTCTCCACCAAGGAAGTTTTCCGCTGGTTGAATGATTCTTTC CCCGCCCTCCTCTCGCCCCAGGGACATATAAAGGCAGTTGTTGGCACACCCAGCCAGCAGA CGCTCCCTCAGCAAGGACAGCAGAGGACCAGCTAAGAGGGAGAGAAGCAACTACAGACCC CCCCTGAAAACAACCCTCAGACGCCACATC]CCCTGACAAGCTGCCAGGCAGGTTCTCTTCC TCTCACATACTGACCCACGGCTCCACCCTCTCTCCCCTGGAAAGGACACCATGAGCACTGAA AGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAGACAGGGGGGCC CCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGAT

53. >TNF_01

CATGGGTTTCTCCACCAAGGAAGTTTTCCGCTGGTTGAATGATTCTTTCCCCGCCCTCCTCTC GCCCCAGGGACATATAAAGGCAGTTGTTGGCACACCCAGCCAGCAGACGCTCCCTCAGCAA GGACAGCAGAGGACCAGCTAAGAGGGAGAGAAGCAACTACAGACCCCCCCTGAAAACAACC CTCAGACGCCACATC[CCCTGACAAGCTGCCAGGCAGGTTCTCTTCCTCTCACATACTGACC CACGGCTCCACCCTCTCTCCCCTGGAAAGGACACCATGAGCACTGAAAGCATGATCCGGGA CGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAGACAGGGGGGCCCCAGGGCTCCAGGC GGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATCGTGGCAGGCGCCACCAC[G/A]CTCTTCT GCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGGGAAGAG]GTGAGTGCCTGGCCAGCCT TCATCCACTCTCCCACCCAAGGGGAAATGGAGACGCAAGAGAGGGAGAGAGATGGGATGG GTGAAAGATGTGCGCTGATAGGGAGGGATGGAGAGAAAAAAACGTGGAGAAAGACGGGGAT GCAGAAAGAGATGTGGCAAGAGATGGGGAAGAGAGAGAGAGAAAGATGGAGAGACAGGAT GTCTGGCACATGGAAGGTGCTCACTAAGTGTGT

54. >TNF_02

AGGAGAGAGATGGGGGAGATAAGGAGAGAAGAAGATAGGGTGTCTGGCACACAGAAGACA CTCAGGGAAAGAGCTGTTGAATGCCTGGAAGGTGAATACACAGATGAATGGAGAGAGAAAA CCAGACACCTCAGGGCTAAGAGCGCAGGCCAGACAGGCAGCCAGCTGTTCCTCCTTTAAGG GTGACTCCCTCGATGTTAACCATTCTCCTTCTCCCCAACAG[TTCCCCAGGGACCTCTCTCTA ATCAGCCCTCTGGCCCAGGCAGTCAGTAAGTGTCTCCAAACCTCTTTCCTAATTCTGGGTTT GGGTTTGGGGGTAGGGTTAGTACCGGTATGGAAGCAGTGGGGGAAATTTAAAGTTTTGGTC TTGGGGGAGGATGGATGGAGGTGAAAGTAGGGGGGTATTTTCTAGGAAGTTTAAGGGTCTC AGCTTTTTCTTTTCTCTCTCCTCTTCAGGATCATCTTCTCGAACCCCGAGTGACAAGCCTGTA GCCCATGTTGTAG]GTAAGAGCTCTGAGGATGTGTCTTGGAACTTGGAGGGCTAGGATTTGG GGATTGAAGCCCGGCTGATGGTAGGCAGAACTTGGAGACAATGTGAGAAGGACTCGCTGAG CTCAAGGGAAGGGTGGAGGAACAGCACAGGCCTTAGTGGGATACTCAGAACGTCATGGCCA GGTGGGATGTGGGATG ACAG ACAG AGAGG ACAGG AACCGG ATGTGGGGTGGGCAG AGCTC GAGGGCCAGGATGTGG

55. >TNF_04

AGGACTCGCTGAGCTCAAGGGAAGGGTGGAGGAACAGCACAGGCCTTAGTGGGATACTCA GAACGTCATGGCCAGGTGGGATGTGGGATGACAGACAGAGAGGACAGGAACCGGATGTGG GGTGGGCAGAGCTCGAGGGCCAGGATGTGGAGAGTGAACCGACATGGCCACACTGACTCT CCTCTCCCTCTCTCCCTCCCTCCAG[CAAACCCTCAAGCTGAGGGGCAGCTCCAGTGGCTGA ACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGAGATAACCAGCTGGTGG TGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTCAAGGGCCAAGGCTGCCC CTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCCGTCTCCTACCAGACCAAG GTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAGACCCCAGAGGGGGCTGAG GCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTCCAGCTGGAGAAGGGTGACC GACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTTGCCGAGTCTGGGCAGGTCTA CTTTGGGATCATTGCCCTGTGAGGAGGACGAAtC/T]ATCCAACCTTCCCAAACGCCTCCCCTG CCCCAATCCCTTTATTACCCCCTCCTTCAGACACCCTC[A/C]ACCTCTTCTGGCTCAAAAAGA GAATTGGGGGCTTAGGGTCGGAACCCAAGCTTAGAACTTTAAGCAACAAGACCACCACTTCG AAACCTGGGATTCAGGAATGTGTGGCCTGCACAGTGAAGTGCTGGCAACCACTAAGAATTCA AACTGGGGCCTCCAGAACTCACTGGGGCCTACAGCTTTGATCCCTGACATCTGGAATCTGGA GACCAGGGAGCCTTTGGTTCTGGCCAGAATGCTGCAGGACTTGAGAAGACCTCACCTAGAA ATTGACACAAGTGGACCTTAGGCCTTCCTCTCTCCAGATGTTTCCAGACTTCCTTGAGACAC GGAGCCCAGCCCTCCCCATGGAGCCAGCTCCCTCTATTTATGTTTGCACTTGTGATTATTTAT TATTTATTTATTATTTATTTATTTACAGATGAATGTATTTATTTGGGAGACCGGGGTATCCTGG GGGACCCAATGTAGGAGCTGCCTTGGCTCAGACATGTTTTCCGTGAAAACGGAGCTGAACA ATAGGCTGTTCCCATGTAGCCCCCTGGCCTCTGTGCCTTCTTTTGATTATGTTTTTTAAAATAT TTATCTGATTAAGTTGTCTAAACAATGCTGATTTGGTGACCAACTGTCACTCATTGCTGAGCC TCTGCTCCCCAGGGGAGTTGTGTCTGTAATCGCCCTACTATTCAGTGGCGAGAAATAAAGTT TGCTTAGAAAAGAA]ACATGGTCTCCTTCTTGGAATTAATTCTGCATCTGCCTCTTCTTGTGGG TGGGAAGAAGCTCCCTAAGTCCTCTCTCCACAGGCTTTAAGATCCCTCGGACCCAGTCCCAT CCTTAGACTCCTAGGGCCCTGGAGACCCTACATAAACAAAGCCCAACAGAATATTCCCCATC CCCCAGGAAACAAGAGCCTGAACCTAATTACCTCTCCCTCAGGGCATGGGAA 56. >MAG_01

TGGGGTGGGAGAGGGCGGCAGGAATTCACGCGGCATGTCGGGAATGCTGATACTGTGAAA CCCAGTCATTGATGGCTCTGGGTCCCTGCCCGCCACCCCCAGGCCCCGGCCGTGGGACAT CTGCTCCCTCACTCCACTCGCCACACCCCTCAGTCTCACCCCCGTACCCCGATGCGGTCGT TCCCCCTTCCCTCCCCACA[GTTCTCTGACACCCCAGCTTGGAGGGAGTTGTTGCCAGAGAG TGGCTTCGAGGCTGTGTGGGAGGGTCCCAGGCACAATGGGAGGGCCACATGGGCAGCCTG ACAACAGGTCACAACCCATGCAGGAGATACTGAAGCGGGGGTGGGTTGGGTGCCTCAATCC CGCCCCCTTGCACCTGAGTGACTCTTGTTGCATGCAGGTTGTCTGGCGGCTTCAGGTGGAC CCAGAAGACGTCCCCAACTCAGGGAGATTCAGGTGAGGGGCAGGGTACCAACTCTCTTCCC TTGCTTCAGCTTTGC]AATGCTGGCCCTGCCTTGGCTCTCTGGTTCTTACTTTCTGGAGATCT CCAGGGGCATCACGGTGACAAAGATAATGATCAGCACATCATCACTGCATAGAGACAGGACA TGCAGCAAAGACTGCAGACCAACTGTGTGGCCTTGGGCGAGTCACTTAACCTCTCTGGACCT CAGCTATAAAATGAGGATAATGCATCTTC 57. >MAG_02

ACAACCATTTCCACAAAAAAGAAGAAAAATTAACTGGGTGTGGGGTGGCGCATACCAGAAGC TGAGACAAGAGGATAACACGAGCTCAGGATTTTGAGGCTATAGTGAGCTGTTATTGTGTCAC TGCATTCCAGCCCGGGCAATGAAACAAGACCCTGTCTCAGAAAAATAAGTAAATAAATGCATA AATAAATAATAAT[AGCAGCAGCAGCTAACATATGAATGGGCCCCTTCCTGAAGCCCAGATGG AACACCCCCTTTCACTTCCCCCAGCCTTTAACCCTCTCCTCTCCCTTTCCAGCGATCACTCAC TCGCTGTACAGAATGATATTCCTCACGGCACTGCCTCTGTTCTGGATTATGATTTCAGGTAA[ C/T]GGCTGACAGGTGCTGGGGACCTAAAGGCTTTGGCCCCTGAGCAGGTTGGAGGTGGGTC CCCGCAGCCCCCCGGCA]TGTGGTTGGGGATGGGAGCCGGAGGGGGTGATCGGGTAGGAC GTGTCCCTGAGCCTCAGCTCTCCTGCTTGCCCGCAGCCTCCCGAGGGGGTCACTGGGGTG CCTGGATGCCCTCGTCCATCTCGGCCTTCGAAGGCACGTGCGTCTCCATCCCCTGCCGCTT TGACTTCCCGGATGAGCTGCGGCCCGCTGTGGTGCAT 58. >MAG_03

GCGATCACTCACTCGCTGTACAGAATGATATTCCTCACGGCACTGCCTCTGTTCTGGATTAT GATTTCAGGTAACGGCTGACAGGTGCTGGGGACCTAAAGGCTTTGGCCCCTGAGCAGGTTG GAGGTGGGTCCCCGCAGCCCCCCGGCATGTGGTTGGGGATGGGAGCCGGAGGGGGTGAT CGGGTAGGACGTGTCCCTGAGCCTCAGCTCTCCTGCTTGCCCGCAG[CCTCCCGAGGGGGT CACTGGGGTGCCTGGATGCCCTCGTCCATCTCGGCCTTCGAAGGCACGTGCGTCTCCATCC CCTGCCGCTTTGACTTCCCGGATGAGCTGCGGCCCGCTGTGGTGCATGGTGTCTGGTACTT CAATAGCCCCTACCCCAAGAACTACCCCCCGGTGGTCTTCAAGTCGCGCACCCAAGTAGTC CACGAGAGCTTCCAGGGCCGCAGCCGCCTCCTGGGGGACCTGGGCCTGCGAAACTGCACC CTCCTGCTCAGCAACGTCAGCCCCGAGCTGGGCGGGAAGTACTACTTCCGTGGGGACCTG GGCGGCTACAACCAGTACACCTTCTCAGAGCACAGCGTCCTGGATATCGTCA]GTGAGTCCC CAGCGGTTGTGCAGGCACCGGGAGCTGGGGCAGCGGGGCGGGAAGGAGTGTGGCCGGAA GGCCTCCCCGCACCTTCCCCAGCAGGCCTGGATGGCAGATCTGGGAGGTGCTGATTTGGCT GGGGGTGCAAACCTCAAGGCCCACGCAGACCATGCAGATGACAGACATGAACAAAGCAGG GCCCCAAAATAGTCTTGCTGCCCTCAGGGGGAAACAGGTGCTGCTACTCTTTTGGAAACACC TG

59. >MAG_04

TTACGATGGCGCTCTGGTGGCTCCGTGGAGGGCTCCGGGGTGACCAAGAGGAGGAAGGGT AAAGGGAATTCTGAATCTGGAGGCAGGGAGCGGAGGCGATACCGTTGAGGAGTACCATTGC CAGCAATGGAGGTGGACAAGGAGGAGGGTGGGTGGGGTGGGACCGGGACCGTAGCCCAG TGCTGCTTTCTCAGCCCTCC[CTTTCCCCGCCTCGTATAGACACCCCCAACATCGTGGTGCC CCCAGAGGTGGTGGCAGGCACGGAGGTGGAGGTCAGCTGCATGGTGCCGGACAACTGCCC AGAGCTGCGCCCTGAGCTGAGCTGGCTGGGCCACGAGGGGCTGGGGGAGCCCGCTGTGC TGGGCCGGCTGCGGGAGGACGAGGGCACCTGGGTGCAGGTGTCACTGCTGCACTTCGTGC CCACGAGGGAGGCCAACGGCCACAGGCTGGGCTGCCAGGCCTCCTTCCCCAACACCACCC TGCAGTTCGAGGGCTACGCCAGCATGGACGTCAAGTGTGAGCCTGGGT]GCGGGCGGGGC GGGGTGGGGCGGGGTGGGGCGGGGTCCGGGGAGGGGGTGGACCTGGGGATGCGGCCGG AGGCGGGGCCGGGCCGTGATGGGGGCGGGGCCATGCCCAGGGCCAGGCAGGGATTGGG GGGTTGGGTGGGACGGGGGCGGAACCAGGCAGTCCTGGGGCGGGGCCAAGGCTGAGGGC GGGGCCGGACAGTGTTGGGGGCGGGGCCGGGCTGGG 60. >MAG_05

CGGGGCCGGGCCGTGATGGGGGCGGGGCCATGCCCAGGGCCAGGCAGGGATTGGGGGG TTGGGTGGGACGGGGGCGGAACCAGGCAGTCCTGGGGCGGGGCCAAGGCTGAGGGCGGG GCCGGACAGTGTTGGGGGCGGGGCCGGGCTGGGAGAGGGCACTGGGCCGGTTCCCCAGC ACCTGCTCACTAACCTCGCTGTGT[CGCGGGCCTTAGACCCCCCGGTGATTGTGGAGATGAA CTCCTCGGTGGAGGCCATCGAGGGCTCCCACGTGAGCCTGCTCTGTGGGGCTGACAGCAA CCCCCCGCCGCTGCTGACCTGGATGCGGGACGGGACAGTCCTCCGGGAGGCGGTGGCCG AGAGCCTGCTCCTGGAGCTGGAGGAGGTGACCCCCGCCGAAGACGGCGTCTATGCCTGCC TGGCCGAGAATGCCTATGGCCAGGACAACCGCACCGTGGGGCTCAGTGTCATGTGTGAGTG GCCCACTCTGTGCGTCCACACGC]CCACCTGCAGCCGAGAGATAAAGGGAAAGGGGCCTCA TCCAGGGCGAGCATGGGCTGGGTCCCGAGGGGACCGGCCATAAACAGTCGAGGCCAAGGT AGACAGGGGGGTTGCAAGTCAAGGTGTACCTTCATTCTTTCCACAAGAATCTGGGGAACACC TGCTCTGCCTCATCCTCCTTCCAGGACAAGACCCAGGCCTG 61. >MAG 06 ATGAGAAAAATGAGGCCCAGAGAGGTTAAGATGTGGGTCCACACACAACTGGACAGGGGTA GAGTAGGGATCTGAAGACAAGCATGCTGGCTACCAAGCTGCTGTTCTTGGAAATGAGATAGC CAGGACTGGGGTCACCTGAGCCTTCCTGAACCGGTGTGCTAGGTTTGGGGTGGGATCTGGG GTCATATCTGGGGATGGTAGTTGGCTGGCAGAAGAAGCACCTCCTGGGTTCTGACCATCAG TCCCG[TCCTACCCCGCAGATGCACCCTGGAAGCCAACAGTGAACGGGACAATGGTGGCCG TAGAGGGGGAGACGGTCTCTATCTTGTGCTCCACACAGAGCAACCCGGACCCTATTCTCAC CATCTTCAAGGAGAAGCAGATCCTGTCCACGGTCATCTACGAGAGCGAGCTGCAGCTGGAG CTGCCGGCCGTGTCACCCGAGGATGATGGAGAGTACTGGTGTGTGGCTGAGAACCAGTATG GCCAGAGGGCCAC[C/T]GCCTTCAACCTGTCTGTGGAGTGTGAGTACCTTCCGCTCCCCTAT GCηGGGGATGGACGGTTCCGTGGGGGACACCAGGGTTACTGTGGGTGCCCACGCATCCCA ATCAGTATTGGCTTTGCCTGTCCTCCGCAGAGACAAGGAAGGGAGGGCAGGGAAGCTGAAT TCACAGCAGGAAAATAAAATCCCATCTGAGAATATTGTGTTCCCACATCCGGGAGTGGGCTT TTTTTTTTTTTTTTTTTTTTGAGACAGAGTATTGAGTCTTGCTCTGTCACCTAGGCTGGAGTGC AGTGGC 62. >MAG_07

CAAGGCCCCAGGCGTGGGTTAGTGAAGCTTGCAGTGAAAACAGGCAGCCGGCGGGGTCGT AGTGAGGTCAAGGCGCTCTCAGTCAGGACAGAGAAAAAAGGAGGGGAAATTGGAGGGCCCT ACAGGAAGCTACCGCCCCCATCCTTGGCCACACTGGCCTTGCCTTGAGCCAAGGAGTCTCC[ G/C]GGGCCGGGCCTCGCGTT[GGCTCCGGGCCACCCTCAGACCTGATTTTGCCCCTGCAGT CGCCCCTGTGCTCCTCCTGGAGTCCCACTGCGCGGCAGCCCGAGACACGGTGCAGTGCCT GTGCGTGGTGAAGTCCAACCCGGAGCCGTCCGTGGCCTTTGAGCTGCCATCGCGCAATGTG ACCGTGAACGAGAGCGAGCGGGAGTTCGTGTACTCGGAGCGCAGCGGCCTCGTGCTCACC AGCATCCTCACGCTGCGGGGGCAGGCCCAGGCCCCGCCCCGCGTCATCTGCACCGCGAGG AACCTCTATGGCGCCAAGAGCCTGGAGCTGCCCTTCCAGGGAGCCCGTGAGTGGCGTGGA CTTGGGGTG]GGAGCCACAGGAGGGAGCGGGCACGTCTTAGATCCAAGCTCCCAAGGCTGA CCAACAGCCACAGAGCATGGGCTATGCAGATTGACAGAAAGGTCAAATTCTCCCTTTCCGGT TGGAGAGGAGAAGCCGCCCTGAGTTTGCCCCGAGTTTGCTAGGACCTTTGAGGCATGAGCC CCTCCCCAGGGCCCTCTAGCATGAAA 63. >MAG_08 ACCAACAGCCACAGAGCATGGGCTATGCAGATTGACAGAAAGGTCAAATTCTCCCTTTCCGG TTGGAGAGGAGAAGCCGCCCTGAGTTTGCCCCGAGTTTGCTAGGACCTTTGAGGCATGAGC CCCTCCCCAGGGCCCTCTAGCATGAAAGGGATTGCCCTGGCACGAGGAGGCTCCGTGCCA ATCAGTCAGTGCAAGGA[TGCCCCGGCTGTGTGACTACATTGACTGTCATCCCAGCATGTCT CCAAAGTTCTCAGGTGTCGTCACCACCACCCATAGCCCTAAGGGCGCCTGGGTCTTTTCTGT CCTCAGATCGACTGATGTGGGCCAAGATCGGGCCTGTGGGCGCCGTGGTCGCCTTTGCCAT CCTGATTGCCATCGTCTGCTACATTACCCAGACACGCAGGAAGTGAGTGCCAGCTGGGGCT GATCTGGGGATGGGAGTCTCCAAAAAGGGGACCTGGTGGGAGATGGAGGCCCAGAGTGGG TGGGGGAAGGCA]GCACCATAAGTGTAGAGAAGGCAGATTCTGTTCTGGGAATGTTCAGCTG GACAGAGGAGAGAGGGTTCCTGTTAATTCCAGCCCCTGCTGGTCAGGGGCACACCAGGGC CTGGGCTGAGCCCTTTACACACATCATTTGAGACCTGTTTGCCCACATTCTATTTTGACAGCC TCCCTATCTCTAGGAACTCTCCCCTACACACTCCAGTGTGGTGGGGAAAGCCCAGGTACCCC ACTGCAGCCACAGCAG 64. >MAG_09

AGAAAGACCCAGAGCCTATGAGGGGAACCTGGAGAATCCAGGTGGGGGTCCTGAAAAACG GCAGAGCTCAGGGGCCAGGTGGCTCGTCCCCAGCCGGGCAGGGGCCACAGAGGTGGGAA GGATGGGCTGTGTGGGTAGGAGAGGCTGGTGGTTCTGAAAGGGCTGCTTGCCACATCTTAG AGATGGGTGGGAGAACTCTG[AGGTCCCCTGAGCCAAACTCCTAAAACACGTGGGGGTGCA G AAAGGG AGGGCAGAG AG AGGTCTG ACGAGTCCTGCCCTGCAG AAAG AACGTGACAG AG A GCCCCAGCTTCTCGGCAGGGGACAACCCTCCCGTCCTGTTCAGCAGCGACTTCCGCATCTC TGGGGCACCAGAGAAGTACGAGGTAAGGACCAGGCTCCAGGCTGGCCTGGGAACCTGGAT GCCAGGGACACTGAAGGCCTGGGAAAGGCCTGTGAGGCCAAGGGGCAGGGGAGTGGGAG CGGCCTCTCACAGGAGGAGA]GGAAGGACATTCCAGGGCTGGGTTGGACCTGGAGGCTGG GGAGGAGGTGCCCAGGCCGAAGCTGTGTAGGGGGCGATGGGACGTGGGGCCTAAGGGCC CCCTCCCCTCCCTGCCTGTGTCTGTGACTGCATTTCCTTCTCCAATAGTCCAAAGAGGTTTCT ACCCTGGAATCTCACTGAGTGCCCCAGGAGGTAGGTTCC

65. >MAG_10

AGAAGAAGCAGCTTCCTGGAGAAACTGAATTTGTAGGCAAATTTCAAGTTCAGCAATGATTAA CACTGGCAGAAGCTCCAGAGTGGGACCTGGTGACCGCAGGGCTCGCTGGGCCTGCGGTCC TTGAGAAAGGAGGTTCTCGCAGGGATTTATTTGGGACTGAACTCAGGAGCTCTGAGGGTGC AAACGCTCTGTCCTCTGCATTGGGAAAAGGCAGGGAGCAGGACCCTGCTAATGGGCGGTTT[ CCCCTCTTAGAGCGAGAGGCGCCTGGGATCTGAGAGGAGGCTGCTGGGCCTTCGGGGTGA GCCCCCAGAGCTGGACCTGAGCTATTCTCACTCGGACCTGGGGAAACGGCCCACCAAGGAC AGCTACACGCTGACGGAGGAGCTAGCTGAGTATGCTGAAATCCGGGTCAAGTGAAGGAGCT GGGGGCAGCCTGCGTGGCTGACCCCCCTCAGGACCCTCGCTGGCCCCCACTGGCTGTGGG CTCCCTTCCTCCCAAAAGTATCGGG[G/T]GCTGGGGCAGGAGGGGAGTGAGGCAGGTGACA GTGAGGTCCTGGGGGCCTGACCTCCCCCTCCTTCCCAGCTGCCCCTCCCTGCCAGCACCCC CACGCCCTCATTACGGCTCCTCTCTAACCTCCTTTACCCTCATCTGTCTGGAGGGGAGCTCT GTCTGTC[C/G]GTGTTATTTATTGCTACTTCCTGCCTGGTCTCCTGCCCCCACACCTGGCCCT GGGGCCTGTACAAAAGGGACATGAAATAAATGCCCCAAAGCC]AAATGCCAGTCTAGATC[C/T ]TGATGCTTTCTGACCCGCCTTTGGGCAGCCTGCCATCCCACCGTCTACAGAACGATGACAG AATTTCTCCTTGCCCTCGGCTGAGCCTGGTATGCAGGCAAGGGCCCAGGGATTTTAGCCTTG AACCCAGGGCCAGTGGCCACTAAGTTGCTCCCACTCTGAGCTGGTAGCTGCGAGCTGGGTC TGGTTTGACTTATGGATGATTTCACATAAAAATCCTCATGCTGGTTTTTGCCGCAGTCAGATC AGCTGACAGCACCAG

66. >MPO 01 AAAAAAAAAAAAAAAGGCTGGGGACAATGCTGGCCCCTCCTTTCCTGCCCCTTCCCCCCATT TCAGGGGCCCCTCTGTGTGTACCTTCCAACCCCAGTGGGGGAGGAGAAAGAGTTCAGTCTC CAGGATCAGACCTTCCTCTACCTCACCCCACCCCCAGCTTAGAGGACATAAAAGCGCAGATT GAGCTAAGAGGAGCT[GACAATATCAGGTGAGCTGTGGAGGTGGGGTCCTTGGAAGCTGGA TGACAGCAGCTGGCAAGGGGATAAGAGAGCAGTGAGCCCCTCCCTCAAGGAGGTCTGGCTT TATCCA[T/C]AGACAGGGCCCTCTGAGGTGGGGCTGAGGTACAAAGGGGGATTGAGCAGCC CAGGAGAAGAGAGATGGGGGTTCCCTTCTTCTCTTCTCTCAGATGCATGGTGGACTTAGGAC CTTGCTGGGCTGGGGGTCTCACTGCAGAGATGAAGCTGCTTCTGGCCCTAGCAGGGCTCCT GGCCATTCTGGCCACGCCCCAGCCCTCTGAAGGTGCTGCTCCAG]GTAACAGTTCCCAAGGT GGGAGAAGATGGTGTGTTGGGGTGGTTGTGTTCCAGAGACCCCTTTTCTCAGAGCAGGCCT TCCTAGCTCTGGGGCCTGATAGGGGGTTGGGGCCCATTCCTGACTTTGTGATCC[C/T]TGCT CTGGGCAGCT[G/T]TCCTGGGGGAGGTGGACACCTCGTTGGTGCTGAGCTCCATGGAGGAG GCCAAGCAGCTGGTGGACAAGGCC 67. >MPO_02 CAGAGATGAAGCTGCTTCTGGCCCTAGCAGGGCTCCTGGCCATTCTGGCCACGCCCCAGCC CTCTGAAGGTGCTGCTCCAGGTAACAGTTCCCAAGGTGGGAGAAGATGGTGTGTTGGGGTG GTTGTGTTCCAGAGACCCCTTTTCTCAGAGCAGGCCTTCCTAGCTCTGGGGCCTGATAGGG GGTTGGGGCCCATTCCTGACTTTGTGATCC[C/ηTGCTCTGGGCAG[CT[G/T]CCTGGGGGAG GTGGACACCTCGTTGGTGCTGAGCTCCATGGAGGAGGCCAAGCAGCTGGTGGACAAGGCC TACAAGGAGCGGCGGGAAAG]GTGGGGCACGAGGCACTGCCCAGCTCTGGGCAAGGATGT CCCAGGCCTTTCAGAGAAGCAGCAGGCAGCAGGGAGCTTGAAGGTGGGAGAGGGGGACTA TGGGGACCCATGTGGACTCCCTTTCTGTCTGTCTGTCCCTGTGTTTCTGGATGGGAGAACAG CTTAAAAGCCATCCTTCCCAAAGCCTTGCCTCTGTCTGGACACCCAGGTCCATATCCTTTTTA TAAAAG 68. >MPO_03

TCTGTCCCTGTGTTTCTGGATGGGAGAACAGCTTAAAAGCCATCCTTCCCAAAGCCTTGCCT CTGTCTGGACACCCAGGTCCATATCCTTTTTATAAAAGGAAGCCTTCCTCCCACCCGTGGGC CTGCCTGCATGGTCCTGCATGTCTGCCCCTGGGCTGGGGCTCTGCTGGGTGGGTCTGTATC CCTTCTCTGGCCCTCACTCCTCCTTTCTCCAAGCAG[CATCAAGCAGCGGCTTCGCAGCGGC TCAGCCAGCCCCATGGAACTCCTATCCTACTTCAAGCAGCC[G/A]GTGGCAGCCACCAGGAC GGCGGTGAGGGCCGCTGACTACCTGCACGTGGCTCTAGACCTGCTGGAGAGGAAGCTGCG GTCCCTGTGGCGAAGGCCATTCAATGTCACTG]GTACTGTTGCCCATCACACCCCAGGTCCC TGCTCCACTAGTGACTCCTCCTAGGGACCCCAGCCGTCTCTCAGTGATCCCCTCAACTTCTT CCTCCAGGGAGTCTCAGGAGTCTCCAGGGCTCCTCAGCCTCAGGTTGCCTGGGATAGGAAG TGAGGCGGCTCAGCTCCCCCATTGTTCTTTCCCCCGGCAGATGTGCTGACG 69. >MPO 4 GGAGAGGAAGCTGCGGTCCCTGTGGCGAAGGCCATTCAATGTCACTGGTACTGTTGCCCAT CACACCCCAGGTCCCTGCTCCACTAGTGACTCCTCCTAGGGACCCCAGCCGTCTCTCAGTG ATCCCCTCAACTTCTTCCTCCAGGGAGTCTCAGGAGTCTCCAGGGCTCCTCAGCCTCAGGTT GCCTGGGATAGGAAGTGAGGCGGCTCAGCTCCCCCATTGTTCTTTCCCCCGGCAG[ATGTGC TGACGCCCGCCCAGCTGAATGTGTTGTCCAAGTCAAGCGGCTGCGCCTACCAGGACGTGGG GGTGACTTGCCCGGAGCAGGACAAATACCGCACCATCACCGGGATGTGCAACAACAGGTGC GGCTGGCTGGGGGTGGCTGCAGGAACCGGGCTCAGAGAGGCGTCCCGGACGCCACAAGC CTCCCGGTGTCAGCGCCCTGTCCTCCCCTGCAGACGCAGCCCCACGCTGGGGGCCTCCAA CCGTGCCTTTGTGCGCTGGCTGCCGGCGGAGTATGAGGACGGCTTCTCTCTTCCCTACGGC TGGACGCCCGGGGTCAAGCGCAACGGCTTCCCGGTGGCTCTG]GTGAGCGCCGGCGGGCA GAGGGGGCGAGGCCCGGCCACGCGGTGCGCGGACCCAGGCGCCAGCTGATCTCCGTGTC CCGCAGGCTCGCGCGGTCTCCAACGAGATCGTGCGCTTCCCCACTGATCAGCTGACTCCGG ACCAGGAGCGCTCACTCATGTTCATGCAATGGGGCCAGCTGTTGGACCACGACCTCGACTT CACCCCTGAGCCG 70. >MPO_06

CCCCTGCAGACGCAGCCCCACGCTGGGGGCCTCCAACCGTGCCTTTGTGCGCTGGCTGCC GGCGGAGTATGAGGACGGCTTCTCTCTTCCCTACGGCTGGACGCCCGGGGTCAAGCGCAA CGGCTTCCCGGTGGCTCTGGTGAGCGCCGGCGGGCAGAGGGGGCGAGGCCCGGCCACGC GGTGCGCGGACCCAGGCGCCAGCTGATCTCCGTGTCCCGCAG[GCTCGCGCGGTCTCCAAC GAGATCGTGCGCTTCCCCACTGATCAGCTGACTCCGGACCAGGAGCGCTCACTCATGTTCA TGCAATGGGGCCAGCTGTTGGACCACGACCTCGACTTCACCCCTGAGCCGGCCGCCCGGG CCTCCTTCGTCACTGGCGTCAACTGCGAGACCAGCTGCGTTCAGCAGCCGCCCTGCTTCCC GCTCAAG]GTGGCCCTGCTTCCCGCCCACTGCCTGGGTTGGGAGAGGGGAGATTGTTTCTG GAAGGGGCCATCTCCCTTCTGTGCCCAGGTTTCCTTTCCCAGACGCTGAGGAAGGCTGGCC CTGCCTCCCTTGTGTCCACAGCACTGGCTGCTCAGCTATGACCTGTCTCCTTCCTGCGCCTG GGCTCAGCCAGCTGGCAGCCAGGGCCGTCCATTTGCTCACTGCCTC 71. >MPO_07

AGGCCTGGCGGTGCCCAGACCCAGGGGTTGCCCAGGTTCCCAGTTCAGTGTTCTGCTCATT AACCCTGCACCTCAGAGGCTGTTGCTGATGGCGCCCTAGGCAGCGATCCCTTTCGGGCCTC CGGAGGCCTCTCTGCAGGTTGAGGGTACCAGAGGTCCTGAGGGCAGGGGGAGATCCAGTT CTGCCTGGGCACCTTCCTTGCCCTCGGTGAGCCAGTCTAGCCTCTCTCTGTGCCTCAGfATC CCGCCCAATGACCCCCGCATCAAGAACCAAGCCGACTGCATCCCGTTCTTCCGCTCCTGCC CGGCTTGCCCCGGGAGCAACATCACCATCCGCAACCAGATCAACG[C/T]GCTCACTTCCTTC GTGGACGCCAGCATGGTGTACGGCAGCGAGGAGCCCCTGGCCAGGAACCTGCGCAACATG TCCAACCAGCTGGGGCTGCTGGCCGTCAACCAGCGCTTCCAAGACAACGGCCGGGCCCTG CTGCCCTTTGACAACCTGCACGATGACCCCTGTCTCCTCACCAACCGCTCAGCGCGCATCC CCTGCTTCCTGGCAG]GTCAGCTTTGGGGTGGGGACCAGAGGTGGCATAGGAGATGTTCCC TGTTGGAGCCACAGTGAGTCTGTTTGTGAGCAGCTTGTGGGTTTGTACTTAGAGAGACTGTC CTCACCAGCCATTACTATCAACTTCATGATATTAATCCAGTTGCCTTGGTAACAAGTCAGATG GAGCCAGAAAAGCAGAAAAGCAAACAACCTCTCCAACCCTAAGATGGAGACCCAGGCATGG CTGAGGAGCC

72. >MPO_08 GAGCATCCCCAACCAGCAGCGGCCCTGAGCTGAGGCAGAAGCTATCATTGTGGACTGGGG CATCAGGGAAGGCCTCCTAGAGGAGTGTAAATTGGGGATAGTTTGAAAAGATGGATGGGGA GGAGGGGTGAGTAGGAGGCATTTCAGGCCTTGGCTGGGGAGGGGGTTTCAGTGGAGCAAA TCTTTTCTGGGATGGAGGCCTTAAGAATGACAGTGGCTTTTGCCTCCCCAAG[GGGACACCC GTTCCAGTGAGATGCCCGAGCTCACCTCCATGCACACCCTCTTACTTCGGGAGCACAACCG GCTGGCCACAGAGCTCAAG AGCCTGAACCCTAGGTGGG ATGGGG AG AGGCTCTACCAGGA AGCCCGGAAGATCGTGGGGGCCATGGTCCAG]GTAGGCCGTCTTGAACACCGGGCACACGG GATCCAGATGTGTCCCTGCAACATCCTAGCTGTGTGACCTTGGGCAAGTTCCTAACGCTCCT GAGCCTTGCCTTCTTCATCCATGAGGCTGTAAGGATTATAATACATATATGAAAACACCTTTC AGATAGTAAGTGCTTGACAAAGCCTCCTTCCCTTCCCTCTCCTTCTTCGCAG 73. >MPO_09

ACCCAGCCAGCAAGCAGTAGAACTCTATTTATGCCTCTCAGTGCCACTCTGTTAGGCCCAGG TCCGGTATTGTGGGAGGCTATTCCCTGACCATAGAGGGATGGAAGGGGTCCCCGAAGCCAA GAGCAGGCAGAGACTCTGGCCCTCCTGTGCTGCCAGGCGGCATTTGCTGTGGAGGAGTGG GTGGAGAGGCCATTCCAAATGACTTGTCTTTAGtATCATCACTTACCGGGACTACCTGCCCCT GGTGCTGGGGCCAACGGCCATGAGGAAGTACCTGCCCACGTACCGTTCCTACAATGACTCA GTGGACCCACGCATCGCCAACGTCTTCACCAATGCCTTCCGCTACGGCCACACCCTCATCC AACCCTTCATGTTCCGCCTGGACAATCGGTACCAGCCCATGGAACCCAACCCCCGTGTCCC CCTCAGCAGGGTCTTTTTTGCCTCCTGGAGGGTCGTGCTGGAAG]GTAAGCAGGACCTAGGC CAGGAGCGAGTGGGCTGACAGCTAAAGGTGGGGTAGGGATCACCTTGGCTCTAGGGAGCT AGGGTGGGGAGCAGTCTGCTTTCCTCCCATCTTGGAGATCTGGTCTGACTCTCTAGCCTCAG TTCCTCTGACTCTGCTTCCATATCTGATAATAAACAGTGGGGTGGGGATGGCCCTCAGAGGG AACTGGCTACTTCCTATGTGTTGTGGC 74. >MPO_10

CTGAATGGCATAATCTCCTGAGACCTATATGTCCCTGGGGTCATGTAGTGACCGGTGAGGAC CTGCTCACTGGGGCCACCACCTTGGCACCAGGCACTGCTTGTGCCCAGCCCTCTTCTCGAA TCCTCCTGACCCTACCTGGACTTGTCCCTGACTCCAATCTGAGCTCTGATACTGAGCCAGAT ACTTCCCCTGACCTGGCTCCTCTGGTCCCCAG[GTGGCATTGACCCCATCCTCCGGGGCCTC ATGGCCACCCCTGCCAAGCTGAATCGTCAGAACCAAATTGCAGTGGATGAGATCCGGGAGC GATTGTTTGAGCAGGTCATGAGGATTGGGCTGGACCTGCCTGCTCTGAACATGCAGCGCAG CAGGGACCACGGCCTCCCAG]GTGAGGGGCTGCAGGAGTCTCCCCTGATGCTCACCTCCCC TGAGCTGCCTCCTAGGTAGCCCATCACCCCCCTTCCCACTCTAGGGTCCCTGCCCTCTCCAA AGCATATTAGAGGCACTTTGCTCTCAGGAAGTAGCCTGAGGCCAGGCCCCTGCCTTTTCCCG GACCCACCTGATAAATTTCCAGCTCCTCTCAACCTCCTTTGCATGCTG

75. >MPO_l l

TAGGAGGGCAAGAGAAAGACAGAGAGGGTCCCAGAGAGGCCCAGTTGTGCCCCTTGGTCTA AGCCAAAGGTACAGGGTTCCTTGAGGTGAGGTCCTTCCCTCCCTCTATGACCTTGGTTGTGT TGGGAAGGTGGGTTTTCTGGGCTGCTGGCGATATGTGAATCTTCCCTGCTGTCTCCAGTGAC CTCCCCACCTTGAAGCAGAGAGACCTGCCCATAGCCACCTGTCCCCTCCCCCATGCAG[GAT ACAATGCCTGGAGGCGCTTCTGTGGGCTCCCGCAGCCTGAAACTGTGGGCCAGCTGGGCA CGGTGCTGAG[G/A]AACCTGAAATTGGCGAGGAAACTGATGGAGCAGTATGGCACGCCCAAC AACATCGACATCTGGATGGGCGGCGTGTCCGAGCCTCTGAAGCGCAAAGGCCGCGTGGGC CCACTCCTCGCCTGCATCATCGGTACCCAGTTCAGGAAGCTCCGGGATGGTGATCG]GTGAG GAGGGGCAGGCGTCGTGGGCCGCTGGGTGGCTGTGGGCCCATCCTTGACTCTCTTGGAGC CCAAATTTCCTCCTGTCAGTTGAAGGACTGGAGGGAGTCAGTAATTTTCCAGTGTGTTCCAG GAATCCTCCAGATGCCCTGGAGTGCCCCTAATGTGCCCTGAACCTGTTGGGGGTGCAGCAA GGAAAGACCTGGACCCCTGGTTGTAAAGGGT

76. >MPO_12

GGTAAGGGAAAGGCCACTGGGCAGCTGTGCTTTACTCTGCACGATGAGTGGAGCATCACTT

GTGTGAAAGCCCCTGGGCTGCCCAAGGGCCTGGGGCCCTCCTGTGCTTCCAGGTGGCATTT

GTTGTGGCTTTGTTATATCCTGGGAGCAGCACAAGCCCATCGATGCCCTGCCAGCCCAGAAT ATCCTTGGGCACAGTGTCCATGGGTGTTCCCC[A/C]TGC[A/C]G[GTTTTGGTGGGAGAACGA GGGTGTGTTCAGCATGCAGCAGCGACAGGCCCTGGCCCAGATCTCATTGCCCCGGATCATC TGCGACAACACAGGCATCACCACCGTGTCTAAGAACAAC[A/G]TCTTCATGTCCAACTCATAT CCCCGGGACTTTGTCAACTGCAGTACACTTCCTGCATTGAACCTGGCTTCCTGGAGGGAAGC CTCCTAGAGGCCAGGTAAGGGGGTGCAGCAGTGAGGGGTATATCTGGGCTGGCCAGTTGG AACCACGGAGATCTCCTTGCCCTAGATGAGCCCAGCCCTGTTCTGGGTGCAGCTGAGAAAA TGAGTGACTAGACGTTCATTTGTGTGCTCATGTATGTGCGAAGTATATAAATTGGCTTTTCAT GCGTGTGTGTTGTCTGAACATGGGGAGTGTTTCATGGGTTATGTGTATGTGCCATTTATGTG AGTGTGTGTTTGTGCTGATGAGAATACTGAGTATGTGGAAGGCAGCAGAGCGGACTGGTGA GGAGCACAGCTCAGGAACTAGACTGCCTGGGTTCCAATCCTGGCTCTGTGGCTTGCTAGCT ATGTGACCTTG AGCAAATTACCCTCCTTAAACAAG AGTTTTCTTCCTTGTAAATTACATCTGTC ATGGTTTCTTGGAGGGCCCACTTGTATCCTCTGGTTCTTCATTTATTGAGCACCTACTACATG CAAGGCACTGTACTAGGCGTGAGAAGCATATAGAGGCAAGAAAGAGATACCAAGATGCCAT CTGTGTCCTGGTTAGCAGAGCTGGACCAGTGGTGCCTTGGAGGGATAAGCCAGCTGCAGCT GGGCTGTGTGGTTGACTTATGGGCCCAGCCAGCCAGGCTCAGGCCATGGCTCCCCTTTTTC TTCCTCACCCTGATTTCTTGCTTATTCACTGAAGTTCTCCTGAAGAGGAACTGGGCCTGTTGC CCTTTCTGTACCATTTATTTGCTCCCAATGTTTATGATAATAAAGGCACCGCTGATGGGGACC TCC]ACTCTGTCTGTGTCTGAGGAGGAACTGGCGCTTTTGCAGAGGCTTACTCTGGGCTCTG AGCTTGAACCAGTGTGGTCTGTGCTCAGGGCCCTGTGTTTCTGAACCGAGGGTGAGGATGT TGGGGAGTTTTCCTTTGAGATCCGTACGTGGAGGGCAGCCATCTCTTGGAAGCCTGGGGGC CGGGGCATGCGGTGCAGACCCTCCTCCCTCACCTTCCACC

77. >MCPl_pro

AGCGAGAGTCCAACCCAGGTTTGTGCCAGAGCCTAACCCAGGCTTGTGCCGAGATGTTCCC AGCACAGCCCCATGTGAGAGCTCCCTGGCTCCGGGCCCAGTATCTGGAATGCAGGCTCCAG CCAAATGCATTCTCTTCTACGGGATCTGGGAACTTCCAAAGCTGCCTCCTCAGAGTGGGAAT TTCCACTCACTTCTCTfCACGCCAGCACTGACCTCCCAGCGGGGGAGGGCATCTTTTCTTGA CAGAGCAGAAGTGGGAGGCAGACAGCT[A/G]TCACTTTCCAGAAGACTTTCTTTTCTGATTCA TACCCTTCACCTTCCCTGTGTTTACTGTCTGATATATGCAAAGGC]CAAGTCACTTTCCAGAGA TG ACAACTCCTTCCTG AAGTAG AG ACATGCTTCCAACACTCAGAAGCCTATGTGAACACTCA GCCAGCAAAGCTGGGAAGTTTTTCTCTGTGACCATGGGCTAATTGGTCTCCTTCTCTGGATT GTGGCTTTATCAGATAAAAACAAGTGGTCATGCCACAGGATGTCTATAAGCCCATTGATTCTG GGATTCTATGAGTGATGCTGATATGACTAAGCCAGGAGAGACTTA

78. >MCP1_01 TAGTTTCCTCGCTTCCTTCCTTTTCTGCAGTTTTCGCTTCAG AGAAAGCAG AATCCTTAAAAAT AACCCTCTTAGTTCACATCTGTGGTCAGTCTGGGCTTAATGGCACCCCATCCTCCCCATTTG CTCATTTGGTCTCAGCAGTGAATGGAAAAAGTGTCTCGTCCTGACCCCCTGCTTCCCTTTCCT ACTTCCTGGAAATCCACAGGATGCTGCATTTGCTCAGCAGATTTAACAGCCCACTTATCAC[T CATGGAAGATCCCTCCTCCTGCTTGACTCCGCCCTCTCTCCCTCTGCCCGCTTTCAATAAGA GGCAGAGACAGCAGCCAGAGGAACCGAGAGGCTGAGACTAACCCAGAAACATCCAATTCTC AAACTGAAGCTCGCACTCTCGCCTCCAGCATGAAAGTCTCTGCCGCCCTTCTGTGCCTGCTG CTCATAGCAGCCACCTTCATTCCCCAAGGGCTCGCTCAGCCAGGTAAGGCCCCCTCTTCTTC TCCTTGAACCACATTGTCTTCTCTCTGAGTTATCATGGACCATCCAAGCAGA]CGTGGTACCC ACAGTCTTGCTTTAACGCTACTTTTCCAAGATAAGGTGACTCAGAAAAGGACAAGGGGTGAG CCCAACCACACAGCTGCTGCTCGGCAGAGCCTGAACTAGAATTCCAGCTGTGAACCCCAAAT CCAGCTCCTTCCAGGATTCCAGCTCTGGGAACACACTCAGCGCAGTTACTCCCCCAGCTGCT TCCAGCAGAGTTTGGGGATCAGGGTAATCAAAGAGAGGGTGGGTGTGTAGGCTG

79. >MCP1 )2

TCCCCAGCTGATCTTCCCTGGTGCTGATCATCTGGATTATTGGTCCGTCTTAATGACACTTGT AGGCATTATCTAGCTTTAACAGCTCCTCCTTCTCTCTGTCCATTATCAATGTTATATACCCATT TTACAGCATAGGAAACTGAGTCATTGGGTCAAAGATCACATTCTAGCTCTGAGGTATAGGCA GAAGCACTGGGATTTAATGAGCTCTTT[G/C]TCTTCTCCTGCCTGCCTTTTGCTTTTTCCTCAT[ GACTCTTTTCTGCTCTTAAGATCAGAATAATCCAGTTCATCCTAAAATGCTTTTTCTTTGTGGT TTATTTTCCAGATGCAATCAATGCCCCAGTCACCTGCTG[T/C]TATAACTTCACCAATAGGAAG ATCTCAGTGCAGAGGCTCGCGAGCTATAGAAGAATCACCAGCAGCAAGTGTCCCAAAGAAG CTGTGATGTGAGTTCAGCACACCAACCTTCCCTGGCCTGAAGTTCTTCCTTGTGGAGCAAGG GA]CAAGCCTCATAAACCTAGAGTCAGAGAGTGCACTATTTAACTTAATGTACAAAGGTTCCC AATGGGAAAACTGAGGCACCAAGGGAAAAAGTGAACCCCAACATCACTCTCCACCTGGGTG CCTATTCAGAACACCCCAATTTCTTTAGCTTGAAGTCAGGATGGCTCCACCTGGACACCTATA GGAGCAGTTTGCCCTGGGTTCCCTCCTTCCACCTGCGTTCCTCCTCTAGCTCCCATGGCAGC CCTT 80. >MCP1_03

ACATCACTCTCCACCTGGGTGCCTATTCAGAACACCCCAATTTCTTTAGCTTGAAGTCAGGAT GGCTCCACCTGGACACCTATAGGAGCAGTTTGCCCTGGGTTCCCTCCTTCCACCTGCGTTCC TCCTCTAGCTCCCATGGCAGCCCTTTGGTGCAGAATGGGCTGCACTTCTAGACCAAAACTGC AAAGGAACTTCATCTAACTCTGTCCTCCCTCCCCACAG[CTTCAAGACCATTGTGGCCAAGGA GATCTGTGCTG ACCCCAAGCAG AAGTGGGTTCAGG ATTCCATGG ACCACCTGG ACAAGCAA ACCCAAACTCCGAAGACTTGAACACTCACTCCACAACCCAAGAATCTGCAGCTAACTTATTTT CCCCTAGCTTTCCCCAGACACC[C/T]TGTTTTATTTTATTATAATGAATTTTGTTTGTTGATGTG AAACATTATGCCTTAAGTAATGTTAATTCTTATTTAAGTTATTGATGTTTTAAGTTTATCTTTCAT GGTACTAGTGTTTTTTAGATACAGAGACTTGGGGAAATTGCTTTTCCTCTTGAACCACAGTTC TACCCCTGGGATGTTTTGAGGGTCTTTGCAAGAATCATTAATACAAAGAATTTTTTTTAACATT CCAATGCATTGCTAAAATATTATTGTGGAAATGAATATTTTGTAACTATTACACCAAATAAATAT ATTTTTGTACAAAA]CCTGACTTCCAGTGTTTTCTTGAAGGAAATTACAAAGCTGAGAGTATGA GCTTGGTGGTGACAAAGGAACATGATTTCAGAGGGTGGGGCTTACATTTTGAAGGAATGGGA AAGTGGATTGGCCCCGGTCTTCTCCACTGGGTGGTCTCCTCTGAGTCTCCGTAGAAGAATCT TTATGGCAGGCCAGTTAGGCATTAAAGCACCACCCTTCCAGTCTTCAACATAAGCAGCCCAG AGTCCAAT

81. >CXCR3 01

CTGTCTCAGGCTTCCAAGTAGTTAGGACTACAGGCACATGCCACCATGCCCGGCTGGCT^"

TTTATTTTTGGTAGAGATGGAGCCTCGCTATGCTGCCCAGGCTGGTCTCAAACTCTTGGCCT TAAGTGATCCTCTTGCCTCAGCCTCCCCAGTAGCTGGGATTACAGGAATGAGCCACTGCACC TAGCTGAAATTTTTAAGAAGGTGGATCTCCTCTGCAGACTTATTTCTCTACCCAGCCTTTACA ATCATGCAAAGATCAACTCAAGGCCAGGACAGATGAGTTCCAATCTATGGA[GCACTGACCCT ACCAGTGCAGGCAGTAGGGTTGCCCTTCACTTCTCAGCTGCATTGCTTCCTCTTCAGACCTC TCTTCTCAAAGGACCTGCCCCCAGCCAGTCATCCTCTGCCCAGCTTTTCTGGTCCCAAGCTT GTAGCCAGCTCCTCCAGAGAGGTTTCACCCAGTCACGGAAACTCTGTGGCCTGAGGTTTAG GGAGGTCTGGTAGAGGTAACTCCCTGGAAGAGGCTGCTGCTGAGAACTGCCTGAAACTCCC ACTTCCTCTGTGACTGCAGGTTTCCAACCACAAGCACCAAAGCAGAGGGGCAGGCAGCACA CCACCCAGCAGCCAGAGCACCAGCCCAGCCATGGTCCTTGAGGTAAGTGCTG]CTGCCCAG CCAGGCCAGGCCAGAATTCGAAGTGGAAAACCCGGGGCATCAGGGGAATGCCAGGGCTGG CCCACAGCCCAGGGTCACCACAGGGTTGGGTGAGTAGCTGGAGGCCGCATGGGTTGTGGC AGAAACAGCACTGGGGAATTGGGAACCCAGCTTGGCCACTGACCCTGGGTGCCTCTCCTCT CCTCTCTGGCTTCGGTGTCTCGTCTGCAAAATGGGGGGGGCGGGGGGCAAGTAGACTCGA AGGCTCCCTTCAGGAGACTTGGAACTTTGACTCTTGGCGTG 82. >CXCR3_02

GGAGAGCAGGGAGAGAGAGGACAGTGGGCAGAGAGGGCTCTGGGCACTGGAGGGACGCT CTTCTTCCTGCCCAGGGGTCCCTGGGCCGATGGGATCACGCAGAAGAATGCGAGAGAAGCA GCCTTTGAGAAGGGAAGTCACTATCCCAGAGCCCAGGCTGAGCGGATGGAGTTGAGGAAGT ACGGCCCTGGAAGACTGGCGGGGACAGTTATAGGAGGAGCTGCTCAGAGTAAATCACAGAC TAAATCAGACTCAATCACAAAAGAGTTCCTGCCAGGCCTTTACACAGCCCCTTCCTCCCCGTT CCC[GCCCTCACAGGTGAGTGACCACCAAGTGCTAAATGA[C/ηGCCGAGGTTGCC[G/A]CCC TCCTGGAGAACTTCAGCTCTTCCTATGACTATGGAGAAAACGAGAGTGACTCGTGCTGTACC TCCCCGCCCTGCCCACAGGACTTCAGCCTGAACTTCGACCGGGCCTTCCTGCCAGCCCTCT ACAGCCTCCTCTTTCTGCTGGGGCTGCTGGGCAACGGC[G/A]CGGTGGCAGCCGTGCTGCT GAGCCGGCGGACAGCCCTGAGCAGCACCGACACCTTCCTGCTCCACCTAGCTGTAGCAGAC ACGCTGCTGGTGCTGACACTGCCGCTCTGGGCAGTGGACGCTGCCGTCCAGTGGGTCTTTG GCTCTGGCCTCTGCAAAGTGGCAGGTGCCCTCTTCAACATCAACTTCTACGCAGGAGCCCTC CTGCTGGCCTGCATCAGCTTTGACCGCTACCTGAACATAGTTCATGCCACCCAGCTCTACCG CCGGGGGCCCCC[G/A]GCCCGCGTGACCCTCACCTGCCTGGCTGTCTGGGGGCTCTGCCTG CTTTTCGCCCTCCCAGACTTCATCTTCCTGTCGGCCCACCACGACGAGCGCCTCAACGCCAC CCACTGCCAATACAACTTCCCACAGGTGGGCCGCACGGCTCT[G/A]CGGGTGCTGCAGCTG GTGGCTGGCTTTCTGCTGCCCCTGCTGGTCATGGCCTACTGCTATGCCCACATCCTGGCCG TGCTGCTGGTTTCCAGGGGCCAGCGGCGCCTGCGGGCCATGCGGCTGGTGGTGGTGGTCG TGGTGGCCTTTGCCCTCTGCTGGACCCCCTATCACCTGGTGGTGCTGGTGGACATCCTCAT GGACCTGGGCGCTTTGGCCCGCAACTGTGGCCGAGAAAGCAGGGTAGACGTGGCCAAGTC GGTCACCTCAGGCCTGGGCTACATGCACTGCTGCCTCAACCCGCTGCTCTATGCCTTTGTAG GGGTCAAGTTCCGGGAGCGGATGTGGATGCTGCTCTTGCGCCTGGGCTGCCCCAACCAGA GAGGGCTCCAGAGGCAGCCATCGTCTTCCCGCCGGGATTCATCCTGGTCTGAGACCTCAGA GGCCTCCTACTCGGGCTTGTGAGGCCGGAATCCGGGCTCCCCTTTCGCCCACAGTCTGACT TCCCCGCATTCCAGGCTCCTCCCTCCCTCTGCCGGCTCTGGCTCTCCCCAATATCCTCGCTC CCGGGACTCACTGGCAGCCCCAGCACCACCAGGTCTCCCGGGAAGCCACCCTCCCAGCTC TGAGGACTGCACCATTGCTGCTCCTTAGCTGCCAAGCCCCATCCTGCCGCCCGAGGTGGCT GCCTGGAGCCCCACTGCCCTTCTCATTTGGAAACTAAAACTTCATCTTCCCCAAGTGCGGGG AGTACAAGGCATGGCGTAGAGGGTGCTGCCCCATGAAGCCACAGCCCAGGCCTCCAGCTCA GCAGTGACTGTGGCCATGGTCCCCAAGACCTCTATATTTGCTCTTTTATTTTTATGTCTAAAAT CCTGCTTAAAACTTTTCAATAAACAAGATCGTCAGGACCAGGGCATGTTCGTGCATCA]TTAC AGTCAGCCCAGCCCACCTGGGCTCCAGGGGCACTTCCTGGTTCTCCCTGCCTGGCCCTGG GTCTGTGCCAGCCCATCCTGCCTTCATCAATGTCTGTCTGCAGCTTTGTCTCTGCCCTCGTG GGCACTCCTGTTCTACTCACAGGG AAACACCCAAGTACATGGGTGCAG AGTGAGCAGTTAG GCAGCTGGTTGGCATAATTGGGGAAGGGGCCATCAGACATGAACACGAGAGCCCTGCACTC CAGCAGCTCAGGACAGGAGGCAAGATGTGTGTGAAACTAGCGAAACCCAGCAGCCTGGGC CATGGGGCACATAAGTGGCACAGTGAACCCAG 83. >IL12A_01

TGATGAGTGAATGATTTGCCTACCCCTTCCAGTACTAGGCTGGAGGTCGTGGTTAGGGCCCA TCCCTACGCAGGACATGCAAAGTGGGAGGCACTCCTCTCTCTACGTCGGCAGGGGGCGCTG CACAGCTGCGGGGCGGGGTAGCTTAGACACGGGGCGTCCGGCTAAGGCCGGGGACCCAG GGTGGTGGGCGGGGTGTCCCGCCCGCCTGTGGACCCCGCGCAGTAACTGCGAACATTTCG CTTTCATTTTGGGCCGAGCTGGAGGCGGCGGGGCCGTCCCGGAACGGCTGCGGCCGGGCA CCC[C/G]GG[GAGTTAATCCGAAAGCGCCGCAAGCCCCGCGGGCCGGCCGCACCGCACGTG TCACCGAGAAGCTGATGTAGAGAGAGACACAGAAGGAGACAGAAAGCAAGAGACCAGAGTC CCGGGAAAGTCCTGCCGCGCCTCGGGACAATTATAAAAATGTGGCCCCCTGGGTCAGCCTC CCAGCCACCGCCCTCACCTGCCGCGGCCACAGGTCTGCATCCAGCGGCTCGCCCTGTGTC CCTGCAGTGCCGGCTCAGCATGTGTCCAGCGCGCAGTGAGTACTCAGCCCGCCAGGTCTTT GGCTCGCTCGGGTGCGGAGGGGCGGC]TGCTTGGGAAGAGTGGGTAGAAACTCAAGTCTGC CTAAGGAGAGACTGGAACAGCAGCAGCCGTCTCCTGCAAAGAGGAATAAGAATAGGGGTCT CACCGTGTGCTAAATAGGGCATGTCTCTTTTCATCTCGAAACAGCCTGATGAGCTATCATTAT GCCCACTTCGTAGAGGAGAAACTGAGGCCCAGCGTGGGAGATTTCCTGCTTTCCTGCCTAG GGTCCCTCAGCTACAAACAGAAGGCAGATCCTAGCCAGTTCTAAAGTCAGGCTTGGCCGGG

84. >IL12A_02

TTCACCACCTGGTCTGGGTTTCCCTGATCAAAAACATGTAGGCTTTCTCTGGGTGAGTGTTG GGTTCAACACCCTTGTCCAAGCTCATCTCTAGACCCTCACAGGGAGCTGGCTTCTAGCCCTA GAATAGAGTGGCGCTTTGTAATAACTCGAGTCATCTCTCAGGTGTTGAAGGAAAAGTGTTGG AAATGGGTTGAGGGAGGTGGGTGCCAAGCATGAATGGATGGGTG[AAGGTGGCCAGAATGG AGGGAAGGTGGTGCAGGCAGGCCATCCAGGCTGAAGCTCCTCCACCTGCTCCTCTTCCTTC CAGGCCTCCTCCTTGTGGCTACCCTGGTCCTCCTGGACCACCTCAGTTTGGCCAGAAACCTC CCCGTGGCCACTCCAGACCCAGGAATGTTCCCATGCCTTCACCACTCCCAAAACCTGCTGA GGGCCGTCAGCAACATGCTCCAGAAGGTGAGCCTTTCCTGTCCTCTCCACTGTGGACCTGC ACCCTCCCTGAGGAAGGGGCCTCTGATCCTCCCCTCTGG]TACCTGATGGAACTGCAGAGAA ATTGTGGAAGTTCATTAGCAGCTGTCAACAGCAGGAGAGGGAACTTTACAAATGGCCCAAGT GTTAAAGAGTCCTAGTGAAATTGTGTCTCCAGAGAAAGCAAGAGTAGTAATAAATTATAATGA TGTTGGTTTTGGCTATGTCTACACTGAGTAAAGTGGATATTTGCAGTGTTCCTGTAGCCTGCC AACAGAGATA

85. >IL12A_03

GTGTCACAGTGAGGTGTGGAGGCTGGTTAGCACAGGCTGTTGACATGATTTATTGTGTTTAC ATAATGAAAAAATATGTAATCCAGAGAAACATGCCCCAAGCTTAGGGAGAGGAGGGTGAGAG ACAGAATGTAAGGAATCTATTTTCTTTTGTATTATGAAGAACCAGAATTTCCTGCAAGTCAAAG TGACAGAGGTCAAGGGCAGCCAGCCGGAGCCT[TCCTGGCACCCTGGCTTACCAGCCTTGT GGGGTGCCAGGTGCATTATCAATGTTATAAACTGAGTTTCTCCTTCATTTTTTATAGGCCAGA CAAACTCTAGAATTTTACCCTTGCACTTCTGAAGAGATTGATCATGAAGATATCACAAAAGATA AAACCAGCACAGTGGAGGCCTGTTTACCATTGGAATTAACCAAGGTATAAAGGATTTCCTCC CAGAGCATGCAGTGTGGTTAAAAACTGTGCATCAAATCTCACCTGCTTCTAAAAATTCACGTη TCTGTATCCATCATTATGGATTTTAACTGTCCTACTTCAGAAGTTAGATTTGGGAGAAAAATTA TTTTTAAAAAATGGTTTTTTTTGCAACAATGTGAATACACTTAACACTTAAAAATAGTTCAGATG CTAAATATTATGATATGTGTTTTTACCATAATAAAAAAAATTTGAGACCTGAAGAGTCAGAAAG ATTTATA

86. >IL12A_4,5

GTGGTTAAAAACTGTGCATCAAATCTCACCTGCTTCTAAAAATTCACGTTTCTGTATCCATCAT TATGGATTTTAACTGTCCTACTTCAGAAGTTAGATTTGGGAGAAAAATTATTTTTAAAAAATGG TTTTTTTTGCAACAATGTG AATACACTTAACACTTAAAAATAGTTCAGATGCTAAATATTATGAT ATGTGTTTTTACCATAATAAAAAAAATTTGAGACCTGAAGAGTCAGA[AAGATTTATACTAAGAA TTAATACTTTGATATATGATTTTTTCCCTCTAGAATGAGAGTTGCCTAAATTCCAGAGAGACCT CTTTCATAACTGTAAGTCAAAAAATGAAAAGTTTCAGCCTGTATGATGAATTCATATCACTGAT GTCTGATTATTTTTTCCTCTAGAATGGGAGTTGCCTGGCCTCCAGAAAGACCTCTTTTATGAT GGTAAG ACACACAGCTCTTTCCTCAAATGCAATGGGGG AAATGTTTTTAGCqCATCTCAATG GATACTTCCCCATCTTGTCATGTCACCCAGGCCCTGTGCCTTAGTAGTATTTATGAAGACTTG AAGATGTACCAGGTGGAGTTCAAGACCATGAATGCAAAGCTTCTGATGGATCCTAAGAGGCA GATCTTTCTAGATCAAAACATGCTGGCAGTTATTGATGAGCTGATGCAGGTAAGACTTCATTC TA 87. >IL12A_06

GCCTAAATTCCAGAGAGACCTCTTTCATAACTGTAAGTCAAAAAATGAAAAGTTTCAGCCTGT ATGATGAATTCATATCACTGATGTCTGATTATTTTTTCCTCTAGAATGGGAGTTGCCTGGCCT CCAGAAAGACCTCTTTTATGATGGTAAGACACACAGCTCTTTCCTCAAATGCAATGGGGGAA ATGTTTTTAGCC[CATCTCAATGGATACTTCCCCATCTTGTCATGTCACCCAGGCCCTGTGCC TTAGTAGTATTTATGAAGACTTGAAGATGTACCAGGTGGAGTTCAAGACCATGAATGCAAAGC TTCTGATGGATCCTAAGAGGCAGATCTTTCTAGATCAAAACATGCTGG.CAGTTATTGATGAGC TGATGCAGGTAAGACTTCATTCTATCAGTGAGAGCACCTTTTTCATGCTAAAGATAACCAGCC AGGGTCTTTGATAAAGAGATATAAAAAGAGGTCTGGAGGCCTTTTAAAGGC]CTGACAGACCT ACATTTTCAAGAAGACAGCCTTGAGGGTGCCGTCTATAGGGAGCACAAATGTGAGCAGATCA CATTATGAAAAGCAG ACTCCAAAGTATTCACTCTGTGGTATCCCCCACACTCGGCAAATGTTT TTGTGCATTTTCTTATGTCAGCCTCAAAACAACCATATGGGATCTGCACAAAGGAGGGAACCA AACCTTAGGAG

88. >IL12A )7

AGATGTCATTTTAAAGGAACTGTTTCTTTCTAAGACACAACTCCCACTGATGATTTTTTCTAAA TAGTTTTAAGGGTCTTTTCAG AGCTCATTG AAGATGGATGTGCTTGG AAAATGAGTATTTCTTT TCTCATTCTGCCTGGTGATCTGGCTGAGAGTAGATTTGGATTGGGTTTAGGAGTGGCATAAG GGACTGAGTTGCAGGCTCTGAGACATGTACTGGCTTCACTCATTTTTATGAATGAATATTTGA ATTTTGGAATACCATGTAAGTCATGC[TTACTGTTCATTCTCCTAGGCCCTGAATTTCAACAGT GAGACT[G/A]TGCCACAAAAATCCTCCCTTGAAGAACCGGATTTTTATAAAACTAAAATCAAGC TCTGCATACTTCTTCATGCTTTCAGAATTCGGGCAGTGACTATTGATAGAGTGATGAGCTATC TGAATGCTTCCTAAAAAGCGAGGTCCCTCCAACCGTTGTCATTTTTATAAAACTTTGAAATGA GGAAACTTTGATAGGATGTGGATTAAGAACTAGGGAGGGGGAAAGAAGGATGGGACTATTA CATCCACAT[A/G]ATACCTCTGATCAAGTATTTTTGACATTCACTGTGGTTANATTGGTTTTAAG CCCTCATGAATGAATTGCTAAGAAGGTATTATATCCATCCTGAAGGTGTTTTTCATTCACTTTA ATAGAAGGGCAAATATTTATAAGCTATTTCTGTACCAAAGTGTTTGTGGAAACAAACATGTAA GCATAACTTATTTTAAAATATTTATTTATATAACTTGGTAATCATGAAAGCATCTGAGCTAACTT ATATTTATTTATGTTATATTTATTAAATCATTTATCAAGTGTATTCTG AAAAATATTTTTAAGTGT TCTAAAAATAAAAGTATTGAATTAAAGAGATTCTGCAATTTTηCTAATGTACTTTTAAGTGTTAA AATA[C/T]ACATTGTGGGAAAATTGAAAACTCTGATGAGACTTAACAAAATTACTCTGGAAAGA ATGCCACAATATTCTTATTCCTTTCCTAGTCCCTTTCATCTCATTTTAAAGGGACCCTAGTAAG ACAAGATATGCTTTACTACTAAGGCAGCCAAGTGAGTCATGGTTTTTGAGGGTTTATTATTTTT GTTCAACATAAGACTAAAAGTATGCTGTGCATTAGAAAAATACTTCATAGTATTCTTCAACC

89. >IP10_01

AACTGTAAAAGTTTAAGTGTTGAGAAAAAGCATTATAGTTAGAATGGATTGCAACCTTTGTTTT TTTCTATATGCAATGAAGTTCTTTTTTTCAAGAAACAGTTCATGTTTTGGAAAGTGAAACCTAA TTCACTATTACCAAAAAAAGAGGAGCAGAGGGAAATTCCGTAACTTGGAGGCTACAATAAATA ATACCCTTCGAGTGCC CATGGGACTTCCCCAGGAACAGCCAGCAGGTΓΠTGCTAAGTCG ACTGTAATGCCCTTATCCAATCAGAATTAGGGAGGGAAAATGGCTTTGCAGATAAATATGGCA CACTAGCCCCACGTTTTCTGAGACATTCCTCAATTGCTTAGACATATTCTGAGCCTACAGCAG AGGAACCTCCAGTCTCAGCACCATGAATCAAACTGCCATTCTGATTTGCTGCCTTATCTTTCT GACTCTAAGTGGCATTCAAGGTAAGGAACATCAAAGGATACTTAATTTGTAAAATGAGAAATA GGAATAGGTATAAATTCTAAAAATACAGAAATAATG]TATTTGTAAAAGTTTCACTGCATGCTTA TAAATAAGAGGGAAATAAATAGAGATTCCCTCAGATCATAAAACTTATATGAATTGAAGTGAG AGAAACAAATAGAATAAGAGAAAGAGAAGGAAAAAGGGAAGGAGGACAGAAGAGATGGGGA AGAGGGAGGATAGAGAGAGAAAATGTGAGGGAATGCGGACAGAGATGAGATACAGATACTT CCTTACCTAACTAAGCTCAATGAACCACATGAACTGTGCTTAAGGGTTTGACTTTATAATCAA CAAGCTGCAATTCTTTTCTTCCAG

90. >IP10 )2

GAAAAAGGGAAGGAGGACAGAAGAGATGGGGAAGAGGGAGGATAGAGAGAGAAAATGTGA GGGAATGCGGACAGAGATGAGATACAGATACTTCCTTACCTAACTAAGCTCAATGAACCACA TGAACTGTGCTTAAGGGTTTGACTTTATAATCAACAAGCTGCAATTCTTTTCTTCCAGATAATC AACTCTTTAATCATTTACAGTTGTGTTATGATGTGATCCATTCCTCCTCAGATTAAGTGACTAT TTGCTGATATGGGGATATAGGTTCTGCTAAATACCACCAGTCTACATTAA[ATGCCTAAAATGA ACACTGTGCTAACCTTCTCTGCTGTTCCTCTTTTCCTACAGGAGTACCTCTCTCTAGAACTGT ACGCTGTACCTGCATCAGCATTAGTAATCAACCTGTTAATCCAAGGTCTTTAGAAAAACTTGA AATTATTCCTGCAAGCCAATTTTGTCCACGTGTTGAGATCATGTGAGTGAAATCCCATCTGAT TATCACTTCCCTGGTTGTAATTATATACTGTATTAAAΗATGTAATGATAATAAAAAAAGATCAG TAAAGGGTTTGTGATGATTCTAAAACTAATGTACAGCAAACAAAAACATGCAGAGTGAAACTT AAATGTCTGACTTCAGAACTGCGTATGCCATCTGTTTTATTGACCCAACACAGTTTTAAATATT TTCATCCCTATTTATTTCTACAGTGCTACAATGAAAAAGAAGGGTGAGAAGAGATGTCTGAAT CCAGAATCGAAGGCCATCAAGAATTTACTGAAAGCAGTTAGCAAGGAAAGGTAGGTTTGCTG TTGCCTGCAGCCGAATTGCTCT

91. >ΓPIO_03

CTCTCTCTAGAACTGTACGCTGTACCTGCATCAGCATTAGTAATCAACCTGTTAATCCAAGGT CTTTAGAAAAACTTG AAATTATTCCTGCAAGCCAATTTTGTCCACGTGTTG AG ATCATGTG AG TGAAATCCCATCTGATTATCACTTCCCTGGTTGTAATTATATACTGTATTAAATATGTAATGATA ATAAAAAAAGATCAGTAAAGGGTTTGTGATGATTCTAAAACTAATGTAC[AGCAAACAAAAACA TGCAGAGTGAAACTTAAATGTCTGACTTCAGAACTGCGTATGCCATCTGTTTTATTGACCCAA CACAGTTTTAAATATTTTCATCCCTATTTATTTCTACAGTGCTACAATGAAAAAGAAGGGTGAG AAGAGATGTCTGAATCCAGAATCGAAGGCCATCAAGAATTTACTGAAAGCAGTTAGCAAGGA AAGGTAGGTTTGCTGTTGCCTGCAGCCGAATTGCTCTTTAGGAAACGGCAATCTTGGGAGTC AGAA]ATACTTGCATTGTGGTTTGTGCTGCAATCGCTGGTTTAAAAGTATGTTACCACCACGC CCTCCCCTACCTCCATTTATTTAAATGCTGAGGCACCATCTTGTGTGATAAGTATCAGAAGTT ACCCTGATTACCAGTCAACCTTGAAGTACAGCTATAACTATCTAAGCAAAACTGACAACATTT TCCCCAAGTCTTTCATGGTTGAAAAAAGCAACCCCTATAATCCATAATGAATGCATAGCAGCA GGAAAGCTCAGTTATCTATTCTATGAACTCGGTACTTTCCAAACACAACCCAATCTGAAGCCA GAGTCAGA[C/G]TATCACACTTTT

92. >ΓPIO_04

TTAGGAAACGGCAATCTTGGGAGTCAGAAATACTTGCATTGTGGTTTGTGCTGCAATCGCTG GTTTAAAAGTATGTTACCACCACGCCCTCCCCTACCTCCATTTATTTAAATGCTGAGGCACCA TCTTGTGTGATAAGTATCAGAAGTTACCCTGATTACCAGTCAACCTTGAAGTACAGCTATAAC TATCTAAGCAAAACTGACAACATTTTCCCCAAGTCTTTCATGGTTGAAAAAAGCAACCCCTAT AATCCATAATGAATGCATAGCAGCAGGAAAGCTCAGTTATCTATTCTATGAACTCGGTACTTT CCAAAC[ACAACCCAATCTGAAGCCAGAGTCAGA[C/G]TATCACACTTTTATATCCCCTTTCTC TTCTTACAGGTCTAAAAGATCTCCTTAAAACCAGAGGGGAGCAAAATCGATGCAGTGCTTCC AAGGATGGACCACACAGAGGCTGCCTCTCCCATCACTTCCCTACATGGAGTATATGTCAAGC CATAATTGTTCTTAGTTTGCAGTTACACTAAAAGGTGACCAAT[G/C]ATGGTCACCAAATCAGC TGCTACTACTCCTGTAGGAAGGTTAATGTTCATCATCCTAAGCTATTCAGTAATAACTCTACC CTGGCACTATAATGTAAGCTCTACTGAGGTGCTATGTTCTTAGTGGATGTTCTGACCCTGCTT CAAATATTTCCTCACCTTTCCCATCTTCCAAGGGTACTAAGG AATCTTTCTGCTTTGGGGTTTA TCAGAATTCTCAGAATCTCAAATAACTAAAAGGTATGCAATCAAATCTGCTTTTTAAAGAATGC TCTTTACTTCATGGACTTCCACTGCCATCCTCCCAAGGGGCCCAAATTCTTTCAGTGGCTACC TACATACAATTCCAAACACATACAGGAAGGTAGAAATATCTGAAAATGTATGTGTAAGTATTCT TATTTAATGAAAGACTGTACAAAGTAGAAGTCTTAGATATTGTTTTCAGTGTACATGGAATAAC AATGTATATATTTCCTTGTAATTAAGTACTATGTATCAATGAGTAACAGGAAAATTTTAAAAATA CAGATAGATATATGCTCGCATGTTACATAAGATAAATGTGCTGAATGGTTTTCAAAAATAAAAA TGAGGTACTCTCCTGGAAATATTAAGAAAGACTATCTAAATGTTGAAAGA[T/C]CAAAAGGTTA ATAAAGTAATTATAACTAAGATGAAGTGCCTTGTGTG]TCACTTGGTTGGGATATTTATTTCATA AGAAACTTAGATTGGAGAAATCTATGGCCTGGAGAAGAAGGTGGCATGGGCAGAAGACAAAT GAGTTAGAGAATTACCACTCTCTCTCCTTCCAACTGTAATCTCCTGAAAGGCCCATCATATAA GATCCTACAGAACTAATGTAGCATAACAGAGCTTGGCCTAATCTCCAAATCCCTATAGCCAAA TTTCTTTTTTTTTTAATCTCTTATTTTTTTAGACACAGGGTCTTCCTCTGTCACCCAAGCCGGA GTGCAATGGTGCAATCATAGCTCACTGCAGCCTCGAAACTCCTGGGCTCA

93. >NOD2_EXON1

TTAGTGAGAACAGCACTAAGGCCAGGTTCTCCTCCCCAGATGTTTAAGATGAGACAGGACAA TGCCTGCTCAGAGACAGGGCCTGGCTGAATTGGCCCTCAGGATTCTCTCTGCTCTGAGGTTT CTGGAAGAAGGCCAGGGCAGAGGTGTGGTGATGTAGCTGCTGGGAGGACAGAGCTCCGAG TCACGTGGCTTGGGCGGGCCTCCCCTTCCTGGTGTCCACAG AAGCCCAACGTCACTAGCTG GGGTGTGTATGGCTCACACGTAGGCCAGGCTGCCCTAGGCTTGGTGTGCAAGGGAggggcccc tacttacttgtggcctgtcccctcgtgaatgtgtctcatgtccccagtggggtttttcagtgagggtcatggtctccaggatgcacaaggctTT GTGCCAGAATTGCTTGGAATTGCCTAGTTCTGGAAGGCTGGTTGGCCAACTCTGGCCTCCG GCTTTTCCTTTGGGAATTTCCCTTGAAGGTGGGGTTG GTAGACAGATCCAGGCTCACCAGTC CTGTGCCACTGGGCTTTTGGC[G/A]TTCTGCACAAGGCCTACCCGCAGATGCCATGCCTGCT CCCCCAGCCTAATGGGCTTTGATGGGGGAAGAGGGTGGTTCAGCCTCTCACGATGAGGAGG AAAGAGCAAGTGTCCTCCTCGGACATTCTCCG'XIGTAAGAGGAGCAGGCATTGTCCCGTCCC AGCTTGATCCTCAGCCTTCTTTCATCCTTGGCCGCGACATGCTCCCAGGCCTGGGGTCAGAT GGGGAGTGCTGACTCTGTTTCTGGGCTGTTTTCTGGGGAGAATGGGTCGGCGGGTTTTTTTC CCCAGGACCTGGGCAGGGTCAATGGTGGGGGCCGCTGTCGCATCCTTGGCTGGTGTTTCC ACAGCTGAGAACCACTCCAGGGCCAAGCCCAGAGCTTATTCTACCCTTTTTTGTCCTCTCTTC CCCTGTCCTCGGCCACCCCACCCTCTTGGCTCCTCTGCTTAGATGTGGGCACAAGGAGGAG AACTCCTTGGCCTGAGAGAACTACCTTAGATCCTGGCTTCCAGTGGCCTCTGCAGGGGGGT ACACCCTCTCTCCCAAGCAGCCAGACACACAAGTAACCTCATTGCCTCAGTTTCCCCATCTG ACCAGCACAGGGC

94. >NOD2_EXON2

GGCTAATTTTTGTATTTTTAGTAGAGACAGCGTTTCACCGTGTTGGCCGGGCTGGTCTAGCG CTCCTGATCTCAAGTGACCTTGGGAGATCTCTTGCTCCTAATATTACCTCAAGCCTTTTTAAA CGTTTTAAGCCGGAGACCAAGCATGGATATGGGAGTTAGGGGTCTTGATTTAATTCTTGGTT GCTTCAAACTCTGTGGAACCTTGAGGTGTTTCTTGCCTTCTCTGGGTCTCAATTTTCACATCT ATATGGTGGGGAGCTTGGATTGGGTAATGTCTGAGGCTAGAACCATGGCCAACTCGGGTTC TGCTGGGGCTGACTTGCCCTGGCCTTCCCTGACCACCCTGCATCTGGCTTCTGGAGAAG[T/ G]CCC[G/ηCACTGACCTTGTTCTCCTCCCCAG[GTTGTGAAATGTGCTCGCAGGAGGCTTTTC AGGCACAGAGGAGCCAGCTGGTCGAGCTGCTGGTCTCAGGGTCCCTGGAAGGCTTCGAGA GTGTCCTGGACTGGCTGCTGTCCTGGGAGGTCCTCTCCTGGGAGGACTACGAGGGCTTCCA CCTCCTGGGCCAGCCTCTCTCCCACTTGGCCAGGCGCCTTCTGGACACCGTCTGGAATAAG GGTACTTGGGCCTGTCAGAAGCTCATCGCGGCTGCCCAAGAAGCCCAGGCCGACAGCCAG TCCCCCAAGCTGCATGGCTGCTGGGACCCCCACTCGCTCCACCCAGCCCGAGACCTGCAGA GTCACCGGCCAGCCATTGTCAGGAGGCTCCACAGCCATGTGGAGAACATGCTGGACCTGGC ATGGGAGCGGGGTTTCGTCAGCCAGTATGAATGTGATGAAATCAGGTTGCCGATCTTCACAC CGTCCCAGAGG GTGAGGCACTCCTGGTGTGCATCACAGAGTTCTCAGGAAAGGGGTGCTTA GTCACCAAGACTGATTTGTCCTCATGAAGTCAGCCTGTGGGGTAACTTGGTCCATGGGATTT CCCCTAAAAAGGTAGCCAGGCAGGTAAAATTTGCTCTTGACTCTTGGCAGGAAACGTACAAC TCTTTCTTTCTTCTTTTCTTTTCTTTTTCTCACTCTGTTACCCTGGCTAGAATGCAGTGGCACA ATCATAGCTCACTGTAGCCTTGAATTCCTGCGCTCAAGTGATCTTCTGGCCTTAGAGTAGCTG GGACTACGGCTGCTGTACCACCATGAACAGCTAATTTTTTTTTTTTCTTTTAGAGATGGGGTG TTGCTATGTTGCCCAGGCTGGTCTCCAGCTCCTGGCTTTAAGCAATCCTCCCGCCTTGGCCT CCCAAACTGTTGGGATTGCAGGCATGAGCCACTTTGCCTGGCCAACAGAACACTTCTG

95. >NOD2_EXON3

CAGGTGCATGGGCAGGTTAGGAGTTTAGTTTTGAATATGTTGGAGGTGTTTATGAAACTTTTA AGTGGAGATGGAAAATAGGCAGTTGGATGTGCAAGTCCAGGGTTCAGGGAGACAGTTCAGG CTGGAGATGAAGATGTGGGAGTCTGAGGAGAGATTGTATTCAAATATTCAATCCATGAGACT TGATGAAATCACTTCTCTTCCAAATGATTTACAGCCTGCAGAATCATTTTCCCTATCTTTGTAG GTTTATGTCTTCATTTTGTTTCATTTATTTTTCAGTTATTCACTGTTTTAGTGAGTTTTGAGTAG GAGCCAGATTGGATGCATGCGTTCAATTCACCATCCAACACTGTATTAACTACTTGAAACTCA TGTGGTTGTTCGGTTGTTTTTTTGACCTTTTATTCTGGATGGAAGAGAGATGCTTATGAAGTT GCAGTAATCAGTAAGCCTTCCCACATTGCTCCATCAGCCTTCCTGGAAGAATAATGTCTTCTG CCTTTCCTGTAG[GCAAGAAGGCTGCTTGATCTTGCCA[C/T]GGTGAAAGCGAATGGATTGGC TGCCTTCCTTCTACAACATGTTCAGGAATTACCAGTCCCATTGGCCCTGCCTTTGGAAGIGTA GGTGTATGTTCTCAGTTAATCAGAAAGGGAAGGGCAGTCAGTGCAGATCCATGGTTAAGAGC AGAACACACCTCGGTTAACATCCCATATGCTGGCAGTATAGCCTCCCTATGACTCAATTTCCT TGTTTTAAGGCTAGCACCACCCCGTCTCATTGGGATTTTGGGAGCATTAAAAGGACAAAAGC GTGTAATGTTAGCTATTAGCTTTCATTATCTCCCACACAGTATACTGACAATTGGGCTACCATA TATTGAGGGCTAACTAAAGGTGTTACTTACCATCCAAACTCTCATTATCTGTACCGAAAAGAT ATGGACACATGTTTTGAGTTAGGGCTGGTATCTCTTGATCTCTGAAATTTAGCAGCTCACAAT GGGAAACTCAAGAACCAAGTGGATCTAGAGACTCTGGTATCCCTCAGTGCCCAGGGTCACC ACCCAAACTCAGGAACAGGAGGGGCTTGGACCGCACC

96. >NOD2 EXON4 ACCCCGAGGCCTTCCCTTGCTAGGTCCACCCAGATCAATCAGGATCATCTCCCCATCTCGAA GTTTAACTTTATCACATCTCAGAGTTCCTTTTGCCACGTAAGGTAACATATTCACAGGTTCTGA GAATCCGGACATGGACATCTTTGAGGGTCTATTGTTGTGCCTACTATATCCATGAATAATAAT GATAATAAGCACCATTTTTTGAGAGTTTGCCATGTCAGATATTCTTTTAAACTGTATTTTATCTC GCTGCCTCCTGAAAAAATCCTTCCAGGTGTATATTGTCCCCATTTTTACAGATGAGAGAACTG AGGCCCAGAAAGGCTAAATGGCTTGCCCAAGTGTATGGTGGACCCAGGTTTTCAAACTCAG GTGTGTCTGGCTTCAGAGACTGGGCTCCTGAGCCCTTAAGCCCTTTGTTCCCCTTTAGAAAA AGTCACCTGAGGCTGAGTGGTGAAGGGATTTATCCAAAGCCACCCGGCCACTATGGCAGGA CAGATATCAGAATACAGGTCTTCCGATCCCAGCCCAGAGCCCCTTCCCGTCATCTAGAACTC CTCCTGGTGTCAGTAATGATAACGGCAGTCACTGATGTCTTTTGAGCACTTACTTTGTGTTGA GCACTTACACTGTGCTAAGCACTTGACATAGGTCATCTTAGTTGATCCGTGTAAAACTCTGTG AGGTAGTGACCAACATTTCTCCCACCTTACAGAGGTGGAAACTGAGGGTTAGGAAGTTTCCT TGACTGTCCTCAAAGTGCACAGCTTGTGAATGGAGGAGCCAGGATGGGCGCCCGCTGGCTC TCCTATCCCTTCAGTTATGTCAGCGTCCCCCGCAGCAGCCCATTGTCTGGTTAGGTCCCGTC TTCACCATGGTGCCACCTTCATCTGCCTCTTCTTCTGCCTTCCAG[CTGCCACATGCAAGAAG TATATGGCCAAGCTGAGGACCACGGTGTCTGCTCAGTCTCGCTTCCTCAGTACCTATGATGG AGCAGAGACGCTCTGCCTGGAGGACATATACACAGAGAATGTCCTGGAGGTCTGGGCAGAT GTGGGCATGGCTGGA[C/T]CCCCGCAGAAGAGCCCAGCCACCCTGGGCCTGGAGGAGCTCT TCAGCACCCCTGGCCACCTCA[A/G]TGACGATGCGGACACTGTGCTGGTGGTGGGTGAGGC GGGCAGTGGCAAGAGCACGCTCCTGCAG[C/T]GGCTGCACTTGCTGTGGGCTGCAGGGCAA GACTTCCAGGAATTTCTCTTTGTCTTCCCATTCAGCTGCCGGCAGCTGCAGTGCATGGCCAA ACCACTCTCTGTGCGGACTCTACTCTTTGAGCACTGCTGTTGGCCTGATGTTGGTCAAGAAG ACATCTTCCAGTTACTCCTTGACCACCCTGACCGTGTCCTGTTAACCTTTGATGGCTTTGACG AGTTCAAGTTCAGGTTCACGGATCGTGAACGCCACTGCTCCCCGACCGACCCCACCTCTGT CCAGACCCTGCTCTTCAACCTTCTGCAGGGCAACCTGCTGAAGAATGCCCGCAAGGTGGTG ACCAGCCGTCCGGCCGCTGTGTCGGCGTTCCTCAGGAAGTACATCCGCACCGAGTTCAACC TCAAGGGCTTCTCTGAACAGGGCATCGAGCTGTACCTGAGGAAGCG[C/T]CATCATGAGCCC GGGGTGGCGGACCGCCTCATCCGCCTGCTCCAAGAGACCTCAGCCCTGCACGGTTTGTGC CACCTGCCTGTCTTCTCATGGATGGTGTCCAAATGCCACCAGGAACTGTTGCTGCAGGAGG GGGGGTCCCCAAAGACCACTACAGATATGTACCTGCTGATTCTGCAGCATTTTCTGCTGCAT GCCACCCCCCCAGACTCAGCTTCCCAAGGTCTGGGACCCAGTCTTCTTCGGGGCCGCCTCC CCACCCTCCTGCACCTGGGCAGACTGGCTCTGTGGGGCCTGGGCATGTGCTGCTACGTGTT CTCAGCCCAGCAGCTCCAGGCAGCACAGGTCAGCCCTGATGACATTTCTCTTGGCTTCCTG GTGCGTGCCAAAGGTGTCGTGCCAGGGAGTACGGCGCCCCTGGAATTCCTTCACATCACTT TCCAGTGCTTCTTTGC[C/T]GCGTTCTACCTGGCACTCAGTGCTGATGTGCCACCAGCTTTGC TCAGACACCTCTTCAATTGTGGCAGGCCAGGCAACTCACCAATGGCCAGGCTCCTGCCCAC GATGTGCATCCAGGCCT[C/ηGGAGGGAAAGGACAGCAGCGTGGCAGCTTTGCTGCAGAAG GCCGAGCCGCACAACCTTCAGATCACAGCAGCCTTCCTGGCAGGGCTGTTGTCCCGGGAGC ACTGGGGCCTGCTGGCTGAGTGCCAGACATCTGAGAAGGCCCTGCTC[C/T]GG[C/ηGCCAG GCCTGTGCCCGCTGGTGTCTGGCCCGCAGCCTCCGCAAGCACTTCCACTCCATCCCGCCAG CTGCACCGGGTGAGGCCAAGAGCGTGCATGCCATGCCCGGGTTCATCTGGCTCATCCGGA GCCTGTACGAGATGCAGGAGGAGCGGCTGGCTCGGAAGGCTGCACGTGGCCTGAATGTTG GGCACCTCAAGTTGACATTTTGCAGTGTGGGCCCCACTGAGTGTGCTGCCCTGGCCTTTGT GCTGCAGCACCTCCGGC[G/A]GCCCGTGGCCCTGCAGCTGGACTACAACTCTGTGGGTGAC ATTGGCGTGGAGCAGCTGCTGCCTTGCCTTGGTGTCTGCAAGGCTCTGTA]GTGAGTGTT[A/ qCTGGGCATTGCTGTTCAGGTATGGGGGAGCACCATCAAGGCTAAGTGTGGGAGCACCGA GCTGGGCTCTAGAAGTCTGGGCCCAGCTTCGCCTCTGCCACCCTGCTTTGCAACACTGCCC AGATCCCTTCCCTTCTGGGCCTTAATTTCAATATGTGATGATGACAGCCACACTTTATTGACT GGCCTATGTGCTGGGTCTGGTGCTATGCTTTCCGGAATGACCTCATCTAATCTCTACAACCA CCCTGGCGGGTAGGCAGGAATGTTATTATCTCCATTATCCTTGACTTGAGGCTCAGAGAAGT GAAGTAACTTGTCCAGGAAATGGCAGAGCTGGGGTTCACAAATTGCATCATTCTGATTACAG GTTTTCTGCCTCCCACCAGTCTATGGATACACTTCAGAGGCTCCCTGAAAACCTTGAGGTCA CTTGCAGAAAGTTTTGTGTAGTATGTGTCCGTATCAGGAACAACACCAAATCAGAGGTGACTT GTGCCCCATCAGAGACTTTAACACCCCAACCAGATGGGAATTTCAGGACCCAAGAAATAGAA AGTGGCTGCAGGGTTACAACTACTGTTGGATTCCTGAGGTAGCACAGTGTCCAAACAGGATT TCAGCACTACCCGTATTGCTTAGAGCCCCAGCCAAAGATGTGAGGTTTTGCCCTTTGGAGAA TCTGTGCCCCTGAACTCGGGGGCCTCTTTCCACATCTTGGGGGCAGGCAAGGGCAGAGGGT GTGCCTAGGCCTGCGGATCAGCATGCGACAGATTCCCCAACATCCTTCCAGCTTGAAAGGG GAT

97. >NOD2_EXON5

TCATCCAGCTGGTCTACTGTCTGCTGACCTAGATGATGGTAAATTGTCCCCAGGGGTAGCCT GTCTAGTTCAGGCTGCACCTTTCGCATATATCAGCTCCTTTCCACCATCATCCCCTTTGTGAG GCTGCTGTGATTATCATGTTCCTTTTGCAGAGATGGAAACATTGCCTCAAATTAGCTCTGTCA TTTCCTAAGGATTCCAGGGTTCTTTAGTAGGGGGTCTGGATCCTACGTCCTGGGCCATCCCC ATCATAGTGCACCACGTCACCTCCCTGGCCAGGGACCGTGGGGTCTCCACTTTTTTGGGGT GCTCCATCTATGCAGGGTTTCCTGGAAGCACAGATGCTGGCACTTCAGGGATGAATGAAAGT CTTTTTGGGGGATTTGTAGATTTTTTTCTTGTCTTACTAGCTCCATTTTCAAATGTATTTATTTT GTCTCTTTAG[TTTGCGCGATAACAATATCTCAGACCGAGGCATCTGCAAGCTCATTGAATGT GCTCTTCACTGCGAGCAATTGCAGAAGTTAGC]GTAAGTCAGCCTGGGCTGTGGACAATGGG CTCCAAGTGCCCTGGTCTCACCCCAGGTCGTGCAGCCTGGGAAGCTGTGAGTGATGGGCTG GGGCAGGGGCTGTTTGCATGATGGGGGGTGCAGGTGATTCCTGCCCAGAGGGGAAGGGCA ACCCTGGGATTTGGTGCTCACTGTCCAATGTGCTTTGCTTCTGTGTCTCCTCTCTTCTGGAAC TGAACAGTCTATTCAACAACAAATTGACTGACGGCTGT[G/A]CACACTCCATGGCTAAGCTCC TTGCATGCAGGCAGAACTTCTTGGCATTGAGGTGAGCCCAGGTTTTCCTTATTCCCTGGAAA CTATTTTTTGCCCCATTCCTGAGTCAGTCTGATCTGGTCTTGGCCTGGCACTGCCCACACTG GCTCCTGACCTCCTGATTGAATGCAGGGACAGTGTCTCATTTTAAGCAGGGGTTCTCTAATG CTGTGATCTCCCCAGTAAACTCTGGACTAGCTCTGCTGAGGACTTCCTGTCTTTTGACCTTTA GCCCGTAGGGCAAGAAAGCTTTTCTAGGCCCCTTTCCTTTTCTGTGTCTAAGAGTGTCACAG CTTTCTGGGTTTACTGAGTTCCACGATGCATGTTGAGCTCGTCCTGGTGGGGGAGGCATACA CAGTTACTTGCCACCCCAGCTGTGGCAGCGAGTTGCTGCAACACTCCCAGGAGGTCCTTTC ACCACTCAGAGCATGCAAGGTTTGCAGTCCATCTGGTTCTGCATTTCTGCTACTCCAGTGTCT CCCAGTTTCAACAGGAGTCTCTCTCTCTCCTACCTGATGCCTTTAAATTGCCCCTCTAGCTGG CCGCTGGGTTGGCCTGGCTTCTCTCTCCTTCTCTC

98. >NOD2_EXON6

TCATCCAGCTGGTCTACTGTCTGCTGACCTAGATGATGGTAAATTGTCCCCAGGGGTAGCCT GTCTAGTTCAGGCTGCACCTTTCGCATATATCAGCTCCTTTCCACCATCATCCCCTTTGTGAG GCTGCTGTGATTATCATGTTCCTTTTGCAGAGATGGAAACATTGCCTCAAATTAGCTCTGTCA TTTCCTAAGGATTCCAGGGTTCTTTAGTAGGGGGTCTGGATCCTACGTCCTGGGCCATCCCC ATCATAGTGCACCACGTCACCTCCCTGGCCAGGGACCGTGGGGTCTCCACTTTTTTGGGGT GCTCCATCTATGCAGGGTTTCCTGGAAGCACAGATGCTGGCACTTCAGGGATGAATGAAAGT CTTTTTGGGGGATTTGTAGATTTTTTTCTTGTCTTACTAGCTCCATTTTCAAATGTATTTATTTT GTCTCTTTAGTTTGCGCGATAACAATATCTCAGACCGAGGCATCTGCAAGCTCATTGAATGTG CTCTTCACTGCGAGCAATTGCAGAAGTTAGCGTAAGTCAGCCTGGGCTGTGGACAATGGGC TCCAAGTGCCCTGGTCTCACCCCAGGTCGTGCAGCCTGGGAAGCTGTGAGTGATGGGCTGG GGCAGGGGCTGTTTGCATGATGGGGGGTGCAGGTGATTCCTGCCCAGAGGGGAAGGGCAA CCCTGGGATTTGGTGCTCACTGTCCAATGTGCTTTGCTTCTGTGTCTCCTCTCTTCTGGAACT GAACAG[1 CTATTCAACAACAAATTGACTGACGGCTGT[G/A]CACACTCCATGGCTAAGCTCCT TGCATGCAGGCAGAACTTCTTGGCATTGAG_jGTGAGCCCAGGTTTTCCTTATTCCCTGGAAAC TATTTTTTGCCCCATTCCTGAGTCAGTCTGATCTGGTCTTGGCCTGGCACTGCCCACACTGG CTCCTGACCTCCTGATTGAATGCAGGGACAGTGTCTCATTTTAAGCAGGGGTTCTCTAATGC TGTGATCTCCCCAGTAAACTCTGGACTAGCTCTGCTGAGGACTTCCTGTCTTTTGACCTTTAG CCCGTAGGGCAAGAAAGCTTTTCTAGGCCCCTTTCCTTTTCTGTGTCTAAGAGTGTCACAGC TTTCTGGGTTTACTGAGTTCCACGATGCATGTTGAGCTCGTCCTGGTGGGGGAGGCATACAC AGTTACTTGCCACCCCAGCTGTGGCAGCGAGTTGCTGCAACACTCCCAGGAGGTCCTTTCA CCACTCAGAGCATGCAAGGTTTGCAGTCCATCTGGTTCTGCATTTCTGCTACTCCAGTGTCT CCCAGTTTCAACAGGAGTCTCTCTCTCTCCTACCTGATGCCTTTAAATTGCCCCTCTAGCTGG CCGCTGGGTTGGCCTGGCTTCTCTCTCCTTCTCTC

99. >NOD2_EXON7

TCTGGGGCTTCTCCGAAGCTCTCCGAGGTGTCTGGATTCAGTTGCAGCAGGAGCCTTCCTT GCTGGGATCTTCCCCCACCCCTAGCCTTGGCCCTCCCTCTCTCCTTCCTTTCTGGAAGGCTC AGTGGGCCCCACCCCTCCCTCCAGCCACCTGGACCTGCCCAGCGCTCTTGTGCAACAGGTA AAGCCTACCTGTAGCAACAACAGATCTGGGAAGGCTGCAGAGGGCACGATGGGGTCTGGAT CGAGGGCGGCTGAGACCAGAGGGAAAGGTGTGACCCTGAGTCACCCTCGCTGTCCCGGGG AAACCACCTCCCAGGACAGCTGCCTACTGTGGCTCCTGCCTGGAATTGTCACACTGCTGTGC AAACAGCGTCCCGCTGCCCCTTTCCCTTTGCTGGGGGAAAATGAAGTTGTGGGAGCCGCTG AGTAAACTAGACCTAGCAGCGAGGGCACCTGATGTGGCTGCTGCCTCCCGGGCAGGTCTTC AATGCTTTCTTCCTGTGTTTCCCTGGCCAGGGCACAGACGGCCCTCCTTTTCTGCCTGCCGC TGTGTTCTCTCAGCCTCCTCTGTCTTCCCTTCCAG[GCTGGGGAATAACTACATCACTGCCGC GGGAGCCCAAGTGCTGGCCGAGGGGCTCCGAGGCAACACCTCCTTGCAGTTCCTGGG1GTA GGTTGGATTCCAGGAAGAGGGACCTGCATGGAGGGGCTTGGGACTTTTGAGGATTTAGGGG CAGGTGAAACTCTTCAGCCAGGAGGCCCCAGAGGCAGCCCAGCTCCAGTGGGGAGGACAA GCCAGGGAGAGAGTGGGCGGCCCTTGACTGCCACCTTCATACTTGGTCTATGCCTGACAAA CAGGAAGTTTGGGATGTTGGGGCTAGGGGAGGACAGTGCCCACGAGCTGGTGACAGGAAG CCCTCTGATCCTCAGGGGGCGCTAGGGCTGTACTTTAGCTGCATATTAAAACCACCTGGAAG CTTCTAAACACTATTGCCAGGCCTCCCACCCCAGACTGATGAAATGCAAATATCTAGGTGCA AGGCCCAGGTATCAGGAGTTTTAAAAAGCTTCCCAGGGGATGTACAGCCAGGGGTGAGGAC CCCTGACCTAAGAAAGAGAAGGAAATGGGGAAGGATAGGAAGGCACCCAGGATAAGAGGG GCTGTGCTAGGTCCCTCGGAGCTCTTGCTCCCTGTAGGACCATGCTAGGGCCTGCCAGGGA GGGGAGTACCCCAACCTGCAGCCCCAGGGTGGGCTTCCTCTGTTTGCTAGGCACCCAGGCT TGCACCTGTGCTGTTTCC 100. >NOD2_EXON8

TTTTGGAAAGGGATGTTTTCAAACTACAGTGAGTCAGAGGAGGATGGCCCAGAAGCTGGGG GAGTTGAAGCTGATGGCGTGAAGGAATTAGGGGTGTTAGGAAGAAGCAGGAGATAAAGAGC TAGCTTGCAGAAGAAGTGTTAGACTTGTTATGGGCAGGTACTGGAGGGTAGCTAAGGACTTG TGGGTGGCAGTTACCAGGAAGCGTATCTGAACTAAGTGTCAGAAAAAGTGTCACAACTGTAA ATTACTCTTGTCAGTGAGTTCCTGTCCTTAAGGGTTAGGGCTGGGTAGCCCTCTACTATTCTC TAAGTCTGTAATGTAAAGCCACTGAAAACTCTTGGGTTAAGTTTGGCCATCCCACCCAAAAGA TGGAGGCAGGTCCACTTTGCTGGGACCAGGAGCCCCAGTGAGGCCACTCTGGGATTGAGT GGTCCTGCCCCTCTGGCTGGGACTGCAGAGGGAGGAGGACTGTTAGTTCATGTCTAGAACA CATATCAGGTACTCACTGACACTGTCTGTTGACTCTTTTGGCCTTTTCAG[ATTCTGG[G/C]GC AACAGAGTGGGTGACGAGGGGGCCCAGGCCCTGGCTGAAGCCTTGGGTGATCACCAGAGC TTGAGGTGGCTCAG]GTAAGCTTCAGAGTCTATCCTGCAGTTTTCTTGGGGAGATCAGGTGAA GAGGGAGGAGCTGGGGCCAGTTCTGAAGGTCTTTGAACTTTATTTCTACCCCACAATGTTAG GCAATGGAGTAAGGAAAAAAGACCATTGGATTTCAAGAGAGGACACTCGAGTCTTTCTGGGT GACTTGGAAATGTCCCTTGTCCTCTCAGGGTTTTGATACAGTATCTGTAAATTGAAGATATTG GGCTGGATCAGGTACATTTTATCTTAAGGACCAATTCCAATCCATTGGTAGTGGGTGCCCAG TGCACCACATTAAAAAGAATTCTAAGGCTGCACCTGGGCTTAAAGAAGAGCACTATAATCAAT TAGTGATGTCTAAAAAAGCTAAAAAAAAAAAAAAAAGAGCACTGCATTCAATTAGTGATGTCTA AA GGGTAGAAAAAAAAAAAAAAAGAAAAAAGAAAGAGCACCGCAATCAATTAGTGATGTCT GAAATGGAGCAGACCAGGAGAGCACCACGAATTTTGCCCTCCATAGGTTAGCTCATCTCTGA GGTCTTTCCCTGCTCTGACATACTTTTGTTCCAT

101. >NOD2_EXON9

AGCTTGAGGTGGCTCAGGTAAGCTTCAGAGTCTATCCTGCAGTTTTCTTGGGGAGATCAGGT GAAGAGGGAGGAGCTGGGGCCAGTTCTGAAGGTCTTTGAACTTTATTTCTACCCCACAATGT TAGGCAATGGAGTAAGGAAAAAAGACCATTGGATTTCAAGAGAGGACACTCGAGTCTTTCTG GGTGACTTGGAAATGTCCCTTGTCCTCTCAGGGTTTTGATACAGTATCTGTAAATTGAAGATA TTGGGCTGGATCAGGTACATTTTATCTTAAGGACCAATTCCAATCCATTGGTAGTGGGTGCC CAGTGCACCACATTAAAAAGAATTCTAAGGCTGCACCTGGGCTTAAAGAAGAGCACTATAAT C TTAGTGATGTCTAAAA GCTAAAAAAAAAAAAAAAAGAGCACTGCATTCAATTAGTGAT GTCTAAAAAGGGTAGAAAAAAAAAAAAAAAGAAAAAAGAAAGAGCACCGCAATCAATTAGTGA TGTCTGAAATGGAGCAGACCAGGAGAGCACCACGAATTTTGCCCTCCATAGGTTAGCTCATC TCTGAGGTCTTTCCCTGCTCTGACATACTTTTGTTCCATGATTACCTCCAG[CCTGGTGGGGA ACAACATTGGCAGTGTGGGTGCCCAAGCCTTGGCACTGATGCTGGCAAAGAAC[G/A]TCATG CTAGAAGAACTCTG]GTGAGTTTGGGGGATTCTCTGCTCTGGGGAAGTGGATCACAATCTCT GTTGATCCCCTGGCCTCATCCATAGGAGCGGTTGTGTGGACAGACAAAGGTGGATGATTGA GTGATTGACTGATTGATTGATTGTGTTTGTCTTTATATGTACTGAGTGGTATGAAGCTTATAGA GCCTGGTATGTACATGCTAATTTTTTTATTTAATAAAATATATGGGTTTGCTGGTTTGGTGACT GCCTCCACATGGCATAAGTGTTAAGAGCACAGACTCTGTAATCAAGCAGGCCGTGATCTTAG GCAAGTTAAATAACAATTTCAGAATCTCAAGTTTCATGTCTGTAAAATGAGGGTAAGAATACTT CCAACCATAAAGGATTTTTGCAAGAATTAGATAAAGTAGTGCCTGTGAAGACCTTAATATAGT GCCTGGCATATTTGTAAGTGCTCCATAAATGTTAAATTAGAATAATGGCAGGGTTACTACTAC TATTACTGCTGCTGCTGCTGCTGCTGCTGCTACAACTACTATAGTACTGTGACTACTACTACT AATAAAGTTTTGTTATTTTAAAGTGATTTTGAGTTCCTAGGAGCACTGGGTAT

102. >NOD2_EXON10

CTATAGAGGTTTAAACAAGGAAAGGGTTTATTTTTTCCTGTATAGGCAGCTGGATGTAGGCAG TGTAGGGTTTGTACAGTGGCTACAAGAGGCCAGGAGGGGTCTCAGCTCTGTCTCATTCTCTT CCTGTTCCATCATTCTTAGCCTGTGACTTCATTCACATGGTTGGTTGTCTCATGATCACAGGA TGGCTGCTCCAGGTGCAGCACTACTTCTGTATTCCCGGATTCGATCTATATACCCAGGAAAG CCATCTGGGTTCTCTCCTTTAAAAAGCATTCCTGGAAGCCCCACCTGTCGACTTCCCCTTATG TATCAACCATGTGTATGTCACTTGACCAACCCACTTGTATGTTGTTTGACCAGCCCTGGCTGC AATGGAGAGTGGGAAATACAGTTTTTTCACCAAGTGCATGGCTGTCCAAATGAAATGAGACTT CCATTAATAAGGAAGAAAGGAAAGATGGAGATCAGGAAGCTGGGGGATCAGGGAACTTATTA CATTG AG AGCCCTTGGAGTGAATTCTCTTGCAAATATGTCCCTGGAATTG AGAATCCCCACAA CGTACTTTATCTGTTCTTTCTTTATCCATGAGTTTGGGTTTTCAGATGTTGGATTTCCTATATG GGGGGCATGTGAGTTCATCATCTTCCATAATCAATGTTGTATCAACTGGATTTTCTCTCTTCTT CTCACCAGICCTGGAGGAGAACCATCTCCAGGATGAAGGTGTATGTTCTCTCGCAGAAGGAC TGAAGAAAAATTCAAGTTTGAAAATCCTGA JGTAAGGAACCCATAAGCAGGAAACAGGACAA TAATTGCTGGCCTTTGGAAGGGGCATTTCTGAATAAGATCTGGGCCGCTCTCCGCTGGGCTA ACTCATGTGAGGTGGCCTGGTAGAACAGCTTGCCTTGGTCTAGGTGGACAAGGATTCCAGT GCAAGTTGTTTATCTGGGAGGTGGTCCCAGTAAATGCTGATAGGAGAGTGGTGAAGTGAGAT GGGGAAGTGAAGGTAACCAATAAAGGGGAGTTATCAAGCCAGTTATCAATGAGGGAAATTGG AGCTCAGTACTCTGGGGCACTCCTGGAGCCAGTGCAGAACACACATGGTCACCTACCCAAC CAATGGGCAAGAAAGCCATGGCATTTATCCACCAACCCTCTGTCCTTCCTATGTTGATGTGC GCTCATGGGGCACTGATTCTCCAGCACTTCCAGCTCACCCTCACCCAGCTGAACATGCTTCT GGGGTCAGGAGAATGGCCTCAGGCAGAGAGTGGAAGGTCTTCTCTGCAAGCAGTGGCTGG GGAGGTGATGTGATGGGGAGTACTGTGGCCTCCTCCAGTGGCTGACTCAGTGGCTTGGGAC TTGTGCCACAAAGAGATGGACAGCTCAGGTGAACATGAACCCACCTAGTGACCATCATGGGT TTGTCAGGGTGCTCTCTGAGGCTGATGCCAAAATTCTTATTTCAAGTAGACCTCAGGAACCC CATCAGAT

103. >NOD2_EXON11

CCGTTTTCATGCTGATGATAAAGATATACCCAAGACTGGGCACTTTATGAAAGAAAGAGTTTT

ATTGAACTTACAGTTCCACGTGGCTGGGGAGGTCTCACAATCATGGCTGAAGGTGAAAGGCA

CATCTCACATGGCAGCAGACAGGAGAAGAGGGCTTGTTCAGGGAAACTCCCCTTTTTAAAAC CATCAGATATCATGAAACTTATTTACTGTAATGAGAACAGGATGGGATTCAATTACCTTCCACT GGGTCGCTCCCACAACACGTGGGAATTCAAGAGATTTGGGTGGGGACACAGCCAAACCATA TCAAGTACTGTGCAAGTGTTTTAGGCATGCAGAGAGTGGTGGGTCTTCCCAGCAAGCAGAGT GTGGGGAGGTAATGGGGGACTGGTGGCTGACTTAATGGCCCAGGACCCATGCCACAAGGA GATGGATGGTGGATGTGAATAGGAGCCTGCTTACACCCATCACAATTTAGATTCTTATGCTC GATGGCACGGGTACTCTTTTAGGCCCATTTTACCAATGAGGAGATTGGGACTAATTTGCTCG AGATCAAAAAAGAAGTGGTGTAGGTGGGATTTAAACCCAGGATGTCTAGCACTAAAATGCAG GTACTTAACCACTATCCTAAGGGAGTGGCTACTTAATTTGATAAACTCATCTAGTGAATGGAA GAGAGACGGTTACATTTCACTGATGGTACTGAGCCTTTGTTGATGAGCTCATTGGGAATCTC AGACATGAGCAGGATGTGTCTAAGGGACAGGTGGGCTTCAGTAGACTGGCTAACTCCTGCA GTCTCTTTAACTGG ACAGTTTCAAGAGG AAAACCAAG AATCCTTGAAGCTCACCATTGTATCT TCTTTTCCAG[GTTGTCCAATAACTGCATCACCTACCTAGGGGCAGAAGCCCTCCTGCAGGC CC[C]TTGAAAGGAATGACACCATCCTGGAAGTCTG)GTAAGGCCCCTGGGCAGGCCTGTTTT AGCTCTCCGAACCTCAGTTTTTCTATCTGTAAAATGGGGTGACGGGAGAGAGGAATGGCAGA ATTTTGAGGATCCCTTCTGATTCTGACATTCAGTGAGAATGATTCTGCATGTGAAGGATCTGA TTCTCTGTCTAAGAAAGAAGTCTTTACCTCTTTAAGTAGGGAGCAATGATTTCATTTTTAAACC TTGACTATTTATTCAGCAACTTCTCTGCTCTATGAGATAGTGTAGGAATGGGGATGTGGTTGA AGAATGAAAAGAAAAGTCAGCTCCCGCCCTCCTAGAAATTGCATCTGCCTTCACAGGTCAAG GATATTGGATCAGACCTTCTGCGGTTCTGAATGGAGATTACACAGGTTAGGAGCAGGTTGCA CAGTGTTTCCAATTCTCTATAATTAAAGCCATAGACTTTCATGTATTGAAAAAAGCAAGAATTG CATTCTTGACAGATTCTTTCATTGCCTTAAAAAGAATGACTAGCCTTGGGAGTCTGGGCAGCT GGGTCCAGTGTTGTAGACTTTCTCTCTGCTGAGCCACAGCTTCAAAGATTTGTCCTTCTTGTT TCCAGGGATCTATTTCTCAGACAATAAGTAAAGGCTTTCCCTGGCCTAATGTGCTGTAAGTGA ATGCTACTATATATGTTCCAGGCACTGGGCTAGAGACTAATATTTAAAAGCCAGGAAATTTCC TATAGAAAATCTATATCTCAGGGTTTTCTCAAAAGAGCTGGGAACTCTGGATGCCCATTCATG ATTCCAGTAGTTAACCAGAGTACAAGAAGGGCTGAGTCTTCTCAGATGGGCAAACC

104. >NOD2_EXON12_UTR

AGAGGTTCAACACCATACCTTGTCTCTCAAAAAATAAAAAATTCAGCTGGGT GCGGTGTAGTTCCTAGCCACTTGGGAGGCTGGGATGGAAGGATCCCTTGAA CCCAGGAGTTCAAGGCTGCAGTGGGCCATGATTGCATCACTGCACAGGCGA CAGAATTAGATCCCATCTCTTAAAAAAATAAAAAATTTAAAAGTGACTTCAAAA ATCTATGCTGTGATGGAGAGATTTTTCCTTCTGTATGATTGTGATAGCTCTGT GGCCTATGACGTCATCAGGTTCTGGGCAAAGTGTAGGTTTTCTGTTTCTTTG TTTTTGAAACCATTGCACAGTCCTAAGAAACATCACATTCTGGGTCCTGGGC ACCAGCCAACATGAGGTTGATATTTTAAGGGGTCTGATGTTATTTGCTGCCT GTTGATGGAACTTGGGAGGGCACCAGGGTTTGCTCATTGCATTCTTGACAG ATTCTCTTATTGCCTTAAAAAGAATCACTGGCCTTGGGGAGTCTGTGGCTGG CTGGGTGCAGTGTTGTGGACTCTCTCTGCAGAGTCATGGAGCCTTGTTCAG AATGCTTCCTGAGCTGCCCTGGTTGGCCAAGGGTAAAAACAGCCCTGACTT CCCTGCAAGAAACACTGCAGCTGGGCCAGAGAGTCAGCCCATCCCAGGCAT GGGTTTAAAAAGTGGAGGCTTTTGTTTGAAAGCCCTGCTCTAATTTTGTCCT CACTCAAACCTCTGTTCACTTGATCTGCTTTAG[GCTCCGAGGGAACACTTTC TCTCTAGAGGAGGTTGACAAGCTCGGCTGCAGGGACACCAGACTCTTGCTT TGAAGTCTCCGGGAGGATGTTCGTCTCAGTTTGTTTGTGAGCAGGCTGTGA GTTTGGGCCCCAGAGGCTGGGTGACATGTGTTGGCAGCCTCTTCAAAATGA GCCCTGTCCTGCCTAAGGCTGAACTTGTTTTCTGGGAACACCATAGGTCACC TTTATTCTGGCAGAGGAGGGAGCATCAGTGCCCTCCAGGATAGACTTTTCC CAAGCCTACTTTTGCCATTGACTTCTTCCCAAGATTCAATCCCAGGATGTACA AGGACAGCCCCTCCTCCATAGTATGGGACTGGCCTCTGCTGATCCTCCCAG GCTTCCGTGTGGGTCAGTGGGGCCCATGGATGTGCTTGTTAACTGAGTGCC TTTTGGTGGAGAGGCCCGGCCTCTCACAAAAGACCCCTT[A/C]CCACTGCTC TGATGAAGAGGAGTACACAGAACACATAATTCAGGAAGCAGCTTTCCCCATG TCTCGACTCAT[C/T]CATCCAGGCCATTCCCCGTCTCTGGTTCCTCCCCTCCT CCTGGACTCCTGCACACGCTCCTTCCTCTGAGGCTGAAATTCAGAATATTAG TGACCTCAGCTTTGATATTTCACTTACAGCACCCCCAACCCTGGCACCCAGG GTGGGAAGGGCTACACCTTAGCCTGCCCTCCTTTCCGGTGTTTAAGACATTT TTGGAAGGGGACACGTGACAGCCGTTTGTTCCCCAAGACATTCTAGGTTTG CAAGAAAAATATGACCACACTCCAGCTGGGATCACATGTGGACTTTTATTTC CAGTGAAATCAGTTACTCTTCAGTTAAGCCTTTGGAAACAGCTCGACTTTAAA AAGCTCCAAATGCAGCTTTAAAAAATTAATCTGGGCCAGAATTTCAAACGGC CTCACTAGGCTTCTGGTTGATGCCTGTGAACTGAACTCTGACAACAGACTTC TGAAATAGACCCACAAGAGGCAGTTCCATTTCATTTGTGCCAGAATGCTTTA GGATGTACAGTTATGGATTGAAAGTTTACAGGAAAAAAAATTAGGCCGTTCC TTCAAAGCAAATGTCTTCCTGGATTATTCAAAATGATGTATGTTGAAGCCTTT GTAAATTGTCAGATGCTGTGCAAATGTTATTATTTTAAACATTATGATGTGTG AAAACTGGTTAATATTTATAGGTCACTTTGTTTTACTGTCTTAAGTTTATACTC TTATAGACAACATGGCCGTGAACTTTATGCTGTAAATAATCAGAGGGGAATA AACTGTTGAGTCAAAACJAGCCATCTTCCTTGTGACCAAACATTTAAAAATATT CTGGCTGGGCACAGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCC GAGGTGGGCAGATCACCTGAGGTTGGGGGTTTGAGACCAACCTGACCAACA TGGAGAAACCCTGTCTCTACTAAAAATAGTGGAGGTTGCAGTGAGCCAAGAT CACACCGTTGT

Claims

WHAT IS CLAIMED IS:

1. An isolated polynucleotide comprising a nucleic acid sequence selected from the group consisting of: (a) a nucleic acid sequence comprising at least 15 contiguous nucleotides of a nucleic acid sequence selected from the group consisting of the variant sequences of Table 4, and (b) a nucleic acid sequence that is fully complementary to a nucleic acid sequence of (a).

2. An isolated polynucleotide according to Claim 1, wherein the polynucleotide is a nucleic acid probe for the detection of loci associated with multiple sclerosis.

3. An isolated polynucleotide according to Claim 2, wherein said polynucleotide is conjugated to a detectable marker.

4. An array of polynucleotides comprising: two or more isolated polynucleotides comprising at least one polynucleotide of Claim 1.

5. A method for detecting in an individual a polynucleotide, the method comprising:

(a) contacting a nucleic acid sample from an individual with a polynucleotide probe, wherein said polynucleotide probe comprises a nucleic acid sequence selected from the group consisting of:

(i) a nucleic acid sequence comprising at least 15 contiguous nucleotides of a nucleic acid sequence selected from the group consisting of the variant sequences of Table 4; and,

(ii) a nucleic acid sequence that is fully complementary to a nucleic acid sequence of (i); and,

(b) detecting specific hybridization between said polynucleotide probe and said nucleic acid sample as indicative of the presence of a multiple sclerosis polynucleotide in said nucleic acid sample.

6. A method according to Claim 5, wherein said detecting step comprises detecting hybridization between said nucleic acid sample with an array of polynucleotides comprising: two or more isolated polynucleotides comprising at least one polynucleotide probe of Claim 5.

7. The method of Claim 5, wherein said nucleic acid sample is a genomic DNA sample.

8. The method of Claim 5, wherein said nucleic acid sample is a RNA sample.

9. A computer-readable storage medium for storing data for access by an application program being executed on a data processing system, comprising: a data structure stored in the computer-readable storage medium, the data structure including information resident in a database used by the application program and including: a plurality of records, each record of the plurality comprising information identifying a polymoφhisms shown in Table 4.

10. The computer-readable storage medium of claim 9, wherein each record has a field identifying a base occupying a polymoφhic site and a location of the polymoφhic site.

11. The computer-readable storage medium of claim 10, comprising at least 10 records, each record comprising information identifying a different polymoφhism shown in Table 4.

12. A signal carrying data for access by an application program being executed on a data processing system, comprising: a data structure encoded in the signal, said data structure including information resident in a database used by the application program and including: a plurality of records, each record of the plurality comprising information identifying a polymoφhism shown in Table 4.