KR101911074B1 - Single Nucleotide Polymorphisms Determining Trypanosomiasis-resistance of N'Dama breeds and Use Thereof - Google Patents

Abstract

The present invention provides a kit for sorting sleeping sickness resistance cow N′Dama varieties and a method for detecting N′Dama variety-specific markers. The present invention provides a difference in genome pattern between N′Dama and other livestock varieties using a combined method based on theoretical and statistical approaches to diverse varieties of various small breeds. The present invention relates to ossification control, nervous system and immune system development which may be involved in evolution of N′Dama-specific phenotypes. The above shows insight into detecting genetic-specific genetic signals from a genome.

Description

N'Dama breed-specific single nucleotide polymorphism and its use (Single Nucleotide Polymorphisms Determining Trypanosomiasis-resistance of N'Dama breeds and Use Thereof)

The present invention relates to sleep apnea resistant N'Dama variety-specific single nucleotide polymorphisms and uses thereof.

Cows are an economically and socially important resource in Africa. Approximately 150 unique cattle breeds in sub-Saharan Africa [1]. The unique African cattle that have lived in isolated areas for a long time have been under environmental pressure. This imposes limitations on strong adaptation and allows individuals to adapt to the harsh environment [2]. Some varieties, in particular, were resistant to fatal local diseases that reduced survival and productivity [3]. In addition to environmental factors, artificial selection has also led to several breeds of expression traits that improve the production of dairy products and meat quality [4, 5].

Rapid outbreaks of large-scale genetic variation inventory led to identification of genes or loci that regulate phenotypic traits [6]. Long-range genomic analysis ultimately improves understanding of the role of specific genetic signatures to adapt to the environment. Several genome analyzes have recently been conducted to study diversity and genetic background in various African cattle breeds [7, 8, 9, 10, 11]. For example, to improve the production of sustainable livestock, the SNP analysis, which is prevalent in genomes in small African zebu, has found candidate positions [11]. The discovery of this location on the genome has enabled the discovery of genetic diversity and functional annotation of the genome that are associated with the phenotypic traits of a particular variety. Trypanosomes are a major concern that can lead to serious economic losses and health problems in Africa [12]. Sleeping sickness is an infectious agent that is transmitted by a tsetse fly. This can cause fatal diseases in mammals, including humans and livestock. In particular, T. congolense, T. vivax, and T. brucei are major African pathogenic sleeping pills of cattle [12]. Most cows, including non-African and some African varieties (Boran, Kenana and Ogaden), are very susceptible to sleeping sickness. Several studies have shown that the tolerance of bovine susceptibility to bovine spongiform encephalopathy is inherently different when exposed to natural infections caused by wild-type flies [13, 14]. Specifically, N'Dama varieties are naturally less susceptible to sleeping sickness than other cows, so they can survive better and maintain high productivity in sleeping-sick areas [13, 15]. Trypanotolerant varieties, including N'Dama, are also less susceptible to other important infectious diseases such as helminthiasis [13], ticks and tick-borne disease [3], and streptothricosis [ 16].

Most studies on resistance to bovine susceptibility have focused primarily on the comparison of N'Dama and Boran varieties. However, there are not many comparative studies between N'Dama and other susceptible varieties. Here we focused on the genetic diversity analysis between N'Dama and Ogaden livestock to find the N'Dama specific genetic traits. Ogaden cattle are one of the representative varieties that play a valuable economic role, including the production of beef and dairy products, but they are known to be susceptible to sleeping sickness [2].

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

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The present inventors have sought to identify a genetic signature of the N'Dama variety resistant to sleeping sickness that exhibits a high survival rate under harsh environmental conditions. As a result, the present invention was accomplished by identifying SNPs specific for N'Dama resistant to sleeping sickness through comparative genome-wide analysis of cows of various breeds.

Accordingly, it is an object of the present invention to provide a kit for screening sleep apnea resistant N'Dama varieties.

Another object of the present invention is to provide a method for detecting a sleeping dog-resistant N'Dama variety-specific marker.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, the present invention provides a polynucleotide comprising a single nucleotide polymorphism site of the USH2A (Usher syndrome 2A) gene at position 13720 of SEQ ID NO: 1 (GenBank SNP database rs110332182) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having G (guanine) at the 13720th nucleotide position of the first sequence of the Sequence Listing and a single base polymorphic site having G (guanine) at the 4520th amino acid of SEQ ID NO: Valine. ≪ / RTI >

According to another aspect of the present invention, there is provided a single base polymorphism (SNP) region of ACAD9 (acyl-CoA dehydrogenase 120fa0mily, member 9) gene, a single base of the 1558th position (GenBank SNP database rs135578554) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences comprising a polymorphic site.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having C (Cytosine) at the 1558th nucleotide position of the second sequence of the sequence listing and arginine (SEQ ID NO: Arginine).

According to another aspect of the present invention, there is provided a single nucleotide polymorphism (SNP) region of the archaelysin family metallopeptidase 1 (AMZ1) gene, comprising 10-100 nucleotide polymorphisms Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to a continuous nucleotide sequence.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having A (Adenine) at the 610th nucleotide position of the sequence listing 3 and a 204th amino acid sequence of SEQ ID NO: Isoleucine).

According to another aspect of the present invention, the present invention encompasses a single nucleotide polymorphism (SNP) region of the archaelysin family metallopeptidase 1 (AMZ1) gene, a single nucleotide polymorphic site of the 340th position of SEQ ID NO: 3 (GenBank SNP database rs109821810) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences that hybridize to the nucleotide sequence of the N'Dama variety.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphic site having A at position 340 of the nucleotide sequence of SEQ ID NO: 3 and asparagine at position 114 of SEQ ID NO: AMZ1 protein.

According to another aspect of the present invention, there is provided a method for detecting a single nucleotide polymorphism (SNP) region of a cytidine and dCMP deaminase domain containing 1 (CDADC1) gene, Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences comprising a polymorphic site.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphic site having C at position 1438 of nucleotide position in the sequence listing 4 and a nucleotide polymorphism site in which the 480th amino acid of SEQ ID NO: 20 is Proline CDADC1 protein.

According to another aspect of the present invention, the present invention relates to a polynucleotide polynucleotide polynucleotide (polynucleotide polymorphism) having a single nucleotide polymorphism (SNP) region of EML1 (echinoderm microtubule associated protein like 1) Lt; RTI ID = 0.0 > N'Dama < / RTI > variety selection kit comprising a primer or a probe that specifically binds to two consecutive nucleotide sequences.

According to a specific embodiment of the present invention, the N'Dama varieties have a single base polymorphism site having A at position 1765 nucleotide of the sequence listing 5 and EML1 protein wherein the 589th amino acid of SEQ ID NO: 21 is isoleucine .

According to another aspect of the present invention, the present invention provides a method for detecting a single nucleotide polymorphism (SNP) region of an EOMES (eomesodermin) gene comprising 10-100 contiguous nucleotide sequences comprising a single nucleotide polymorphic site at position 763 of SEQ ID NO: Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to N'Dama.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having A at position 763 of the nucleotide sequence of SEQ ID NO: 6 and an EOMES protein wherein the 255th amino acid of SEQ ID NO: 22 is arginine .

According to another aspect of the present invention, there is provided a polynucleotide comprising a single nucleotide polymorphism (SNP) region of an opioid binding protein / cell adhesion molecule-like (OPCML) gene, Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having A at the 157th nucleotide position of SEQ ID NO: 7 and a 53rd amino acid at the 53rd nucleotide position of SEQ ID NO: OPCML protein.

According to another aspect of the present invention, there is provided a single base polymorphism (SNP) region of a PIK3C2G (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 gamma) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences containing a nucleotide polymorphic site.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having G at the 70th nucleotide position of the sequence listing 8 and a PIK3C2G protein having the 24th amino acid valine of SEQ ID NO: .

According to another aspect of the present invention, the present invention provides a single base polymorphism (SNP) region of a PIK3C2G (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 gamma) gene at position 347 of SEQ ID NO: The present invention provides a kit for screening sleep apnea resistant N'Dama varieties comprising a primer or a probe specifically binding to 10-100 consecutive nucleotide sequences containing a single nucleotide polymorphic site of the nucleotide polymorphism region of the nucleotide polymorphism in the nucleotide sequence of the nucleotide polymorphism region of the nucleotide sequence of the nucleotide polymorphism region.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having A at position 347 nucleotide position of SEQ ID NO: 8 and a nucleotide polymorphism at position 116 of SEQ ID NO: PIK3C2G protein.

According to a further aspect of the present invention, the present invention provides a polynucleotide encoding a single nucleotide polymorphism (SNP) region of the SLIT3 (slit guidance ligand 3) gene, a single nucleotide polymorphic site at position 1814 of SEQ ID NO: 9 (GenBank SNP database rs110101818) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences containing the nucleotide sequence of SEQ ID NO:

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having G at the 1814th nucleotide position of the Ninth Sequence Listing of the Ninth Sequence, and a Serine homologous polynucleotide having the 605th amino acid of the Sequence Listing No. 25 sequence SLIT3 protein.

According to another aspect of the present invention, there is provided a single base polymorphism (SNP) region of a TIGAR (TP53 induced glycolysis regulatory phosphatase) gene, wherein the base sequence polymorphism region comprises a single nucleotide polymorphic site at position 272 of SEQ ID NO: Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to a continuous nucleotide sequence.

According to a specific embodiment of the present invention, the N'Dama variety includes a single base polymorphism site having G at position 272 of the nucleotide position of SEQ ID NO: 10 and a TIGAR protein having arginine at position 91 of SEQ ID NO: .

According to another embodiment of the present invention, the present invention includes a single base polymorphism (SNP) region of the TPST1 (tyrosylprotein sulfotransferase 1) gene, a single base polymorphism site at position 704 of the sequence listing No. 11 (GenBank SNP database rs383100152) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences that hybridize to the nucleotide sequence of the N'Dama variety.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having C at the 704th nucleotide position of the 11th sequence of SEQ ID NO: 11 and a 235th amino acid at position 23 of the sequence listing is Threonine TPST1 protein.

According to another aspect of the present invention, the present invention provides a single base polymorphism (SNP) region of a complementary component 1, r subcomponent-like (C1RL) gene, a single base of the 367th position (GenBank SNP database rs207500281) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences comprising a polymorphic site.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism region having T (Thymine) at the 367th nucleotide position of the sequence listing 12 and a 123 base amino acid sequence of SEQ ID NO: Lt; / RTI > protein.

According to another embodiment of the present invention, the present invention provides a single base polymorphism (SNP) region of a complement component 1 (r subcomponent-like) gene of C1RL Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences containing a nucleotide polymorphic site.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphic site having G at the 559th nucleotide position of SEQ ID NO: 12 and an aspartic acid at position 187 of SEQ ID NO: ). ≪ / RTI >

According to another aspect of the present invention, there is provided a single base polymorphism (SNP) region of a complementary component 1, r subcomponent-like (C1RL) gene, comprising 10 base pairs of a base sequence polymorphism site at position 1344 of SEQ ID NO: Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to -100 consecutive nucleotide sequences.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphic site having C at the 1344th nucleotide position of SEQ ID NO: 12 and Histidine at position 448 of SEQ ID NO: Lt; / RTI > protein.

According to another aspect of the present invention, there is provided a polynucleotide comprising a single base polymorphism (SNP) region of a complement component 1, r subcomponent-like (C1RL) gene and a single base polymorphism site at position 1458 of SEQ ID NO: Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphic site having C at position 1458 nucleotide of SEQ ID NO: 12 and a C1RL protein having asparagine at position 486 of SEQ ID NO: .

According to another aspect of the present invention, the present invention provides a single nucleotide polymorphism (SNP) region of DDX54 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 54) resistant nucleoside N'Dama variety selection kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences comprising a single nucleotide polymorphic site of the nucleotide polymorphism region of SEQ ID NO:

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having A at position 397 nucleotide position of SEQ ID NO: 13 and DDX54 protein serine at position 133 of SEQ ID NO: .

According to another aspect of the present invention, there is provided a polynucleotide encoding a single base polymorphism (SNP) region of NOX5 (NADPH oxidase, EF-hand calcium binding domain 5) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences containing the nucleotide sequence of SEQ ID NO:

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphic site having G at position 1015 nucleotide of SEQ ID NO: 14 and a nucleotide polymorphism at position 339 of SEQ ID NO: 30 in which the 339th amino acid is glycine NOX5 protein.

According to another aspect of the present invention, the present invention encompasses a single base polymorphism (SNP) region of RANBP17 (RAN binding protein 17) gene, a single base polymorphism site at the 160 th position of Sequence Listing 15 (GenBank SNP database rs385712825) Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to 10-100 consecutive nucleotide sequences that hybridize to the nucleotide sequence of the N'Dama variety.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphic site with a T at the 160 th nucleotide position of the sequence listing 15. The RANBP17 has a sequence that is the 54th stop codon (TAG) of Sequence Listing 31 sequence.

According to another aspect of the present invention, the present invention provides a single base polymorphism (SNP) region of the SET binding factor 2 (SBF2) gene, wherein the SNP region comprises 10-100 nucleotide polymorphic sites comprising the single nucleotide polymorphic site at position 4888 of SEQ ID NO: Resistant N'Dama variety screening kit comprising a primer or a probe that specifically binds to a continuous nucleotide sequence.

According to a specific embodiment of the present invention, the N'Dama variety has a single base polymorphism site having A at position 4888 nucleotide position of SEQ ID NO: 16 and SBF2 protein wherein asparagine at position 1630 of SEQ ID NO: .

As used herein, the term " nucleotide " is a deoxyribonucleotide or ribonucleotide present in single or double stranded form and includes analogs of natural nucleotides unless otherwise specifically indicated (Scheit, Nucleotide Analogs, John Wiley, New York (1980); Uhlman and Peyman, Chemical Reviews, 90: 543-584 (1990)).

As used herein, the term " single nucleotide polymorphism (SNP) " refers to the occurrence of a single nucleotide (A, T, C or G) in the genome that is different between members of a species or between individual chromosomes DNA sequence identity. For example, if three DNA fragments of different entities (eg, AAGT [A / A] AG, AAGT [A / G] AG, and AAGT [G / It is called two alleles (C or T), and almost all SNPs generally have two alleles. Within a population, SNPs can be assigned to a minor allele frequency (MAF; the lowest allele frequency in locus found in a particular population). There are variations in the human population, and one common SNP allele in the geological or ethnic group is very rare. Single bases can be changed (substituted), removed (deleted), or added (inserted) to the polynucleotide sequence. The SNP can cause a change in the translation frame.

Single nucleotide polymorphisms can be included in coding sequences of genes, non-coding regions of genes, or in intergenic regions between genes. SNPs in the coding sequence of a gene do not necessarily cause changes in the amino acid sequence of the target protein due to the degeneracy of the genetic code. SNPs that form the same polypeptide sequence are called synonymous (also called silent mutations) and SNPs that form other polypeptide sequences are said to be non-synonymous. Non-consensual SNPs can be missense or nonsense, and mismatch changes produce other amino acids while nonsense changes form non-mature termination codons. SNPs that are not in the protein-coding region can cause gene silencing, transcription factor binding, or non-coding RNA sequences.

As used herein, the term " primer " means an oligonucleotide in which the synthesis of a primer extension product complementary to a nucleic acid chain (template) is induced, that is, the presence of a polymerizing agent such as a nucleotide and a DNA polymerase, It can act as a starting point for synthesis at suitable temperature and pH conditions. Preferably, the primer is a deoxyribonucleotide and is a single strand. The primers used in the present invention may include naturally occurring dNMPs (i.e., dAMP, dGMP, dCMP and dTMP), modified nucleotides or non-natural nucleotides. In addition, the primers may also include ribonucleotides.

The primer of the present invention may be an extension primer that is annealed to a target nucleic acid and forms a sequence complementary to the target nucleic acid by a template-dependent nucleic acid polymerase, which extends to a position where the immobilization probe is annealed, It occupies the area that is annealed.

The extension primer used in the present invention comprises a hybridization nucleotide sequence complementary to the first position of the target nucleic acid. The term " complementary " means that under certain annealing or hybridization conditions the primer or probe is sufficiently complementary to hybridize selectively to the target nucleic acid sequence and is substantially complementary and perfectly complementary , And preferably means completely complementary. As used herein, the term " substantially complementary sequence " as used in connection with a primer sequence is intended to encompass a complete sequence as well as a sequence that is comparable to that of the sequence to be compared, Inconsistent sequences are also included.

The primer should be long enough to be able to prime the synthesis of the extension product in the presence of the polymerizing agent. The suitable length of the primer is determined by a number of factors, such as the temperature, the application, and the source of the primer, but is typically 15-30 nucleotides. Short primer molecules generally require lower temperatures to form a sufficiently stable hybrid complex with the template. The term " annealing " or " priming " means that the oligodeoxynucleotide or nucleic acid is apposited to the template nucleic acid, which polymerizes the nucleotide to form a complementary nucleic acid molecule to the template nucleic acid or a portion thereof .

The sequence of the primer does not need to have a sequence completely complementary to a partial sequence of the template, and it is sufficient if the primer has sufficient complementarity within a range capable of hybridizing with the template and acting as a primer. Therefore, the primer in the present invention does not need to have a perfectly complementary sequence to the above-mentioned nucleotide sequence, which is a template, and it is sufficient that the primer has sufficient complementarity within a range capable of hybridizing to the gene sequence and acting as a primer. The design of such a primer can be easily carried out by a person skilled in the art with reference to the above-mentioned nucleotide sequence, for example, by using a program for primer design (for example, PRIMER 3 program).

In the present specification, the term " nucleic acid molecule " has the meaning inclusive of DNA (gDNA and cDNA) and RNA molecules, and the nucleotide, which is a basic constituent unit in the nucleic acid molecule, includes not only natural nucleotides, (Scheit, Nucleotide Analogs, John Wiley, New York (1980); Uhlman and Peyman, Chemical Reviews, 90: 543-584 (1990)).

When the starting material in the kit of the present invention is gDNA, the separation of gDNA can be carried out according to conventional methods known in the art (Rogers & Bendich (1994)).

When the starting material is mRNA, the total RNA is isolated by a conventional method known in the art (see Sambrook, J. et al., Molecular Cloning, A Laboratory Manual, 3rd ed. Cold Spring Harbor Press (1987) and Chomczynski, et al., ≪ RTI ID = 0.0 > Ausubel, < / RTI > FM et al., Current Protocols in Molecular Biology, John Willey & P. et al., Anal. Biochem. 162: 156 (1987)). The isolated total RNA is synthesized by cDNA using reverse transcriptase. Since the total RNA is isolated from cows (e.g., Ankole, Boran, Kenana, N'Dama, Ogaden, Angus, Jersey, Holstein or Korean)), the mRNA has a poly-A tail at its end, CDNA can be easily synthesized using an oligo dT primer and a reverse transcriptase using the oligonucleotide probe (see PNAS USA, 85: 8998 (1988); Libert F, et al., Science, 244: 569 , J. et al., Molecular Cloning, A Laboratory Manual, 3 ^rd ed. Cold Spring Harbor Press (2001)).

In the kit of the present invention, identification of the specific sequence can be performed by applying various methods known in the art. For example, techniques that may be applied to the present invention include fluorescence in situ hybridization (FISH), direct DNA sequencing, PFGE analysis, Southern blot analysis, single-strand conformational analysis (SSCA, Orita et al., PNAS, USA 86: 2776 (1989)), RNase protection analysis (Finkelstein et al., Genomics, 7: 167 (1990)), dot blot analysis, denaturing gradient gel electrophoresis (DGGE, Wartell et al., Nucl. Acids Res. (Modrich, Ann. Rev. Genet., 25: 229-253 (1991)) using a protein recognizing a nucleotide mismatch (e.g., mutS protein of E. coli) But are not limited to, allelic-specific PCR.

Sequence changes result in differences in base-linkage within the single-stranded molecule, leading to the appearance of different bands of mobility, and SSCA detects this band. DGGE analysis uses a denaturing gradient gel to detect sequences that represent wild type sequences and other mobility.

Other techniques generally use probes or primers complementary to sequences comprising the SNPs of the invention.

For example, in an RNase protection assay, a riboprobe complementary to a sequence comprising the SNPs of the present invention is used. The riboprobe is hybridized with DNA or mRNA isolated from human, and then cleaved with an RNase A enzyme capable of detecting a mismatch. If there is a mismatch and RNase A recognizes, a smaller band is observed.

In the analysis using a hybridization signal, a probe complementary to the sequence containing the SNP of the present invention is used. In this technique, hybridization signals of the probe and the target sequence are detected to directly determine the risk of the disease.

As used herein, the term " probe " means a linear oligomer having a natural or modified monomer or linkage comprising a deoxyribonucleotide and a ribonucleotide that can hybridize to a particular nucleotide sequence.

Preferably, the probe is single stranded for maximum efficiency in hybridization. The probe is preferably a deoxyribonucleotide.

As the probe used in the present invention, a sequence complementary to the sequence including the SNP may be used, but a sequence substantially complementary to the sequence that does not interfere with the specific hybridization is used It is possible. Preferably, the probe used in the present invention comprises a sequence that can hybridize to a sequence comprising 10 to 30 consecutive nucleotide residues comprising the SNP of the present invention. More preferably, the 3'-end or the 5'-end of the probe has a base complementary to the SNP base. Generally, the stability of the duplex formed by hybridization tends to be determined by the agreement of terminal sequences, so that in a probe having a base complementary to the SNP base at the 3'-terminal or 5'-terminal, If the part is not hybridized, such a duplex can be disassembled under stringent conditions.

Suitable conditions for hybridization include, but are not limited to, Nucleic Acid Hybridization, A Practical Approach, Hayes, BD, et al., Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, IRL Press, Washington, DC (1985). ≪ / RTI > The stringent condition used for hybridization can be determined by controlling the temperature, the ionic strength (buffer concentration) and the presence of a compound such as an organic solvent, and the like. This stringent condition can be determined differently depending on the sequence to be hybridized.

In accordance with another aspect of the present invention, the present invention provides a method for screening polynucleotides encoding the nucleotide polymorphism (SNP) region of the USH2A (Usher syndrome 2A) gene in a bovine biological sample to provide information necessary for screening of sleeping- A single nucleotide polymorphic site at position 13720 of the first sequence (GenBank SNP database rs110332182)

A single base polymorphism (SNP) region of the ACAD9 (acyl-CoA dehydrogenase family, member 9) gene, a single base polymorphism site at position 1558 (GenBank SNP database rs135578554)

As a single base polymorphism (SNP) region of the AMZ1 (archaelysin family metallopeptidase 1) gene, a single base polymorphism site at the 610th position of the 3rd sequence and a single base polymorphism site at the 340th position (GenBank SNP database rs109821810)

A single nucleotide polymorphism (SNP) region of CDADC1 (cytidine and dCMP deaminase domain containing 1) gene, a single nucleotide polymorphism site at position 1438 (GenBank SNP database rs109691868) of Sequence Listing 4,

A single nucleotide polymorphism (SNP) region of EML1 (echinoderm microtubule associated protein like 1) gene, a single nucleotide polymorphism site at position 1765 of Sequence Listing 5,

A single nucleotide polymorphism (SNP) region of the EOMES (eomesodermin) gene, a single nucleotide polymorphism site at position 763 of SEQ ID NO: 6,

A single nucleotide polymorphism (SNP) region of an opioid binding protein / cell adhesion molecule-like (OPCML) gene, a single nucleotide polymorphism site at position 157 of SEQ ID NO:

A single nucleotide polymorphism (SNP) site of the PIK3C2G (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 gamma) gene, a single nucleotide polymorphism site at position 70 of SEQ ID No. 8, a nucleotide polymorphism site at position 347 (GenBank SNP database rs380908276 ) Single nucleotide polymorphic site,

The single nucleotide polymorphism (SNP) site of the SLIT3 (slit guidance ligand 3) gene, the single nucleotide polymorphic site of the 1814th position (GenBank SNP database rs110101818)

A single nucleotide polymorphism (SNP) region of TIGAR (TP53 induced glycolysis regulatory phosphatase) gene, a single nucleotide polymorphism site at position 272 of SEQ ID NO: 10,

Single base polymorphism (SNP) region of the TPST1 (tyrosylprotein sulfotransferase 1) gene, single nucleotide polymorphism site at position 704 (GenBank SNP database rs383100152) of SEQ ID NO: 11,

(SNP) region of the 367th position (GenBank SNP database rs207500281) of SEQ ID No. 12 as the single nucleotide polymorphism (SNP) region of the C1RL (complement component 1, r subcomponent- Single nucleotide polymorphism (SNP) site at position 1344, single nucleotide polymorphism site at position 1458, single nucleotide polymorphism (SNP) site at position 1458,

Single nucleotide polymorphism (SNP) region of DDX54 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 54) single nucleotide polymorphism site at position 397 of Sequence Listing 13 (GenBank SNP database rs385853893)

A single nucleotide polymorphism (SNP) region of NOX5 (NADPH oxidase, EF-hand calcium binding domain 5) gene, a single nucleotide polymorphism site at position 1015 of SEQ ID No. 14,

A single nucleotide polymorphism site of the 160th position of SEQ ID NO: 15 (GenBank SNP database rs385712825) as the single nucleotide polymorphism (SNP) region of the RANBP17 (RAN binding protein 17) gene, and

Detecting a single base polymorphism site selected from the group consisting of a single base polymorphism site at position 4888 of SEQ ID NO: 16 sequence as a single base polymorphism (SNP) site of a SET binding factor 2 (SBF2) Provides a method for detecting N'Dama variant-specific markers of sleep apnea.

As used herein, the term "biological sample " refers to all materials of an organism including nucleic acids, and biological samples usable in the nucleic acid amplification reaction of the present invention include viruses, bacteria, tissues, cells, hair, oral tissues, But are not limited to, blood, lymph, bone marrow fluid, saliva, milk, urine, feces, ocular fluid, semen, brain extract, spinal fluid, joint fluid, mammary fluid, ascites, amniotic fluid or cell tissue fluid. As a biological sample, blood contains whole blood, plasma, or serum.

According to a specific embodiment of the present invention, the biological sample is whole blood, plasma or serum.

The step of detecting the single nucleotide polymorphism (SNP) region of the present invention is performed by a microarray method or a gene amplification method.

When the present invention is carried out by a gene amplification method, PCR (polymerase chain reaction) using a primer is preferably carried out.

The term " amplification reaction " as used herein refers to a reaction to amplify a nucleic acid molecule. A variety of amplification reactions have been reported in the art, including polymerase chain reaction (PCR) (US Pat. Nos. 4,683,195, 4,683,202 and 4,800,159), reverse-transcription polymerase chain reaction (RT-PCR) (Sambrook et al., Molecular Cloning. (LCR) (see, for example, A Laboratory Manual, 3rd Ed. Cold Spring Harbor Press (2001)), Miller, HI (WO 89/06700) and Davey, C. et al (EP 329,822) 17, 18), Gap-LCR (WO 90/01069), repair chain reaction (EP 439,182), transcription-mediated amplification (9) anscription-mediated amplification; TMA) 19 (WO 88/10315), self sustained sequence replication (WO 90/06995), selective amplification of the target polynucleotide sequence 6,410,276), consensus 9,1 priming polymerase chain reaction (CP-PCR) (US Patent No. 4,437, ap5), arbitrary primed polymerase chain reaction (AP- PCR (US Pat. Nos. 5,413,909 and 5,861,245), nucleic acid sequence based amplification (NASBA) (U.S. Pat. Nos. 5,130,238, 5,409,818, 5,554,517, and 6,063,603) But are not limited to, strand displacement amplification and loop-mediated isothermal amplification (LAMP). Other amplification methods that may be used are described in U.S. Patent Nos. 5,242,794, 5,494,810, 4,988,617 and U.S. Patent No. 09 / 854,317.

PCR is the most well-known nucleic acid amplification method, and many variations and applications thereof have been developed. For example, touchdown PCR, hot start PCR, nested PCR and booster PCR have been developed by modifying traditional PCR procedures to enhance the specificity or sensitivity of PCR. In addition, real-time PCR, differential display PCR (DD-PCR), rapid amplification of cDNA ends (RACE), multiplex PCR, inverse polymerase chain reaction chain reaction (IPCR), vectorette PCR and thermal asymmetric interlaced PCR (TAIL-PCR) have been developed for specific applications.

For more information on PCR see McPherson, M.J., and Moller, S.G. PCR. BIOS Scientific Publishers, Springer-Verlag New York Berlin Heidelberg, N.Y. (2000).

When the method of the present invention is carried out using a primer, the nucleotide sequence of the marker of the present invention is analyzed by confirming the gene amplification reaction. Since the present invention detects the nucleotide sequence of the marker of the present invention, the nucleotide sequence of the marker of the present invention is determined from the sample (for example, genomic DNA) to be analyzed, and the N'Dama variety of the target sample can be confirmed have.

In a most preferred embodiment of the invention, the amplification process is carried out according to the polymerase chain reaction (PCR) set forth in U.S. Patent Nos. 4,683,195, 4,683,202 and 4,800,159.

The method of the present invention may be implemented in a microarray manner. When the method of the present invention is based on the microarray method, the probe is immobilized on the solid-phase surface of the microarray.

The probe used in the method of the present invention has a sequence complementary to 10-100 consecutive nucleotide sequences on each gene comprising the above-mentioned SNPs of the present invention.

The nucleotide sequence of the marker of the present invention to be referred to in the production of the probe can be confirmed by GenBank.

For example, a single nucleotide polymorphic site having a G at the 13720th nucleotide position of the first sequence, which is a marker of the present invention, has a nucleotide sequence in the GenBank SNP database rs110332182, and a probe can be designed with reference to this sequence.

In the microarray of the present invention, the probe is used as a hybridizable array element and immobilized on a substrate. Preferred gases include, for example, membranes, filters, chips, slides, wafers, fibers, magnetic beads or non-magnetic beads, gels, tubing, plates, polymers, microparticles and capillaries, as suitable rigid or semi-rigid supports. The hybridization array elements are arranged and immobilized on the substrate. Such immobilization is carried out by a chemical bonding method or a covalent bonding method such as UV. For example, the hybridization array element may be bonded to a glass surface modified to include an epoxy compound or an aldehyde group, and may also be bound by UV on a polylysine coating surface. In addition, the hybridization array element may be coupled to the gas through a linker (e.g., ethylene glycol oligomer and diamine).

On the other hand, the sample DNA to be applied to the microarray of the present invention can be labeled and hybridized with the array elements on the microarray. Hybridization conditions can be varied. The detection and analysis of the hybridization degree can be variously carried out according to the labeling substance.

The label of the probe may provide a signal to detect hybridization, which may be linked to an oligonucleotide. Suitable labels include fluorescent moieties (e.g., fluorescein, phycoerythrin, rhodamine, lissamine, and Cy3 and Cy5 (Pharmacia)), chromophores, chemiluminescent moieties, magnetic particles, (Such as P32 and S35), mass labels, electron dense particles, enzymes (alkaline phosphatase or horseradish peroxidase), joins, substrates for enzymes, heavy metals such as gold and antibodies, streptavidin, biotin , Hapten having specific binding partners such as digoxigenin and chelating groups. Markers can be obtained by a variety of methods routinely practiced in the art, such as nick translation (Multilamer Biotechnology, Multiprime DNA labeling systems booklet, "Amersham" (1989)) and kaination method (Maxam & Gilbert, Methods in Enzymology, 65: 499 (1986)). The labeling can be performed by fluorescence, radioactivity, colorimetry, gravimetry, X-ray diffraction or absorption, magnetic, enzymatic activity, mass analysis, Hybridized high-frequency, and nano-crystal.

The nucleic acid sample to be analyzed can be prepared using mRNA obtained from various biosamples. Instead of the probe, the cDNA to be analyzed may be labeled and subjected to a hybridization reaction-based analysis.

When a probe is used, the probe is hybridized with the cDNA molecule. In the present invention, suitable hybridization conditions can be determined by a series of procedures by an optimization procedure. This procedure is performed by a person skilled in the art in a series of procedures to establish a protocol for use in the laboratory. Conditions such as, for example, temperature, concentration of components, hybridization and washing time, buffer components and their pH and ionic strength depend on various factors such as probe length and GC amount and target nucleotide sequence. Detailed conditions for hybridization are described in Joseph Sambrook, et al., Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. (2001); And M.L.M. Anderson, Nucleic Acid Hybridization, Springer-Verlag New York Inc .; N.Y. (1999).

For example, high stringency conditions were hybridized under conditions of 0.5 M NaHPO4, 7% sodium dodecyl sulfate (SDS) and 1 mM EDTA at 65 ° C, followed by hybridization in 0.1 x SSC (standard saline citrate) /0.1% SDS at 68 Lt; 0 > C. Alternatively, high stringency conditions means washing at < RTI ID = 0.0 > 48 C < / RTI > in 6 x SSC / 0.05% sodium pyrophosphate. Low stringency conditions mean, for example, washing in 0.2 x SSC / 0.1% SDS at 42 ° C.

After the hybridization reaction, a hybridization signal generated through the hybridization reaction is detected. The hybridization signal can be carried out in various ways depending on, for example, the type of label attached to the probe. For example, when a probe is labeled with an enzyme, the substrate of the enzyme can be reacted with the result of hybridization reaction to confirm hybridization. Combinations of enzymes / substrates that may be used include, but are not limited to, peroxidases (such as horseradish peroxidase) and chloronaphthol, aminoethylcarbazole, diaminobenzidine, D-luciferin, lucigenin (bis- (10-acetyl-3,7-dihydroxyphenoxazine), HYR (p-phenylenediamine-HCl and pyrocatecN-1), TMB (tetramethyl benzidine) (2-azino-di- [3-ethylbenzthiazoline sulfate]), o-phenylenediamine (OPD minioethylnaphthol / pyroinine, alkaline phosphatase and bromochloroindolyl phosphate (BCIP) (NBT), naphthol-AS-B1-pN-spNate, noethyl ECF substrate, glucose oxidase, t-NBT (nitroblue tetrazolium) and m-PMS (phenzaine methosulfate) When the probe is labeled with gold particles, silver nitrate is used to stain the silver Therefore, when the method of detecting the marker of the present invention is carried out based on hybridization, specifically (i) a step of hybridizing a probe having a sequence complementary to the nucleotide sequence of the marker of the present invention to a nucleic acid sample (ii) detecting whether or not the hybridization reaction has occurred, by analyzing the intensity of the hybridization signal by the hybridization process, it is possible to determine whether or not the N'Dama variety is present, that is, the nucleotide If the hybridization signal for the sequence is stronger than the normal sample, it is determined to be a N'Dama variety.

The method of detecting the snake-resistant N'Dama variety-specific marker of the present invention differs from that of the snake-resistant N'Dama variety screening kit in order to avoid the excessive complexity of the present specification.

The features and advantages of the present invention are summarized as follows:

(a) The present invention provides a screening kit for screening for sleeping-sickness-resistant N'Dama varieties and a method for detecting the N'Dama-variant-specific markers.

(b) The N'Dama variety-specific SNP markers identified in the present invention provide novel SNP markers not known in the art.

(c) The present invention provides a difference in genome pattern between N'Dama and other livestock varieties using a combined method based on theoretical and statistical approaches to diverse genomes of various small breeds.

(d) is associated with ossification control, nervous system and immune system development that may be involved in the evolution of the N'Dama peculiar phenotype of the present invention, which provides insight into the detection of a genotype-specific genetic signal from the genome Show.

Figure 1 schematically depicts an overview of the system analysis of the genes to identify genetic signatures of sleeping-sickness-resistant N'Dama.
Figures 2a to 2c show the distributional differences of the mutual information of SNP annotated genes between breed pairs including Boran, N'Dama and Ogaden varieties. Figure 2a shows the distribution of the mean and maximum values of the MI among the 3 breed pairs for each gene. All SNPs were tinned with 16669 genes. The X-axis represents the number of SNPs annotated by the gene, and the MI score is displayed on the y-axis. The mean MI was calculated by averaging the MI scores of all SNPs annotated by the gene. The maximum MI is the maximum of the MI scores of all SNPs annotated by the gene. I (N; B), I (N; O) and I (B; O) mean MI between N'Dama and Boran, N'Dama and Ogaden, and Boran and Ogaden varieties. Figure 2b shows the MI ratio distribution between the pair of Boran, N'Dama and Ogaden. The upper and lower graphs show the average and maximum MI ratio distributions among the three breed pairs, respectively. Figure 2c is the difference in distribution between Boran, N'Dama and Ogaden varieties calculated by KL divergence.
FIG. 3 shows the distribution of the number of SNPs and the logarithmic ratio that distinguish between N'Dama and Ogaden in each chromosome. The bars of light gray with black, gray and pattern represent the number of SNPs identified by the weighted MI, the intersection of MI and XP-CLR, the MI with significant p value (1.0e-2) and XP-EHH. The blue value means a concentrated chromosome with a p-value of less than 1.0e-2 in the Fisher's exact test. The line graph is the ratio of the identified SNPs to the total SNPs for each chromosome. Since the ratio is on a negative logarithmic scale, the lower the percentage of SNPs that distinguish the N'Dama and Ogaden varieties, the higher the value. In all graphs, the left y axis represents the number of SNPs, and the right y axis represents the ratio value.
Figures 4A-4C show the N'Dama breed genes identified via wMI. Figure 4a shows the correlation network of 30 genes selected using the wMI of the SNP type between N'Dama and Ogaden varieties. The circle represents the gene, including the SNP identified by wMI, and the dark gray octagon represents the gene annotated in the GO analysis. A dark red line shows a strong positive correlation, and a dark green line shows a strong negative correlation (pairs of genes with correlation coefficients greater than 0.45 or less than-0.25 are connected). FIG. 4B shows a GO analysis of extracted genes by adjusting thresholds from the constructed correlation network. The vertical line represents the FDR correction p-value (0.05). Figure 4C shows the genotypic profile of identified genes including ACCN1, CTNNA2, FHIT and USH2A. N'Dama and Ogaden varieties. ≪ tb >< TABLE > Each logo is composed of A (A / A), T (T / T), G (G / G), C ), F (G / T), H (C / T) and I (C / G). The table above shows the type of SNP allele for each variety and the value in parentheses represents the number of samples with each allele for the four genes.
Figures 5a to 5c show genes of N'Dama varieties identified based on MI and XP-CLR. Figure 5a shows the correlation network of 131 genes selected using the SN of the SNP type between N'Dama and Ogaden and XP-CLR. The circles represent the genes identified by MI and XP-CLR and the dark gray octagons represent the genes annotated in the GO analysis. A dark red line indicates a strong positive correlation, and a dark green line indicates a strong negative correlation (a pair of genes having a correlation coefficient of greater than 0.9 or less than -0.4 is connected). Figure 5B shows the GO analysis of extracted genes by adjusting the threshold value from the constructed correlation network. The vertical line represents the FDR correction p-value (0.05). Figure 5c shows that the genotypic profiles of 10 representative SNP positions of each gene, including CALCR, FGF23 and CDK6, show a distinctly different pattern between N'Dama and Ogaden varieties. The table above shows the type of SNP allele for each variety and the value in parentheses represents the number of samples with each allele for the three genes.
Figures 6a to 6c show genes of N'Dama varieties identified based on MI and XP-EHH. Figure 6a shows a correlation network of 117 genes selected using the SNP type MI and XP-EHH between N'Dama and Ogaden. The circles represent the genes identified by MI and XP-CLR and the dark gray octagons represent the genes annotated in the GO analysis. A dark red line shows a strong positive correlation, and a dark green line shows a strong negative correlation (a pair of genes having a correlation coefficient of greater than 0.9 or less than -0.5 is connected). Figure 5b shows the GO analysis of excised genes (except for miRNAs) by adjusting the threshold from the constructed correlation network. The vertical line represents the FDR correction p-value (0.05). Figure 5c shows that the genotypic profiles of 10 representative SNP positions of each identified gene, including CALCR, FGF23 and CDK6, show a distinctly different pattern between the N'Dama and Ogaden varieties. The table above shows the type of SNP allele for each variety and the value in parentheses represents the number of samples with each allele for the three genes.
Figure 7 shows amino acid substitutions by missense and nonsense mutations of the genes identified by wMI, MI / XP-CLR and MI / XP-EHH. Twenty miscellaneous mismatches and nonsense mutations in the identified genes represent the amino acid substitutions distinguished from amino acid substitutions in the reference locus (UMD 3.1), human and mouse, in N'Dama.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Throughout this specification, "%" used to denote the concentration of a particular substance is intended to include solids / solids (wt / wt), solid / liquid (wt / The liquid / liquid is (vol / vol)%.

Example

Materials and Experiments

Samples, DNA resequencing and SNP detection

(10 Ankoles, 10 Boran, 9 Kenana, 10 N'Dama and 9 Ogaden) and four commercial cattle (10 Angus, 10 Jersey, 10 Holstein and 23 Hanwoo) DNA was isolated from a whole blood sample of G-DEXTMIIb genomic DNA extraction kit (iNtRoN Biotechnology, Korea) and paired-end reads were generated from the separated DNA using Illumina HiSeq2000. 3 μg of the genomic DNA was sheared into the ~ 300 bp insert using the Covaris System. The fragment of sheared DNA was terminated, amplified with a polyA-tail, coupled with an adapter, and amplified using a TruSeq DNA Sample Prep. Pair-end sequencing on the Illumina HiSeq 2000 platform using the TruSeq SBS Kit v3-HS (Illumina, USA) (https://www.illumina.com/documents/products/datasheets/datasheet_hiseq2000.pdf) Respectively. Finally, sequence data was generated using the Illumina HiSeq system.

For the 6.5 billion leads (~ 644 Gbp) from the genomes of five native African sow varieties (Ankole, Boran, Kenana, N'Dama and Ogaden) and four commercial cattle (Angus, Jersey, Holstein and Hanwoo) The quality inspection was conducted through the package (http://www.bioinformatics.babraham.ac.uk/projects/fastqc). Pair-end sequence reads were aligned to UMD 3.1 using Bowtie and default parameters (except for the "- no-mixed" option). The UMD 3.1 reference genome (ftp://ftp.ensembl.org/pub/release-75/fasta/bos_taurus/) obtained from the Ensembl database (release 75) was used as the small reference genome of the assembly. The size of the reference genome sequence UMD 3.1 is 2.67 Gb. The overall alignment rate of the leads to the reference genome was 98.84% of the average read depth in the genome range of ~ 10.8X. On average in all samples, the lead value accounted for 98.56% of the UMD3.1 reference genome.

We used Picard (http://picard.sourceforge.net) and SAMtools for downstream processing and variant calling. Potential PCR duplicates were filtered using Picard ("REMOVE_DUPLICATEDS = true" option in "MarkDuplicates"), and indexes in baseline and bam files were created with SAMtools. We also implemented a local multiple sequence real line to correct misalignment due to the presence of INDELs ("RealignerTargetCreator" and "IndelRealigner") and used GATK 3.1 to generate candidate SNPs ("UnifiedGenotyper" and "SelectVariants" "). When mutations were extracted and converted to variant call format (VCF), variants were filtered to minimize false variability ("VariantFiltration"). Variations were filtered using the following options: QUAL (Phred-scaleed quality score) <30; MQ0 (number of leads with zero mapping quality)> 4; QD (Variation Dependency / Quality Depth) <5; FS (Phred-scale p value using Fisher's exact test)> 200. BEAGLE was used to explain the missing genotype and deduce haplotype phases. Finally, we have obtained ~ 37 million SNPs.

We also conducted genotyping of 45 African cattle samples using blood samples using the Bovine SNP50 Genotyping BeadChip (Illumina, USA). After filtering the SNPs with a GeneCall score of 0.7 or less, common gene loci of SNP chips and DNA resequencing data were extracted and evaluated for agreement. In addition, we performed enrichment analysis using SNPSift, which focused on non-synonymous SNPs (MISSENSE and NONSENSE) to detect significant variant-specific SNPs. SNPSift CaseControl calculates the number of genotypes present in the two factors and then calculates the p value using the Fisher exact and Cochran-Armitage trend tests. In general, one of the elements is a fixed genetic model that can be dominant, recessive or co-dominant. The other is the breed information applied to this study to identify the breed-specific in-enriched SNP. As a result, our team has divided 2 * 2 (dominant or recessive coding / breed-specific group information, specific varieties, N'Dama versus other varieties) or 2 * 3 (joint dominant coding / And the Fisher exact and Cochran-Armitage trend tests for 2-by-2 and 2-by-3 partitioned tables, respectively. A total of 37,363,436 SNPs were applied to the test and Bonferroni correction was used for multiple calibration tests. After identifying significant N'Dama variety-specific Enriched SNPs, each SNP was annotated using snpEff.

Data representation

All SNP alleles were converted to binary numbers, including 0 and 1, to effectively demonstrate variant-specific SNP mutations. '0' represents the major allele at the SNP position of all the samples, and '1' represents the minor value regardless of the allele. This biallelic expression can effectively identify variety-specific SNPs by explicitly characterizing the ratio of major or minor alleles at each SNP position per breed. Specifically, the alleles of the i-th SNP are modified as follows:

,

,

와 Major(i)는 i 번째 SNP 대립 유전자이고 모든 소 샘플에 대해 i 번째 SNP 위치에서 가장 빈번한 대립 유전자이다. 각 품종 당 SNP 위치의 0과 1 값은 각각 "conserved"와 "mutated"로 각각 나타낸다.here

And Major (i) are the i-th SNP allele and the most frequent allele at the i-th SNP position for all small samples. The 0 and 1 values of the SNP position for each variety are shown as "conserved" and "mutated", respectively.

Mutual Information Analysis

Informational theoretical measures have emerged as a useful way to quantify the dependence of many genetic variables. In particular, the mutual information (MI) of two random variables is an entropy-based measure for measuring interdependencies between variables. Although there have been several studies using the MI method to analyze biological phenomena, most have been applied to gene expression data. This study proposes an MI-based hybrid approach combined with statistical methods for detecting variant-specific SNPs from large genome sequences.

In genetic association studies, MI can be used to measure genetic factors and phenotypic dependence by defining genetic characteristics and phenotypic classes as random variables. Extracting differential genetic variation from tens of millions of SNPs can be resolved by finding a separate variable from a large set of variables. Given a SNP position variation set X = {x1, ..., xn} and a varieties class variable y, define a function F (X; y) that selects a variable by measuring the association between the SNP position and the breed class.

Where X ^* is a set of selective SNP variable pairs, xi and xj represent two SNP variables of the chromosome, and θ represents a threshold value for selecting a SNP variable. The MIE also represents a mutual information estimator.

When two random variables, SNP and C, represent a genetic variable and a phenotype class, the SNP value set is composed of possible alleles and the value set of C is defined as {N'Dama, other cows}. MI I (SNP; C) quantifies the reduction of phenotypic class C uncertainty due to information contained in the genetic variation of the SNP.

Where H (SNP) is the entropy of the SNP. H (SNP | C) represents the conditional entropy of a SNP for a given C and can be found using a chain rule. Hence, by definition of entropy H, MI can be reconstructed into a joint probability distribution p (SNP, C) as follows.

I (SNP; C) is nonnegative and p (SNP, C) = p (SNP)

In this study, the relationship between three or more variables was quantified as an MIE function and conditional MI was calculated to measure the effect of two gene loci on the varieties. The conditional MI is defined as:

I (C; SNP1, SNP2) was defined as MIE. MIEs can be obtained with the MI chain rule as follows:

MIE quantifies the association between SNPs in two genetic loci and varieties. I (C; SNP1 | SNP2) is also not negative and is zero if there is no dependency between the three variables. This property is suitable for identifying two distinct locus haplotypes that determine the phenotype of the bovine.

The weighted MI between the ith gene and the variant C (wMI) is defined by interpolating the number of SNPs annotated by the gene and the average MI of the gene.

Where gi is the set of SNPs annotated by the i-th gene and represents a constant for adjusting the two factors. If the gene has more SNPs and the average MI between the gene SNP and the breed variable is greater, the wMI of the gene provides a larger value.

XP-CLR and XP-EHH test

We performed a cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) test to detect selective pressures in N'Dama and Ogaden livestock. The XP-CLR score uses XP-CLR 1.0 (https://reich.hms.harvard.edu/software) for selective sweep observations involving multiple-genetic locus allele frequency discrimination modeling between two populations Respectively. A non-overlapping sliding window of 50 kb, a maximum number of SNPs of 600 in each window, and a correlation coefficient of 0.95 for XPP-CLR results were used. Areas with XP-CLR scores in the top 1% of the empirical distributions (XP-CLR> 224.2) were designated candidate sweeps in N'Dama and Ogaden varieties.

We also used XP-EHH to identify select genetic loci based on comparisons of genome-wide SNP genotypes between populations. The XP-EHH scores were detected using the software xpehh (http://hgdp.uchicago.edu/Software/), which increased in frequency to one of the population or to the proximal anchor point. This means that SNPs that are selected in one population but not in another population are detected. Thus, extreme XP-EHH scores potentially represent the choice of a particular group. The XP-EHH scores are also directional. Positive scores are likely to have occurred in group A, while negative scores indicate that group B has taken place. The genome is divided into non-overlapping portions of 50 kb to facilitate comparisons of intergenic genomic regions before computing the maximum XP-EHH score of all SNPs in each segment. In order to consider the SNP frequency, we have binned the genome window by 500 SNP units according to the number of SNPs. Within each bin, for each window i, the percentage of windows with statistical values greater than the statistical value of i was defined as the empirical p value. The XP-EHH results with positive scores indicate the choice of N'Dama, whereas the negative scores indicate the choice of Ogaden.

We selected a region with a positive XP-EHH score at a p value of less than 1%, which we regard as a strong signal in the N'Dama variety.

Finally, in the XP-CLR and XP-EHH tests, the selected genomic region was tinned with the closest gene (UMD 3.1). A gene that partially or completely spans the window region (-25 to +25 kb) was defined as a candidate gene.

Genetic interchange network formation by genetic mutation among varieties

The gene correlation network is characterized by the correlation of gene mutations to livestock varieties. Genetic variation patterns based on transformed SNP alleles distinct from livestock varieties are used to construct a gene-gene interaction network. The networks constructed from annotated genes and quantitative changes at the gene level are as follows:

(1) genes were selected based on the significance level p-value <1.0e-3 for the intersections of wMI, MI and XP-CLR, and MI and XP-EHH.

(2) Allelic pairs of selected SNPs were transformed into three values by adding three values of 0, 1, and 2 to the state of change. If the SNP allele pair at one position is of major homozygous or alternative homozygous type, the converted SNP value is 0 or 2. When the allele pair shows heterozygosity, the value is 1. For example, an allele of a SNP locus pair belongs to "AA", "AT" or "TT" and "A" is a major allele of the SNP pair. Then, for all samples, convert the SNP values at this position to 0, 1, or 2, respectively. This value is defined as the SNP variance of each sample.

(3) The selected SNPs are annotated by genes in which these SNPs are located.

(4) Calculate the average of the SNP values calculated in (2) for each gene. This mean value is defined as the variation of the gene.

(5) Calculate the Pearson correlation coefficient of all gene pairs from the gene mutation of the small-breed sample calculated from (4):

Here, gi and gj represent the i-th and j-th gene mutations. σi and Cov (gi, gj) s mean the standard deviation of gi and the covariance of gi and gj.

(6) The genes are connected to each other by two genes with significant correlation coefficient.

To investigate N'Dama-specific traits including resistance to sleep deprivation, gene interaction networks were constructed of N'Dama and Ogaden varieties. We also selected positive and negative thresholds to link the two genes. To calculate the correlation coefficient between extracted genes, we implemented the source code using Python 2.7 scipy package and Cytoscape 3.2.1 for network visualization.

Finally, the DAVID 6.7 (Database for Annotation, Visualization and Integrated Discovery, https://david-d.ncifcrf.gov/tools.jsp) is used to generate the gene for the constructed network to statistically determine the over- Were analyzed. Go analysis was performed with DAVID as the default parameter with DA level set to "all", count threshold (minimum number of genes for the GO term) set to 2, and EASE threshold set to 0.1. EASE score was modified Fisher exact p-value rather than naive Fisher exact test.

result

In order to find the genetic signatures of N'Dama, we used a method based on information theory and statistical methods to compare them in the field genome (Fig. 1).

Summary of Sequencing, Assembly, and SNP Detection

It has 11X genome coverage from the genomes of each individual of five varieties of African cattle (Ankole, Boran, Kenana, N'Dama and Ogaden, 48) and four varieties of commercial cattle (Angus, Hanwoo, Hostein and Jersey, 53) Producing 6.5 billion leads or ~ 644 Gbp. These leads were aligned to 98.84% in the reference genome sequence UMD3.1. A total of 37 million SNPs were obtained after correcting PCR redundant sequences and misaligned leads.

In addition, we found that 94.92% of the bovine SNP 50 Genotyping Bead Chip SNPs and resequencing were genotypically similar in overall samples. This helps to provide confidence in the accuracy of SNP extraction.

Discovery of specific SNPs based on mutual information (MI)

We extracted candidate SNPs that distinguish between N'Dama and other cattle breeds using mutual information (MI) that estimates the association strength between SNP location and breed. Thus, our analysis was designed to detect differential SNPs with high dependence between two adjacent loci and haplotypes of the breed. Averaging the results of 2793 common genes of N'Dama and 5 other varieties, we identified about 2.6 million SNPs. The extracted SNP showed a high MI value (maximum value = 0.691) and a significant p value (2.13e-6). To overcome the deviations caused by small sample size, a lower p-value was chosen compared to other studies to estimate statistical significance (p-value less than 1.0e-3). Overall, this result shows that the haplotype pattern of N'Dama is clearly different from the haplotype pattern of other livestock. In addition, the region containing the extracted SNP may serve as a potential marker to distinguish the N'Dama variety.

Differences in SNP distribution between Boran, Ogaden and N'Dama varieties identified by MI

From a pair of datasets consisting of N'Dama-Boran, N'Dama-Ogaden, and Boran-Ogaden of three different animal breeds, including Boran, Ogaden and N'Dama, The distribution difference was confirmed. We calculated the MI value between each SNP location variable and the varieties of the pair data set. To analyze the difference of MI distribution between N'Dama and other varieties, 37,363,436 SNP positions were annotated with 16,699 genes. For the analysis, the sum, maximum value, average value, and the number of SNPs counted in each gene were calculated for the MI values of all SNPs of the gene. Figure 2 shows the distribution of the mean and maximum values of the MI of SNPs in each gene for the three pairs of data sets I (N; B), I (N; O) and I (B; In Figure 2a, the I (B; O) values are lower than the I (N; B) and I (N; O) values. This means that the N'Dama variety had a SNP pattern distinct from the Boran and Ogaden varieties. These differences may be related to the unique characteristics of N'Dama varieties, such as resistance to African sleeping sickness. The difference in N'Dama between the other two varieties can also be seen clearly in Figure 2b, which compares the ratio distribution of the MI values of I (N; B), I (N; O) and I (B; O) . The distribution of I (N; B) and I (N; O) were similar, but the distribution of I (B; O) clearly showed a different pattern. Considering the differential distribution of SNPs with larger MI values, N'Dama has a unique SNP pattern that may be related to the strain-specific characteristics including sleeping-sickness resistance. Finally, FIG. 2C shows the KL-Divergence value of the MI distribution among the pair data sets of the three cultivars. KL-divergence is a widely used asymmetric measure of the difference between two distributions. The larger the KL-divergence value, the greater the difference between the two distributions. Thus, this result indicates that the Boran and Ogaden varieties are different in relation to the SNP pattern that N'Dama may affect the specific trait.

Detection of Genetic Signatures in N'Dama

We used the weighted mutual information (wMI) to analyze genomes for SNPs of different breeds. For a given gene, wMI is defined as the sum of two factors, the normalized number of SNPs assigned to the gene and the average MI value of the SNP of the gene. The proposed wMI is considered to be differential information between the degree of genetic variation of the gene and the breed. Figure 3 is a graph showing the effect of each of the 30 chromosomes, as well as the MI and XP-CLR, MI and XP-EHH crossings of each chromosome and Fisher's exact test, with the degree of enrichment of each chromosome, Show distribution. The Fisher's exact test is performed using a 2x2 partition table consisting of two factors: whether the SNP is contained on a particular chromosome, and whether the SNP is identified by each method. We also present a distribution of genes with significant SNPs identified by the same three methods for each chromosome. Although SNPs were found on all chromosomes, the number of SNPs did not exist throughout the chromosome. In particular, a relatively large number of SNPs were detected on chromosome 5 when the intersection of MI, XP-CLR, MI and XP-EHH was applied. The distribution of SNPs for each chromosome provides information on the location of the genome under selective pressure and allows discrimination between N'Dama and Ogaden varieties.

The N'Dama-specific SNPs identified by wMI

Thirty genes with specific SNPs between N'Dama and Ogaden were identified by wMI analysis.

We established a correlation network with identified genes. The network was generated based on the correlation coefficient of gene mutations obtained by calculating the SNP variance annotated by each gene. The SNP variation is the difference in alleles of the same SNP position in the small sample. This indicates the degree of homozygosity or heterozygosity of the SNPs, defined as the ratio of homozygous or heterozygous alleles to all samples of the breed. For example, the homozygosity of SNP_1 to breed_1 is large when the SNP_1 allele pair in most samples of breed_1 is "AA". The heterozygosity of SNP_1 to breed_2 is high when the SNP_1 allele pair in most breed_2 samples is "AT".

The constructed network shows that ACCN1, CTNNA2, FHIT and USH2A function as the main hubs of the network (FIG. 4A). The heterozygosity or homozygosity of SNPs in many genes of the network is strongly associated with the SNPs of the four genes. ACCN1 encodes a sodium channel protein that is expressed both in the central nervous system and in the peripheral nervous system. It regulates neuronal activity in a pH-dependent manner. The various physiological roles of ACCN1 in the nervous system include synaptic plasticity, learning, fear, pain sensation, and neurodegenerative diseases [22]. CTNNA2 is known as a linker between the cadherin receptor and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system, and is involved in a variety of neuronal functions including modulation of surprise responses [23]. The FHIT protein is a member of the histidine triad gene family of nucleotide hydrolases involved in purine metabolism. This gene contributes to gene expression regulation and tumor suppressor factors essential for cell proliferation and survival [24]. USH2A is found in the basal membrane of the cochlea and retina, and is believed to participate in the adhesion and nerve fiber guidance of pre- and post-synaptic membranes. Mutations in the USH2A gene are associated with subtypes of Usher syndrome, the most frequent cause of hearing loss in humans [25].

In addition, the GO analysis was performed on the genes extracted by the threshold value (greater than 0.8 or less than -0.3) of the correlation coefficient in the constructed network. Many terms are related to the cognitive function ('learning', 'learning or memory' and 'recognition'), the perception system ('sensory perception of the sound' and 'sensory perception of mechanical stimulation') and the nervous system (FDR adjusted p-value <0.05) (Fig. 4b), which were related to the "sensory perception of mechanical stimulation", "synaptic transmission"

These results suggest that N'Dama can be distinguished from other animal breeds by nervous systems associated with sensory perception, learning or memory, as well as surprise responses that require a neuromuscular system. Figure 4c also shows the genotype profile for each SNP position of the four genes mentioned. Interestingly, the genotypes of the identified SNPs showed different patterns between N'Dama and Ogaden varieties. The genotype of N'Dama was biased toward homozygotes and found to be more homogeneous in the population than Ogaden.

The N'Dama-specific SNPs identified as MI and XP-CLR

In the next step, we identified genes that represent genetic signatures that contribute to the development of the N'Dama-specific phenotype. Two lists of genes were generated containing 2793 genes from the MI assay and 220 genes from XP-CLR. The 131 genes commonly found between these two lists represent a series of functional genes that promote N'Dama's adaptation to the local environment.

Correlated networks based on identified genes have shown that in many genes the genotype of the SNP is negatively associated with a common transcription factor or a single herb gene known as GTF2IRD1 (Figure 5a). GTF2IRD1 has been extensively studied in the brain and embryo in association with Williams-Beuren syndrome, a rare neurodevelopmental disorder [26]. Chimge et al. [27] observed overexpression of GTF2RD1 in mouse embryonic fibroblasts and reported that GTF2IRD1 regulates many genes involved in various biological processes such as immune response, cell cycle, cell signaling, and transcriptional regulation. Overexpression of GTF2IRD1 changes the levels of ATOH7, IL1RL2, OASL and OPRD1 expression [27]. When the SNP type is defined based on the degree of heterozygosity or homozygosity of the SNPs for all samples, the association of the SNP type between GTF2IRD1 and the mentioned target gene is also determined using the combined measure of MI and XP-CLR Correlation network. This result can be interpreted as a change in the biological interaction of GTF2IRD1 with the target gene in N'Dama, unlike other African livestock and commercial varieties. In addition, the genotypic profile of the gene showed differences between N'Dama and Ogaden varieties.

We also performed GO analysis with the gene selected by the threshold value (greater than 0.97 or less than -0.5) of the correlation coefficient in the constructed network. There was a significant number of terms including 'hormone secretion regulation' and 'ossification control' (FDR adjusted p-value <0.05) (FIG. 5b).

Terms associated with the emergence of ossification enhanced by genes including CALCR, FGF23, and CDK6 provide a pathway that can provide deeper insights into some aspects of the N'Dama specific trait. In particular, CALCR is a high affinity receptor for the peptide hormone calcitonin. This receptor is associated with maintaining calcium homeostasis and is known to increase renal calcium release and is also involved in the regulation of osteoclast-mediated bone resorption [28]. FGF23 is a phosphate homeostasis and vitamin D metabolism modulator. This protein has been reported to negatively regulate osteoblast differentiation and mineralization of the matrix. Finally, CDK6, a member of protein kinases, is an important regulator of cell cycle progression. RUNX1, a transcription factor that controls the differentiation of hematopoietic stem cells into mature blood cells, prevents bone marrow differentiation [30]. We have also identified IL1RL1 and IL1RL2 in established networks consistent with observations of the initial response of the host immune system to trypanosomes infection, including activation of macrophages that secrete inflammatory-promoting molecules such as IL-1 [31 , 32]. In particular, it has been previously reported that T. brucei infection increases IL-1 secretion. Apart from GO analysis, we showed that N'Dama and Ogaden have distinct patterns of homozygosity and heterozygosity for the SNP alleles of CALCR, FGF23, and CDK6 (FIG. 5c). Taken together, these results indicate that genetic diversity occurred between N'Dama and Ogaden in genes associated with ossification control.

MI &lt; / RTI &gt; and XP-EHH

117 common genes were identified from the 2793 gene list of MI and the 239 gene list of XP-EHH.

 Correlation network analysis performed on these genes showed that in many of these genes, the genotype of the SNP was negatively associated with the herb gene RASAL1 (Fig. 6A). RASAL1 is a member of the ras GTPase activating protein family and has recently been described as a tumor suppressor gene in a variety of cancers [34,35]. The SNP allele of RASAL1 in N'Dama represents a homozygous type, unlike the Ogaden variety.

GO analysis of the genes extracted by the threshold of correlation coefficient (0.97 or less or -0.5 or less) in the constructed network was significantly higher in terms of "immune system development" (FDR adjusted p-value <0.05) (FIG.

CARD11, FOXP1 and SP1 were significant in 'development of immune system'. In particular, CARD11 is important for the signaling of T and B lymphocytes in the innate and adaptive immune systems, and it transmits the signal of the antigen receptor to the transcription factor NF-kB [36, 37]. FOXP1 belongs to the subfamily P of the family of fork headboxes (FOX) transcription factors, which plays an important role in embryonic development and adipocyte-specific gene transcription control during adulthood. More specific functions of FOXP1 include myocardial cell proliferation regulation, motor neuron development regulation, and B cell development regulation. Similar to the results of MI and XP-CLR analysis, ossification-related terms were chosen to have a significant p-value (the modified Fisher exact p-value <0.05) due to genes including SP1 and SP7. SP1 is a zinc finger transcription factor involved in many cellular processes including cell differentiation, apoptosis, immune response, and osteogenic differentiation of dental stem cells. SP7, on the other hand, is a skeletal-specific transcription factor necessary for the activation of various genes in bone differentiation and osteogenesis [42]. Other studies have also reported that some SP7-expressing osteoblastic precursors cross stromal cartilage and form stromal cells in the marrow space where hematopoiesis occurs. Figure 6c shows SNP profiles for SP1 and SP7 genes between N'Dama and Ogaden varieties. Two genes in N'Dama and Ogaden, respectively, showed opposite humoral SNP patterns. These results indicate that SNP variants are involved in gene regulation between N'Dama and Ogaden varieties.

In addition, 8 miRNAs (bta-miR-369, bta-miR-377, bta-miR-409b, bta-miR- miR-3957) showed similarity in SNP mutation (Fig. 6A). Specifically, these miRNAs are in close proximity to each other on chromosome 21 from 67,598,000 to 67,604,800, and five of them constitute the miR-154 family, including bta-miR-369, -377, -409b, -410 and -656. Homologs of the miR-154 family found in humans are known to be overexpressed in idiopathic pulmonary fibrosis. Recent evidence also suggests that the function of these miRNA families is associated with bone development. Li et al. [46] showed that miR-410 and miR-154 expression decreased in tension-treated adipose tissue-derived mesenchymal stem cells (ADSCs) and miR-154 directly regulated WNT11, leading to WNT / PCP pathway And the inhibition of osteogenesis differentiation by ADSC. These results indicate that SNP mutants can induce differential expression of miRNAs that affect expression of target genes between N'Dama and Ogaden cultivars.

Identification of N'Dama specific missense, nonsense mutation

Finally, we looked at protein-level variations by focusing on unequal SNPs and investigated what kind of physiological changes in N'Damao caused them. After performing three measurements, N'Dama-specific missense or nonsense mutations with the annotated genomic location and coding effect on the identified genes were observed.

All observed mismatches or nonsense mutations are summarized in Table 1.

Twenty mismatch mutations in 15 protein coding genes and one nonsense mutation in RANBP17 are summarized. Many annotated genes are associated with the immune system (C1RL, EOMES and TPST1), the nervous system (AMZ1, DDX54, EML1, OPCML, SBF2, SLIT3 and USH2A) and cellular metabolism (ACAD9, CDADC1, NOX5 and TIGAR) systems.

In addition, 15 mutations among the 20 missense mutations altered their chemical properties. Eleven mutations are located in the functional region and nine in the inter-domain region (Table 1). AMZ1, C1RL and PIK3C2G showed multiple protein mutations. These mutations were not found in the functional domain, but the amino acid properties were changed. Remarkably, C1RL showed four mutations, all of which changed in amino acid character and two mutations were present in the functional region, including the CUB and trypsin-like serine protease domains. Several proteins, including CUB and trypsin-like serine protease domains, are involved in complement activation, tissue modification and cell migration. Its physiological role is not well understood, but it has been suggested that C1RL is involved in the complement pathway during inflammation. We also found one nonsense strain (rs385712825) with an important p-value value (7.82e-11). This SNP was located in RANBP17, which is a member of the importin-beta superfamily of lymph node transporter receptors. In humans, RANBP17 is the site of repeated chromosome 5 breakpoints detected in T cell acute lymphoblastic leukemia, and transcriptional activation of these genes occurs during hematopoiesis using the enhancer elements of the TCR delta gene [48].

We also compared the amino acids coded by 20 nonsense and one nonsense mutation of N'Dama to the corresponding amino acids of reference locus (UMD 3.1), human and mouse (FIG. 7). Interestingly, amino acid substitutions at mutant sites were only found in N'Dama, clearly distinguishing N'Dama from other animal breeds and species. It means that a mutated allele affects coding changes that alter the function of the identified gene.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

<110> cnkgenomics co., Ltd. <120> Single Nucleotide Polymorphisms Determining          Trypanosomiasis-resistance of N'Dama breeds and Use Thereof <130> PN170156 <160> 32 <170> KoPatentin 3.0 <210> 1 <211> 16447 <212> DNA <213> Bos taurus <400> 1 atgaattgcc tggctctttc tctgggcttc ggcctcttgt ttccggtccc tgaaacatgg 60 cctctttgcct actttgcttc catctcatgg gctgactctc agggcttgtt cccaaggctg 120 gagaatgtgg cagccttcaa gaaggtttcg gtggtgccaa cccaagcaac gtgcggaatc 180 ccagcccaaa gcactttctg tcagagctct gccacacccg agggccttcg ggtctgtcct 240 cagaggctgt gtgttcagga ttgcccttac cgatcatcgc cccccaccta cgccaacctc 300 ttctcagcag gcctcagggg ttgcatcatt aaagaccagc gtgacctgag tcccaactcc 360 cataccatt ctgcaagttt catttttgga aatcaccaga gttgctttgc ctctcctcct 420 gctcccaggc tggcggcatc atttactcta gctgtgtggt tgaaacttga gcaaggaggt 480 gtaatgtgtg ttatagaaaa aacagcggat gggcagattg tattcaaact tacaatatct 540 gagaaagaga ccatgtttta ttaccgcaca gtaaatggtt tgcagcctcc aataaaagta 600 atgacactgg ggagaattct tgtgaagaaa tggattcatc ttagtgtgca ggtacaccag 660 acaaaaatca gtttcttcat caatggtttg gaaaaggata atgcagcttt tgatgcaaga 720 actctaagtg gttcaattac agattttgcc tctggtacca tgcaaatagg acagagctta 780 aatggttcag agcagtttgt tggaagaatg caagattttc gattatacca agtggcgctt 840 acaaacagag agattcagga agttttctcc agagatctac ccagattgca tatccagtca 900 cattgccgtt gccctggcag ccaccctcgt gtccatcgtt tggaacagcg gtactgcatt 960 cctaatgacg cagaagacac aaccaaaaac agggtgttac ggctgaatcc tgaagcccat 1020 cctctttctt ttgtcaatga taacaacgtt ggtacttcgt gggtgtcaca tgtgtttaca 1080 aacatgaccc agcttagtca aggagtgacc atttccatag atttggaaaa tggacagtat 1140 caggtgtttt atattatcat tcagttctct agtccacaac caacagcagt aaggattcag 1200 aggaaaaagg aggacagcct agattgggag gattggcaat attttgctag aaattgcagc 1260 actttcagaa tgaaaaacaa tggagatttg gcaaattctg attctgtcaa ctgtcttcaa 1320 cttcccaatt ttcctccata ttcctgtggg aatgtcacgt ttagcgtcct gacacctgga 1380 ccaaatcagc gtcctggata caataatttc tataataccc catcacttca agagttcgtt 1440 aaggccaccc aagtacgact tcatttccat gggcagtacc atacgactga gactcctgtc 1500 agccccagac acagatacta tggggtcaat gaaatcacca tcactggaag gtgtcaatgc 1560 tatggtcatg ccaatcactg tgacacaaca agccagccct atagatgcct ctgctctcag 1620 gaaagtttca ctgaaggact tcattgtgat cgctgcctgc ctctttataa taacaagcct 1680 ttccgccaaa gtgatcatgt tcatgccttt aactgtaaac cctgtgagtg caacagccat 1740 tccagaagct gccactacaa catctcagtg gatccctttc catttgagca ctacagagga 1800 ggtggaggag tttgtgatga ctgtgagcat aacactgcag gaaagaactg tgagctgtgt 1860 aaggattact ttttccgaca agttggtgca gatccttcag ccatagatgt ttgcagaccc 1920 tgtgattgtg ataaagttgg cacaagaaac agtagcttcc tttgtgatca gatcggaggc 1980 cagtgtaatt gtaagagaca tgtgtctggc agacagtgca atcagtgcca gaacggattc 2040 tacaacctcc aggagtggga tcctgatggc tgcagtccgt gcaactgtaa tacctctggg 2100 acagtggatg gagatattac ctgtcaccca aattcaggcc agtgcaagtg caaagcaaat 2160 gttattgggc tcagatgtga tcactgcaat tttgggttta aatttctcca aagttttaat 2220 gacgatggat gtgagccctg ccagtgtaac ctccacggct cagtgaacag actctgcaat 2280 cctctttctg ggcagtgtga gtgcaaaaag gaagccaaag gacttcaatg tgacacctgc 2340 agagaacact tttacggact ggacgccacc ggttgtaagg cctgtgactg tgatgtggcg 2400 gggtcccggc ctgggacggt ctgtgatgct tggacaggac agtgcgtctg caagcccaac 2460 gttgggggaa gacgctgcag tgagtgtgtg gaggggtact tctaccagcc gcaaaaccgt 2520 tctttcctct gcctgccttg taactgcgat aggactggga ccgtaaatgg ctctctgctc 2580 tgtgacaaat cgacaggaca gtgtccctgc aaattaggag taacaggtct tcactgcaat 2640 cagtgtgagt ctcacaggta ccatctgacc gttggcagtt ttcagggctg ccagatgtgt 2700 gagtgtgatc ccctggggac attacctggg accatttgtg acccactcag tggccagtgc 2760 ccatgtttgc ctaaccgtca aggaagaagg tgtaatcagt gtcaaccagg cttttatatt 2820 tctccaggca atgccactgg ctgcctgcca tgttcatgcc acaccactgg tgcagttaat 2880 cacatctgta atagcttgac tggtcagtgt gtttgccaag atgcttccat tgctggacaa 2940 agttgtgact attgtaaaga tctttacttt ggatttgatt ctctaactgg gagatgtcag 3000 ccttgcaatt gtcatctctc gggagcctta aatgaaacct gtcacttggt cacaggccag 3060 tgtttctgta aacgatttgt tactggatca aagtgtgata cctgtgttcc caatgcaagc 3120 catttggata tcagcaaccc gttgggctgt agcaaaactc catcccagca acctccaccc 3180 agaggacaag ttcaaagttc ttctgctatc aatctttcct ggagtccacc tgattctcca 3240 aatgcccacc ggcttactta cagtttattc agggacgatt tcgaaatcta cacagttgaa 3300 gatcaatacc catacagtat tcagtacttc ttagacactg ccctggtgcc atatacctcg 3360 tattcctatt atatcttgac cagcagcgtg catggttcaa cacgaagcac agctgtcacc 3420 tacaggacaa aaccagggac cccagtggga agtttgaatt taagttatat cagccctgtt 3480 agctcagact ctgtgacact tacctgggct tcaccttcaa atcgttctgg tcctattgag 3540 aagtatattt tgtcctgtgc tcctcttcat gatgtccagc cctgttctcc ctatgaaggc 3600 ccagagacca ccactaccat ctggaatctg cttccattca ccaagtaccg ttttgctgtg 3660 caggcgtgta ctagtggggg ctgtttgcac agcacccctt tgacagtgac caccgcccag 3720 gcagctccca gaaggctggg tccacccaag gtgcggaaga tcagttccac agagcttcac 3780 gtagaatggg ctccaccgat ggaaccaaat ggcataatta taagatatga actgtatatg 3840 aaaagactga agtctagtgg agaaacaagg tcagcagaaa gtcaagtttt tcagagcagt 3900 ggctggctcg gtcctcaccc tcttgcagaa tcagccaatg aaaatgctct agaacctcca 3960 gaaacaacca cagtcatcac tggcttggag ccatacacca agtacaagtt tagagtctta 4020 gctgtgaaca tggctgggag tgtgtcttct gcctggacca caggaagaac gggagaatca 4080 gcgcctatat ttgtgatgcc cccttcagtc tccccactgt ctcctcactc gctcaatgtg 4140 tcctgggagc tgccaccgga cagtgttaca agaggaaaag ttgtggggta taacatcagt 4200 atgatttctg aacaatcacc tcaacagtct tatccaatgg tagttccaca ggtattgtat 4260 actgctaaat cccaagaact atcttatatt gtaaaaggac taaaacctta taggatatac 4320 aactttacta tttctctctg caactcagtt ggctgtgtaa ccagtgcttc agaagcagga 4380 cagactttag catcagcacc agcccaactg aggccgcctc tggttgaagg aatcaacagc 4440 acaaccatgc atcttaggtg gctggcacct gaagagcaga atggaccttc tcctgtgtat 4500 caactggaaa ggagagagcc atccctaccg gctccgaggg ccatggtgat gaaagggact 4560 cgcttcacag gacatggata ttataagttc cccagctcca ctcacccagt caatacagac 4620 ttcacgggta ttaaagccag ctttcgaaca agggtgcctg aaggtttgat tgtctttgcg 4680 gcatcacctg gcaatcagga agagtatttt gcaattcagt tgaagaatgg acgcccgtat 4740 tttctttttg atcctcaggg gtctgcagtg gaagttacca caactaatga tgatggtaaa 4800 caatatagtg atggcaaatg gcatgagata attgctatta ggcatcaagg tttgggccaa 4860 atcacacttg atgggctgtt cacaggctct tcagccacca cgaatggtgg tactgttatt 4920 ggagagaaca caggagtgtt tgtgggtggg ctgccacagg gttacaccat tctcagaaag 4980 gattctgaca tagtccaaaa gggttttgtg ggctgtctca aggatgtgta tttcatgaag 5040 aattataatc cctctgctac ttgggagcat ctggtttggc agagttctga agagcaaacc 5100 aatgtgcata acgactggga gggatgcccc acttcactcc aagagggagc ccagtttcta 5160 gggacagggt tcctggagct ttatccatac ttgtttcatg gtggaatgga ctttgaaatt 5220 tcttttaagt tcagaactga ccaactgaat ggattgctgc ttttcattta taacaaagat 5280 ggacctgatt ttcttgcaat ggagctgaag agtggaatat tgagcttccg gctaaatact 5340 agtcttactt ttacacaagt ggatctttgg ccggggctgt cctactgtga tggaaagtgg 5400 aataaagtga tcattaaaaa aaatgattcc atcatatcag caagcatgaa tgaactgatg 5460 gagcacgtgt cagagtccag agcccaggcg ctgatggtga attcccccgt ctatgtggga 5520 ggaatcccac aggagctgca tgacccctat aaacacctga agctggaaca aggtttcggt 5580 ggttgcatga aggatgtgaa gtttgcacgg ggtgctgtca ttaacttggc atccgtgtcc 5640 agtggtgctg tcagagtcaa tctggatgga tgcttgtcaa ctgacagtgc tgctaagtgc 5700 aggggagatg actccatcct ggtgtaccgg ggagaaaagc ggactgctta tgagagccat 5760 ctccagccgt tcacagaata cctgtatcga gtaacagcct cacatgaagg aggttcggta 5820 catagcgatt ggagccgggg ccgcacaaca ggagcagctc cacaaagtgt gccaagtccc 5880 tcaggagtcc gcagcataaa tggctatagc atcgaggtga cctgggatga acctgttgtg 5940 gctagaggtg taattgagaa gtatatcctg agagcctaca gtgaggatgc tcttggtcca 6000 ccccacacac cctctgccag ctctgagctt gtcgatacca acaccttcac aggcatattg 6060 acaggcttgc tacccttcaa aaactatgca gtaaccctag ctgcttgcac tttggctggc 6120 tgtaccgaga gcttgcatgc attgaacatc tctactccac aagaagcccc acaacaggtt 6180 cagccaccag tagccaaatc ccttccccat tctttgttac tctcctggaa tccacca 6240 aaagctaatg gtattataac tcagtactct ttatatatgg atgggatgct aatctactca 6300 ggcaatggag agaactacac agtcacagat ttagcagcat ttacacctca ccaatttctg 6360 ctcagtgctt gcacacatgt gggatgtaca aacagctccc tggtcatact gtccaccgca 6420 cagctgccac cagaacacgt ggatcccccc attctgactg tcctggattc tagaactgta 6480 tacattcagt ggaaacaacc aagaaaagta aatggaattc tggagcgcta tatgttatat 6540 atttcaaatc acacacatga ttttacagtt tgggatgtca tctataacag cacagaactt 6600 tttcaggatc acactctgca gtacctttta cctggtaata aatatctcat caaactggca 6660 gcttgcacgg ggggcgggtg cacagtgagt aaggccagcc aggccctgac tgaggagagg 6720 acccccgaag gcgtgccagc tcccagagtg aacccagact cctctcactc ctttaacatc 6780 tcctggactg agcctgagca tccgaatggt gttatcacaa gttacgggct gtatctcgat 6840 ggtatattaa ttcacaactc ctcagaactc agttgtcatg cttctggatt cgctccttgg 6900 agcttgcatt ccttcagggt ccaagcctgc acggccagag gttgtgctct gggcccactg 6960 gtggaaaatc gaactctgga agctcctcct gaaggaacag taaatgtgtt tgtcaaaaca 7020 gaaggatccc gaaaagccca cgtgaggtgg gaaccgcctt ttcaccctaa tggacgcttg 7080 atgtactcag tcctttttac tggcactttc tatgctgacc aagcaggtga taactacact 7140 cttctgaatg gcacacaaat catgcacagt ggtgaagaga ccaacctttg ggtgctcatc 7200 aacggattgg ttccttttac gaactacaca gtacaagtga atgtttccaa tagccaaggc 7260 agcttgatga gtgatcctgt aatgatttca atgcctccag gggctccaga tggcgtgctg 7320 cctccgaggc tttcatctgc cactccaacc agtcttcagg ttgtctggtc tacaccagct 7380 cggaacaacg cccccggctc tcccagatac caactccaga tgaggcctgg ccactccacc 7440 catgggtttc tagagctatt ttccaatcct tctgcatcgt taaactacga agtgagagat 7500 ctccaaccat acacagagta tgaatttcgg ttggttgcct ccaatggatt tggcagtgcc 7560 catagctctt ggattccgtt catcaccgca gaggacaaac ctggacctgt agaccctcca 7620 attatcctgg acaagaagtc aagaatgatg ttggtcacct ggcagcatcc tttaaagtgc 7680 aatgggctc ttacccatta taacatttac caacatggcc gcctcagctt ggaaacttct 7740 ggaaatgtca ctaatggcac agtgacccat ttacacccac atacggccta tgcgtttcaa 7800 gtagaagctt gtacttcaaa agggtgttcc ctgtcagcag attcccagac tgtttggaca 7860 ctcccagatg caccagaagg tatcctgagt ccagagttgt tctctgatac cccaacatcc 7920 gtgatcatat cttggcaacc ccccacccat cccaacggct tgctggagaa ctccacaatc 7980 cagagaagag tccaagggaa ggaggcagtt accaccctgg tgactctccc aggaagtcat 8040 cccaggaggt ttattgacaa gacttcttct cttagcccgt ggacaaagta tgagtatcga 8100 gtgctgatga gcactgctgg tggagggaca aacagcagtg attgggcaga agtgaccact 8160 agaccctcgc gacctgctgg ggtgcagccc cccgaggtgg atgtgttagg acccgatgca 8220 gccaaggtca cttggaagcc cccactcatc ctgaatggag acatccttaa ctacgagatc 8280 cgcatgcctg accctcacat cacgatcacc aatgttactt cttctgtgtt aagtcatgtc 8340 gttactcatc tgattccttt cactaattac tccgtcacca ttgtggcttg ctcagggggt 8400 aacgggtatc taggggggtg cacagagagc ttccctaccc acgtgaccac ccctcccgcc 8460 ctgcctcagg atcttggccc attgtccgtg gttccactaa gtgaatcata tgttgggatt 8520 tcctggcagc caccatccag gccaaacgga cctgatttga gatatgagct tctgagatgt 8580 aaaatccagc aaccacttgc atcaaatccc ccagaagatt taaatatgtg gcacaatatt 8640 tattcaggaa ctcagcggtt ttatgaagat aagggtctta gcaggtttac gacgtatgcg 8700 tataaggtct ttgtacataa cagtgtgggt tttacaccaa gtcaagaagc gacagtgaaa 8760 acattagctg ggcgtccgga gagaggagcc aatgtcactg tgactgttct taaccacacg 8820 gccatagacg tgagatgggt gaaaccaact tttcaagacc tacaaggtga tgttgagtat 8880 tatacacttt tttggagttc tgctacctcc aatgaatctc gaaaaatcct cccagatgta 8940 cactctcacg tcattggcca cttaaatcca aacacagagt atcggatttt catctctgtt 9000 ttcaacggag tcgccagcat caacagtgaa gtgctgcatg caaccacttg cgatggggag 9060 cctcagggca tgcttcctcc agaggttgtc atcatcaaca gtacagctgt acgtgtcatc 9120 tggacagctc cttcaaaccc aaatggtgtt gtcactgaat attccgtcta tgtaaataat 9180 cagctctaca agactggaat aaatgtgcct gggtctatca ttctgagaga gctgtctccc 9240 ttcactgtct atgacatcca ggttgaagtc tgcacaaaat atgcctgtgt aaaaagcaac 9300 agaacccaaa tcacgactgt ggaagatact ccaagtgata taccgactcc cacaattcat 9360 ggcatcgctt caagatccct tcaaatcttt tggatgtctc cagggaggcc aagtggcatc 9420 attcttggat atgatctctt acggaaaaca tggcgtccgt gctctaaaac taagaagtta 9480 atgaaggacc accctggtgg actctgcaag gcagtggagt gtcaaaaaca tgaacttctt 9540 tgtggaacca ggtgctactc ccctgaggct aaggtttgtt gtaatggatc tctctatgac 9600 cctcggcctg gacatgcctg ttgtgaagag aagtacatag catttgtttt gaactcaact 9660 ggagtttgtt gtggtggccg cttacgagag agacaaccaa atcatcagtg ttgctcaggg 9720 tattatatta gaattctacc aggtgaagta tgttgtccag atgaacagca caatcgggtt 9780 tccgctggcc taggcaactc ctgctgtggc agaatgccgt actccacctc aggaaagcag 9840 atttgctgtg ctgggaggct ccatgatggc catggccagc agtgctgtgg tggacagatt 9900 gtgagcaaag atttcgagtg ctgcggggga gaggaagagg gtgtggtata cagtcgcctt 9960 ccagggatgt tctgttgtgg gctggattat gtgaatatgt cagataccat atgctgctca 10020 gcttccagtg gagagtctaa agcacatgtt aaaaagaatg acccagtgcc agtaaaatgc 10080 tgtgagactg aacttattcc aaagagccag gaatgctgta atggagttgg atataatcct 10140 ttgaaatatg tttgctctga caagatttca actggaatga tgatgaagga aacgaaagca 10200 tgccgaaccc tctgcctgac gtccatggaa gccacagcac actgcggcag gtgcgacttc 10260 aactttacca gccacgtttg tacggtgatg agaggatctc acagttccgt caggaaggaa 10320 tcaatggaag aaatatgttc atctgctgaa gagactgttc atacgggaag tgtaaacaca 10380 ctgtctttca cagatgtgaa cctggagccc tacatgatgt atgaatatag gatttctgca 10440 tggaatcgct atgggcgagg attcagcaag gcagttagag ccagaacaaa agaagatgtg 10500 cctgaaggag tgagtccccc caggtggaca aaaatggatc atcttgatga tgtaatagtc 10560 ttaagctgga agaaacctat acaatcaaat ggtcctatta ttgcctacat tcttctccga 10620 aatggaattg aatgttttcg aggaacatca ctgagcttct ctgatacgga aggaattcag 10680 ccctttatgg aatattcata ccagctgaaa gcttgcacag ttgctggctg tgctactagc 10740 agcaaggtcg ttgcagctac cacccaagga atcccgcaga atatccctcc gcctagagtc 10800 acggccccca gtgcagaggc tctgcatgtg agttggcatg tccctccgaa gccaaatggc 10860 gtcattaaag agtaccagct caggcaggtc gggaaaggtc tcatctacac tgacaccact 10920 gacaggaggc agcatacggt cacaggtctc cagccataca ccaactacag cttcacactt 10980 agggcttgta catctgctgg atgcacttca agtgagcctt ttctaggtca cactctgcag 11040 gcagcccctc aaggagtttg ggtgacacct cgacacattg tagtcaattc tacaacagtg 11100 gagttatttt ggagcccgcc agaaaagccc aatggcctcg tttctcaata tcagttgagt 11160 cgtaatggaa gcttgatttt cctggggggc agtgaggagc acaacttcac tgataaaaac 11220 ctggagccca acagcagata tgtttataag ttagaagcca caactggagg tggcagcagt 11280 ccaagtgatg agtacattat acagacacct atattaacgc cagaagaaat ccagcctcca 11340 tataacatca cagtaatcgg gccttattcc atatttgtag cttggacacc accagggatc 11400 cttgtcccca aaatgcctgt ggagtacaat gtcttactca atgctggaag tgcaacacct 11460 ctgatctcct ctgttggtca tcatcaatcc atccttctgg aaaacttggc tccattcaca 11520 cagtatgaga taaggataca agcatgccaa aaaggaggtt gtggagttag cagtaggatg 11580 tttgccaaaa cagctgaagc tgcccccatg gatctaaatt cccctattct taaggcactg 11640 gggtcagctt gcatagaggt taaatggatg ccacctaaaa aaccaaatgg agtcatcatc 11700 aactacttta ttcacagacg tcctactggc attgaagagg aatcccttgt gtttgtctgg 11760 tcagaaggag cccttgaatt tattgacgat gcagacactt tgaggccttt cacgctctat 11820 gagtatcggg tcagagcctg taactccagg ggctctgtgg acagtccgtg gtcatcagca 11880 cgaactctgg aagccccacc tcaagatttc ccggcacctt gggctcaagt caccggtgcc 11940 cattcagttc tgttgaactg gaccgagcca gactctccca atggcatcat cttccagtat 12000 cgtgtggttt accaacagaa aactgatgac ccgaccttga acttctctgc tgtgcatgct 12060 ttcacagtga tgggaaccag ctatcaagcc cacctgtttg gtttggaacc cttcaccaca 12120 tatcacattg gtgttgtggc cacaaaccag gcaggagaag tttcaagccc ctggactctg 12180 gttcagaccc tcgaatcttc ccccagtggg ctgagcaact tcacagtgga gcagaaagag 12240 aatgggaggg cactgctgct gcagtggtca gagcctgcga gaaccaatgg tgtgattaag 12300 acatacaatg tcttcagtga ggacgtcctg gagtacactg gcctgaatcg tcagtttctc 12360 ttccgacgct tggacccctt cacactctac accctgaccc tggaggcctg caccagggcg 12420 ggctgtgcac actcggcgcc ccagcctctc tggacggagg aagccgcccc cgactctcag 12480 ccggccccca ccatccagtc ggtgggctcc accagcgttg agctgagctg gtcggagccc 12540 attaaaacca acggaaagat aattcgctat gaagtgattc gcagatgctt cgagggaaaa 12600 gcttggggga atcagacaat ccaggctgat gagaaaattg ttttcataga atctaatact 12660 gagaggaata catttatata taatgacaca ggtctgcagc catggatgca ttgtgaatac 12720 aaagttcaca cttggaactc agctggccac gcctgcagct cttggagtgg ggtgaggacc 12780 aggcaggcac ctccagatgg cctttgtcca cctgaggtag cccaggtatc tgtgaatccc 12840 cccaaagtgc tgatttcctg ggtccctcca gagcagccta atggcatcat ccagtcctac 12900 aggctgcaga ggaatggagt gctctatcct ttcagctttg atgctgtgac tttcaattac 12960 acagatgaga agctgctccc tttctccact tacagctatg gggtcacagc ctgcaccagc 13020 cggggctgct ctgccagcac gaccaccagc atcacaaccc ttgaggctgc ccctgcaggg 13080 gtccaccctc cggctctgag gaccatcagc gccactcaga taaatgtatc ttggtccccg 13140 ccatcgattc agaatggaga gatcactcag tatttactca ggttggatgg taaagagtat 13200 ctcgctgggc agaacctgac tctgttggtt tcccacctgc agccttatac acagtataat 13260 ttctccctgg tggcgtgtac caagggaggc tgcacagcga gcatgccaga atctgcctgg 13320 acaatggagg ccccaccaca gaacatggac cctccaaaac tgcaagttac gggctcagaa 13380 tccatagaaa tcacctggaa actgcccaga atcccaaatg gccggatcag aagctatgag 13440 ctgaggaggg atggaacaat tgtgtacact ggcctggaaa ctcggtacca tgactttact 13500 ctcaccccag gtgtggagta cggctatacg gtgatggcca acaacagtca agggggtgtt 13560 ttgagtccac ttgtcaaaga tcgaaccagc ccctcagcgc cttcagggat ggaacctccg 13620 agattgctgg ccaagggccc tcaggagatc ttcgtgacct gggatcctcc agtaaggaca 13680 aatggtcgta ttgtcaacta taccctcttc atccgtgacc tgtttgaaag agaaacaaaa 13740 atcatacaca taaacacaac tcataattcc tttggtccac agtcgttcat ggtaaaccag 13800 ttgaaaccat ttcacaggta tgaagttcga atccaagcct gcaccaggct gggctgtgtg 13860 tcaagtgact ggacgttcat agagaccctg gaggttgcac cgcagcagca accccctccc 13920 catctagagg tgcagatggc tccagggggg ttccagccca ccgtttccct tctgtggaca 13980 ggacccctcc aaccaaatgg aagagtttta tattatgaat tgtacagaag acaaatagca 14040 actcagcctg aaaagtcaaa accagtgcta gcctataatg gaagctcaag ctcttttatg 14100 gatgttgaac tactgccttt tacagagtat gaataccagg tctgggccgt gaattcagca 14160 ggtaaagccc ccagcagctg gacgcggtgt agaactggac ctgccccccc ggaaggtctc 14220 aaggccccca agttccatgc ggtttctgcc acccaagcag tggtcaacat cagcaccccc 14280 cagaagccca acgggattgt cactctctac agattgttct ccaggagcac cagcggggcc 14340 cagacagtgc tggctgaagg cctggccacc cagcagactc ttcacagcct gcagcccttc 14400 acgacctact ccattggggt ggaggcctgc acttgcttca gttgttgtag ccaagggcca 14460 acagcagagc tgagaactcc tcctgctcca cccgcaggat tgtcctctcc gcaaatccag 14520 atgctggcct caaggacagc ctccttccag tggagtccgc cactgttccc caacggtgtt 14580 attcaaagct atgagctcca actctacaag gcatgtcctc cagattcagc caccccctgt 14640 acccccagcc aaactgagac caagtacagg gggccagggc agagagccag cctcgagggt 14700 ctccagccct acaccaccta caagctgagg gtggtggccc acaacgaggt gggcagcaca 14760 gtcactgaat ggatcagctt cgtcacccaa aaagaattgc cgcagtaccg tgccccgatc 14820 tcagtggaca gcaacctgtc cgtggtgtgt gtgaactgga gcaactcctt cctgctgaat 14880 gggcggctga aggagttcgt cctgaccgac ggaggacagc gcctctacag tggcctcgac 14940 accaccctct atatcccgag gaccgcggac aaaactttct tttttcaggt catctgcatt 15000 acagaagaag gaagtgctaa gacgcctttg atccaatatg atacctccac tggatttggc 15060 ctggtgctga caactcctgg agaaaagaaa ggatcaagaa gcaaaagcac ggagttctac 15120 agcgagttgt ggttcatagt gttaatggca gtgctgggct tgattttgtt ggccattttc 15180 ctgtctctga tactacagag aaaaatccac aaagaaccat atatcagaga gaggcctccc 15240 ctagtgcctc ttccaaaacg aaggtctcca ctgaatgtct acccacccgg ggaaacccat 15300 gtgggcttag ctgataccaa aatcccccgg tctgggacac ctgtgagcat taggagcaac 15360 cgaagcctgt ctgttctgcg catcccaagt cagagtcacg gcagtcagac ctattcccaa 15420 ggctctctcc accggagtgt cagccaactc atggacattc aagacaagaa ggtcttgata 15480 gacgactcac tgtgggaaac catcatgggc catgacagcg gactgtatgt ggatgaagag 15540 gacctgatga acgccatcaa gggtttcagc tctgtgacta aggaacacac cacattcacc 15600 gacacccacc tgtgaaggat ggaaacctgt aagacataag ctggatgcag gccccacccc 15660 ccatcaccac tgggttatca gatatcataa atgctgaaaa gctattgctt gtcatgttgt 15720 aatcctttaa agatgagtgt ttttgaaatt atttctccct aatcgaggtc taagttgttt 15780 ttctggcagt ctaaaatgag gggtttctga aattttatgt ccaagtgaaa atgcttattt 15840 tgctctcctt attttgagga cactaagcac gtaactgtca cttggctatg tttggcagtg 15900 acacggctat ttaaatgaat attcagtggc aatttcaggt tggcccacag ttgctacagg 15960 taagttacta atttaaaagc taaggggttc ttctgagagg atgtcattgc tgctgcttta 16020 agcagcagaa cactgcttct gctctcagct cctggtttat ggaagttgaa ataaaccagt 16080 gaggaaccat tctagtaaca gctgcaaaat caaatcccaa tgtcagatca agctgaaaca 16140 ctcaaagaga aacaaactgc attgaggcta tacatttgac tgtgtaggtt tctatttgat 16200 tatgatgttt agggataagt atttaccaaa ccacatatac ttataaatgt ctgttcttac 16260 atgtatgaat cttctaaaaa tctgaggaac aagcagctaa cttatatatt tcaaagagaa 16320 aaatgaactg ttttgatatt ttacataatt ttgacactct agtcattact ttttatagaa 16380 ttctgtcaat tcactgaata cccaggaata ccttcacctt ggcacattct atatggaaac 16440 tactgtt 16447 <210> 2 <211> 1698 <212> DNA <213> Bos taurus <400> 2 agccccgtgt actgcaggta ccagttccac agggccccag tgcactgcac ggagggccag 60 ccgcacggga cccacgtgta cttccaggac gtcaacgtca tcttcctagg ggccatgcac 120 cccagcgacc tgagggagta cctggagggg ccccccatgg tggtagaagt gcacgaccgg 180 gccgcaagt ccgagggctg ttcccgcaag cccaccctgt ttggggagga ccccctggac 240 gcgcacctca acctccaggc cctcatctcc cccagagaca cggagagcaa cccctttgag 300 acccaggaga agatgtggga cccgcatggc gtggcccagg tcagctttgc cgacctcctc 360 ctcggccaca agtacctgaa cctggccgcc cctgtgcgca gctgcgagcc ctgggccgcc 420 cccctgggcc acggccgcag gagcaggcac gcggcggggc cccggggccc cagggacggc 480 gtgccgcatg ggctgatgcc gccgggggac tacctggagg ccagctgcct gctgaagctg 540 cgtgtggatg tggcggtgcc tctgcgcggt gggctgggcg gcgccgaccc cgtgctttcc 600 cggttcggcc gcgtggtctt cgtgttcgag tccaggcggc tctccctgct gcacagcctc 660 ctgcaggacg tcaccatgat caacgccagg gccctggccc tggactccta cccgctggag 720 gacattcaac agatcctgtc cgccttcaag atccgggtga agacccagga gcagcccgac 780 ctggacgtgc tcaccggcgt ccacctgctg gacgggaagg tccacttcct cgtcctggag 840 ggcctggccg accacggcct ccagcggctg tgggcccgtc accagagccg ggtcccgcgg 900 gcggaacagg gtcccttcaa ggcgctctac aactcgcagc tgcgcttccg ccggcgcctc 960 tacgccgacc tggagacggt cctgtaccgc gtgcggctgt tccggccgct ggcgcagctg 1020 gtgcagcaag cggcgctcta cgtgcgcaga gcggtcccgc cgcaggtgtt ccaggcgctg 1080 agcaggatct actgcatatg ccgttacagc tccaggctca gggaggtgat cacgggagac 1140 ctgctgccct cctcggccat gatcaaggag ctgagccagg agtttgggat gcccatgtcc 1200 cagggagacc tcacagagca gaagctgcta gccgtggccc ctgccccaag tctcgaggac 1260 ttgcggagcc ggaagtccac cctggcgtca gagatccact cccaccagga gccgggcagg 1320 aggttcacat actcacagaa gtacctgtca gccacggtgg ggcctctgga cccagaggag 1380 gaggagagga gggcccgcag ggagtcccgt caggcctggc gcacgcccaa cggcttccag 1440 acggcgggtc tccacagcat gggcacaacc tggcccctgc ggctgccgcc catcagcgct 1500 gccacggagg agtggaggga gaaggccctg ttcaccaact tgctggagcc agtgctgtgg 1560 cgggagaggt ggggctggga ccggcgccac caggacttca acctgtacac acggccgccg 1620 gagttcctgg agcttccgcc tgcgcccaag cccagggcag cgaggagcag acgggggccc 1680 ggacacagcc ctgctcga 1698 <210> 3 <211> 1500 <212> DNA <213> Bos taurus <400> 3 atgctgcagt gccggccggc cgaggagttc agcttcgggc cccgggccct gaaggacgcg 60 ctgctgtcca ctgaccccgc cctgcggcag ctctacacag ccgccttctc cccggccgag 120 aggctcttcc tggccgaggc ctacaacccc cggaggacgc tctttggcac actgctcatc 180 cgcacggcct tcgactggct ccttagccgc cccgaggccc ctgaggactt ccagaccttc 240 catgccgccc tgccgccccg gaagcagagc ctcgctcgga agcacattta ccttcagccc 300 ataggtctga gcgagggtcc agcgggcagt gtgcttctgg accagctgcg aagctgcacg 360 ccgccctcc cactgctcgt cccgccccgg tcaggacccc gacaggctcc agctccacac ggatggcatc 480 ctgtccttcc tgaagagcag caagccgggg gatgctctgt gtgtgctggg cctcacgctg 540 tccgacctgt acccttgcga ggcctggacc ttcaccttcg gcacgttcct tccggggcac 600 gaagtgggcg tctgcagctt tgcccggttc tcgggggagt tcctgccgcg agagcccagc 660 acgcctgacc tggtggaggt ggaggcggag gcggctgcag atggccccga ggtgcccctg 720 caggatggag gccaggccgt gtgcttcagc gccctgggga tggtccagtg ttgcaaggtc 780 acgtgccacg agctgtgtca cctcctgggc ctgggaaact gccgctggct ccggtgcctc 840 atgcagggcg cgctgcgcgt ggacgaggcc ctgcgccggc ccctggacct ctgccccatc 900 tgcctgcgca agctgcagca cctgctgggc ttcaggctgg tggacaggta caagagactc 960 tacgcctgga cacaagcggc agcagggacg cagccgagcc cagcggcagt gggggaaccg 1020 tctgtgtcgg aggacaccct tccctgcagt gcagactcgg ggctgtgttg tgagagcgac 1080 tcggagccgg gcagcagcct gtcggagccc ctgtcccccg acgcctggag ccaggccttc 1140 cccgcgggcc tcgagctgga tgctgaggac gggctgggct ccctggcagc cgcggagggc 1200 ccgggggagg ccctggcaga gcacgggcgc tggctggccg cctgcatcca ggccctggag 1260 agggacgtga gcgaggggga gctggagcgg gtggatggcg ccgtggacgc gctggccccc 1320 tgggacctgt tcacggggcg gctcccggcc tcccgacagg acctgccctg tggccgcgac 1380 ggcgcggggc tgcgcagggt cctgggggac acgttctcct ccctccggag gaggctgagc 1440 gctcgcaggc cgtccagggc cgagtcaccc ctccggcgcc agaaggcgga ggacgactag 1500                                                                         1500 <210> 4 <211> 1551 <212> DNA <213> Bos taurus <400> 4 atgagagaag cggggcagat gcaaaatctg gagagcgcgg gggccggacg gtcagtcagc 60 acccagacgg gcagtatgac cggtgaaata ccaaggcttt ctaaagtcaa ccttttcact 120 ctgctcagtc tctggatgga actcttccca gcagtgaaaa cccaaagaca gaaatctcag 180 tctaaaacta gtaatccttc ccccgcccct ctttctaaaa atcatacatt tacaagacta 240 tttataagaa agaaaaaagt gaagagaact ggtcttgtgg tggtgaaaaa tatgaaaatt 300 gttggtctcc actgttcaag tgaagattta catgctggga aaattgctct gataaaacat 360 gggtcaaagc tgaaaaactg tgatctctat ttttccagaa agccatgttc tgcttgtttg 420 aaaatgattg taaatgctgg agttaatcga atttcatatt ggcctgctga cccagaaata 480 agtttgctca ctgaggcttc tggtttcgaa gatgcaaagt tagatgccaa agcagtggaa 540 agactgaagt caaacagtcg ggcccacgtg tgtgtcttac ttcagccttt ggtctgttac 600 atggtgcagt ttgtagaaga gacctcttac aaatgtgact ttattcaaaa aatttccaaa 660 acattgccag acactaactt tgatttttat tctgaatgta aacaagagag aataaaagaa 720 tatgaaatga tatttttggt ttccaatgaa gaaatgcata agcaaatact gatgactata 780 ggtttggaga acttgtgtga gaatccgtac tttagcaatc taaggcagaa catgaaagac 840 cttgtccttc ttctggccgc agtagcttcc agcgtgccca actttaaaca ctacggattt 900 tattgtggca acaccgaaca cagtaatgaa attcacaatc aaagtttgcc acaagaaatt 960 gcaaggcact gcatgattca ggccaggtta ctggcatatc gaactgagga tcataaaaca 1020 ggagtcgggg cagtcatctg ggcggaagga aaatctagaa gttgtgatgg cacaggcgcc 1080 atgtacttca taggatgcgg ttataacgct tttcctgttg gatccgagta tgctgacttt 1140 ccgcacatgg atgacaaaca gaaagacaga gaaataagga aattcagata catcgtacat 1200 gctgaacaga atgccttaac atttaggtgt caagaaataa agccagaaga aagaagtatg 1260 atttttgtga ccaagtgccc ttgtgatgaa tgtgtacctt taattaaagg tgcaggcata 1320 aaacaaatct atgcagggga tgtagatgtt ggaaaaaaga aggcagacat ctcttacatg 1380 agatttgggg aagttgaagg tgtcagcaaa tttacatggc aactgaatcc atcaagaact 1440 ggtgttcttg agcaaaatga gcctgaaagc agagagaatg gcgtgctggg atccgtagcc 1500 ctggatgaag aaccacacca gaacaagaag ctgcgtcttg caaaccacta a 1551 <210> 5 <211> 2472 <212> DNA <213> Bos taurus <400> 5 atgtcggacg gcgagggccc ctcagccgat gacagcgctt ctgctgccag cagcatggag 60 gtgacagacc gcatcgcctc cctggagcag cgagtccagc tgcaggagga cgacatccag 120 ctgctcaagt cggctctggc cgatgtggtt cggaggctga gcgtcaccga ggagcagcag 180 gccgtgctca gcaggaaagg gcctaccaaa gcaagaccac tggtgcagac cttgccttta 240 agaaccacgg tcaacaacgg cactgtggta ccaaagaaac ccagtggctc cctgccagcg 300 cccccggggg cccggagaga acccgctgtg cctgccgcag ccaagagatt aaacaggtct 360 gtgagccttc tcagtgctta cacactgaac agatccacgg ccagtaccgt caagaggacc 420 agctcatctg aacgggtgtc tcctggcggt cgaagggaaa gctatgggga ttccaaaggg 480 aaccggaacc gcacaggatc caccagcagt tcttctagtg gcaaaaagaa cagtgaaagc 540 aaacccaagg agccggtctt cagcgcagaa gaaggatatg taaaaatgtt tcttcgtgga 600 cgccctgtta ccatgtacat gcccaaagat caagtggatt cttacaattt ggaagcaaaa 660 gtagaactgc caaccaagag actgaagctg gaatgggcac gaagctacgg gtacaggggt 720 cgagactgcc gtaataacct gtacttgctc ccgacgggcg agaccgtcta tttcatcgcg 780 tcggtggtcg tgctgtacaa cgtggaggag cagcttcaga ggcattacgc gggccacaat 840 gacgacgtga agtgccttgc agttcacccc gatagggtca caatagccac aggacaagtc 900 gcaggcacgt ccaaggatgg aaaaaagcag cagttacccc cacacgtgcg catctgggat 960 tccgtgacgc tgaatacgct gcatgtcgtc ggaatcgggt ttttcgaccg agccgtcacc 1020 tgtatcgcat tctcaaaatc taatggaggc agcaacctct gtgcggtgga cgactccaac 1080 gaccacgtgc tgtccgtgtg ggactggcag aaggaagaga ggctggcgga cgtcaagtgt 1140 tcgaacgaag ctgtatttgc cgcggatttc caccccaccg acaccaatat aatcgtaacc 1200 tgtggaaagt cccacctcta cttctggacg ctagaaggaa gctcccttat taagaagcaa 1260 ggattgtttg agaagcaaga aaagccaaag ttcgtcctct gtgtgacttt ttctgaaaac 1320 ggtgacacca tcaccggaga ttcaagtggc aacatcctgg tatggggaaa aggtacgaat 1380 cgaataagct acgtggttca aggggcccac gagggcggta ttttcgcact ttgtatgtta 1440 agggacggca cgcttgtgtc gggaggaggg aaggaccgca agctcatttc ttgggatgga 1500 aattaccaga agcttcataa aaccgagatt ccagaacagt ttggccccat acggacagtg 1560 gccgaaggaa aaggcgatgt gatattgata ggcacgacca gaaactttgt tctgcagggc 1620 acactgtcgg gggacttcac acccatcact cagggtcaca ctgatgagct ctggggactg 1680 gccgtccatg cctccaaacc tcagttcctg acctgtgggc acgacaggca cgccaccctg 1740 tgggacgccg tgggtcaccg gcccgtctgg gacaaagtca tagaggatcc agctcagtct 1800 tctggttttc atccttcagg gtctgtggtt gcagtcggaa cactgactgg gaggtggttt 1860 gtgttcgaca cagaaacaaa agacttggtc accgtccaca cggatggaaa cgaacagctc 1920 tccgtgatgc gttactcacc agctcaggcc ttcttgacag gtgcttttgg agcacattgc 1980 ttgggtgttt gtatatatat ggagagagag aaatctaaaa aagtcttttt aatccatacg 2040 tgctccctcc ctccctgcag tttcgtaact tttctttttt gggggcaact ctttacatat 2100 gagaaaatcg attgggtgcc atctggttca cggcagcagg gagcgtgtcc tgagtcccgt 2160 ggggtccatg cagcagcaga gcagtttgaa gccaaccaag aaagtgcctc actatgggca 2220 gaaggaaccc ctggaagggc agacgcagca accatttgcc acgagcattt ccagcacacg 2280 tactccagca cttctgaccc ttctcccggg cttagcgttc actgccctcc atgtctttcc 2340 tcccaggctc ccagccacgt gtacagtggg cacagcagtc acgtcaccaa cgtcgatttc 2400 ctctgcgacg acagccacct catctccacc ggcggcaaag acacaagcat catgcagtgg 2460 cgggttgtgt ag 2472 <210> 6 <211> 2077 <212> DNA <213> Bos taurus <400> 6 atgcagttag gggagcagct cttggtgagc tctgtgaacc tgcccggcgc gcacttctac 60 ccgctggagg gggcgcgagg aggcggcggc gggagcgccg gccacctccc gggagcggct 120 ccctcgcctc agaggctgga cttagacaaa gcgcccaaga agttctcggg cagtctctcg 180 tgcgaggcgg cgagcgggga acctgcggcc gccggcgcgg gggcccccgc aaccatgctc 240 agtgacgccg acgccgggga cgcctttgcc agcgccgctg ccgtggccaa gccggggccc 300 ccggacggcc gcaagggctc cccctgcggg gaggaggagc tgccctcggc cgccgcagcc 360 gctgcggccg ccgccgcggc tagcgcgcgc tactccatgg acagcctgag ctcggagcgc 420 tactacctcc agtcccccgg gcctcagggc tcggagctgg cggctccctg ctcgctcttc 480 ccgtaccagg cggcggccgg ggcgccccac gggtctgtgt acccggctcc caacggggcg 540 cgctacccct acggctccat gctgcccccc ggcggcttcc ccgcggccgt gtgcccaccc 600 gggagggcgc agttcggcac gggagccggt gcgagcggcg gcgcgggcgg cggcggcggt 660 ggaggcggcc cgggcgcgta tcagtacggc cagggggctc cgctctacgg gccgtaccca 720 gcggcggcag ccgcaggtac ctgcggagga ctagggggtc tgggggttcc cggctccggc 780 ttccgcgccc acgtctacct gtgcaaccgg cctctgtggc tcaaattcca ccgccaccaa 840 accgagatga tcattacgaa acagggcaga cgcatgtttc cttttttgag cttcaacata 900 aacggactca atcccaccgc ccactacaac gtgttcgtag aagtggtgct ggcggacccc 960 aaccactggc gcttccaggg gggcaaatgg gtgacctgcg gaaaagcgga caataacatg 1020 cagggcaaca aaatgtatgt tcaccccgag tctcctaaca ctggttccca ctggatgaga 1080 caggagattt cttttgggaa gttaaaactc accaataaca aaggcgcaaa caacaacaac 1140 acccagatga tagtcttaca gtctttacac aagtaccagc cgagactgca cattgttgaa 1200 gtcacagagg atggcgtgga ggacttgaat gagccctcta agacacagac cttcactttc 1260 tcagaaacgc agttcattgc tgtgaccgcc tatcaaaaca ccgatataac tcaactaaag 1320 attgatcaca atccctttgc aaaaggcttc agggacaact atgattcatc ccatcagatt 1380 gtccccggag gtcggtacgg cgttcagtcc ttcttcccgg agccctttgt caacacttta 1440 cctcaagccc gatattacaa tggtgagaga accgtgccac agaccaacgg cctcctttca 1500 ccccaacaga gcgaagaggt ggccaaccct ccccagcggt ggcttgtcac gcctgtccag 1560 caacctggga caaacaaaat agacatcggt tcctatgagt ctgagtattc ttccagcacc 1620 ttgctcccgt atggcattaa atccttgccc ctccagacgt cccatgccct ggggtactac 1680 cccgaccctg gcttcccagc gatggcaggg tggggaggca gaggctctta tcagagaaag 1740 atggcagctg gactcccatg gacctcccga acaagccccc cagggttctc tgaagatcag 1800 ctctccaagg agaaagtcaa agaagaaatt ggctcttctt ggatagagac acccccatcc 1860 atcaaatctc tcgactccaa cgattcgggg gtatacacca gtgcttgtaa gcgaaggcgg 1920 ctgtctccta gcacctctag caatgaaaat tctccctcca taaagtgtga ggacattaac 1980 gctgaagaat acagtaaaga ctcctcaaaa ggcatggggg gttattatgc tttttacaca 2040 actccctaaa gagttatttt aaccttgtca aaatgag 2077 <210> 7 <211> 312 <212> DNA <213> Bos taurus <400> 7 atgtctggtc gtgggaaggg tggcaaaggc ctcggcaagg ggggtgctaa gcgccatcgc 60 aaagtcttgc gggacaacat tcagggtatt actaagccag ctatccggcg tctggctcgt 120 cgtggaggcg tcaaacgtat ctctggtctt atctacgaag agactcgtgg ggtgctcaaa 180 gtgtttctgg aaaatgtgat ccgggacgcg gtcacctata cggagcatgc taagcgcaag 240 actgttaccg ccatggatgt ggtctatgcg ctcaaacgtc agggccgtac cctttacggt 300 tttgctggtt ga 312 <210> 8 <211> 4706 <212> DNA <213> Bos taurus <400> 8 atggcatatt actggaaaac agatctaaat tccagtgaat cacatgaaaa gcagcaggag 60 caccaagaat tcccctcctt gaatcaacct cttttttcta gcctagtcag tctaggtttt 120 gataatgtag tagaggagat cagtaacaaa atcccactct gtcagagaga aatcgaagaa 180 aatgcctttt ttgtgcccag tgcactacac tgggactcaa gaacacattc attagatgaa 240 atacaccaaa cgtccttgaa tgaattcact tctaaaagct cagaactctc ctgtcaccaa 300 gttagggaaa caccagtaat tggttttagt aggcattctg tgctaccaaa tcctcaaaac 360 atcaataaag gaagctcttg gggaaatccc ataggaaaat accacggtgc tgatgattac 420 ggattcaata ttttgcctct atcatctacc agtctggata aaaataattc acagagtcaa 480 ctggaaaatg aaaatcataa ctaccatata ggatttgaaa gcagcgttct tcctatatac 540 ccattcttgt caactaactt gatgccgaaa gaagaaaaca aaagcaggag aaatatgaac 600 gttgtagagt cttctctgat gccctttcaa ggttcttctc tacccaggac atgggaaagt 660 acacacccaa agaacactga gctgacaggt tgttccattc agctggttga agtagctcaa 720 ggcagtaata tgagtttggc atccttttgc aacaaagtaa aaaaaataag agaaacatat 780 catgccgctg acatggattc caattctggg aagatttgga gcacgactac agcatttcca 840 tataagctct tttctaatac taagtttaat ataaatattt ttactgataa ctcaacaaaa 900 ggacttcatt ttatcccatg tgctaattat cttgtcaaag acctaattgc cgaaattcta 960 catttttgca tgaatgacca gttattcccc agagatcatc tcttaagtat atgtggccat 1020 gaagaatttt tacaaaatga tcactatttg ggaagccaca gagtatttca gaaaaataaa 1080 tctgttattc aacttcatct acagaaaaag agagacactc caggaacatt atctcgaaag 1140 catgaagatg accacagtca gttttatctg aaccaacttc tagaatttat gcatatctgg 1200 aaagtatcca gacagtgtct ctcaacagta atccaaaaat atgactccca cctgaaatac 1260 ttattgaaaa ctcagcaaaa tgtggacaat gttattgaag aagtaaaaag tatatgcagt 1320 gttctgggat gtgtggagac caaacaaatt acagatgcta taaatgaact aaatcttatt 1380 cttcagagaa aaccaaagaa tcttcatcaa aattcagaca cttcagcaaa aggtttgata 1440 gagaaagtga caaccgaact atccacatcc atctgtcagc taattgatat ccattgcagc 1500 agcttctgtg cagatttcca gcctctacac gcacctctgt atagtgtctc ctgtgtaaat 1560 cttgggctcc attcccacct tagcttcaca gtgtatgcag ctcacaatat tccagaaacc 1620 tgggtgcaca ggatcaattt tcctctcgaa ataaaatcac ttccaaggga atccatgctc 1680 actataaaat tgtttgggat tacctatgca accaatgcag atttattggc ctggacttgt 1740 tttccactgt ttccaaaaca cagatccatt ctcgggtctg cgctattcag catgacatta 1800 caaagtgagc ctcccatgga aatgattgct ccaggagtgt gggatgtaag tcagccatcc 1860 ccagtgaccc tgcagattga ttttccagct actgagtggg agtatatgaa acttgattct 1920 gaagagaatg gaagtgatct tgaagaacca ccaaaagaat gtttaaaaca tattgccaga 1980 ctgtcacaga aacagactcc catactcctc tctgaggaaa agagaagata cttatggttt 2040 tatcgcttct actgcaacaa tgaaaactgc tcccttcctt tggtcttggg aagtgcccct 2100 ggatgggatg aaagaactgt ttcagaaatg cataccattt taagaagatg gaaattctct 2160 caccctttgg aggcacttgg acttttgact tcaagttttc cagatcaaga aattcgtaac 2220 gtggcagttc agcagttaga caacctcttg aatgatgaac tactggaata tctcccacag 2280 ctagttcagg ctgtcaagtt tgaatggaac cttgagagtc ctctggtgca acttctgtta 2340 caccgctcac tacaaagtgt ccagattgcc catcgtcttt actggctgct aaaggatgca 2400 cagaatgaag cttattttaa aatctggtat cagaagctat tggctgcact ccaattctgt 2460 gcaggaaaag ccttgaggga tgagttttcc aaggagcaga aacttatcaa gattctggga 2520 gacattgggg aaaaagtcaa gactgctagt gaccctcaaa gacaggaggt gctgaagaag 2580 gagcttggca gactagaaga attcttttgg tgtacaaaga cctgtcacct ccctctgaac 2640 cctgccctat gcgtacaggg gatcgatggt gatgcatgtt catatttcac atctaatgct 2700 ttgccgttga agattacctt cattaatgcc aatccaatgg gcaaaaacat cagtgtcatt 2760 tttaaggctg gagatgatct ccgtcaggat atgcttgttc tgcagattat tcaagtgatg 2820 gacaatattt ggctgcagga gggcctggat atgcaaatgg tcatttatag atgtctatcc 2880 acaggaaaag gccaagggtt ggtgcagatg gtgcctgatg ctgtaaccct agcaaaaatc 2940 catcgctgtt ttggaccgat aggacccctg aaagaaaata caatcaaaaa atggttcagt 3000 cagcataacc ctttaaaggc ggattatgaa aaggtcttaa ggaacttctt ctattcctgt 3060 gctggctggt gtgtggtaac gttcatccta ggagtctgcg accgacacaa tgacaatatc 3120 atgctgacaa agtcgggcca catgtttcat attgactttg gaaaattcct gggtcacgcg 3180 caaacatttg gagggataaa aagggaccga gcccctttta tttttacttc agagatggag 3240 tactttatta cagagggtgg gaaaaaccca cagcatttcc aagattttgt ggagctttgc 3300 tgtcgagctt ataatattgt cagaagacac agccggctgc tcttgaacct gctagaaatg 3360 atgttacatg caggattgcc cgagctaagc ggaatccaag acctgaaata tgtgtataat 3420 aatcttcgtc cacaagatac agacctggaa gcaacaagtc attttaccaa gaaaataaag 3480 gaaagtctgg agtgcttccc tgtgaaattg aataacttga tccatacact tgcacaaatg 3540 acagccataa gccctgccaa attgacttca cagacgtttt cccaggaatc ctgtatgtca 3600 ggtgcaagca ggtcaatcca aagagcaaca gtcttagggt tcagcaagaa aaccagccat 3660 ctgtatctaa tccaggtgac tcacagtaac aacgaaacaa gcctgacaga aaagtcattt 3720 gaccagtttg caaaacttca cagccaactt caaaagcagt ttgcatcact gaccctccca 3780 gagtttcctc actggtggca cttacctttt acaaattcag atcacaaaag gttcagagat 3840 ctaaatcatt acatggaaca gatattaaat ggatcgtatg aagttgcaaa cagtgattgt 3900 gtacttagct tttttctctc tgagcctgtg gaacaagcag tgaaagaatc atcagctgtg 3960 gacctaggtg agaagtttgc tgacaagaag cctaaagtgc agttagtcat atcctacaaa 4020 gacgcgaagc tgaccatact tgtgaagcac atgaaaaaca tccatctccc agatggctcc 4080 gcgcccagcg cacatgttga attttatctt ttaccgtatc ccagtgaagc ccggaggagg 4140 aaaacaaaat ctgttccaaa atgtactgac cccacttaca atgagattgt agtatatgat 4200 gaagtcacag agctccaagg acatgtctta atgcttattg taaagagcaa aaccacgttt 4260 gtaggcaa ttaacatcca actctgcagt gtcacactca atgaagaaaa atggtatcca 4320 ctaggtaaca gtataatttg agcattgctt tgaacataca gattcattaa ctactcatat 4380 ttttttcact tttgggcctc tctatcacaa gatcaggaca tttttttaat caaaggtagt 4440 gtggtaaatt aaggacacag agaaaagaaa tcagaatcaa tgtttttagt tatttattct 4500 ctgtgtattt cactgttttc ttagaaccat ttctccaatt gattgtgtaa attcaatatg 4560 taaaataata aaaggatatt ttagtgtatc ttttaaatca aacatgcgtg cactttataa 4620 ttatgtgcct atagttaaaa gcaatacttt taatgtagtt ttcaaaaaaa accaaagcaa 4680 ataaatctta tcacttcaag acctaa 4706 <210> 9 <211> 4020 <212> DNA <213> Bos taurus <400> 9 accctcaaca acaacaacat cagccgcatc ctggtcacca gcttcaacca catgccgaag 60 attcgaacct tgcgcctcca ctccaaccac ctgtactgtg actgccacct ggcctggctc 120 tcggactggc tgcgacagcg gcggaccgtc ggcccgttca ctctctgcat ggctcctgtg 180 cacctgcggg gcttcaacgt ggcagacgtg cagaagaagg agtacgtgtg ctcaggcccc 240 cactcagagc ctccagcctg caatgccaac tccatttcct gcccttcagc ctgcacttgc 300 agtaataaca tcgtggactg tcgagggaag ggcctgacag agattcccgc caacttgcca 360 gagggcatcg ttgaaatacg cctggaacag aactccatca aatccatccc tgctggagcc 420 ttcacccagt acaagaaact gaagcgcata gacatcagca agaatcagat ctcagacatt 480 gctccagatg ccttccaggg tctgaagtca ctcacgtcac tggtgctcta tgggaacaag 540 atcacggaga ttcccaaggg actatttgat gggctggtgt ccctgcagct gctcctcctc 600 aatgccaaca agatcaactg cctgcgggtg aacacgttcc aggacctgca gagcctcagc 660 ctgctctccc tgtatgacaa caagctgcag accatcagca aggggctctt tgcccctctg 720 caggccatcc agacactcca cttggcccaa aacccgttcg tgtgcgactg ccacttgagg 780 tggctggctg actacctgca ggacaacccc attgagacca gcggggcccg ctgcagcagc 840 ccacgccggc tggccaacaa gcgcatcagc cagatcaaga gcaagaagtt ccgctgctca 900 ggctcggagg attaccgcag caggttcagc agcgagtgct tcatggacct cgtgtgccca 960 gacaggtgcc gctgtgaggg caccatcgtg gactgctcca accagaagct ggcccgcatc 1020 cccagccacc tccccgaata cgtcaccgac ctgcgactaa acgacaatga gatatctgtt 1080 cttgaggcca ctggcatctt caagaagttg cccaacctgc ggaaaataaa cttgagtaac 1140 aacagaatca aggaggtgaa agagggcgct tttgatggcg cggccagcgt gcaggagctg 1200 gtgctgacgg ggaaccagct ggagacggcg cacgggcgcg cgttccgcgg cctcagcggc 1260 ctcaagacct tgatgctgag aagtaacctg atcagctgtg tgagcaatga cacctttgct 1320 ggcctgagct cagtgaggct gctctctctc tacgacaatc ggatcaccac catcaccccc 1380 ggagccttca ccacgcttgt ctctctgtct accataaacc tgctatccaa ccccttcaac 1440 tgcaactgcc accttgcctg gctcgggaag tggctgagga agagacggat agtcagcggg 1500 aacccccggt gccagaagcc cttcttcctc aaagagattc ccatccagga cgtggccatc 1560 caggacttca cctgtgacgg caacgatgag agcagctgcc agctgggtcc gcgctgcccc 1620 gagcagtgca cctgtgtgga gacggtggtg cgctgcagca accgggggct ccgtgccctt 1680 cccaaaggca tccccaagga cgtgacggag ctgtacctgg aaggaaacca cttaacagcc 1740 gtgcccaagg agctatccag cttccgacat ctgacactca ttgacctgag caacaacagc 1800 atcggcatgc tgaccaacta caccttcagc aacatgtctc acctctctac cctgatcctg 1860 agctacaacc ggctgcggtg catccccgtc cactccttca acgggctgcg gtccctccga 1920 gtgctcaccc tccatggcaa cgacatctcc agtgttcccg aaggctcctt caatgacctg 1980 acgtctcttt cccatctgct cctacacact ttcccaatga actacaattc ttctatctgc 2040 caactgtctc gatatattac tcccttcaat gggtatagtg aatttcaaat ttcaggttgt 2100 tccaaagtta cccctaaaaa tttcttagat gaattaatac ttgcctctta catccacagg 2160 aatttgccac cagggccagt ggacatcggc atcgtggcca agtgtgaccc ctgcctctcc 2220 agcccgtgca agaacaacgg cacatgcagc caggaccccg tggaggggca ccgctgcgcc 2280 tgctcccacg gctacaaggg cagagactgc accgtgccca tgaacacctg cattcagaac 2340 ccctgtctgc acggaggcac ctgccacctg agcgagaccc acaagggtgg gttcagctgc 2400 tcctgccctc tgggcttcga ggggcagcgg tgtgagatca acccagacga ctgcgaggac 2460 aacgactgcg agaacaacgc cacctgcgtg gacggggtca acaactacgt gtgtgtgtgc 2520 ccgccaaact acacgggtga gctgtgcgac gaggtcattg accactgtgt gccggggatg 2580 aacctctgtc agcatgaggc caagtgcatc tccctggaca gaggattcag gtgcgaatgc 2640 ccccctggct acagcgggaa gctctgcgag gtggacgatg atgactgcgc cgcccaccgg 2700 tgccgccatg gggcccagtg tgtggacgcg gtcaatggct acacgtgcat ctgcccccag 2760 ggcttcagtg ggctccactg tgagcacccc ccacccatgg tcctgctgca gaccagcccc 2820 tgtgaccagt acgagtgcca gaatgggcag tgcattgtgg tgcagcagga gcccacctgc 2880 cgctgccccc cgttcgccgg cccgaggtgc gagaagctca tcaccgtcaa cttcgtgggc 2940 aaggactcct acgtggagct ggcctcagcc aaggtccggc cccaggccaa catctctctg 3000 caggtggcca cggacaagga caacggcatc ctcctctaca agggggacaa cgaccccctg 3060 gcactggagc tgtaccaggg ccacgtgagg ctcgtctacg acagcctgag ctcgccgccg 3120 accacetgg acagcgtgga gactgtgaat gatgggcagt ttcacagcgt ggagctagtg 3180 atgctaaacc agaccctgaa cctggtggtg gacaaaggag cccccaaaag cctgggaaag 3240 ctccagaagc agccagcagt gagcatcaac agccccctct accttggagg catccccacc 3300 tccaccggcc tctcagcctt gcgccagggc atggaccggc cgctgggtgg tttccacggc 3360 tgcatccacg aggtgcgcat caacaacgag ctccaggact tcaaggccct ccccccacag 3420 gccctgggcg tctcgccggg ctgcaagtcc tgcagcgtgt gcaggcacgg cctgtgccga 3480 gccgtggaga aggacagcgt ggtgtgtgag tgccacccag gctggaccgg cccgctgtgc 3540 gaccaggagg cccgcgaccc ctgccttggc cacagctgca tccaggggaa gtgtgtggca 3600 tccggaacct cctacgtgtg caggtgcacc gaaggctatg gaggggcctt gtgcgaccag 3660 aagaatgact ccaacagcgc ctgctcaacc ttcaaatgtc accagggaca gtgccacgtc 3720 tcagatcgag gggagcccta ctgcctgtgc cggcctggct ttagtgggga gcactgtgaa 3780 caagaaacgc cttgcctcgg agaggtggtc cgagaggtga tccgccgcca gaagggttat 3840 gcatcatgtg ccacggcctc caagatacct gtcatggagt gtcgtggggg ctgcgggccc 3900 cagtgctgcc agcccacccg cagcaagcgg cggaagtacg tctttcagtg cacagacggc 3960 tcctcgttcg tggaagagct ggagagacac ttagagtgcg gctgccgccc gtgttcctaa 4020                                                                         4020 <210> 10 <211> 813 <212> DNA <213> Bos taurus <400> 10 atgacgcgct tcgctctgac cgtggtccgg catggagaaa caagacttaa caaggagaaa 60 ataattcaag gacaaggaat agatgagcct ctttcagaaa ctggatttaa acaagcagct 120 gctgctggta tatttcttaa agatgtgaag tttactcatg ttttctccag tgaccttaca 180 aggacaaagc agaccgtgca tgggattttg gagaagagca aattttgcaa agatatgaca 240 gtaaagtatg attcaagact ccgagaaagg aaatatgggg ttgcagaagg caggccgctg 300 agcgagctga gggccatggc caaagcggca ggggaggagt gcccagcatt cacaccgcct 360 ggaggagaga ccttggacca gctgaaaagg cgtgggaaag acttttttga atttctttgt 420 caactgatcc tgaaagaagc cggtcagaat gaacagtttt cccaggaagc cccgagcagc 480 tgtctggaaa gttccctggc agagatattt cctttaggga agaactgtgc ctccacgttt 540 aactctgaca gcggcacccc gggcctagca gccagtgtct tagtcgtgag tcatggcgcc 600 tacatacgaa gcctgttgga ttactttctg actgacctca agtgctcgtt cccagcgact 660 ctgagcaggt ccgagctcac gtcagtcagc cctaacacag ggatgactgt cttcatccta 720 aactttgaga aaggaggcaa agggagacca actgcccagt gtgtgtgtgt gaacctccag 780 ggccacctgg ccggggtgaa caaaactccc taa 813 <210> 11 <211> 1113 <212> DNA <213> Bos taurus <400> 11 atggttggaa aactgaagca gaacttacta ttggcatgtc tggtgattag ttctgtgact 60 gtattttact tgggccaaca cgccatggaa tgccatcacc gaatagaaga acgtagccaa 120 cccctcaaac tggagaacat aaagaccact gtgcgaactg ccctggacat caaggccaat 180 aaaacctttg cctatcacaa agatatgcct ttaatattta ttggaggtgt gccacggagt 240 ggaaccacgc tcatgagggc catgctagat gcacaccctg acattcgctg tggagaggaa 300 caggagtag aaaatacgct tggatgaggc tggtgtcacc gatgaagtgc tggattctgc catgcaggcc 420 ttcttactag aaatcattgt gaagcatggg gagccagccc cttatttatg taataaagat 480 ccttttgccc tgaaatcctt aacttacctt gctaggttat tccccaatgc caaatttctc 540 ctgatggtcc gagatggccg ggcatcagtg cattcaatga tttctcgaaa agttactata 600 gctggatttg acctgaacag ctatagggac tgtttgacca agtggaatcg tgccattgag 660 accatgtata accagtgtat ggaggttggc tataaaaaat gcatgttagt tcactatgag 720 caacttgtct tacatccaga acggtggatg agaacagtct taaagttcct ccaaattcct 780 tggaaccact cagtattaca ccatgaagag atgattggaa aagctggggg agtatctctg 840 tcaaaagtgg agagatctac agaccaagtc atcaagccag tcaatgtggg agctctatca 900 aaatgggttg ggaagatacc tccagatgtt ttacaagaca tggcagtgat tgcacccatg 960 cttgccaaac ttggatatga cccatatgcc aatccaccta actatggaaa acctgatccc 1020 aaaatccttg aaaacaccag aagggtctat aaaggagaat ttcagcttcc tgaatttctt 1080 aaagaaaaac ctcagtctga gcaggtggag tag 1113 <210> 12 <211> 1464 <212> DNA <213> Bos taurus <400> 12 gccccacccc ctcaactttg gagcctgcag ctttggggga agcctcactc cacccgctgc 60 ccaggcaaca tgtggtggtt cctcctctgg ggcgtcctcc aggctttccc cacgcagggg 120 tccgtggtgc tcctggccca gtggctgccc cagaagctga cgtcccctgg gtacccggag 180 ccatacgtca aaggccagga gagctccacg gacatcgagg ctccagaggg ctatgttgtg 240 aggctcctgt tccaggactt tgacctggag ccatccccgg actgtgagcg ggactccgtc 300 acactcacag ccagtgggat ggatcttggc cagttctgcg ggcaacaggg ctccctgctg 360 ggcaggcccc ctggtcagaa ggagtttgtg tcctcaggga acagtttgcg gctgaccttc 420 agtgcaccag cctctgaaga caagacccca ggcttccaca agggcttcct ggctctctac 480 caagccgtgg ctgtgaatta tactcagccc atcaaccagg ccactggggg ccccaaggcc 540 atccccacac ctggagacaa ccccactgag atccagagct gctgccagga gccctattac 600 gaggccaagc cctcagggac actcacttgc actgcccagg tgccctggaa gcagacccag 660 ccccatttcc 720 cagacccggg agtcccttgg cgcctccaga gctgagctgg gcagcttccc ctggcaggcc 780 ctcaccagca tctatggcag gggcggcggg gccctgctgg gcgaccgctg ggttctcacc 840 gcagcccaca ccatctaccc caaggacagc attttgctcg ggaggaaccg gagcgcccag 900 gtgttcctgg gccacacgga cacagaccag atgctggagc tgggccgcca ccccgtgcgc 960 cgcgtggtcg tgcacccaga ctaccatcag gaggagcccc atgacttcca cggagacatc 1020 gcgctcctgg agctggagcg cagcgttccc ctaggccccc acctcctccc agtctgcctg 1080 ccggaccgcg aggccctgta ccggcccggc cggtggggct acgtcagcgg cttcggcgtg 1140 gagatggact ggctgagcac caagctcaag tactcgcggc tgcccgtggc cccgagggca 1200 gcctgcgagg cctggctccg ggagaggcag aggcccgagg cattcaccga tggcatgttc 1260 tgcgccgggg accagacgcg gccgcagagt gtctgccaag gggacagcgg cggcgccttc 1320 gtggtgtggg acgatcgcac ccagcgctgg gtggccacgg gcatcgtgtc ctggggcatc 1380 gggtgtggcg aggggtacgg cttctacacc aaagtgctcg actatgtgga ctggatccgg 1440 ggagtgatgg gtgagaagga ctga 1464 <210> 13 <211> 2631 <212> DNA <213> Bos taurus <400> 13 atggctgccg gcacgcgccc ggcggccgca ccgcggtcca gagctaccat ggcccagtgg 60 aagaagaaga aggggctccg gaagcgccgg ggtgcggcgt cccagtccca cagcagcgac 120 tcggaggacg gcgagtttga ggtccaggca gaagatgacg cccgggccca gaagctggga 180 cctggcagac ccttacccac tttccccacc tcggaatgca cctcggacgt ggagccagac 240 acgcgggaga tggtgcgagc tcagaacaag aagaagaaga aatcaggagg cttccagtcc 300 atgggcctga gctacccagt cttcaaaggc atcatgaaga agggctacaa ggtgccgaca 360 cccatccaga ggaagaccat cccaatgatc ctggacggca aggatgtggt ggcaatggcc 420 cggacgggca gcggcaagac cgcctgcttc ctcatcccca tgttcgagag gctcaagacc 480 cacagcgccc agactggggc ccgtgccctc atcctctcgc ccacccgaga gctggccctg 540 cagaccatga agttcaccaa ggagcttggc aagttcactg gcctcaagac tgccctgatc 600 ctgggtgggg acaagatgga agaccagttt gcagccttgc acgaaaatcc cgacataatc 660 atcgctaccc ctgggcgctt ggtgcatgtg gctgtggaga tgaacctgaa gctgcagagt 720 gtggagtacg tggtattcga tgaggccgac aggctctttg aaatgggctt cgcagagcag 780 ctccaggaaa tcatcggccg cctccccggg ggccaccaga ctgtcctgtt ctctgccaca 840 ctgcccaagc tgctggtgga gttcgcccga gctggcctga ctgagcccgt gctcatccgg 900 ttagatgtgg actctaaact caacgagcag ctcaagacct ccttcttcct ggtgcgggag 960 gatgccaagg ccgcggtgct gctccacctg ctgcgcaacg tggtgcggcc ccaggaccag 1020 acggtcgtgt ttgtggccac caagcaccac gcggagtatc tcagcgagct gctggcaacc 1080 caaggggtga gctgtgccca catctacagc gcgctggacc agacagcccg caagattaac 1140 ctggccaggt tcacgcacgg caagtgctcg gccctcatcg tgactgacct ggccgcccgg 1200 ggcctggaca tcccacttct ggacaacgtc atcaactaca gcttccccgc caagggcaag 1260 ctcttcctgc accgcgtggg tcgcgtggcc cgggccggcc gaagtggcac ggcctactcc 1320 ttggtggccc ccgacgaggt cccctacctg ctggacctac acctgttcct gggccgtgct 1380 ctgacccttg cccgtccccc tgaggagccc tcaggcacgg aaggcgggga tggcgtactg 1440 ggccgggtgc cgcagggcgt ggtggacgac gaggactgcg gcctgcggac cagcctggag 1500 gcatcgctgg agctgcgggg cctgagccgc gtggccaaca atgcccagca gcagtatgtg 1560 cgctcacggc cggcgccctc gcccgagtcc atcaagaggg ccaaggagct ggacctcgcc 1620 gggctgggcc tacacccgct cttcagctct cgcttccagc aggaggagct gcagcggctc 1680 aggctggtgg acagcatcag gaactaccgc tcccgggcga ccatctttga gatcaatgcc 1740 tccagccgcg acctgagcag ccaggtgatg cgcgccaagc gggagaagga ccgcaaagcc 1800 atcgccagct tccagcaggg acggcaggag cggcaggagg gcccggcggg cccaaccccg 1860 agcctcccag caccgcagga ggagcagcct gagaaggagg aggtggcagg agagagtgta 1920 gaggacgtct tcacggaagt tgtcggccgg aagcggcagc agccaggacc ccaacgagga 1980 gccaagaggc ggagggagga ggcccgccag cgggaccagg cattctacat cccctaccgg 2040 cccaaggatt ttgacagcga gcggggcctg agcatcggcg gggacggggg cgccttcgag 2100 cagcaggtgg ctggtgcagc gctggacctg atgggagatg aagcccagag cctgaccagg 2160 ggccggcagc agctcaggtg ggatcggaag aagaagcggt ttgtggga gtcaggacaa 2220 gaggacaaga aaaagatcaa gaccgagagt ggccgctaca tcagcagctc ctacaagcgg 2280 gacctctacc aaaagtggaa acagaaacag aaaatcgatg atcgtgactc agaagaagaa 2340 ggaacttttg accgccgtgg cccagagcga agaggtggga agcgtggccg agggcaaggt 2400 gcatcccagc cccgcacccc tggcaccccc gcaggccgcg tgctctcaga gctcaagacc 2460 aagcagcaga tcctgaagca gcggcgccga gcccagaaga tgcgcttcct gcagcgtggg 2520 ggcctgaagc agctctctgc ccgcaaccgg cgccgagccc aggagctgca gcagggcgcc 2580 tttggccggg gtgccccttc caagaagggc aagatgagga agaggatgta a 2631 <210> 14 <211> 2268 <212> DNA <213> Bos taurus <400> 14 atgaatgccg aggaggatgc caagtggctt cagtgggtga cgcaccagtt taagaccatt 60 gcgggagaag atggggaaat caacctgcaa gacttcaaaa aagccctgaa ggtgaaagag 120 tttttctttg ctgagagatt ctttgtcctg tttgactcgg atggaagtgg caccatcaca 180 cttcaggagc tgcagaaggc actgaccctg cttatccacg gcagccccat ggacaaactc 240 aaattcctct tccaggtgta tgacgtcgat ggtaagcatc ctttgtggga tgggaggagg 300 actcagaggg agggacaaag ggaacggccc gtctcagtga ctgcccagca ctgggcttca 360 tcttcgcctg aaacaggcag cggctccatt gacgccgacg agctgcgcac cgtgctgcag 420 tcgtgcctgt acgagagcgc catctcgctg cccaaggaga agctagacca gctgacgctg 480 gcgctcttcg agtccgccga taaggactgc agcggcacca tcactttcga ggagctccga 540 gatgagttgc agcgcttccc cggggttctg gagaacctga ccatcagtgc tgctcactgg 600 ctaacgcctc cagctcccca gcgacaccgg cgccaacctc gcctgctgac ctctgcctac 660 tggcacaacc accgcagcca tgtgctctgc ctggccgtct tcgtgggcct ccacatgctg 720 ctgtttgccc tggcagctag tgcctaccgg gccttcggat ccagcgtcat ggtggccaag 780 ggctgcggcc agtgcctcaa ctttgactgc agcttcattg cggtgctgat gctcaggcgc 840 tgcctcacgt ggctgcgggc cacgtggctg gcccaggtcc tgccgctgga ccacaacatc 900 cagttccacc agcttatggg ctacgtggtg gttgggctct ccctcgtgca caccgtggcc 960 ccgtggtga atttcgcgct ccaggctcag tctgagacca gccccttccg gttttgggaa 1020 ctcctgctc ccacgaggcc tggcatcggc tgggtccacg gctcggcctc cccgactggc 1080 gtggctctgc tcctgctgct gcttctcatg ttcgcctgct ccagctcctg tgtccgcagg 1140 agtggccact ttgaggtgtt ctactggacc cacctgtcct acctccccat gtggctcctg 1200 ctcatcctgc acgggcccaa cttctggaag tggctgctgg tccctggcac gttgttcttc 1260 ctggagaaaa ccatcagcct ggcagcatcc cgcatggcgg ccctgcacat cgtggaagtc 1320 aatctcctcc cttccaaggt cactcatctc ctcatcaaga ggccccctct tttccactac 1380 agacctggtg actacttgta tctgaacatc cccagcattg cacgctacga gtggcacccc 1440 ttcaccatca gcagtgctcc tgagcagaaa gacaccatct ggctacacat ccggtcccag 1500 ggccagtgga ccaacaggtt gtttgagtca ttcaagaaac cagagccagt gttctgtggt 1560 tccaagaggc tctcgaggag gttggagatg aagaggagtc agaggaagcc ccaggtctcc 1620 gagatgtcct ctgagaacca ccagttctgt aacatcaagt gctacatcga tggcccttat 1680 gggaccccca ctcgcaggat ctttgcctcc gagcatgctg tgctcattgg tgcaggcatt 1740 ggcatcacgc cctttgcctc catcctgcag agcatcttat acagacacca gaagagaaag 1800 cacatttgcc ccaattgcca gcactcctgg atggagagtg gtcaggatga ggacatgaaa 1860 ctccacaagg tggacttcat ctggattaac cgagaccagc agtctttcga gtggtttgtg 1920 agcctgctga ccaaactgga gatggaccag gccgaggaga cgcaggtagg ccgttttctg 1980 gagctgcaca tgtacatgac ctctgcactg agcaagaacg acataaaggc cattggtctg 2040 cagatggccc tcgacctcct ggccaagaag gagaagaagg actccatcac gggcctccag 2100 acacgcaccc agcctgggcg gcctgattgg aacaaggtgt tccagaaggt ggccgctgag 2160 aagaaaggca aggtgcaggt cttcttctgt ggctccccgg ctctggccaa gatcctcaag 2220 ggccactgtg agcagttcag cttcaagttt ttccaagaga acttctag 2268 <210> 15 <211> 954 <212> DNA <213> Bos taurus <400> 15 aaaaagcaaa ttcgagtaat tttcttattt gagttcatgt gttgtaaaac ggagagaca 60 gctcataaca acaacacatt ttgcccagaa actgctaatg aacattgcag tcagtggctc 120 aagaagtttt gcaaaggaga cgatgagagc cttgaaaatg agcacagtag ctggctattg 180 gaagttgaca atgaccaact gagagccggc attgaaactg gtcctcttac aactgcacaa 240 gaagttgctg aagaactcaa tgtcgaccat tctgtcattt ggcatttgaa gcaaattgga 300 aaggtgaaaa aggttgataa atacatgttt cataagctga ccaaaaattt taaaaactgt 360 cgctttgaag tggcgtcttc tcttattctc cgcaacaaca acaacgagcc atttctcaat 420 cagattgtga cttgtgatga aaagtggatt ttatacaatg gaccaagaag aagctctaaa 480 gcacttccca aagccaaact tgaacccaaa aaaaggtcat ggtcactgat ggtccgctgc 540 cgctttctga atccccgtga aaccattaca tctgagaagt atgctcagca aattgaagag 600 atgcatcaaa aactgcagtg cctgcagcca gcattgatca acagaaaagg cccagttctt 660 ttctacaaca acgcccgact gcatatcgca cgaccgatgc ttcaaagatg gaatgaattg 720 ggctgtgaag ttttgcctcg tctgccatat tcacctgacc tctcaccaac cgaccaccac 780 gtcttcaagc atatcgactt tgttcaggga aaatgcttcc acaaccagcg ggaagcagaa 840 aatgcttttc atgagttcat cgaatcccaa agcgtggatt tttatgctgc aggaataaac 900 aaacttattt ctcattggca aaaatgtgtt gattgtaatg gttcctattt tgat 954 <210> 16 <211> 5550 <212> DNA <213> Bos taurus <400> 16 atggccaggt tggctgacta cttcatcgta gtcggctacg accacgagaa gccagggtca 60 ggagcaggtc tggggaaaat aatccagaga tttccacaga aggactggga tgatacacct 120 tttccacagg gaattgaatt gttttgtcag cctggcggat ggcagctgtc cagagagagg 180 aagcaaccaa cgttttttgt ggtggtcctg acagatattg actcagatcg acattactgc 240 tcgtgtctaa ccttttatga agcagagatc aatcttcagg gaacaaagaa ggaagagact 300 gaaggtgaag tggaagtgtc tggtttgatt cagcctgcgg aagtgtttgc tcccaaaagc 360 ctggtgttgg tatccagatt agattatcca gaaattttta gggcttgcct gggtttgatc 420 tacactgtat atgtggacag tctgaatgtc tccttggaaa gtctcattgc aaacttgtgt 480 gcgtgtcttg tcccagcggc tggagggtct cagaagctgt tttccttggg tgcaggagac 540 agacagctga tccagactcc cttgcatgac agtcttcctg tcacaggaac tagtgtggct 600 ctcctgttcc agcagttagg aattcagaat gtcctcagcc tcttttgtgc ggtccttaca 660 ctctgcaagt ctggagtcat taatgtttcc tcttaaatat agttaccctt atattcctat tctcccggct 780 cagctcctgg aagttctgag ttccccgacg cctttcatta ttggagtaca ttctgtcttt 840 aaaactgatg ttcatgaact tttagatgta atcatagctg acttggatgg aggcactatt 900 aaaattcctg aatgtattca cctctcttcc cttccggaac cacttctaca acagactcaa 960 gcagctcttt ctttgattct acacccagat ttggaagtag cagatcatgc ttttccccct 1020 ccacgaacag ctttatccca ctcaaaaatg ctggataagg aagtgcgtgc agtttttctt 1080 agattatttg cacaactttt ccaaggatat agatcatgct tacagcttat aagaattcac 1140 gcagaaccag taatacattt tcacaagaca gctttcttgg gacagcgtgg tctagttgag 1200 aatgatttcc tcactaaagt tctcaatgga atggcatttg caggttttgt ttcagaaaga 1260 ggtcctccct atagatcctg tgatctcttt gatgaggtgg tagcttttga agtagagcga 1320 attaaagttg aagaaaataa cccaatgaag atgataaagc atgtcagaga acttgctgag 1380 caactattta aaaatgagaa tccaaaccct catatggcat ttcagaaagt tccacgccca 1440 acagaaggat cccacttgcg agttcatatt cttcctttcc ccaaaattaa tgaaactcgg 1500 gtacaggaat taatacagga aaatcttgct aagaatcaga atgcacctcc tgcttcaaga 1560 gtggaaaaga aatgtgttgt gcctgcaggt ccacctgttg tttcaataat ggataaagtg 1620 acaacagttt tcaacagtgc acagagattg gaagtcgtta gaaactgcat ttcattcata 1680 tttgaaaata aaacattgga gactgaaaag acccttcctg ctgcattgag agcccttaaa 1740 ggaaaggcag caagacagtg tctcactgat gagctgggtt tacatgttca gcagaaccgg 1800 gcaatattag atcatcagca gtttgactac ataataagga tgatgaactg tactctacag 1860 gattgttcca gtttagaaga atataacatt gctgcagcat tactccctct gactagtgct 1920 ttctatagga aactggcccc tggagtcagc cagtttgctt acacctgtgt acaggaccac 1980 cccatttgga cgaatcagca gttttgggag acaacctttt ataatgcggt gcaggaacag 2040 gttcgctccc tgtatctctc ggccaaggag gacaatcatg ccctgcatct gaagcaaaag 2100 gataaacttc ctgatgacca atatcaggag aagacagcga tggacctggc agctgagcag 2160 ctacgccttt ggcccactct gagcaaatcg actcagcagg agctggtgca gcgtgaggaa 2220 agcactgtct ttagtcaggc cattcacttt gcaaacctca tggtcaatct gctggttccg 2280 ctggattcaa gtaaaaacaa gctcctaaga gcgtcagccc caggagattg ggagagtggg 2340 agcaacagca tcgtcacaaa cagtattgca ggaagtgtag ctgagagcta tgatacagaa 2400 agtgggtttg aagattcaga gaataatgac attgccaatt ctgttgtgcg tttcattacc 2460 cgatttattg acaaagtttg tacggagagt ggagttactc aggatcatat caagagcctg 2520 cattgcatga taccaggaat tgtagctatg cacattgaaa ccctagaagc agtgcatcga 2580 gagagtagaa gacttccacc tatacagaag cccaagattc ttagacctgc tctactgcca 2640 ggagaagaaa ttgtttgtga aggccttcga gtcctactgg atcctgatgg aagagaagaa 2700 gccactggag gccttcttgg aggccctcag cttctgccag cagaaggagc cttgttcctt 2760 accacataca gaattctgtt cagagggact ccccatgatc aactagttgg tgagcagaca 2820 gttgtacgaa gtttccccat tgcctccatc accaaggaga agaagatcac aatgcagaac 2880 cagctacaac agaacatgca agaaggactg caggtcacat cggcgtcttt tcagttggtt 2940 aaagtggcat ttgatgaaga agtgagccca gaagtcgtag aggtcttcag gaagcagctg 3000 atgaagctcc gttaccctca gtccgttttt accacctttg cctttgctgc tggacaaact 3060 gccccacaga tcatttcacc caagcagaag gagaagaaca cttcctttcg cactttctcg 3120 aaaaccattg tgaaaggtgc taaaagggca ggcaaaatga cgattgggcg gcagtattta 3180 ctgaagagga ggacagggac gattgtggaa gagagagtga gccgtcctgg atggaatgaa 3240 gacgatgacg tatctgtttc agatgatagt gaactcccca cgagtaccac tctaaaggcc 3300 tcagagaaat ctacaatgga acagctagta gaaaaagctt gtttcagaga ctatcagcgt 3360 ttgggtttgg gaaccataag tggcagctcc tctcgctcta aaccagagta ctttcgaatc 3420 actgcctcca acaggatgta ctcactctgc cggagctatc ctggcctttt agttgtacct 3480 caagctgtac aggacagtag tttaccaaga gtagcccgct gctatcgaca caatcgcctg 3540 cctgttgtat gttggagaaa ctcaagaagc agtaccctgc tcctccgatc tggaggattc 3600 catggaaagg gagtggttgg cctttttaag tctcagaact cccctcaggc agctcctacc 3660 tcctctttag aatcttccag tagcatagaa caagaaaagt acttgcaagc attactgagt 3720 gcagtttctg tccatcagaa actcagtggc aataaccctc ttactgtcag gccagcactt 3780 gctctgtctc caggtgtttg ggcaagtctt cgctctagca ctcgcctgat cagctctcca 3840 acatccttca ttgatgttgg cgcccggctg gcaggcaagg atcactcgac ctccttcagt 3900 aacagcactt acctgcaaaa ccagctcttg aaacgtcaag caacccttta catatttggt 3960 gagaagtcac agctaaggaa cttcaagtta gaatttgctt taaattgtga gtttgttcct 4020 gttgagtatc atgacatccg acaagtgaaa gccagtttca aaaagctgat gagggcttgt 4080 gttccaagtg ccattcctac tgactcagaa gtgaccttcc taagagccct gggagactct 4140 gagtggttcc cacagcttca taggatactg cagctggctg tggttgtttc agaagtactt 4200 gagaatggtt cctcagtttt ggtgtgtttg gaagaaggct gggacatcac tgcacaagtg 4260 acctccctgg ttcagttact cagtgatccc ttttatagga cgcttgaagg cttccggatg 4320 ctggtcgaaa aagagtggct ctcttttggt cataaattca gtcagcggag cagcttgacc 4380 ctcagctgtc agggcagtgg tttcactccg gtcttcctac agttcttaga ttgtgtacac 4440 caggttcaca accagtatcc aactgagttt gaattcaatc tctattactt aaagttcttg 4500 gt; ttagagcacg gaactttatt tgatgataaa ggagacaagc atgctaaaaa aggaatttgt 4620 atttgggagt gtattgatag aatgcacaag aggagtccca ttttctttaa ttatttatat 4680 tcaccagtgg aaatagaggc cctgaagccc aatgtaaacg tttccagcct caagaagtgg 4740 gattactaca tagaggagac gctttccacg gggccctcgt atgactggat gatgctgacc 4800 cccaagcagc tgccctccga agactctgag ctggccggag gagccaggcc ccagagccag 4860 aggagaaccg tgtggccgtg ctacgatgat gtcagctgcg ctcagcccga cgctctcacc 4920 agccttttca gtgaaattga aagactggag cataaattga accaaacccc tgagaagtgg 4980 cagcagctgt gggagcgggt aaacgtggac cttaaagaag agcccagagc agaccatccc 5040 cagagatacc cttcaggctc cccaggaact gtgtccacca acctcccttt ttatcagaag 5100 aggcctcagc tgcaccttcc agacagcaac ctggcagagg agcagaacac tggtgtctcc 5160 ccatccaacg gggtggaccg cagagcagcc acgctgtata gccagtacac gcccaagaac 5220 gacgagaaca ggtcctttga gggaacgctg tacaaaagag gggctttgct gaaaggctgg 5280 aagccccgtt ggtttgtttt ggatgtaaca aagcatcagc tgcgatacta tgactcgggt 5340 gaggacacca gctgtaaggg ccacatcgac ctggctgaag tagaaatggt catccctgcc 5400 ggccccagca tgggcgcccc gaagcacacg agtgacaagg ctttctttga tctcaagacc 5460 agcaaacgtg tgtataactt ctgtgcccag gatggacaga gtgcccagca gtggatggac 5520 aggatccaga gctgtatctc tgatgcctga 5550 <210> 17 <211> 5204 <212> PRT <213> Bos taurus <400> 17 Met Asn Cys Leu Ala Leu Ser Leu Gly Phe Gly Leu Leu Phe Pro Val   1 5 10 15 Pro Glu Thr Trp Leu Phe Ala Tyr Phe Ala Ser Ile Ser Trp Ala Asp              20 25 30 Ser Gln Gly Leu Phe Pro Arg Leu Glu Asn Val Ala Ala Phe Lys Lys          35 40 45 Val Ser Val Val Pro Thr Gln Ala Thr Cys Gly Ile Pro Ala Gln Ser      50 55 60 Thr Phe Cys Gln Ser Ser Ala Thr Pro Glu Gly Leu Arg Val Cys Pro  65 70 75 80 Gln Arg Leu Cys Val Gln Asp Cys Pro Tyr Arg Ser Ser Pro Pro Thr                  85 90 95 Tyr Ala Asn Leu Phe Ser Ala Gly Leu Arg Gly Cys Ile Ile Lys Asp             100 105 110 Gln Arg Asp Leu Ser Pro Asn Ser His Asn His Ser Ala Ser Phe Ile         115 120 125 Phe Gly Asn His Gln Ser Cys Phe Ala Ser Pro Pro Ala Pro Arg Leu     130 135 140 Ala Ala Ser Phe Thr Leu Ala Val Trp Leu Lys Leu Glu Gln Gly Gly 145 150 155 160 Val Met Cys Val Ile Glu Lys Thr Ala Asp Gly Gln Ile Val Phe Lys                 165 170 175 Leu Thr Ile Ser Glu Lys Glu Thr Met Phe Tyr Tyr Arg Thr Val Asn             180 185 190 Gly Leu Gln Pro Pro Ile Lys Val Met Thr Leu Gly Arg Ile Leu Val         195 200 205 Lys Lys Trp Ile His Leu Ser Val Gln Val His Gln Thr Lys Ile Ser     210 215 220 Phe Phe Ile Asn Gly Leu Glu Lys Asp Asn Ala Ala Phe Asp Ala Arg 225 230 235 240 Thr Leu Ser Gly Ser Ile Thr Asp Phe Ala Ser Gly Thr Met Gln Ile                 245 250 255 Gly Gln Ser Leu Asn Gly Ser Glu Gln Phe Val Gly Arg Met Gln Asp             260 265 270 Phe Arg Leu Tyr Gln Val Ala Leu Thr Asn Arg Glu Ile Gln Glu Val         275 280 285 Phe Ser Arg Asp Leu Pro Arg Leu His Ile Gln Ser His Cys Arg Cys     290 295 300 Pro Gly Ser His Pro Arg Val His His Arg Leu Glu Gln Arg Tyr Cys Ile 305 310 315 320 Pro Asn Asp Ala Glu Asp Thr Thr Lys Asn Arg Val Leu Arg Leu Asn                 325 330 335 Pro Glu Ala His Pro Leu Ser Phe Val Asn Asp Asn Asn Val Gly Thr             340 345 350 Ser Trp Val Ser His Val Phe Thr Asn Met Thr Gln Leu Ser Gln Gly         355 360 365 Val Thr Ile Ser Ile Asp Leu Glu Asn Gly Gln Tyr Gln Val Phe Tyr     370 375 380 Ile Ile Gln Phe Ser Ser Pro Gln Pro Thr Ala Val Arg Ile Gln 385 390 395 400 Arg Lys Lys Glu Asp Ser Leu Asp Trp Glu Asp Trp Gln Tyr Phe Ala                 405 410 415 Arg Asn Cys Ser Thr Phe Arg Met Lys Asn Asn Gly Asp Leu Ala Asn             420 425 430 Ser Asp Ser Val Asn Cys Leu Gln Leu Pro Asn Phe Pro Pro Tyr Ser         435 440 445 Cys Gly Asn Val Thr Phe Ser Val Leu Thr Pro Gly Pro Asn Gln Arg     450 455 460 Pro Gly Tyr Asn Asn Phe Tyr Asn Thr Pro Ser Leu Gln Glu Phe Val 465 470 475 480 Lys Ala Thr Gln Val Arg Leu His Phe His Gly Gln Tyr His Thr Thr                 485 490 495 Glu Thr Pro Val Ser Pro Arg His Arg Tyr Tyr Gly Val Asn Glu Ile             500 505 510 Thr Ile Thr Gly Arg Cys Gln Cys Tyr Gly His Ala Asn His Cys Asp         515 520 525 Thr Thr Ser Gln Pro Tyr Arg Cys Leu Cys Ser Gln Glu Ser Phe Thr     530 535 540 Glu Gly Leu His Cys Asp Arg Cys Leu Pro Leu Tyr Asn Asn Lys Pro 545 550 555 560 Phe Arg Gln Ser Asp His Val His Ala Phe Asn Cys Lys Pro Cys Glu                 565 570 575 Cys Asn Ser His Ser Arg Ser Cys His Tyr Asn Ile Ser Val Asp Pro             580 585 590 Phe Pro Phe Glu His Tyr Arg Gly Gly Gly Gly Val Cys Asp Asp Cys         595 600 605 Glu His Asn Thr Ala Gly Lys Asn Cys Glu Leu Cys Lys Asp Tyr Phe     610 615 620 Phe Arg Gln Val Gly Ala Asp Pro Ser Ala Ile Asp Val Cys Arg Pro 625 630 635 640 Cys Asp Cys Asp Lys Val Gly Thr Arg Asn Ser Ser Phe Leu Cys Asp                 645 650 655 Gln Ile Gly Gly Gln Cys Asn Cys Lys Arg His Val Ser Gly Arg Gln             660 665 670 Cys Asn Gln Cys Gln Asn Gly Phe Tyr Asn Leu Gln Glu Trp Asp Pro         675 680 685 Asp Gly Cys Ser Pro Cys Asn Cys Asn Thr Ser Gly Thr Val Asp Gly     690 695 700 Asp Ile Thr Cys His Pro Asn Ser Gly Gln Cys Lys Cys Lys Ala Asn 705 710 715 720 Val Ile Gly Leu Arg Cys Asp His Cys Asn Phe Gly Phe Lys Phe Leu                 725 730 735 Gln Ser Phe Asn Asp Asp Gly Cys Glu Pro Cys Gln Cys Asn Leu His             740 745 750 Gly Ser Val Asn Arg Leu Cys Asn Pro Leu Ser Gly Gln Cys Glu Cys         755 760 765 Lys Lys Glu Ala Lys Gly Leu Gln Cys Asp Thr Cys Arg Glu His Phe     770 775 780 Tyr Gly Leu Asp Ala Thr Gly Cys Lys Ala Cys Asp Cys Asp Val Ala 785 790 795 800 Gly Ser Arg Pro Gly Thr Val Cys Asp Ala Trp Thr Gly Gln Cys Val                 805 810 815 Cys Lys Pro Asn Val Gly Gly Arg Arg Cys Ser Glu Cys Val Glu Gly             820 825 830 Tyr Phe Tyr Gln Pro Gln Asn Arg Ser Phe Leu Cys Leu Pro Cys Asn         835 840 845 Cys Asp Arg Thr Gly Thr Val Asn Gly Ser Leu Leu Cys Asp Lys Ser     850 855 860 Thr Gly Gln Cys Pro Cys Lys Leu Gly Val Thr Gly Leu His Cys Asn 865 870 875 880 Gln Cys Glu Ser His Arg Tyr His Leu Thr Val Gly Ser Phe Gln Gly                 885 890 895 Cys Gln Met Cys Glu Cys Asp Pro Leu Gly Thr Leu Pro Gly Thr Ile             900 905 910 Cys Asp Pro Leu Ser Gly Gln Cys Pro Cys Leu Pro Asn Arg Gln Gly         915 920 925 Arg Arg Cys Asn Gln Cys Gln Pro Gly Phe Tyr Ile Ser Pro Gly Asn     930 935 940 Ala Thr Gly Cys Leu Pro Cys Ser Cys His Thr Thr Gly Ala Val Asn 945 950 955 960 His Ile Cys Asn Ser Leu Thr Gly Gln Cys Val Cys Gln Asp Ala Ser                 965 970 975 Ile Ala Gly Gln Ser Cys Asp Tyr Cys Lys Asp Leu Tyr Phe Gly Phe             980 985 990 Asp Ser Leu Thr Gly Arg Cys Gln Pro Cys Asn Cys His Leu Ser Gly         995 1000 1005 Ala Leu Asn Glu Thr Cys His Leu Val Thr Gly Gln Cys Phe Cys Lys    1010 1015 1020 Arg Phe Val Thr Gly Ser Lys Cys Asp Thr Cys Val Pro Asn Ala Ser 1025 1030 1035 1040 His Leu Asp Ile Ser Asn Pro Leu Gly Cys Ser Lys Thr Ser Ser Gln                1045 1050 1055 Gln Pro Pro Pro Arg Gly Gln Val Gln Ser Ser Ser Ala Ile Asn Leu            1060 1065 1070 Ser Trp Ser Pro Pro Asp Ser Pro Asn Ala His Arg Leu Thr Tyr Ser        1075 1080 1085 Leu Phe Arg Asp Asp Phe Glu Ile Tyr Thr Val Glu Asp Gln Tyr Pro    1090 1095 1100 Tyr Ser Ile Gln Tyr Phe Leu Asp Thr Ala Leu Val Pro Tyr Thr Ser 1105 1110 1115 1120 Tyr Ser Tyr Tyr Ile Leu Thr Ser Ser Val His Gly Ser Thr Arg Ser                1125 1130 1135 Thr Ala Val Thr Tyr Arg Thr Lys Pro Gly Thr Pro Val Gly Ser Leu            1140 1145 1150 Asn Leu Ser Tyr Ile Ser Ser Val Ser Ser Asp Ser Val Thr Leu Thr        1155 1160 1165 Trp Ala Ser Pro Ser Asn Arg Ser Gly Pro Ile Glu Lys Tyr Ile Leu    1170 1175 1180 Ser Cys Ala Pro Leu His Asp Val Gln Pro Cys Ser Pro Tyr Glu Gly 1185 1190 1195 1200 Pro Glu Thr Thr Thr Thr Ile Trp Asn Leu Leu Pro Phe Thr Lys Tyr                1205 1210 1215 Arg Phe Ala Val Gln Ala Cys Thr Ser Gly Gly Cys Leu His Ser Thr            1220 1225 1230 Pro Leu Thr Val Thr Thr Ala Gln Ala Ala Pro Arg Arg Leu Gly Pro        1235 1240 1245 Pro Lys Val Arg Lys Ile Ser Ser Thr Glu Leu His Val Glu Trp Ala    1250 1255 1260 Pro Pro Met Glu Pro Asn Gly Ile Ile Ile Arg Tyr Glu Leu Tyr Met 1265 1270 1275 1280 Lys Arg Leu Lys Ser Ser Gly Glu Thr Arg Ser Ala Glu Ser Gln Val                1285 1290 1295 Phe Gln Ser Ser Gly Trp Leu Gly Pro His Pro Leu Ala Glu Ser Ala            1300 1305 1310 Asn Glu Asn Ala Leu Glu Pro Pro Glu Thr Thr Thr Val Ile Thr Gly        1315 1320 1325 Leu Glu Pro Tyr Thr Lys Tyr Lys Phe Arg Val Leu Ala Val Asn Met    1330 1335 1340 Ala Gly Ser Val Ser Ser Ala Trp Thr Thr Gly Arg Thr Gly Glu Ser 1345 1350 1355 1360 Ala Pro Ile Phe Val Met Pro Pro Ser Val Ser Pro Leu Ser Pro His                1365 1370 1375 Ser Leu Asn Val Ser Trp Glu Leu Pro Pro Asp Ser Val Thr Arg Gly            1380 1385 1390 Lys Val Val Gly Tyr Asn Ile Ser Met Ile Ser Glu Gln Ser Pro Gln        1395 1400 1405 Gln Ser Tyr Pro Met Val Val Pro Gln Val Leu Tyr Thr Ala Lys Ser    1410 1415 1420 Gln Glu Leu Ser Tyr Ile Val Lys Gly Leu Lys Pro Tyr Arg Ile Tyr 1425 1430 1435 1440 Asn Phe Thr Ile Ser Leu Cys Asn Ser Val Gly Cys Val Thr Ser Ala                1445 1450 1455 Ser Glu Ala Gly Gln Thr Leu Ala Ser Ala Pro Ala Gln Leu Arg Pro            1460 1465 1470 Pro Leu Val Glu Gly Ile Asn Ser Thr Thr Met Leu Arg Trp Leu        1475 1480 1485 Ala Pro Glu Glu Gln Asn Gly Pro Ser Pro Val Tyr Gln Leu Glu Arg    1490 1495 1500 Arg Glu Pro Ser Leu Pro Ala Pro Arg Ala Met Val Met Lys Gly Thr 1505 1510 1515 1520 Arg Phe Thr Gly His Gly Tyr Tyr Lys Phe Pro Ser Ser Thr His Pro                1525 1530 1535 Val Asn Thr Asp Phe Thr Gly Ile Lys Ala Ser Phe Arg Thr Arg Val            1540 1545 1550 Pro Glu Gly Leu Ile Val Phe Ala Ala Ser Pro Gly Asn Gln Glu Glu        1555 1560 1565 Tyr Phe Ala Ile Gln Leu Lys Asn Gly Arg Pro Tyr Phe Leu Phe Asp    1570 1575 1580 Pro Gln Gly Ser Ala Val Glu Val Thr Thr Thr Asn Asp Asp Gly Lys 1585 1590 1595 1600 Gln Tyr Ser Asp Gly Lys Trp His Glu Ile Ile Ala Ile Arg His Gln                1605 1610 1615 Gly Leu Gly Gln Ile Thr Leu Asp Gly Leu Phe Thr Gly Ser Ser Ala            1620 1625 1630 Thr Asn Gly Gly Thr Val Ile Gly Glu Asn Thr Gly Val Phe Val        1635 1640 1645 Gly Gly Leu Pro Gln Gly Tyr Thr Ile Leu Arg Lys Asp Ser Asp Ile    1650 1655 1660 Val Gln Lys Gly Phe Val Gly Cys Leu Lys Asp Val Tyr Phe Met Lys 1665 1670 1675 1680 Asn Tyr Asn Pro Ser Ala Thr Trp Glu His Leu Val Trp Gln Ser Ser                1685 1690 1695 Glu Glu Gln Thr Asn Val His Asn Asp Trp Glu Gly Cys Pro Thr Ser            1700 1705 1710 Leu Gln Glu Gly Ala Gln Phe Leu Gly Thr Gly Phe Leu Glu Leu Tyr        1715 1720 1725 Pro Tyr Leu Phe His Gly Gly Met Asp Phe Glu Ile Ser Phe Lys Phe    1730 1735 1740 Arg Thr Asp Gln Leu Asn Gly Leu Leu Leu Phe Ile Tyr Asn Lys Asp 1745 1750 1755 1760 Gly Pro Asp Phe Leu Ala Met Glu Leu Lys Ser Gly Ile Leu Ser Phe                1765 1770 1775 Arg Leu Asn Thr Ser Leu Thr Phe Thr Gln Val Asp Leu Trp Pro Gly            1780 1785 1790 Leu Ser Tyr Cys Asp Gly Lys Trp Asn Lys Val Ile Ile Lys Lys Asn        1795 1800 1805 Asp Ser Ile Ile Ser Ala Ser Met Asn Glu Leu Met Glu His Val Ser    1810 1815 1820 Glu Ser Arg Ala Gln Ala Leu Met Val Asn Ser Pro Val Tyr Val Gly 1825 1830 1835 1840 Gly Ile Pro Gln Glu Leu His Asp Pro Tyr Lys His Leu Lys Leu Glu                1845 1850 1855 Gln Gly Phe Gly Gly Cys Met Lys Asp Val Lys Phe Ala Arg Gly Ala            1860 1865 1870 Val Ile Asn Leu Ala Ser Val Ser Ser Gly Ala Val Val Asn Leu        1875 1880 1885 Asp Gly Cys Leu Ser Thr Asp Ser Ala Ala Lys Cys Arg Gly Asp Asp    1890 1895 1900 Ser Ile Leu Val Tyr Arg Gly Glu Lys Arg Thr Ala Tyr Glu Ser His 1905 1910 1915 1920 Leu Gln Pro Phe Thr Glu Tyr Leu Tyr Arg Val Thr Ala Ser His Glu                1925 1930 1935 Gly Gly Ser Val His Ser Asp Trp Ser Arg Gly Arg Thr Thr Gly Ala            1940 1945 1950 Ala Pro Gln Ser Val Ser Ser Ser Ser Val Ser Ser Ile Asn Gly        1955 1960 1965 Tyr Ser Ile Glu Val Thr Trp Asp Glu Pro Val Val Ala Arg Gly Val    1970 1975 1980 Ile Glu Lys Tyr Ile Leu Arg Ala Tyr Ser Glu Asp Ala Leu Gly Pro 1985 1990 1995 2000 Pro His Thr Ser Ser Ser Ser Glu Leu Val Asp Thr Asn Thr Phe                2005 2010 2015 Thr Gly Ile Leu Thr Gly Leu Leu Pro Phe Lys Asn Tyr Ala Val Thr            2020 2025 2030 Leu Ala Ala Cys Thr Leu Ala Gly Cys Thr Glu Ser Leu His Ala Leu        2035 2040 2045 Asn Ile Ser Thr Pro Gln Glu Ala Pro Gln Gln Val Gln Pro Pro Val    2050 2055 2060 Ala Lys Ser Leu Pro His His Leu Leu Leu Ser Trp Asn Pro Pro Gln 2065 2070 2075 2080 Lys Ala Asn Gly Ile Ile Thr Gln Tyr Ser Leu Tyr Met Asp Gly Met                2085 2090 2095 Leu Ile Tyr Ser Gly Asn Gly Glu Asn Tyr Thr Val Thr Asp Leu Ala            2100 2105 2110 Ala Phe Thr Pro His Gln Phe Leu Leu Ser Ala Cys Thr His Val Gly        2115 2120 2125 Cys Thr Asn Ser Ser Leu Val Ile Leu Ser Thr Ala Gln Leu Pro Pro    2130 2135 2140 Glu His Val Asp Pro Pro Ile Leu Thr Val Leu Asp Ser Arg Thr Val 2145 2150 2155 2160 Tyr Ile Gln Trp Lys Gln Pro Arg Lys Val Asn Gly Ile Leu Glu Arg                2165 2170 2175 Tyr Met Leu Tyr Ile Ser Asn His Thr His Asp Phe Thr Val Trp Asp            2180 2185 2190 Val Ile Tyr Asn Ser Thr Glu Leu Phe Gln Asp His Thr Leu Gln Tyr        2195 2200 2205 Leu Leu Pro Gly Asn Lys Tyr Leu Ile Lys Leu Ala Ala Cys Thr Gly    2210 2215 2220 Gly Gly Cys Thr Val Ser Lys Ala Ser Gln Ala Leu Thr Glu Glu Arg 2225 2230 2235 2240 Thr Pro Glu Gly Val Pro Ala Pro Arg Val Asn Pro Asp Ser Ser His                2245 2250 2255 Ser Phe Asn Ile Ser Trp Thr Glu Pro Glu His Pro Asn Gly Val Ile            2260 2265 2270 Thr Ser Tyr Gly Leu Tyr Leu Asp Gly Ile Leu Ile His Asn Ser Ser        2275 2280 2285 Glu Leu Ser Cys His Ala Ser Gly Phe Ala Pro Trp Ser Leu His Ser    2290 2295 2300 Phe Arg Val Gln Ala Cys Thr Ala Arg Gly Cys Ala Leu Gly Pro Leu 2305 2310 2315 2320 Val Glu Asn Arg Thr Leu Glu Ala Pro Pro Glu Gly Thr Val Asn Val                2325 2330 2335 Phe Val Lys Thr Glu Gly Ser Arg Lys Ala His Val Arg Trp Glu Pro            2340 2345 2350 Pro Phe His Pro Asn Gly Arg Leu Met Tyr Ser Val Leu Phe Thr Gly        2355 2360 2365 Thr Phe Tyr Ala Asp Gln Ala Gly Asp Asn Tyr Thr Leu Leu Asn Gly    2370 2375 2380 Thr Gln Ile Met His Ser Gly Glu Glu Thr Asn Leu Trp Val Leu Ile 2385 2390 2395 2400 Asn Gly Leu Val Pro Phe Thr Asn Tyr Thr Val Gln Val Asn Val Ser                2405 2410 2415 Asn Ser Gln Gly Ser Leu Met Ser Asp Pro Val Met Ile Ser Met Pro            2420 2425 2430 Pro Gly Ala Pro Asp Gly Val Leu Pro Pro Arg Leu Ser Ser Ala Thr        2435 2440 2445 Pro Thr Ser Leu Gln Val Val Trp Ser Thr Pro Ala Arg Asn Asn Ala    2450 2455 2460 Pro Gly Ser Pro Arg Tyr Gln Leu Gln Met Arg Pro Gly His Ser Thr 2465 2470 2475 2480 His Gly Phe Leu Glu Leu Phe Ser Asn Pro Ser Ala Ser Leu Asn Tyr                2485 2490 2495 Glu Val Arg Asp Leu Gln Pro Tyr Thr Glu Tyr Glu Phe Arg Leu Val            2500 2505 2510 Ala Ser Asn Gly Phe Gly Ser Ala His Ser Ser Trp Ile Pro Phe Ile        2515 2520 2525 Thr Ala Glu Asp Lys Pro Gly Pro Val Asp Pro Pro Ile Ile Leu Asp    2530 2535 2540 Lys Lys Ser Arg Met Met Leu Val Thr Trp Gln His Pro Leu Lys Cys 2545 2550 2555 2560 Asn Gly Leu Ile Thr His Tyr Asn Ile Tyr Gln His Gly Arg Leu Ser                2565 2570 2575 Leu Glu Thr Ser Gly Asn Val Thr Asn Gly Thr Val Thr His Leu His            2580 2585 2590 Pro His Thr Ala Tyr Ala Phe Gln Val Glu Ala Cys Thr Ser Lys Gly        2595 2600 2605 Cys Ser Leu Ser Ala Asp Ser Gln Thr Val Trp Thr Leu Pro Asp Ala    2610 2615 2620 Pro Glu Gly Ile Leu Ser Pro Glu Leu Phe Ser Asp Thr Pro Thr Ser 2625 2630 2635 2640 Val Ile Ile Ser Trp Gln Pro Pro Thr His Pro Asn Gly Leu Leu Glu                2645 2650 2655 Asn Ser Thr Ile Gln Arg Arg Val Gln Gly Lys Glu Ala Val Thr Thr            2660 2665 2670 Leu Val Thr Leu Pro Gly Ser His Pro Arg Arg Phe Ile Asp Lys Thr        2675 2680 2685 Ser Ser Leu Ser Pro Trp Thr Lys Tyr Glu Tyr Arg Val Leu Met Ser    2690 2695 2700 Thr Ala Gly Gly Gly Thr Asn Ser Ser Asp Trp Ala Glu Val Thr Thr 2705 2710 2715 2720 Arg Pro Ser Arg Pro Ala Gly Val Gln Pro Pro Glu Val Asp Val Leu                2725 2730 2735 Gly Pro Asp Ala Ala Lys Val Thr Trp Lys Pro Pro Leu Ile Leu Asn            2740 2745 2750 Gly Asp Ile Leu Asn Tyr Glu Ile Arg Met Pro Asp Pro His Ile Thr        2755 2760 2765 Ile Thr Asn Val Thr Ser Ser Val Leu Ser His Val Val Thr His Leu    2770 2775 2780 Ile Pro Phe Thr Asn Tyr Ser Val Thr Ile Val Ala Cys Ser Gly Gly 2785 2790 2795 2800 Asn Gly Tyr Leu Gly Gly Cys Thr Glu Ser Phe Pro Thr His Val Thr                2805 2810 2815 Thr Pro Pro Ala Leu Pro Gln Asp Leu Gly Pro Leu Ser Val Val Pro            2820 2825 2830 Leu Ser Glu Ser Tyr Val Gly Ile Ser Trp Gln Pro Pro Ser Ser Pro        2835 2840 2845 Asn Gly Pro Asp Leu Arg Tyr Glu Leu Leu Arg Cys Lys Ile Gln Gln    2850 2855 2860 Pro Leu Ala Ser Asn Pro Pro Glu Asp Leu Asn Met Trp His Asn Ile 2865 2870 2875 2880 Tyr Ser Gly Thr Gln Arg Phe Tyr Glu Asp Lys Gly Leu Ser Arg Phe                2885 2890 2895 Thr Thr Tyr Ala Tyr Lys Val Phe Val His Asn Ser Val Gly Phe Thr            2900 2905 2910 Pro Ser Gln Glu Ala Thr Val Lys Thr Leu Ala Gly Arg Pro Glu Arg        2915 2920 2925 Gly Ala Asn Val Thr Val Thr Val Leu Asn His Thr Ala Ile Asp Val    2930 2935 2940 Arg Trp Val Lys Pro Thr Phe Gln Asp Leu Gln Gly Asp Val Glu Tyr 2945 2950 2955 2960 Tyr Thr Leu Phe Trp Ser Ser Ala Thr Ser Asn Glu Ser Arg Lys Ile                2965 2970 2975 Leu Pro Asp Val His Ser His Val Ile Gly His Leu Asn Pro Asn Thr            2980 2985 2990 Glu Tyr Arg Ile Phe Ile Ser Val Phe Asn Gly Val Ala Ser Ile Asn        2995 3000 3005 Ser Glu Val Leu His Ala Thr Thr Cys Asp Gly Glu Pro Gln Gly Met    3010 3015 3020 Leu Pro Pro Glu Val Valle Ile Asn Ser Thr Ala Val Val Valle 3025 3030 3035 3040 Trp Thr Ala Pro Ser Asn Pro Asn Gly Val Val Thr Glu Tyr Ser Val                3045 3050 3055 Tyr Val Asn Asn Gln Leu Tyr Lys Thr Gly Ile Asn Val Pro Gly Ser            3060 3065 3070 Ile Ile Leu Arg Glu Leu Ser Pro Phe Thr Val Tyr Asp Ile Gln Val        3075 3080 3085 Glu Val Cys Thr Lys Tyr Ala Cys Val Lys Ser Asn Arg Thr Gln Ile    3090 3095 3100 Thr Thr Val Glu Asp Thr Pro Ser Asp Ile Pro Thr Pro Thr Ile His 3105 3110 3115 3120 Gly Ile Ala Ser Arg Ser Leu Gln Ile Phe Trp Met Ser Pro Gly Arg                3125 3130 3135 Pro Ser Gly Ile Ile Leu Gly Tyr Asp Leu Leu Arg Lys Thr Trp Arg            3140 3145 3150 Pro Cys Ser Lys Thr Lys Lys Leu Met Lys Asp His Pro Gly Gly Leu        3155 3160 3165 Cys Lys Ala Val Glu Cys Gln Lys His Glu Leu Leu Cys Gly Thr Arg    3170 3175 3180 Cys Tyr Ser Pro Glu Ala Lys Val Cys Cys Asn Gly Ser Leu Tyr Asp 3185 3190 3195 3200 Pro Arg Pro Gly His Ala Cys Cys Glu Glu Lys Tyr Ile Ala Phe Val                3205 3210 3215 Leu Asn Ser Thr Gly Val Cys Cys Gly Gly Arg Leu Arg Glu Arg Gln            3220 3225 3230 Pro Asn His Gln Cys Cys Ser Gly Tyr Tyr Ile Arg Ile Leu Pro Gly        3235 3240 3245 Glu Val Cys Cys Pro Asp Glu Gln His Asn Arg Val Ser Ala Gly Leu    3250 3255 3260 Gly Asn Ser Cys Cys Gly Arg Met Pro Tyr Ser Thr Ser Gly Lys Gln 3265 3270 3275 3280 Ile Cys Cys Ala Gly Arg Leu His Asp Gly His Gly Gln Gln Cys Cys                3285 3290 3295 Gly Gly Gln Ile Val Ser Lys Asp Phe Glu Cys Cys Gly Gly Glu Glu            3300 3305 3310 Glu Gly Val Val Tyr Ser Arg Leu Pro Gly Met Phe Cys Cys Gly Leu        3315 3320 3325 Asp Tyr Val Asn Met Ser Asp Thr Ile Cys Cys Ser Ala Ser Ser Gly    3330 3335 3340 Glu Ser Lys Ala His Val Lys Lys Asn Asp Pro Val Val Lys Cys 3345 3350 3355 3360 Cys Glu Thr Glu Leu Ile Pro Lys Ser Gln Glu Cys Cys Asn Gly Val                3365 3370 3375 Gly Tyr Asn Pro Leu Lys Tyr Val Cys Ser Asp Lys Ile Ser Thr Gly            3380 3385 3390 Met Met Met Lys Glu Thr Lys Ala Cys Arg Thr Leu Cys Leu Thr Ser        3395 3400 3405 Met Glu Ala Thr Ala His Cys Gly Arg Cys Asp Phe Asn Phe Thr Ser    3410 3415 3420 His Val Cys Thr Val Met Arg Gly Ser His Ser Ser Val Arg Lys Glu 3425 3430 3435 3440 Ser Met Glu Glu Ile Cys Ser Ser Ala Glu Glu Thr Val His Thr Gly                3445 3450 3455 Ser Val Asn Thr Leu Ser Phe Thr Asp Val Asn Leu Glu Pro Tyr Met            3460 3465 3470 Met Tyr Glu Tyr Arg Ile Ser Ala Trp Asn Arg Tyr Gly Arg Gly Phe        3475 3480 3485 Ser Lys Ala Val Arg Ala Arg Thr Lys Glu Asp Val Pro Glu Gly Val    3490 3495 3500 Ser Pro Pro Arg Trp Thr Lys Met Asp His Leu Asp Asp Val Ile Val 3505 3510 3515 3520 Leu Ser Trp Lys Lys Pro Ile Gln Ser Asn Gly Pro Ile Ile Ala Tyr                3525 3530 3535 Ile Leu Leu Arg Asn Gly Ile Glu Cys Phe Arg Gly Thr Ser Leu Ser            3540 3545 3550 Phe Ser Asp Thr Glu Gly Ile Gln Pro Phe Met Glu Tyr Ser Tyr Gln        3555 3560 3565 Leu Lys Ala Cys Thr Val Ala Gly Cys Ala Thr Ser Ser Lys Val Val    3570 3575 3580 Ala Ala Thr Thr Gln Gly Ile Pro Gln Asn Ile Pro Pro Pro Arg Val 3585 3590 3595 3600 Thr Ala Pro Ser Ala Glu Ala Leu His Val Ser Trp His Val Pro Pro                3605 3610 3615 Lys Pro Asn Gly Val Ile Lys Glu Tyr Gln Leu Arg Gln Val Gly Lys            3620 3625 3630 Gly Leu Ile Tyr Thr Asp Thr Thr Asp Arg Arg Gln His Thr Val Thr        3635 3640 3645 Gly Leu Gln Pro Tyr Thr Asn Tyr Ser Phe Thr Leu Arg Ala Cys Thr    3650 3655 3660 Ser Ala Gly Cys Thr Ser Ser Glu Pro Phe Leu Gly His Thr Leu Gln 3665 3670 3675 3680 Ala Ala Pro Gln Gly Val Trp Val Thr Pro Arg His Ile Val Val Asn                3685 3690 3695 Ser Thr Thr Val Glu Leu Phe Trp Ser Pro Pro Glu Lys Pro Asn Gly            3700 3705 3710 Leu Val Ser Gln Tyr Gln Leu Ser Arg Asn Gly Ser Leu Ile Phe Leu        3715 3720 3725 Gly Gly Ser Glu Glu His Asn Phe Thr Asp Lys Asn Leu Glu Pro Asn    3730 3735 3740 Ser Arg Tyr Val Tyr Lys Leu Glu Ala Thr Thr Gly Gly Gly Ser Ser 3745 3750 3755 3760 Pro Ser Asp Glu Tyr Ile Ile Gln Thr Pro Ile Leu Thr Pro Glu Glu                3765 3770 3775 Ile Gln Pro Pro Tyr Asn Ile Thr Val Ile Gly Pro Tyr Ser Ile Phe            3780 3785 3790 Val Ala Trp Thr Pro Pro Gly Ile Leu Val Pro Lys Met Pro Val Glu        3795 3800 3805 Tyr Asn Val Leu Leu Asn Ala Gly Ser Ala Thr Pro Leu Ile Ser Ser    3810 3815 3820 Val Gly His His Gln Ser Ile Leu Leu Glu Asn Leu Ala Pro Phe Thr 3825 3830 3835 3840 Gln Tyr Glu Ile Arg Ile Gln Ala Cys Gln Lys Gly Gly Cys Gly Val                3845 3850 3855 Ser Ser Arg Met Phe Ala Lys Thr Ala Glu Ala Ala Pro Met Asp Leu            3860 3865 3870 Asn Ser Pro Ile Leu Lys Ala Leu Gly Ser Ala Cys Ile Glu Val Lys        3875 3880 3885 Trp Met Pro Lys Lys Pro Asn Gly Val Ile Ile Asn Tyr Phe Ile    3890 3895 3900 His Arg Arg Pro Thr Gly Ile Glu Glu Glu Ser Leu Val Phe Val Trp 3905 3910 3915 3920 Ser Glu Gly Ala Leu Glu Phe Ile Asp Asp Ala Asp Thr Leu Arg Pro                3925 3930 3935 Phe Thr Leu Tyr Glu Tyr Arg Val Val Ala Cys Asn Ser Arg Gly Ser            3940 3945 3950 Val Asp Ser Pro Trp Ser Ser Ala Arg Thr Leu Glu Ala Pro Pro Gln        3955 3960 3965 Asp Phe Pro Ala Pro Trp Ala Gln Val Thr Gly Ala His Ser Val Leu    3970 3975 3980 Leu Asn Trp Thr Glu Pro Asp Ser Pro Asn Gly Ile Ile Phe Gln Tyr 3985 3990 3995 4000 Arg Val Val Tyr Gln Gln Lys Thr Asp Asp Pro Thr Leu Asn Phe Ser                4005 4010 4015 Ala Val His Ala Phe Thr Val Met Gly Thr Ser Tyr Gln Ala His Leu            4020 4025 4030 Phe Gly Leu Glu Pro Phe Thr Thr Tyr His Ile Gly Val Val Ala Thr        4035 4040 4045 Asn Gln Ala Gly Glu Val Ser Ser Pro Thr Leu Val Gln Thr Leu    4050 4055 4060 Glu Ser Ser Pro Gly Leu Ser Asn Phe Thr Val Glu Gln Lys Glu 4065 4070 4075 4080 Asn Gly Arg Ala Leu Leu Leu Gln Trp Ser Glu Pro Ala Arg Thr Asn                4085 4090 4095 Gly Val Ile Lys Thr Tyr Asn Val Phe Ser Glu Asp Val Leu Glu Tyr            4100 4105 4110 Thr Gly Leu Asn Arg Gln Phe Leu Phe Arg Arg Leu Asp Pro Phe Thr        4115 4120 4125 Leu Tyr Thr Leu Thr Leu Glu Ala Cys Thr Arg Ala Gly Cys Ala His    4130 4135 4140 Ser Ala Pro Gln Pro Leu Trp Thr Glu Glu Ala Ala Pro Asp Ser Gln 4145 4150 4155 4160 Pro Ala Pro Thr Ile Gln Ser Val Gly Ser Thr Ser Val Glu Leu Ser                4165 4170 4175 Trp Ser Glu Pro Ile Lys Thr Asn Gly Lys Ile Ile Arg Tyr Glu Val            4180 4185 4190 Ile Arg Arg Cys Phe Glu Gly Lys Ala Trp Gly Asn Gln Thr Ile Gln        4195 4200 4205 Ala Asp Glu Lys Ile Val Phe Ile Glu Ser Asn Thr Glu Arg Asn Thr    4210 4215 4220 Phe Ile Tyr Asn Asp Thr Gly Leu Gln Pro Trp Met His Cys Glu Tyr 4225 4230 4235 4240 Lys Val His Thr Trp Asn Ser Ala Gly His Ala Cys Ser Ser Trp Ser                4245 4250 4255 Gly Val Arg Thr Arg Gln Ala Pro Pro Asp Gly Leu Cys Pro Pro Glu            4260 4265 4270 Val Ala Gln Val Ser Val Asn Pro Pro Lys Val Leu Ile Ser Trp Val        4275 4280 4285 Pro Pro Glu Gln Pro Asn Gly Ile Ile Gln Ser Tyr Arg Leu Gln Arg    4290 4295 4300 Asn Gly Val Leu Tyr Pro Phe Ser Phe Asp Ala Val Thr Phe Asn Tyr 4305 4310 4315 4320 Thr Asp Glu Lys Leu Leu Pro Phe Ser Thr Tyr Ser Tyr Gly Val Thr                4325 4330 4335 Ala Cys Thr Ser Arg Gly Cys Ser Ala Ser Thr Thr Thr Ser Ile Thr            4340 4345 4350 Thr Leu Glu Ala Ala Pro Ala Gly Val His Pro Ala Leu Arg Thr        4355 4360 4365 Ile Ser Ala Thr Gln Ile Asn Val Ser Trp Ser Pro Pro Ser Ile Gln    4370 4375 4380 Asn Gly Glu Ile Thr Gln Tyr Leu Leu Arg Leu Asp Gly Lys Glu Tyr 4385 4390 4395 4400 Leu Ala Gly Gln Asn Leu Thr Leu Leu Val Ser His Leu Gln Pro Tyr                4405 4410 4415 Thr Gln Tyr Asn Phe Ser Leu Val Ala Cys Thr Lys Gly Gly Cys Thr            4420 4425 4430 Ala Ser Met Pro Glu Ser Ala Trp Thr Met Glu Ala Pro Pro Gln Asn        4435 4440 4445 Met Asp Pro Pro Lys Leu Gln Val Thr Gly Ser Glu Ser Ile Glu Ile    4450 4455 4460 Thr Trp Lys Leu Pro Arg Ile Pro Asn Gly Arg Ile Arg Ser Tyr Glu 4465 4470 4475 4480 Leu Arg Arg Asp Gly Thr Ile Val Tyr Thr Gly Leu Glu Thr Arg Tyr                4485 4490 4495 His Asp Phe Thr Leu Thr Pro Gly Val Glu Tyr Gly Tyr Thr Val Met            4500 4505 4510 Ala Asn Asn Ser Gln Gly Gly Val Leu Ser Pro Leu Val Lys Asp Arg        4515 4520 4525 Thr Ser Pro Ser Ala Pro Ser Gly Met Glu Pro Pro Arg Leu Leu Ala    4530 4535 4540 Lys Gly Pro Gln Glu Ile Phe Val Thr Trp Asp Pro Pro Val Arg Thr 4545 4550 4555 4560 Asn Gly Arg Ile Val Asn Tyr Thr Leu Phe Ile Arg Asp Leu Phe Glu                4565 4570 4575 Arg Glu Thr Lys Ile Ile His Ile Asn Thr Thr His Asn Ser Phe Gly            4580 4585 4590 Pro Gln Ser Phe Met Val Asn Gln Leu Lys Pro Phe His Arg Tyr Glu        4595 4600 4605 Val Arg Ile Gln Ala Cys Thr Arg Leu Gly Cys Val Ser Ser Asp Trp    4610 4615 4620 Thr Phe Ile Glu Thr Leu Glu Val Ala Pro Gln Gln Gln Pro Pro Pro 4625 4630 4635 4640 His Leu Glu Val Gln Met Ala Pro Gly Gly Phe Gln Pro Thr Val Ser                4645 4650 4655 Leu Leu Trp Thr Gly Pro Leu Gln Pro Asn Gly Arg Val Leu Tyr Tyr            4660 4665 4670 Glu Leu Tyr Arg Arg Gln Ile Ala Thr Gln Pro Glu Lys Ser Lys Pro        4675 4680 4685 Val Leu Ala Tyr Asn Gly Ser Ser Ser Ser Phe Met Asp Val Glu Leu    4690 4695 4700 Leu Pro Phe Thr Glu Tyr Glu Tyr Gln Val Trp Ala Val Asn Ser Ala 4705 4710 4715 4720 Gly Lys Ala Pro Ser Ser Trp Thr Arg Cys Arg Thr Gly Pro Ala Pro                4725 4730 4735 Pro Glu Gly Leu Lys Ala Pro Lys Phe His Ala Val Ser Ala Thr Gln            4740 4745 4750 Ala Val Val Asn Ile Ser Thr Pro Gln Lys Pro Asn Gly Ile Val Thr        4755 4760 4765 Leu Tyr Arg Leu Phe Ser Arg Ser Thr Ser Gly Ala Gln Thr Val Leu    4770 4775 4780 Ala Glu Gly Leu Ala Thr Gln Gln Thr Leu His Ser Leu Gln Pro Phe 4785 4790 4795 4800 Thr Thr Ser Ile Gly Val Glu Ala Cys Thr Cys Phe Ser Cys Cys                4805 4810 4815 Ser Gln Gly Pro Thr Ala Glu Leu Arg Thr Pro Pro Ala Pro Pro Ala            4820 4825 4830 Gly Leu Ser Ser Pro Gln Ile Gln Met Leu Ala Ser Arg Thr Ala Ser        4835 4840 4845 Phe Gln Trp Ser Pro Pro Leu Phe Pro Asn Gly Val Ile Gln Ser Tyr    4850 4855 4860 Glu Leu Gln Leu Tyr Lys Ala Cys Pro Pro Asp Ser Ala Thr Pro Cys 4865 4870 4875 4880 Thr Pro Ser Gln Thr Glu Thr Lys Tyr Arg Gly Pro Gly Gln Arg Ala                4885 4890 4895 Ser Leu Glu Gly Leu Gln Pro Tyr Thr Thr Tyr Lys Leu Arg Val Val            4900 4905 4910 Ala His Asn Glu Val Gly Ser Thr Val Thr Glu Trp Ile Ser Phe Val        4915 4920 4925 Thr Gln Lys Glu Leu Pro Gln Tyr Arg Ala Pro Ile Ser Val Asp Ser    4930 4935 4940 Asn Leu Ser Val Val Cys Val Asn Trp Ser Asn Ser Phe Leu Leu Asn 4945 4950 4955 4960 Gly Arg Leu Lys Glu Phe Val Leu Thr Asp Gly Gly Gln Arg Leu Tyr                4965 4970 4975 Ser Gly Leu Asp Thr Thr Leu Tyr Ile Pro Arg Thr Ala Asp Lys Thr            4980 4985 4990 Phe Phe Phe Gln Val Ile Cys Ile Thr Glu Glu Gly Ser Ala Lys Thr        4995 5000 5005 Pro Leu Ile Gln Tyr Asp Thr Ser Thr Gly Phe Gly Leu Val Leu Thr    5010 5015 5020 Thr Pro Gly Glu Lys Lys Gly Ser Ser Ser Ser Ser Thr Glu Phe Tyr 5025 5030 5035 5040 Ser Glu Leu Trp Phe Ile Val Leu Met Ala Val Leu Gly Leu Ile Leu                5045 5050 5055 Leu Ala Ile Phe Leu Ser Leu Ile Leu Gln Arg Lys Ile His Lys Glu            5060 5065 5070 Pro Tyr Ile Arg Glu Arg Pro Pro Leu Val Pro Leu Pro Lys Arg Arg        5075 5080 5085 Ser Pro Leu Asn Val Tyr Pro Pro Gly Glu Thr His Val Gly Leu Ala    5090 5095 5100 Asp Thr Lys Ile Pro Arg Ser Gly Thr Pro Val Ser Ile Arg Ser Asn 5105 5110 5115 5120 Arg Ser Leu Ser Val Leu Arg Ile Pro Ser Gln Ser His Gly Ser Gln                5125 5130 5135 Thr Tyr Ser Gln Gly Ser Leu His Arg Ser Ser Ser Gln Leu Met Asp            5140 5145 5150 Ile Gln Asp Lys Lys Val Leu Ile Asp Asp Ser Leu Trp Glu Thr Ile        5155 5160 5165 Met Gly His Asp Ser Gly Leu Tyr Val Asp Glu Glu Asp Leu Met Asn    5170 5175 5180 Ala Ile Lys Gly Phe Ser Ser Val Thr Lys Glu His Thr Thr Phe Thr 5185 5190 5195 5200 Asp Thr His Leu                 <210> 18 <211> 566 <212> PRT <213> Bos taurus <400> 18 Ser Pro Val Tyr Cys Arg Tyr Gln Phe His Arg Ala Pro Val His Cys   1 5 10 15 Thr Glu Gly Gln Pro His Gly Thr His Val Tyr Phe Gln Asp Val Asn              20 25 30 Val Ile Phe Leu Gly Ala Met His Ser Ser Asp Leu Arg Glu Tyr Leu          35 40 45 Glu Gly Pro Pro Met Val Val Glu Val His Asp Arg Asp Arg Lys Ser      50 55 60 Glu Cys Ser Arg Lys Pro Thr Leu Phe Gly Glu Asp Pro Leu Asp  65 70 75 80 Ala His Leu Asn Leu Gln Ala Leu Ile Ser Pro Arg Asp Thr Glu Ser                  85 90 95 Asn Pro Phe Glu Thr Gln Glu Lys Met Trp Asp Pro His Gly Val Ala             100 105 110 Gln Val Ser Phe Ala Asp Leu Leu Leu Gly His Lys Tyr Leu Asn Leu         115 120 125 Ala Ala Pro Val Arg Ser Cys Glu Pro Trp Ala Ala Pro Leu Gly His     130 135 140 Gly Arg Arg Ser Ser His Ala Gly Pro Arg Gly Pro Arg Asp Gly 145 150 155 160 Val Pro His Gly Leu Met Pro Pro Gly Asp Tyr Leu Glu Ala Ser Cys                 165 170 175 Leu Leu Lys Leu Arg Val Asp Val Ala Val Pro Leu Arg Gly Gly Leu             180 185 190 Gly Gly Ala Asp Pro Val Leu Ser Arg Phe Gly Arg Val Val Phe Val         195 200 205 Phe Glu Ser Arg Arg Leu Ser Leu Leu His Ser Leu Leu Gln Asp Val     210 215 220 Thr Met Ile Asn Ala Arg Ala Leu Ala Leu Asp Ser Tyr Pro Leu Glu 225 230 235 240 Asp Ile Gln Gln Ile Leu Ser Ala Phe Lys Ile Arg Val Lys Thr Gln                 245 250 255 Glu Gln Pro Asp Leu Asp Val Leu Thr Gly Val His Leu Leu Asp Gly             260 265 270 Lys Val His Phe Leu Val Leu Glu Gly Leu Ala Asp His Gly Leu Gln         275 280 285 Arg Leu Trp Ala Arg His Gln Ser Arg Val Pro Arg Ala Glu Gln Gly     290 295 300 Pro Phe Lys Ala Leu Tyr Asn Ser Gln Leu Arg Phe Arg Arg Arg Leu 305 310 315 320 Tyr Ala Asp Leu Glu Thr Val Leu Tyr Arg Val Val Arg Leu Phe Arg Pro                 325 330 335 Leu Ala Gln Leu Val Gln Gln Ala Leu Tyr Val Arg Arg Ala Val             340 345 350 Pro Pro Gln Val Phe Gln Ala Leu Ser Arg Ile Tyr Cys Ile Cys Arg         355 360 365 Tyr Ser Ser Arg Leu Arg Glu Val Ile Thr Gly Asp Leu Leu Pro Ser     370 375 380 Ser Ala Met Ile Lys Glu Leu Ser Gln Glu Phe Gly Met Pro Met Ser 385 390 395 400 Gln Gly Asp Leu Thr Glu Gln Lys Leu Leu Ala Val Ala Pro Ala Pro                 405 410 415 Ser Leu Glu Asp Leu Arg Ser Ser Lys Ser Thr Leu Ala Ser Glu Ile             420 425 430 His Ser His Gln Glu Pro Gly Arg Arg Phe Thr Tyr Ser Gln Lys Tyr         435 440 445 Leu Ser Ala Thr Val Gly Pro Leu Asp Pro Glu Glu Glu Glu Arg Arg     450 455 460 Ala Arg Arg Glu Ser Arg Gln Ala Trp Arg Thr Pro Asn Gly Phe Gln 465 470 475 480 Thr Ala Gly Leu His Ser Met Gly Thr Thr Trp Pro Leu Arg Leu Pro                 485 490 495 Pro Ile Ser Ala Ala Thr Glu Glu Trp Arg Glu Lys Ala Leu Phe Thr             500 505 510 Asn Leu Leu Glu Pro Val Leu Trp Arg Glu Arg Trp Gly Trp Asp Arg         515 520 525 Arg His Gln Asp Phe Asn Leu Tyr Thr Arg Pro Pro Glu Phe Leu Glu     530 535 540 Leu Pro Pro Ala Pro Lys Pro Arg Ala Ala Arg Ser Arg Arg Gly Pro 545 550 555 560 Gly His Ser Pro Ala Arg                 565 <210> 19 <211> 499 <212> PRT <213> Bos taurus <400> 19 Met Leu Gln Cys Arg Pro Ala Glu Glu Phe Ser Phe Gly Pro Arg Ala   1 5 10 15 Leu Lys Asp Ala Leu Leu Ser Thr Asp Pro Ala Leu Arg Gln Leu Tyr              20 25 30 Thr Ala Ala Phe Ser Ala Glu Ale Glu Ala Tyr          35 40 45 Asn Pro Arg Arg Thr Leu Phe Gly Thr Leu Leu Ile Arg Thr Ala Phe      50 55 60 Asp Trp Leu Leu Ser Arg Pro Glu Ala Pro Glu Asp Phe Gln Thr Phe  65 70 75 80 His Ala Ala Leu Pro Pro Arg Lys Gln Ser Leu Ala Arg Lys His Ile                  85 90 95 Tyr Leu Gln Pro Ile Gly Leu Ser Glu Gly Pro Ala Gly Ser Val Leu             100 105 110 Leu Asp Gln Leu Arg Ser Cys Thr Glu Ala Phe Phe Leu Gly Leu Gln         115 120 125 Val Arg Cys Leu Pro Ser Val Ala Ala Ala Ser Ile His Cys Ser Ser     130 135 140 Arg Pro Gly Gln Asp Pro Asp Arg Leu Gln Leu His Thr Asp Gly Ile 145 150 155 160 Leu Ser Phe Leu Lys Ser Ser Lys Pro Gly Asp Ala Leu Cys Val Leu                 165 170 175 Gly Leu Thr Leu Ser Asp Leu Tyr Pro Cys Glu Ala Trp Thr Phe Thr             180 185 190 Phe Gly Thr Phe Leu Pro Gly His Glu Val Gly Val Cys Ser Phe Ala         195 200 205 Arg Phe Ser Gly Glu Phe Leu Pro Arg Glu Pro Ser Thr Pro Asp Leu     210 215 220 Val Glu Val Glu Ala Glu Ala Glu Aly Asp Gly Pro Glu Val Pro Leu 225 230 235 240 Gln Asp Gly Gly Gln Ala Val Cys Phe Ser Ala Leu Gly Met Val Gln                 245 250 255 Cys Cys Lys Val Thr Cys His Glu Leu Cys His Leu Leu Gly Leu Gly             260 265 270 Asn Cys Arg Trp Leu Arg Cys Leu Met Gln Gly Ala Leu Arg Val Asp         275 280 285 Glu Ala Leu Arg Arg Pro Leu Asp Leu Cys Pro Ile Cys Leu Arg Lys     290 295 300 Leu Gln His Leu Leu Gly Phe Arg Leu Val Asp Arg Tyr Lys Arg Leu 305 310 315 320 Tyr Ala Trp Thr Gln Ala Ala Gly Thr Gln Pro Ser Ala Ala                 325 330 335 Val Gly Glu Pro Ser Val Ser Glu Asp Thr Leu Pro Cys Ser Ala Asp             340 345 350 Ser Gly Leu Cys Cys Glu Ser Asp Ser Glu Pro Gly Ser Ser Leu Ser         355 360 365 Glu Pro Leu Ser Pro Asp Ala Trp Ser Gln Ala Phe Pro Ala Gly Leu     370 375 380 Glu Leu Asp Ala Glu Asp Gly Leu Gly Ser Leu Ala Ala Ala Glu Gly 385 390 395 400 Pro Gly Glu Ala Leu Ala Glu His Gly Arg Trp Leu Ala Ala Cys Ile                 405 410 415 Gln Ala Leu Glu Arg Asp Val Ser Glu Gly Glu Leu Glu Arg Val Asp             420 425 430 Gly Ala Val Asp Ala Leu Ala Pro Trp Asp Leu Phe Thr Gly Arg Leu         435 440 445 Pro Ala Ser Arg Gln Asp Leu Pro Cys Gly Arg Asp Gly Ala Gly Leu     450 455 460 Arg Arg Val Leu Gly Asp Thr Phe Ser Ser Leu Arg Arg Arg Leu Ser 465 470 475 480 Ala Arg Arg Pro Ser Arg Ala Glu Ser Pro Leu Arg Arg Gln Lys Ala                 485 490 495 Glu Asp Asp             <210> 20 <211> 516 <212> PRT <213> Bos taurus <400> 20 Met Arg Glu Ala Gly Gln Met Gln Asn Leu Glu Ser Ala Gly Ala Gly   1 5 10 15 Arg Ser Ser Thr Gln Thr Gly Ser Met Thr Gly Glu Ile Pro Arg              20 25 30 Leu Ser Lys Val Asn Leu Phe Thr Leu Leu Ser Leu Trp Met Glu Leu          35 40 45 Phe Pro Ala Val Lys Thr Gln Arg Gln Lys Ser Gln Ser Lys Thr Ser      50 55 60 Asn Pro Ser Pro Ala Pro Leu Ser Lys Asn His Thr Phe Thr Arg Leu  65 70 75 80 Phe Ile Arg Lys Lys Lys Val Lys Arg Thr Gly Leu Val Val Val Lys                  85 90 95 Asn Met Lys Ile Val Gly Leu His Cys Ser Ser Glu Asp Leu His Ala             100 105 110 Gly Lys Ile Ala Leu Ile Lys His Gly Ser Lys Leu Lys Asn Cys Asp         115 120 125 Leu Tyr Phe Ser Arg Lys Pro Cys Ser Ala Cys Leu Lys Met Ile Val     130 135 140 Asn Ala Gly Val Asn Arg Ile Ser Tyr Trp Pro Ala Asp Pro Glu Ile 145 150 155 160 Ser Leu Leu Thr Glu Ala Ser Gly Phe Glu Asp Ala Lys Leu Asp Ala                 165 170 175 Lys Ala Val Glu Arg Leu Lys Ser Asn Ser Arg Ala His Val Cys Val             180 185 190 Leu Leu Gln Pro Leu Val Cys Tyr Met Val Gln Phe Val Glu Glu Thr         195 200 205 Ser Tyr Lys Cys Asp Phe Ile Gln Lys Ile Ser Lys Thr Leu Pro Asp     210 215 220 Thr Asn Phe Asp Phe Tyr Ser Glu Cys Lys Gln Glu Arg Ile Lys Glu 225 230 235 240 Tyr Glu Met Ile Phe Leu Val Ser Asn Glu Glu Met His Lys Gln Ile                 245 250 255 Leu Met Thr Ile Gly Leu Glu Asn Leu Cys Glu Asn Pro Tyr Phe Ser             260 265 270 Asn Leu Arg Gln Asn Met Lys Asp Leu Val Leu Leu Leu Ala Ala Val         275 280 285 Ala Ser Ser Val Pro Asn Phe Lys His Tyr Gly Phe Tyr Cys Gly Asn     290 295 300 Thr Glu His Ser Asn Glu Ile His Asn Gln Ser Leu Pro Gln Glu Ile 305 310 315 320 Ala Arg His Cys Met Ile Gln Ala Arg Leu Leu Ala Tyr Arg Thr Glu                 325 330 335 Asp His Lys Thr Gly Val Gly Ala Val Ile Trp Ala Glu Gly Lys Ser             340 345 350 Arg Ser Cys Asp Gly Thr Gly Ala Met Tyr Phe Ile Gly Cys Gly Tyr         355 360 365 Asn Ala Phe Pro Val Gly Ser Glu Tyr Ala Asp Phe Pro His Met Asp     370 375 380 Asp Lys Gln Lys Asp Arg Glu Ile Arg Lys Phe Arg Tyr Ile Val His 385 390 395 400 Ala Glu Gln Asn Ala Leu Thr Phe Arg Cys Gln Glu Ile Lys Pro Glu                 405 410 415 Glu Arg Ser Met Ile Phe Val Thr Lys Cys Pro Cys Asp Glu Cys Val             420 425 430 Pro Leu Ile Lys Gly Ala Gly Ile Lys Gln Ile Tyr Ala Gly Asp Val         435 440 445 Asp Val Gly Lys Lys Lys Ala Asp Ile Ser Tyr Met Arg Phe Gly Glu     450 455 460 Val Glu Gly Val Ser Lys Phe Thr Trp Gln Leu Asn Pro Ser Arg Thr 465 470 475 480 Gly Val Leu Glu Gln Asn Glu Pro Glu Ser Arg Glu Asn Gly Val Leu                 485 490 495 Gly Ser Val Ala Leu Asp Glu Glu Pro His Gln Asn Lys Lys Leu Arg             500 505 510 Leu Ala Asn His         515 <210> 21 <211> 823 <212> PRT <213> Bos taurus <400> 21 Met Ser Asp Gly Glu Gly Pro Ser Ala Asp Asp Ser Ala Ser Ala Ala   1 5 10 15 Ser Ser Met Glu Val Thr Asp Arg Ile Ala Ser Leu Glu Gln Arg Val              20 25 30 Gln Leu Gln Glu Asp Asp Ile Gln Leu Leu Lys Ser Ala Leu Ala Asp          35 40 45 Val Val Arg Arg Leu Ser Val Thr Glu Glu Gln Gln Ala Val Leu Ser      50 55 60 Arg Lys Gly Pro Thr Lys Ala Arg Pro Leu Val Gln Thr Leu Pro Leu  65 70 75 80 Arg Thr Thr Val Asn Asn Gly Thr Val Val Pro Lys Lys Pro Ser Gly                  85 90 95 Ser Leu Pro Ala Pro Pro Gly Ala Arg Arg Glu Pro Ala Val Ala             100 105 110 Ala Ala Lys Arg Leu Asn Arg Ser Val Ser Leu Ser Ser Ala Tyr Thr         115 120 125 Leu Asn Arg Ser Thr Ala Ser Thr Val Lys Arg Thr Ser Ser Ser Glu     130 135 140 Arg Val Ser Pro Gly Gly Arg Arg Glu Ser Tyr Gly Asp Ser Lys Gly 145 150 155 160 Asn Arg Asn Arg Thr Gly Ser Thr Ser Ser Ser Ser Gly Lys Lys                 165 170 175 Asn Ser Glu Ser Lys Pro Lys Glu Pro Val Phe Ser Ala Glu Glu Gly             180 185 190 Tyr Val Lys Met Phe Leu Arg Gly Arg Pro Val Thr Met Tyr Met Pro         195 200 205 Lys Asp Gln Val Asp Ser Tyr Asn Leu Glu Ala Lys Val Glu Leu Pro     210 215 220 Thr Lys Arg Leu Lys Leu Glu Trp Ala Arg Ser Tyr Gly Tyr Arg Gly 225 230 235 240 Arg Asp Cys Arg Asn Asn Leu Tyr Leu Leu Pro Thr Gly Glu Thr Val                 245 250 255 Tyr Phe Ile Ala Ser Val Val Val Leu Tyr Asn Val Glu Glu Gln Leu             260 265 270 Gln Arg His Tyr Ala Gly His Asn Asp Asp Val Lys Cys Leu Ala Val         275 280 285 His Pro Asp Arg Val Thr Ile Ala Thr Gly Gln Val Ala Gly Thr Ser     290 295 300 Lys Asp Gly Lys Lys Gln Gln Leu Pro Pro His Val Val Ile Trp Asp 305 310 315 320 Ser Val Thr Leu Asn Thr Leu His Val Val Gly Ile Gly Phe Phe Asp                 325 330 335 Arg Ala Val Thr Cys Ile Ala Phe Ser Lys Ser Asn Gly Gly Ser Asn             340 345 350 Leu Cys Ala Val Asp Asp Ser Asn Asp His Val Leu Ser Val Trp Asp         355 360 365 Trp Gln Lys Glu Glu Arg Leu Ala Asp Val Lys Cys Ser Asn Glu Ala     370 375 380 Val Phe Ala Ala Asp Phe His Pro Thr Asp Thr Asn Ile Ile Val Thr 385 390 395 400 Cys Gly Lys Ser His Leu Tyr Phe Trp Thr Leu Glu Gly Ser Ser Leu                 405 410 415 Ile Lys Lys Gln Gly Leu Phe Glu Lys Gln Glu Lys Pro Lys Phe Val             420 425 430 Leu Cys Val Thr Phe Ser Glu Asn Gly Asp Thr Ile Thr Gly Asp Ser         435 440 445 Ser Gly Asn Ile Leu Val Trp Gly Lys Gly Thr Asn Arg Ile Ser Tyr     450 455 460 Val Val Gln Gly Ala His Glu Gly Gly Ile Phe Ala Leu Cys Met Leu 465 470 475 480 Arg Asp Gly Thr Leu Val Ser Gly Gly Gly Lys Asp Arg Lys Leu Ile                 485 490 495 Ser Trp Asp Gly Asn Tyr Gln Lys Leu His Lys Thr Glu Ile Pro Glu             500 505 510 Gln Phe Gly Pro Ile Arg Thr Val Ala Glu Gly Lys Gly Asp Val Ile         515 520 525 Leu Ile Gly Thr Thr Arg Asn Phe Val Leu Gln Gly Thr Leu Ser Gly     530 535 540 Asp Phe Thr Pro Ile Thr Gln Gly His Thr Asp Glu Leu Trp Gly Leu 545 550 555 560 Ala Val His Ala Ser Lys Pro Gln Phe Leu Thr Cys Gly His Asp Arg                 565 570 575 His Ala Thr Leu Trp Asp Ala Val Gly His Arg Pro Val Trp Asp Lys             580 585 590 Val Ile Glu Asp Pro Ala Gln Ser Ser Gly Phe His Ser Ser Gly Ser         595 600 605 Val Val Ala Val Gly Thr Leu Thr Gly Arg Trp Phe Val Phe Asp Thr     610 615 620 Glu Thr Lys Asp Leu Val Thr Val His Thr Asp Gly Asn Glu Gln Leu 625 630 635 640 Ser Val Met Arg Tyr Ser Pro Ala Gln Ala Phe Leu Thr Gly Ala Phe                 645 650 655 Gly Ala His Cys Leu Gly Val Cys Ile Tyr Met Glu Arg Glu Lys Ser             660 665 670 Lys Lys Val Phe Leu Ile His Thr Cys Ser Leu Pro Pro Cys Ser Phe         675 680 685 Val Thr Phe Leu Phe Trp Gly Gln Leu Phe Thr Tyr Glu Lys Ile Asp     690 695 700 Trp Val Pro Ser Gly Ser Arg Gln Gln Gly Ala Cys Pro Glu Ser Arg 705 710 715 720 Gly Val His Ala Ala Ala Glu Gln Phe Glu Ala Asn Gln Glu Ser Ala                 725 730 735 Ser Leu Trp Ala Glu Gly Thr Pro Gly Arg Ala Asp Ala Ala Thr Ile             740 745 750 Cys His Glu His Phe Gln His Thr Tyr Ser Ser Thr Ser Asp Pro Ser         755 760 765 Pro Gly Leu Ser Val His Cys Pro Pro Cys Leu Ser Ser Gln Ala Pro     770 775 780 Ser His Val Tyr Ser Gly His Ser Ser His Val Thr Asn Val Asp Phe 785 790 795 800 Leu Cys Asp Asp Ser His Leu Ile Ser Thr Gly Gly Lys Asp Thr Ser                 805 810 815 Ile Met Gln Trp Arg Val Val             820 <210> 22 <211> 682 <212> PRT <213> Bos taurus <400> 22 Met Gln Leu Gly Glu Gln Leu Leu Val Ser Ser Val Asn Leu Pro Gly   1 5 10 15 Ala His Phe Tyr Pro Leu Glu Gly Ala Arg Gly Gly Gly Gly Gly Ser              20 25 30 Ala Gly His Leu Pro Gly Ala Ala Pro Ser Pro Gln Arg Leu Asp Leu          35 40 45 Asp Lys Ala Pro Lys Lys Phe Ser Gly Ser Leu Ser Cys Glu Ala Ala      50 55 60 Ser Gly Glu Pro Ala Ala Aly Gly Ala Gly Ala Pro Ala Thr Met Leu  65 70 75 80 Ser Asp Ala Asp Ala Gly Asp Ala Phe Ala Ser Ala Ala Ala Val Ala                  85 90 95 Lys Pro Gly Pro Pro Asp Gly Arg Lys Gly Ser Pro Cys Gly Glu Glu             100 105 110 Glu Leu Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser         115 120 125 Ala Arg Tyr Ser Met Asp Ser Leu Ser Ser Glu Arg Tyr Tyr Leu Gln     130 135 140 Ser Pro Gly Pro Gly Gly Ser Glu Leu Ala Ala Pro Cys Ser Leu Phe 145 150 155 160 Pro Tyr Gln Ala Ala Gly Ala Pro His Gly Ser Val Tyr Pro Ala                 165 170 175 Pro Asn Gly Ala Arg Tyr Pro Tyr Gly Ser Met Leu Pro Pro Gly Gly             180 185 190 Phe Pro Ala Ala Val Cys Pro Pro Gly Arg Ala Gln Phe Gly Thr Gly         195 200 205 Ala Gly Ala Ser Gly Gly Aly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly     210 215 220 Gly Ala Tyr Gln Tyr Gly Gln Gly Ala Pro Leu Tyr Gly Pro Tyr Pro 225 230 235 240 Ala Ala Ala Ala Aly Gly Thr Cys Gly Gly                 245 250 255 Pro Gly Ser Gly Phe Arg Ala His Val Tyr Leu Cys Asn Arg Pro Leu             260 265 270 Trp Leu Lys Phe His Arg His Gln Thr Glu Met Ile Ile Thr Lys Gln         275 280 285 Gly Arg Arg Met Phe Pro Phe Leu Ser Phe Asn Ile Asn Gly Leu Asn     290 295 300 Pro Thr Ala His Tyr Asn Val Phe Val Glu Val Val Leu Ala Asp Pro 305 310 315 320 Asn His Trp Arg Phe Gln Gly Gly Lys Trp Val Thr Cys Gly Lys Ala                 325 330 335 Asp Asn Asn Met Gln Gly Asn Lys Met Tyr Val His Pro Glu Ser Pro             340 345 350 Asn Thr Gly Ser His Trp Met Arg Gln Glu Ile Ser Phe Gly Lys Leu         355 360 365 Lys Leu Thr Asn Asn Lys Gly Ala Asn Asn Asn Asn Thr Gln Met Ile     370 375 380 Val Leu Gln Ser Leu His Lys Tyr Gln Pro Arg Leu His Ile Val Glu 385 390 395 400 Val Thr Glu Asp Gly Val Glu Asp Leu Asn Glu Pro Ser Lys Thr Gln                 405 410 415 Thr Phe Thr Phe Ser Glu Thr Gln Phe Ile Ala Val Thr Ala Tyr Gln             420 425 430 Asn Thr Asp Ile Thr Gln Leu Lys Ile Asp His Asn Pro Phe Ala Lys         435 440 445 Gly Phe Arg Asp Asn Tyr Asp Ser Ser His Gln Ile Val Pro Gly Gly     450 455 460 Arg Tyr Gly Val Gln Ser Phe Phe Pro Glu Pro Phe Val Asn Thr Leu 465 470 475 480 Pro Gln Ala Arg Tyr Tyr Asn Gly Glu Arg Thr Val Pro Gln Thr Asn                 485 490 495 Gly Leu Leu Ser Pro Gln Gln Ser Glu Glu Val Ala Asn Pro Pro Gln             500 505 510 Arg Trp Leu Val Thr Pro Val Gln Gln Pro Gly Thr Asn Lys Ile Asp         515 520 525 Ile Gly Ser Tyr Glu Ser Glu Tyr Ser Ser Ser Thr Leu Leu Pro Tyr     530 535 540 Gly Ile Lys Ser Leu Pro Leu Gln Thr Ser His Ala Leu Gly Tyr Tyr 545 550 555 560 Pro Asp Pro Gly Phe Pro Ala Met Ala Gly Trp Gly Gly Arg Gly Ser                 565 570 575 Tyr Gln Arg Lys Met Ala Ala Gly Leu Pro Trp Thr Ser Arg Thr Ser             580 585 590 Pro Pro Gly Phe Ser Glu Asp Gln Leu Ser Lys Glu Lys Val Lys Glu         595 600 605 Glu Ile Gly Ser Ser Trp Ile Glu Thr Pro Pro Ser Ile Lys Ser Leu     610 615 620 Asp Ser Asn Asp Ser Gly Val Tyr Thr Ser Ala Cys Lys Arg Arg Arg 625 630 635 640 Leu Ser Pro Ser Thr Ser Ser Asn Glu Asn Ser Pro Ser Ile Lys Cys                 645 650 655 Glu Asp Ile Asn Ala Glu Glu Tyr Ser Lys Asp Ser Ser Lys Gly Met             660 665 670 Gly Gly Tyr Tyr Ala Phe Tyr Thr Thr Pro         675 680 <210> 23 <211> 103 <212> PRT <213> Bos taurus <400> 23 Met Ser Gly Arg Gly Lys Gly Gly Lys Gly Leu Gly Lys Gly Gly Ala   1 5 10 15 Lys Arg His Arg Lys Val Leu Arg Asp Asn Ile Gln Gly Ile Thr Lys              20 25 30 Pro Ala Ile Arg Arg Leu Ala Arg Arg Gly Gly Val Lys Arg Ile Ser          35 40 45 Gly Leu Ile Tyr Glu Glu Thr Arg Gly Val Leu Lys Val Phe Leu Glu      50 55 60 Asn Val Ile Arg Asp Ala Val Thr Tyr Thr Glu His Ala Lys Arg Lys  65 70 75 80 Thr Val Thr Ala Met Asp Val Val Tyr Ala Leu Lys Arg Gln Gly Arg                  85 90 95 Thr Leu Tyr Gly Phe Ala Gly             100 <210> 24 <211> 1446 <212> PRT <213> Bos taurus <400> 24 Met Ala Tyr Tyr Trp Lys Thr Asp Leu Asn Ser Ser Glu Ser His Glu   1 5 10 15 Lys Gln Gln Glu His Gln Glu Phe Pro Ser Leu Asn Gln Pro Leu Phe              20 25 30 Ser Ser Leu Val Ser Leu Gly Phe Asp Asn Val Val Glu Glu Ile Ser          35 40 45 Asn Lys Ile Pro Leu Cys Gln Arg Glu Ile Glu Glu Asn Ala Phe Phe      50 55 60 Val Ser Ala Leu His Trp Asp Ser Arg Thr His Ser Leu Asp Glu  65 70 75 80 Ile His Gln Thr Ser Leu Asn Glu Phe Thr Ser Ser Ser Ser Glu Leu                  85 90 95 Ser Cys His Gln Val Arg Glu Thr Pro Val Ile Gly Phe Ser Arg His             100 105 110 Ser Val Leu Pro Asn Pro Gln Asn Ile Asn Lys Gly Ser Ser Trp Gly         115 120 125 Asn Pro Ile Gly Lys Tyr His Gly Ala Asp Asp Tyr Gly Phe Asn Ile     130 135 140 Leu Pro Leu Ser Ser Thr Ser Leu Asp Lys Asn Asn Ser Gln Ser Gln 145 150 155 160 Leu Glu Asn Glu Asn His Asn Tyr His Ile Gly Phe Glu Ser Ser Val                 165 170 175 Leu Pro Ile Tyr Pro Phe Leu Ser Thr Asn Leu Met Pro Lys Glu Glu             180 185 190 Asn Lys Ser Arg Arg Asn Met Asn Val Val Glu Ser Ser Leu Met Pro         195 200 205 Phe Gln Gly Ser Ser Leu Pro Arg Thr Trp Glu Ser Thr His Pro Lys     210 215 220 Asn Thr Glu Leu Thr Gly Cys Ser Ile Gln Leu Val Glu Val Ala Gln 225 230 235 240 Gly Ser Asn Met Ser Leu Ala Ser Phe Cys Asn Lys Val Lys Lys Ile                 245 250 255 Arg Glu Thr Tyr His Ala Ala Asp Met Asp Ser Asn Ser Gly Lys Ile             260 265 270 Trp Ser Thr Thr Thr Ala Phe Pro Tyr Lys Leu Phe Ser Asn Thr Lys         275 280 285 Phe Asn Ile Asn Ile Phe Thr Asp Asn Ser Thr Lys Gly Leu His Phe     290 295 300 Ile Pro Cys Ala Asn Tyr Leu Val Lys Asp Leu Ile Ala Glu Ile Leu 305 310 315 320 His Phe Cys Met Asn Asp Gln Leu Phe Pro Arg Asp His Leu Leu Ser                 325 330 335 Ile Cys Gly His Glu Glu Phe Leu Gln Asn Asp His Tyr Leu Gly Ser             340 345 350 His Arg Val Phe Gln Lys Asn Lys Ser Val Ile Gln Leu His Leu Gln         355 360 365 Lys Lys Arg Asp Thr Pro Gly Thr Leu Ser Arg Lys His Glu Asp Asp     370 375 380 His Ser Gln Phe Tyr Leu Asn Gln Leu Leu Glu Phe Met His Ile Trp 385 390 395 400 Lys Val Ser Arg Gln Cys Leu Ser Thr Val Ile Gln Lys Tyr Asp Ser                 405 410 415 His Leu Lys Tyr Leu Leu Lys Thr Gln Gln Asn Val Asp Asn Val Ile             420 425 430 Glu Glu Val Lys Ser Ile Cys Ser Val Leu Gly Cys Val Glu Thr Lys         435 440 445 Gln Ile Thr Asp Ala Ile Asn Glu Leu Asn Leu Ile Leu Gln Arg Lys     450 455 460 Pro Lys Asn Leu His Gln Asn Ser Asp Thr Ser Ala Lys Gly Leu Ile 465 470 475 480 Glu Lys Val Thr Thr Glu Leu Ser Thr Ser Ile Cys Gln Leu Ile Asp                 485 490 495 Ile His Cys Ser Ser Phe Cys Ala Asp Phe Gln Pro Leu His Ala Pro             500 505 510 Leu Tyr Ser Val Ser Cys Val Asn Leu Gly Leu His Ser His Leu Ser         515 520 525 Phe Thr Val Tyr Ala Ala His Asn Ile Pro Glu Thr Trp Val His Arg     530 535 540 Ile Asn Phe Pro Leu Glu Ile Lys Ser Leu Pro Arg Glu Ser Met Leu 545 550 555 560 Thr Ile Lys Leu Phe Gly Ile Thr Tyr Ala Thr Asn Ala Asp Leu Leu                 565 570 575 Ala Trp Thr Cys Phe Pro Leu Phe Pro Lys His Arg Ser Ile Leu Gly             580 585 590 Ser Ala Leu Phe Ser Met Thr Leu Gln Ser Glu Pro Pro Met Glu Met         595 600 605 Ile Ala Pro Gly Val Trp Asp Val Ser Gln Pro Ser Pro Val Thr Leu     610 615 620 Gln Ile Asp Phe Pro Ala Thr Glu Trp Glu Tyr Met Lys Leu Asp Ser 625 630 635 640 Glu Glu Asn Gly Ser Asp Leu Glu Glu Pro Pro Lys Glu Cys Leu Lys                 645 650 655 His Ile Ala Arg Leu Ser Gln Lys Gln Thr Pro Ile Leu Leu Ser Glu             660 665 670 Glu Lys Arg Arg Tyr Leu Trp Phe Tyr Arg Phe Tyr Cys Asn Asn Glu         675 680 685 Asn Cys Ser Leu Pro Leu Val Leu Gly Ser Ala Pro Gly Trp Asp Glu     690 695 700 Arg Thr Val Ser Glu Met His Thr Ile Leu Arg Arg Trp Lys Phe Ser 705 710 715 720 His Pro Leu Glu Ala Leu Gly Leu Leu Thr Ser Ser Phe Pro Asp Gln                 725 730 735 Glu Ile Arg Asn Val Ala Val Gln Gln Leu Asp Asn Leu Leu Asn Asp             740 745 750 Glu Leu Leu Glu Tyr Leu Pro Gln Leu Val Gln Ala Val Lys Phe Glu         755 760 765 Trp Asn Leu Glu Ser Pro Leu Val Gln Leu Leu Leu His Arg Ser Leu     770 775 780 Gln Ser Val Gln Ile Ala His Arg Leu Tyr Trp Leu Leu Lys Asp Ala 785 790 795 800 Gln Asn Glu Ala Tyr Phe Lys Ile Trp Tyr Gln Lys Leu Leu Ala Ala                 805 810 815 Leu Gln Phe Cys Ala Gly Lys Ala Leu Arg Asp Glu Phe Ser Lys Glu             820 825 830 Gln Lys Leu Ile Lys Ile Leu Gly Asp Ile Gly Glu Lys Val Lys Thr         835 840 845 Ala Ser Asp Pro Gln Arg Gln Glu Val Leu Lys Lys Glu Leu Gly Arg     850 855 860 Leu Glu Glu Phe Phe Trp Cys Thr Lys Thr Cys His Leu Pro Leu Asn 865 870 875 880 Pro Ala Leu Cys Val Gln Gly Ile Asp Gly Asp Ala Cys Ser Tyr Phe                 885 890 895 Thr Ser Asn Ala Leu Pro Leu Lys Ile Thr Phe Ile Asn Ala Asn Pro             900 905 910 Met Gly Lys Asn Ile Ser Val Ile Phe Lys Ala Gly Asp Asp Leu Arg         915 920 925 Gln Asp Met Leu Val Leu Gln Ile Ile Gln Val Met Asp Asn Ile Trp     930 935 940 Leu Gln Glu Gly Leu Asp Met Gln Met Val Ile Tyr Arg Cys Leu Ser 945 950 955 960 Thr Gly Lys Gly Gln Gly Leu Val Gln Met Val Pro Asp Ala Val Thr                 965 970 975 Leu Ala Lys Ile His Arg Cys Phe Gly Pro Ile Gly Pro Leu Lys Glu             980 985 990 Asn Thr Ile Lys Lys Trp Phe Ser Gln His Asn Pro Leu Lys Ala Asp         995 1000 1005 Tyr Glu Lys Val Leu Arg Asn Phe Phe Tyr Ser Cys Ala Gly Trp Cys    1010 1015 1020 Val Val Thr Phe Ile Leu Gly Val Cys Asp Arg His Asn Asp Asn Ile 1025 1030 1035 1040 Met Leu Thr Lys Ser Gly His Met Phe His Ile Asp Phe Gly Lys Phe                1045 1050 1055 Leu Gly His Ala Gln Thr Phe Gly Gly Ile Lys Arg Asp Arg Ala Pro            1060 1065 1070 Phe Ile Phe Thr Ser Glu Met Glu Tyr Phe Ile Thr Glu Gly Gly Lys        1075 1080 1085 Asn Pro Gln His Phe Gln Asp Phe Val Glu Leu Cys Cys Arg Ala Tyr    1090 1095 1100 Asn Ile Val Arg Arg His Ser Arg Leu Leu Leu Asn Leu Leu Glu Met 1105 1110 1115 1120 Met Leu His Ala Gly Leu Pro Glu Leu Ser Gly Ile Gln Asp Leu Lys                1125 1130 1135 Tyr Val Tyr Asn Asn Leu Arg Pro Gln Asp Thr Asp Leu Glu Ala Thr            1140 1145 1150 Ser His Phe Thr Lys Lys Ile Lys Glu Ser Leu Glu Cys Phe Pro Val        1155 1160 1165 Lys Leu Asn Asn Leu Ile His Thr Leu Ala Gln Met Thr Ala Ile Ser    1170 1175 1180 Pro Ala Lys Leu Thr Ser Gln Thr Phe Ser Gln Glu Ser Cys Met Ser 1185 1190 1195 1200 Gly Ala Ser Arg Ser Ile Gln Arg Ala Thr Val Leu Gly Phe Ser Lys                1205 1210 1215 Lys Thr Ser His Leu Tyr Leu Ile Gln Val Thr His Ser Asn Asn Glu            1220 1225 1230 Thr Ser Leu Thr Glu Lys Ser Phe Asp Gln Phe Ala Lys Leu His Ser        1235 1240 1245 Gln Leu Gln Lys Gln Phe Ala Ser Leu Thr Leu Pro Glu Phe Pro His    1250 1255 1260 Trp Trp His Leu Pro Phe Thr Asn Ser Asp His Lys Arg Phe Arg Asp 1265 1270 1275 1280 Leu Asn His Tyr Met Glu Gln Ile Leu Asn Gly Ser Tyr Glu Val Ala                1285 1290 1295 Asn Ser Asp Cys Val Leu Ser Phe Leu Ser Glu Pro Val Glu Gln            1300 1305 1310 Ala Val Lys Glu Ser Ser Ala Val Asp Leu Gly Glu Lys Phe Ala Asp        1315 1320 1325 Lys Lys Pro Lys Val Gln Leu Val Ile Ser Tyr Lys Asp Ala Lys Leu    1330 1335 1340 Thr Ile Leu Val Lys His Met Lys Asn Ile His Leu Pro Asp Gly Ser 1345 1350 1355 1360 Ala Pro Ser Ala His Val Glu Phe Tyr Leu Leu Pro Tyr Pro Ser Glu                1365 1370 1375 Ala Arg Arg Arg Lys Thr Lys Ser Val Pro Lys Cys Thr Asp Pro Thr            1380 1385 1390 Tyr Asn Glu Ile Val Val Tyr Asp Glu Val Thr Glu Leu Gln Gly His        1395 1400 1405 Val Leu Met Leu Ile Val Lys Ser Lys Thr Thr Phe Val Gly Ala Ile    1410 1415 1420 Asn Ile Gln Leu Cys Ser Val Thr Leu Asn Glu Glu Lys Trp Tyr Pro 1425 1430 1435 1440 Leu Gly Asn Ser Ile Ile                1445 <210> 25 <211> 1339 <212> PRT <213> Bos taurus <400> 25 Thr Leu Asn Asn Asn Asn Ser Ser Ile Leu Val Thr Ser Phe Asn   1 5 10 15 His Met Pro Lys Ile Arg Thr Leu Arg Leu His Ser Asn His Leu Tyr              20 25 30 Cys Asp Cys His Leu Ala Trp Leu Ser Asp Trp Leu Arg Gln Arg Arg          35 40 45 Thr Val Gly Pro Phe Thr Leu Cys Met Ala Pro Val His Leu Arg Gly      50 55 60 Phe Asn Val Ala Asp Val Gln Lys Lys Glu Tyr Val Cys Ser Gly Pro  65 70 75 80 His Ser Glu Pro Pro Ala Cys Asn Ala Asn Ser Ile Ser Cys Pro Ser                  85 90 95 Ala Cys Thr Cys Ser Asn Asn Ile Val Asp Cys Arg Gly Lys Gly Leu             100 105 110 Thr Glu Ile Pro Ala Asn Leu Pro Glu Gly Ile Val Glu Ile Arg Leu         115 120 125 Glu Gln Asn Ser Ile Lys Ser Ile Pro Ala Gly Ala Phe Thr Gln Tyr     130 135 140 Lys Lys Leu Lys Arg Ile Asp Ile Ser Lys Asn Gln Ile Ser Asp Ile 145 150 155 160 Ala Pro Asp Ala Phe Gln Gly Leu Lys Ser Leu Thr Ser Leu Val Leu                 165 170 175 Tyr Gly Asn Lys Ile Thr Glu Ile Pro Lys Gly Leu Phe Asp Gly Leu             180 185 190 Val Ser Leu Gln Leu Leu Leu Leu Asn Ala Asn Lys Ile Asn Cys Leu         195 200 205 Arg Val Asn Thr Phe Gln Asp Leu Gln Ser Leu Ser Leu Leu Ser Leu     210 215 220 Tyr Asp Asn Lys Leu Gln Thr Ile Ser Lys Gly Leu Phe Ala Pro Leu 225 230 235 240 Gln Ala Ile Gln Thr Leu His Leu Ala Gln Asn Pro Phe Val Cys Asp                 245 250 255 Cys His Leu Arg Trp Leu Ala Asp Tyr Leu Gln Asp Asn Pro Ile Glu             260 265 270 Thr Ser Gly Ala Arg Cys Ser Ser Pro Arg Arg Leu Ala Asn Lys Arg         275 280 285 Ile Ser Gln Ile Lys Ser Lys Lys Phe Arg Cys Ser Gly Ser Glu Asp     290 295 300 Tyr Arg Ser Ser Phe Ser Ser Glu Cys Phe Met Asp Leu Val Cys Pro 305 310 315 320 Asp Arg Cys Arg Cys Glu Gly Thr Ile Val Asp Cys Ser Asn Gln Lys                 325 330 335 Leu Ala Arg Ile Pro Ser His Leu Pro Glu Tyr Val Thr Asp Leu Arg             340 345 350 Leu Asn Asp Asn Glu Ile Ser Val Leu Glu Ala Thr Gly Ile Phe Lys         355 360 365 Lys Leu Pro Asn Leu Arg Lys Ile Asn Leu Ser Asn Asn Arg Ile Lys     370 375 380 Glu Val Lys Glu Gly Ala Phe Asp Gly Ala Ala Ser Val Gln Glu Leu 385 390 395 400 Val Leu Thr Gly Asn Gln Leu Glu Thr Ala His Gly Arg Ala Phe Arg                 405 410 415 Gly Leu Ser Gly Leu Lys Thr Leu Met Leu Arg Ser Asn Leu Ile Ser             420 425 430 Cys Val Ser Asn Asp Thr Phe Ala Gly Leu Ser Ser Val Arg Leu Leu         435 440 445 Ser Leu Tyr Asp Asn Arg Ile Thr Thr Ile Thr Pro Gly Ala Phe Thr     450 455 460 Thr Leu Val Ser Leu Ser Thr Ile Asn Leu Leu Ser Asn Pro Phe Asn 465 470 475 480 Cys Asn Cys His Leu Ala Trp Leu Gly Lys Trp Leu Arg Lys Arg Arg                 485 490 495 Ile Val Ser Gly Asn Pro Arg Cys Gln Lys Pro Phe Phe Leu Lys Glu             500 505 510 Ile Pro Ile Gln Asp Val Ala Ile Gln Asp Phe Thr Cys Asp Gly Asn         515 520 525 Asp Glu Ser Ser Cys Gln Leu Gly Pro Arg Cys Pro Glu Gln Cys Thr     530 535 540 Cys Val Glu Thr Val Val Arg Cys Ser Asn Arg Gly Leu Arg Ala Leu 545 550 555 560 Pro Lys Gly Ile Pro Lys Asp Val Thr Glu Leu Tyr Leu Glu Gly Asn                 565 570 575 His Leu Thr Ala Val Pro Lys Glu Leu Ser Ser Phe Arg His Leu Thr             580 585 590 Leu Ile Asp Leu Ser Asn Asn Ser Ile Gly Met Leu Thr Asn Tyr Thr         595 600 605 Phe Ser Asn Met Ser His Leu Ser Thr Leu Ile Leu Ser Tyr Asn Arg     610 615 620 Leu Arg Cys Ile Pro Val His Ser Phe Asn Gly Leu Arg Ser Leu Arg 625 630 635 640 Val Leu Thr Leu His Gly Asn Asp Ile Ser Ser Val Pro Glu Gly Ser                 645 650 655 Phe Asn Asp Leu Thr Ser Leu Ser His Leu Leu Leu His Thr Phe Pro             660 665 670 Met Asn Tyr Asn Ser Ser Ile Cys Gln Leu Ser Arg Tyr Ile Thr Pro         675 680 685 Phe Asn Gly Tyr Ser Glu Phe Gln Ile Ser Gly Cys Ser Lys Val Thr     690 695 700 Pro Lys Asn Phe Leu Asp Glu Leu Ile Leu Ala Ser Tyr Ile His Arg 705 710 715 720 Asn Leu Pro Pro Gly Pro Val Asp Ile Gly Ile Val Ala Lys Cys Asp                 725 730 735 Pro Cys Leu Ser Ser Pro Cys Lys Asn Asn Gly Thr Cys Ser Gln Asp             740 745 750 Pro Val Glu Gly His Arg Cys Ala Cys Ser His Gly Tyr Lys Gly Arg         755 760 765 Asp Cys Thr Val Pro Met Asn Thr Cys Ile Gln Asn Pro Cys Leu His     770 775 780 Gly Gly Thr Cys His Leu Ser Glu Thr His Lys Gly Gly Phe Ser Cys 785 790 795 800 Ser Cys Pro Leu Gly Phe Glu Gly Gln Arg Cys Glu Ile Asn Pro Asp                 805 810 815 Asp Cys Glu Asp Asn Asp Cys Glu Asn Asn Ala Thr Cys Val Asp Gly             820 825 830 Val Asn Asn Tyr Val Cys Val Cys Pro Pro Asn Tyr Thr Gly Glu Leu         835 840 845 Cys Asp Glu Val Ile Asp His Cys Val Pro Gly Met Asn Leu Cys Gln     850 855 860 His Glu Ala Lys Cys Ile Ser Leu Asp Arg Gly Phe Arg Cys Glu Cys 865 870 875 880 Pro Pro Gly Tyr Ser Gly Lys Leu Cys Glu Val Asp Asp Asp Asp Cys                 885 890 895 Ala Ala His Arg Cys Arg His Gly Ala Gln Cys Val Asp Ala Val Asn             900 905 910 Gly Tyr Thr Cys Ile Cys Pro Gln Gly Phe Ser Gly Leu His Cys Glu         915 920 925 His Pro Pro Pro Met Val Leu Leu Gln Thr Ser Pro Cys Asp Gln Tyr     930 935 940 Glu Cys Gln Asn Gly Gln Cys Ile Val Val Gln Gln Glu Pro Thr Cys 945 950 955 960 Arg Cys Pro Pro Phe Ala Gly Pro Arg Cys Glu Lys Leu Ile Thr Val                 965 970 975 Asn Phe Val Gly Lys Asp Ser Tyr Val Glu Leu Ala Ser Ala Lys Val             980 985 990 Arg Pro Gln Ala Asn Ile Ser Leu Gln Val Ala Thr Asp Lys Asp Asn         995 1000 1005 Gly Ile Leu Leu Tyr Lys Gly Asp Asn Asp Pro Leu Ala Leu Glu Leu    1010 1015 1020 Tyr Gln Gly His Val Arg Leu Val Tyr Asp Ser Leu Ser Ser Pro Pro 1025 1030 1035 1040 Thr Thr Val Ser Val Glu Thr Val Asn Asp Gly Gln Phe His Ser                1045 1050 1055 Val Glu Leu Val Met Leu Asn Gln Thr Leu Asn Leu Val Val Asp Lys            1060 1065 1070 Gly Ala Pro Lys Ser Leu Gly Lys Leu Gln Lys Gln Pro Ala Val Ser        1075 1080 1085 Ile Asn Ser Pro Leu Tyr Leu Gly Gly Ile Pro Thr Ser Thr Gly Leu    1090 1095 1100 Ser Ala Leu Arg Gln Gly Met Asp Arg Pro Leu Gly Gly Phe His Gly 1105 1110 1115 1120 Cys Ile His Glu Val Arg Ile Asn Asn Glu Leu Gln Asp Phe Lys Ala                1125 1130 1135 Leu Pro Pro Gln Ala Leu Gly Val Ser Pro Gly Cys Lys Ser Cys Ser            1140 1145 1150 Val Cys Arg His Gly Leu Cys Arg Ala Val Glu Lys Asp Ser Val Val        1155 1160 1165 Cys Glu Cys His Pro Gly Trp Thr Gly Pro Leu Cys Asp Gln Glu Ala    1170 1175 1180 Arg Asp Pro Cys Leu Gly His Ser Cys Ile Gln Gly Lys Cys Val Ala 1185 1190 1195 1200 Ser Gly Thr Ser Tyr Val Cys Arg Cys Thr Glu Gly Tyr Gly Gly Ala                1205 1210 1215 Leu Cys Asp Gln Lys Asn Asp Ser Asn Ser Ala Cys Ser Thr Phe Lys            1220 1225 1230 Cys His Gln Gly Gln Cys His Val Ser Asp Arg Gly Glu Pro Tyr Cys        1235 1240 1245 Leu Cys Arg Pro Gly Phe Ser Gly Glu His Cys Glu Gln Glu Thr Pro    1250 1255 1260 Cys Leu Gly Glu Val Val Arg Glu Val Ile Arg Arg Gln Lys Gly Tyr 1265 1270 1275 1280 Ala Ser Cys Ala Thr Ala Ser Lys Ile Pro Val Met Glu Cys Arg Gly                1285 1290 1295 Gly Cys Gly Pro Gln Cys Cys Gln Pro Thr Arg Ser Lys Arg Arg Lys            1300 1305 1310 Tyr Val Phe Gln Cys Thr Asp Gly Ser Ser Phe Val Glu Glu Leu Glu        1315 1320 1325 Arg His Leu Glu Cys Gly Cys Arg Pro Cys Ser    1330 1335 <210> 26 <211> 270 <212> PRT <213> Bos taurus <400> 26 Met Thr Arg Phe Ala Leu Thr Val Val Arg His Gly Glu Thr Arg Leu   1 5 10 15 Asn Lys Glu Lys Ile Ile Gln Gly Gln Gly Ile Asp Glu Pro Leu Ser              20 25 30 Glu Thr Gly Phe Lys Gln Ala Ala Ala Gly Ile Phe Leu Lys Asp          35 40 45 Val Lys Phe Thr His Val Phe Ser Ser Asp Leu Thr Arg Thr Lys Gln      50 55 60 Thr Val His Gly Ile Leu Glu Lys Ser Lys Phe Cys Lys Asp Met Thr  65 70 75 80 Val Lys Tyr Asp Ser Arg Leu Arg Glu Arg Lys Tyr Gly Val Ala Glu                  85 90 95 Gly Arg Pro Leu Ser Glu Leu Arg Ala Met Ala Lys Ala Ala Gly Glu             100 105 110 Glu Cys Pro Ala Phe Thr Pro Pro Gly Gly Glu Thr Leu Asp Gln Leu         115 120 125 Lys Arg Arg Gly Lys Asp Phe Phe Glu Phe Leu Cys Gln Leu Ile Leu     130 135 140 Lys Glu Ala Gly Gln Asn Glu Gln Phe Ser Gln Glu Ala Pro Ser Ser 145 150 155 160 Cys Leu Glu Ser Seru Ala Glu Ile Phe Pro Leu Gly Lys Asn Cys                 165 170 175 Ala Ser Thr Phe Asn Ser Asp Ser Gly Thr Pro Gly Leu Ala Ala Ser             180 185 190 Val Leu Val Val Ser His Gly Ala Tyr Ile Arg Ser Leu Leu Asp Tyr         195 200 205 Phe Leu Thr Asp Leu Lys Cys Ser Phe Pro Ala Thr Leu Ser Arg Ser     210 215 220 Glu Leu Thr Ser Val Ser Pro Asn Thr Gly Met Thr Val Phe Ile Leu 225 230 235 240 Asn Phe Glu Lys Gly Gly Lys Gly Arg Pro Thr Ala Gln Cys Val Cys                 245 250 255 Val Asn Leu Gln Gly His Leu Ala Gly Val Asn Lys Thr Pro             260 265 270 <210> 27 <211> 370 <212> PRT <213> Bos taurus <400> 27 Met Val Gly Lys Leu Lys Gln Asn Leu Leu Leu Ala Cys Leu Val Ile   1 5 10 15 Ser Ser Val Thr Val Phe Tyr Leu Gly Gln His Ala Met Glu Cys His              20 25 30 His Arg Ile Glu Glu Arg Ser Gln Pro Leu Lys Leu Glu Asn Ile Lys          35 40 45 Thr Thr Val Arg Thr Ala Leu Asp Ile Lys Ala Asn Lys Thr Phe Ala      50 55 60 Tyr His Lys Asp Met Pro Leu Ile Phe Ile Gly Gly Val Pro Arg Ser  65 70 75 80 Gly Thr Thr Leu Met Arg Ala Met Leu Asp Ala His Pro Asp Ile Arg                  85 90 95 Cys Gly Glu Glu Thr Arg Val Ile Pro Arg Ile Leu Ala Leu Lys Gln             100 105 110 Ile Trp Ser Arg Ser Ser Lys Glu Lys Ile Arg Leu Asp Glu Ala Gly         115 120 125 Val Thr Asp Glu Val Leu Asp Ser Ala Met Gln Ala Phe Leu Leu Glu     130 135 140 Ile Ile Val Lys His Gly Glu Pro Ala Pro Tyr Leu Cys Asn Lys Asp 145 150 155 160 Pro Phe Ala Leu Lys Ser Leu Thr Tyr Leu Ala Arg Leu Phe Pro Asn                 165 170 175 Ala Lys Phe Leu Leu Met Val Arg Asp Gly Arg Ala Ser Val His Ser             180 185 190 Met Ile Ser Arg Lys Val Thr Ile Ala Gly Phe Asp Leu Asn Ser Tyr         195 200 205 Arg Asp Cys Leu Thr Lys Trp Asn Arg Ala Ile Glu Thr Met Tyr Asn     210 215 220 Gln Cys Met Glu Val Gly Tyr Lys Lys Cys Met Leu Val His Tyr Glu 225 230 235 240 Gln Leu Val Leu His Pro Glu Arg Trp Met Arg Thr Val Leu Lys Phe                 245 250 255 Leu Gln Ile Pro Trp Asn His Ser Val Leu His His Glu Glu Met Ile             260 265 270 Gly Lys Ala Gly Gly Val Ser Leu Ser Lys Val Glu Arg Ser Thr Asp         275 280 285 Gln Val Ile Lys Pro Val Asn Val Gly Ala Leu Ser Lys Trp Val Gly     290 295 300 Lys Ile Pro Pro Asp Val Leu Gln Asp Met Ala Val Ile Ala Pro Met 305 310 315 320 Leu Ala Lys Leu Gly Tyr Asp Pro Tyr Ala Asn Pro Pro Asn Tyr Gly                 325 330 335 Lys Pro Asp Pro Lys Ile Leu Glu Asn Thr Arg Arg Val Tyr Lys Gly             340 345 350 Glu Phe Gln Leu Pro Glu Phe Leu Lys Glu Lys Pro Gln Ser Glu Gln         355 360 365 Val Glu     370 <210> 28 <211> 487 <212> PRT <213> Bos taurus <400> 28 Ala Pro Pro Pro Gln Leu Trp Ser Leu Gln Leu Trp Gly Lys Pro His   1 5 10 15 Ser Thr Arg Cys Pro Gly Asn Met Trp Trp Phe Leu Leu Trp Gly Val              20 25 30 Leu Gln Ala Phe Pro Thr Gln Gly Ser Val Val Leu Leu Ala Gln Trp          35 40 45 Leu Pro Gln Lys Leu Thr Ser Pro Gly Tyr Pro Glu Pro Tyr Val Lys      50 55 60 Gly Gln Glu Ser Ser Thr Asp Ile Glu Ala Pro Glu Gly Tyr Val Val  65 70 75 80 Arg Leu Leu Phe Gln Asp Phe Asp Leu Glu Pro Ser Pro Asp Cys Glu                  85 90 95 Arg Asp Ser Val Thr Leu Thr Ala Ser Gly Met Asp Leu Gly Gln Phe             100 105 110 Cys Gly Gln Gln Gly Ser Leu Leu Gly Arg Pro Pro Gly Gln Lys Glu         115 120 125 Phe Val Ser Ser Gly Asn Ser Leu Arg Leu Thr Phe Ser Ala Pro Ala     130 135 140 Ser Glu Asp Lys Thr Pro Gly Phe His Lys Gly Phe Leu Ala Leu Tyr 145 150 155 160 Gln Ala Val Ala Val Asn Tyr Thr Gln Pro Ile Asn Gln Ala Thr Gly                 165 170 175 Gly Pro Lys Ala Ile Pro Thr Pro Gly Asp Asn Pro Thr Glu Ile Gln             180 185 190 Ser Cys Cys Gln Glu Pro Tyr Tyr Glu Ala Lys Pro Ser Gly Thr Leu         195 200 205 Thr Cys Thr Ala Gln Val Pro Trp Lys Gln Thr Gln Lys Arg Glu Glu     210 215 220 Ala Pro Arg Cys Val Pro Cys Gly Arg Pro Val Val Pro Ile Ser 225 230 235 240 Gln Thr Arg Glu Ser Leu Gly Ala Ser Arg Ala Glu Leu Gly Ser Phe                 245 250 255 Pro Trp Gln Ala Leu Thr Ser Ile Tyr Gly Arg Gly Gly Gly Ala Leu             260 265 270 Leu Gly Asp Arg Trp Val Leu Thr Ala Ala His Thr Ile Tyr Pro Lys         275 280 285 Asp Ser Ile Leu Leu Gly Arg Asn Arg Ser Ala Gln Val Phe Leu Gly     290 295 300 His Thr Asp Thr Asp Gln Met Leu Glu Leu Gly Arg His Pro Val Arg 305 310 315 320 Arg Val Val Val His Pro Asp Tyr His Gln Glu Glu Pro His Asp Phe                 325 330 335 His Gly Asp Ile Ala Leu Leu Glu Leu Glu Arg Ser Val Pro Leu Gly             340 345 350 Pro His Leu Leu Pro Val Cys Leu Pro Asp Arg Glu Ala Leu Tyr Arg         355 360 365 Pro Gly Arg Trp Gly Tyr Val Ser Gly Phe Gly Val Glu Met Asp Trp     370 375 380 Leu Ser Thr Lys Leu Lys Tyr Ser Arg Leu Pro Val Ala Pro Arg Ala 385 390 395 400 Ala Cys Glu Ala Trp Leu Arg Glu Arg Gln Arg Pro Glu Ala Phe Thr                 405 410 415 Asp Gly Met Phe Cys Ala Gly Asp Gln Thr Arg Pro Gln Ser Val Cys             420 425 430 Gln Gly Asp Ser Gly Gly Ala Phe Val Val Trp Asp Asp Arg Thr Gln         435 440 445 Arg Trp Val Ala Thr Gly Ile Val Ser Trp Gly Ile Gly Cys Gly Glu     450 455 460 Gly Tyr Gly Phe Tyr Thr Lys Val Leu Asp Tyr Val Asp Trp Ile Arg 465 470 475 480 Gly Val Met Gly Glu Lys Asp                 485 <210> 29 <211> 876 <212> PRT <213> Bos taurus <400> 29 Met Ala Ala Gly Thr Arg Pro Ala Ala Ala Pro Arg Ser Ala Thr   1 5 10 15 Met Ala Gln Trp Lys Lys Lys Lys Gly Leu Arg Lys Arg Arg Gly Ala              20 25 30 Ala Ser Gln Ser His Ser Ser Asp Ser Glu Asp Gly Glu Phe Glu Val          35 40 45 Gln Ala Glu Asp Asp Ala Arg Ala Gln Lys Leu Gly Pro Gly Arg Pro      50 55 60 Leu Pro Thr Phe Pro Thr Ser Glu Cys Thr Ser Asp Val Glu Pro Asp  65 70 75 80 Thr Arg Glu Met Val Arg Ala Gln Asn Lys Lys Lys Lys Lys Ser Gly                  85 90 95 Gly Phe Gln Ser Met Gly Leu Ser Tyr Pro Val Phe Lys Gly Ile Met             100 105 110 Lys Lys Gly Tyr Lys Val Pro Thr Pro Ile Gln Arg Lys Thr Ile Pro         115 120 125 Met Ile Leu Asp Gly Lys Asp Val Val Ala Met Ala Arg Thr Gly Ser     130 135 140 Gly Lys Thr Ala Cys Phe Leu Ile Pro Met Phe Glu Arg Leu Lys Thr 145 150 155 160 His Ser Ala Gln Thr Gly Ala Arg Ala Leu Ile Leu Ser Pro Thr Arg                 165 170 175 Glu Leu Ala Leu Gln Thr Met Lys Phe Thr Lys Glu Leu Gly Lys Phe             180 185 190 Thr Gly Leu Lys Thr Ala Leu Ile Leu Gly Gly Asp Lys Met Glu Asp         195 200 205 Gln Phe Ala Ala Leu His Glu Asn Pro Asp Ile Ile Ile Ala Thr Pro     210 215 220 Gly Arg Leu Val His Val Ala Val Glu Met Asn Leu Lys Leu Gln Ser 225 230 235 240 Val Glu Tyr Val Val Phe Asp Glu Ala Asp Arg Leu Phe Glu Met Gly                 245 250 255 Phe Ala Glu Gln Leu Gln Glu Ile Ile Gly Arg Leu Pro Gly Gly His             260 265 270 Gln Thr Val Leu Phe Ser Ala Thr Leu Pro Lys Leu Leu Val Glu Phe         275 280 285 Ala Arg Ala Gly Leu Thr Glu Pro Val Leu Ile Arg Leu Asp Val Asp     290 295 300 Ser Lys Leu Asn Glu Gln Leu Lys Thr Ser Phe Phe Leu Val Arg Glu 305 310 315 320 Asp Ala Lys Ala Ala Val Leu Leu His Leu Leu Arg Asn Val Val Arg                 325 330 335 Pro Gln Asp Gln Thr Val Val Phe Val Ala Thr Lys His His Ala Glu             340 345 350 Tyr Leu Ser Glu Leu Ala Thr Gln Gly Val Ser Cys Ala His Ile         355 360 365 Tyr Ser Ala Leu Asp Gln Thr Ala Arg Lys Ile Asn Leu Ala Arg Phe     370 375 380 Thr His Gly Lys Cys Ser Ala Leu Ile Val Thr Asp Leu Ala Ala Arg 385 390 395 400 Gly Leu Asp Ile Pro Leu Leu Asp Asn Val Ile Asn Tyr Ser Phe Pro                 405 410 415 Ala Lys Gly Lys Leu Phe Leu His Arg Val Gly Arg Val Ala Arg Ala             420 425 430 Gly Arg Ser Gly Thr Ala Tyr Ser Leu Val Ala Pro Asp Glu Val Pro         435 440 445 Tyr Leu Leu Asp Leu His Leu Phe Leu Gly Arg Ala Leu Thr Leu Ala     450 455 460 Arg Pro Pro Glu Glu Pro Ser Gly Thr Glu Gly Gly Asp Gly Val Leu 465 470 475 480 Gly Arg Val Val Gln Gly Val Val Asp Asp Glu Asp Cys Gly Leu Arg                 485 490 495 Thr Ser Leu Glu Ala Ser Leu Glu Leu Arg Gly Leu Ser Arg Val Ala             500 505 510 Asn Asn Ala Gln Gln Gln Tyr Val Arg Ser Ser Pro Ala Pro Ser Pro         515 520 525 Glu Ser Ile Lys Arg Ala Lys Glu Leu Asp Leu Ala Gly Leu Gly Leu     530 535 540 His Pro Leu Phe Ser Ser Arg Phe Gln Gln Glu Glu Leu Gln Arg Leu 545 550 555 560 Arg Leu Val Asp Ser Ile Arg Asn Tyr Arg Ser Ser Ala Thr Ile Phe                 565 570 575 Glu Ile Asn Ala Ser Ser Arg Asp Leu Ser Ser Gln Val Met Arg Ala             580 585 590 Lys Arg Glu Lys Asp Arg Lys Ala Ile Ala Ser Phe Gln Gln Gly Arg         595 600 605 Gln Glu Arg Gln Glu Gly Pro Ala Gly Pro Thr Pro Ser Leu Pro Ala     610 615 620 Pro Gln Glu Glu Glu Pro Glu Lys Glu Glu Val Ala Gly Glu Ser Val 625 630 635 640 Glu Asp Val Phe Thr Glu Val Val Gly Arg Lys Arg Gln Gln Pro Gly                 645 650 655 Pro Gln Arg Gly Ala Lys Arg Arg Arg Glu Glu Ala Arg Gln Arg Asp             660 665 670 Gln Ala Phe Tyr Ile Pro Tyr Arg Pro Lys Asp Phe Asp Ser Glu Arg         675 680 685 Gly Leu Ser Ile Gly Gly Asp Gly Gly Ala Phe Glu Gln Gln Val Ala     690 695 700 Gly Ala Ala Leu Asp Leu Met Gly Asp Glu Ala Gln Ser Leu Thr Arg 705 710 715 720 Gly Arg Gln Gln Leu Arg Trp Asp Arg Lys Lys Lys Arg Phe Val Gly                 725 730 735 Gln Ser Gly Gln Glu Asp Lys Lys Lys Ile Lys Thr Glu Ser Gly Arg             740 745 750 Tyr Ile Ser Ser Ser Tyr Lys Arg Asp Leu Tyr Gln Lys Trp Lys Gln         755 760 765 Lys Gln Lys Ile Asp Asp Arg Asp Ser Glu Glu Glu Gly Thr Phe Asp     770 775 780 Arg Arg Gly Pro Glu Arg Arg Gly Gly Lys Arg Gly Arg Gly Gln Gly 785 790 795 800 Ala Ser Gln Pro Arg Thr Pro Gly Thr Pro Ala Gly Arg Val Leu Ser                 805 810 815 Glu Leu Lys Thr Lys Gln Gln Ile Leu Lys Gln Arg Arg Ala Gln             820 825 830 Lys Met Arg Phe Leu Gln Arg Gly Gly Leu Lys Gln Leu Ser Ala Arg         835 840 845 Asn Arg Arg Arg Ala Gln Glu Leu Gln Gln Gly Ala Phe Gly Arg Gly     850 855 860 Ala Pro Ser Lys Lys Gly Lys Met Arg Lys Arg Met 865 870 875 <210> 30 <211> 755 <212> PRT <213> Bos taurus <400> 30 Met Asn Ala Glu Glu Asp Ala Lys Trp Leu Gln Trp Val Thr His Gln   1 5 10 15 Phe Lys Thr Ile Ala Gly Glu Asp Gly Glu Ile Asn Leu Gln Asp Phe              20 25 30 Lys Lys Ala Leu Lys Val Lys Glu Ser Phe Phe Ala Glu Arg Phe Phe          35 40 45 Val Leu Phe Asp Ser Asp Gly Ser Gly Thr Ile Thr Leu Gln Glu Leu      50 55 60 Gln Lys Ala Leu Thr Leu Leu Ile His Gly Ser Pro Met Asp Lys Leu  65 70 75 80 Lys Phe Leu Phe Gln Val Tyr Asp Val Asp Gly Lys His Pro Leu Trp                  85 90 95 Asp Gly Arg Arg Thr Gln Arg Glu Gly Gln Arg Glu Arg Pro Val Ser             100 105 110 Val Thr Ala Gln His Trp Ala Ser Ser Ser Pro Glu Thr Gly Ser Gly         115 120 125 Ser Ile Asp Ala Asp Glu Leu Arg Thr Val Leu Gln Ser Cys Leu Tyr     130 135 140 Glu Ser Ala Ile Ser Leu Pro Lys Glu Lys Leu Asp Gln Leu Thr Leu 145 150 155 160 Ala Leu Phe Glu Ser Ala Asp Lys Asp Cys Ser Gly Thr Ile Thr Phe                 165 170 175 Glu Glu Leu Arg Asp Glu Leu Gln Arg Phe Pro Gly Val Leu Glu Asn             180 185 190 Leu Thr Ile Ser Ala Ala His Trp Leu Thr Pro Pro Ala Pro Gln Arg         195 200 205 His Arg Arg Gln Pro Arg Leu Leu Thr Ser Ala Tyr Trp His Asn His     210 215 220 Arg Ser His Val Leu Cys Leu Ala Val Phe Val Gly Leu His Met Leu 225 230 235 240 Leu Phe Ala Leu Ala Ala Ser Ala Tyr Arg Ala Phe Gly Ser Ser Val                 245 250 255 Met Val Ala Lys Gly Cys Gly Gln Cys Leu Asn Phe Asp Cys Ser Phe             260 265 270 Ile Ala Val Leu Met Leu Arg Arg Cys Leu Thr Trp Leu Arg Ala Thr         275 280 285 Trp Leu Ala Gln Val Leu Pro Leu Asp His Asn Ile Gln Phe His Gln     290 295 300 Leu Met Gly Tyr Val Val Gly Leu Ser Leu Val His Thr Val Ala 305 310 315 320 His Val Val Asn Phe Ala Leu Gln Ala Gln Ser Glu Thr Ser Pro Phe                 325 330 335 Arg Phe Trp Glu Leu Leu Leu Thr Thr Arg Pro Gly Ile Gly Trp Val             340 345 350 His Gly Ser Ala Ser Pro Thr Gly Val Ala Leu Leu Leu Leu Leu         355 360 365 Leu Met Phe Ala Cys Ser Ser Ser Cys Val Arg Arg Ser Gly His Phe     370 375 380 Glu Val Phe Tyr Trp Thr His Leu Ser Tyr Leu Pro Met Trp Leu Leu 385 390 395 400 Leu Ile Leu His Gly Pro Asn Phe Trp Lys Trp Leu Leu Val Pro Gly                 405 410 415 Thr Leu Phe Phe Leu Glu Lys Thr Ile Ser Leu Ala Ala Ser Arg Met             420 425 430 Ala Ala Leu His Ile Val Glu Val Asn Leu Leu Pro Ser Lys Val Thr         435 440 445 His Leu Leu Ile Lys Arg Pro Pro Leu Phe His Tyr Arg Pro Gly Asp     450 455 460 Tyr Leu Tyr Leu Asn Ile Pro Ser Ile Ala Arg Tyr Glu Trp His Pro 465 470 475 480 Phe Thr Ile Ser Ser Ala Pro Glu Gln Lys Asp Thr Ile Trp Leu His                 485 490 495 Ile Arg Ser Gln Gly Gln Trp Thr Asn Arg Leu Phe Glu Ser Phe Lys             500 505 510 Lys Pro Glu Pro Val Phe Cys Gly Ser Lys Arg Leu Ser Arg Arg Leu         515 520 525 Glu Met Lys Arg Ser Gln Arg Lys Pro Gln Val Ser Glu Met Ser Ser     530 535 540 Glu Asn His Gln Phe Cys Asn Ile Lys Cys Tyr Ile Asp Gly Pro Tyr 545 550 555 560 Gly Thr Pro Thr Arg Arg Ile Phe Ala Ser Glu His Ala Val Leu Ile                 565 570 575 Gly Ala Gly Ile Gly Ile Thr Pro Phe Ala Ser Ile Leu Gln Ser Ile             580 585 590 Leu Tyr Arg His Gln Lys Arg Lys His Ile Cys Pro Asn Cys Gln His         595 600 605 Ser Trp Met Glu Ser Gly Gln Asp Glu Asp Met Lys Leu His Lys Val     610 615 620 Asp Phe Ile Trp Ile Asn Arg Asp Gln Gln Ser Phe Glu Trp Phe Val 625 630 635 640 Ser Leu Leu Thr Lys Leu Glu Met Asp Gln Ala Glu Glu Thr Gln Val                 645 650 655 Gly Arg Phe Leu Glu Leu His Met Tyr Met Thr Ser Ala Leu Ser Lys             660 665 670 Asn Asp Ile Lys Aslan Ile Gly Leu Gln Met Aslan Leu Asp Aslan Leu Aslan         675 680 685 Lys Lys Glu Lys Lys Asp Ser Ile Thr Gly Leu Gln Thr Arg Thr Gln     690 695 700 Pro Gly Arg Pro Asp Trp Asn Lys Val Phe Gln Lys Val Ala Ala Glu 705 710 715 720 Lys Lys Gly Lys Val Gln Val Phe Phe Cys Gly Ser Pro Ala Leu Ala                 725 730 735 Lys Ile Leu Lys Gly His Cys Glu Gln Phe Ser Phe Lys Phe Phe Gln             740 745 750 Glu Asn Phe         755 <210> 31 <211> 1092 <212> PRT <213> Bos taurus <400> 31 Met Leu Ile Phe Leu Leu Lys Ser Leu Ala Glu Leu Glu Ala Leu   1 5 10 15 Cys Thr His Leu Tyr Ile Gly Thr Asp Leu Thr Gln Arg Ile Glu Ala              20 25 30 Glu Lys Ala Leu Leu Glu Leu Ile Asp Ser Pro Glu Cys Leu Ser Lys          35 40 45 Cys Gln Leu Leu Leu Glu Gln Gly Thr Thr Ser Tyr Ala Gln Leu Leu      50 55 60 Ala Ala Thr Cys Leu Ser Lys Leu Val Ser Ser Val Ser Ser Leu Pro  65 70 75 80 Val Glu Gln Arg Ile Asp Ile Arg Asn Tyr Ile Leu Asn Tyr Val Ala                  85 90 95 Ser Gln Pro Lys Leu Ala Pro Phe Val Ile Gln Ala Leu Ile Gln Val             100 105 110 Ile Ala Lys Ile Thr Lys Ser Gly Trp Phe Glu Val Gln Lys Asp Arg         115 120 125 Phe Val Phe Arg Glu Ile Ile Ala Asp Val Lys Thr Phe Leu Gln Gly     130 135 140 Ala Met Glu His Cys Ile Ile Gly Val Ile Ile Leu Ser Glu Leu Thr 145 150 155 160 Gln Glu Met Asn Leu Val Asp Tyr Ser Arg Pro Ser Ala Lys His Arg                 165 170 175 Lys Ile Ala Thr Ser Phe Arg Asp Thr Ser Leu Lys Asp Ile Leu Val             180 185 190 Leu Ala Cys Ser Leu Leu Lys Glu Ile Leu Ala Lys Pro Leu Asn Leu         195 200 205 Gln Asp Gln Asp Gln Gln Asn Leu Val Met Gln Val Leu Lys Leu Val     210 215 220 Leu Asn Cys Leu Asn Phe Asp Phe Ile Gly Ser Ser Ala Asp Glu Ser 225 230 235 240 Ala Asp Asp Leu Cys Thr Val Gln Ile Pro Thr Thr Trp Arg Ala Ile                 245 250 255 Phe Leu Glu Pro Glu Thr Leu Asp Leu Phe Phe Asn Leu Tyr His Ser             260 265 270 Leu Pro Pro Leu Leu Ser Gln Leu Ala Leu Ser Cys Leu Val Gln Phe         275 280 285 Ala Ser Thr Arg Arg Ser Leu Phe Ser Ser Pro Glu Arg Ala Lys Tyr     290 295 300 Leu Gly Asn Leu Ile Lys Gly Val Lys Arg Ile Leu Glu Asn Pro Gln 305 310 315 320 Gly Leu Ser Asp Pro Gly Asn Tyr His Glu Phe Cys Arg Phe Leu Ala                 325 330 335 Arg Leu Lys Thr Asn Tyr Gln Leu Gly Glu Leu Val Met Val Lys Glu             340 345 350 Tyr Pro Glu Val Ile Arg Leu Ile Ala Asn Phe Thr Ile Thr Ser Leu         355 360 365 Gln His Trp Glu Phe Ala Pro Asn Ser Val His Tyr Leu Leu Thr Leu     370 375 380 Trp Gln Arg Met Val Ala Ser Val Pro Phe Val Lys Ser Thr Glu Pro 385 390 395 400 His Leu Leu Asp Thr Tyr Ala Pro Glu Ile Thr Lys Ala Phe Ile Thr                 405 410 415 Ser Arg Leu Glu Ser Val Ala Val Val Val Arg Asp Asn Leu Asp Asp             420 425 430 Pro Leu Asp Asp Thr Thr Thr Val Phe Gln Gln Leu Glu Gln Leu Cys         435 440 445 Thr Val Ser Arg Cys Glu Tyr Glu Lys Thr Cys Thr Leu Leu Val Gln     450 455 460 Leu Phe Asp Gln Asn Ala Gln Asn Tyr Gln Lys Leu Leu His Ser Ala 465 470 475 480 Ser Arg Val Thr Val Asp Met Ala Ile Gln Glu Gly Arg Leu Ala Trp                 485 490 495 Leu Val Tyr Leu Val Gly Thr Val Val Gly Gly Arg Leu Thr Tyr Thr             500 505 510 Ser Thr Asp Glu His Asp Ala Met Asp Gly Glu Leu Ser Cys Arg Lys         515 520 525 Arg Val Phe Gln Leu Ile Ser Leu Met Asp Thr Gly Leu Pro Gln Cys     530 535 540 Ser Asn Glu Lys Ile Glu Leu Ala Ile Leu Trp Phe Leu Asp Gln Phe 545 550 555 560 Arg Lys Thr Tyr Val Gly Asp Gln Leu Gln Arg Thr Ser Lys Val Tyr                 565 570 575 Ala Arg Met Ser Glu Val Leu Gly Ile Thr Asp Asp Asn His Val Leu             580 585 590 Glu Thr Phe Met Thr Lys Ile Val Thr Asn Leu Lys Tyr Trp Gly Arg         595 600 605 Cys Glu Pro Val Ile Ser Arg Thr Leu Gln Phe Leu Asn Asp Leu Ser     610 615 620 Val Gly Tyr Ile Leu Leu Lys Lys Leu Val Lys Ile Asp Ala Val Lys 625 630 635 640 Phe Met Leu Lys Asn His Thr Ser Glu His Phe Pro Phe Leu Gly Ile                 645 650 655 Ser Gly Ser Tyr Ser Leu Ser Asp Phe Arg Cys Arg Thr Ala Phe Tyr             660 665 670 Thr Ala Leu Thr Arg Leu Leu Met Val Asp Leu Gly Asp Glu Asp         675 680 685 Glu Phe Glu Asn Phe Met Leu Pro Leu Thr Val Ser Phe Glu Thr Val     690 695 700 Leu Gln Ile Phe Asn Asn Asn Phe Lys Gln Glu Asp Val Lys Arg Met 705 710 715 720 Leu Ile Gly Leu Ala Arg Asp Leu Arg Gly Ile Ala Phe Ala Leu Asn                 725 730 735 Thr Lys Thr Ser Tyr Thr Met Leu Phe Asp Trp Met Tyr Pro Thr Tyr             740 745 750 Leu Pro Ile Leu Gln Arg Ala Ile Glu Gln Trp Tyr Gly Glu Pro Ala         755 760 765 Cys Thr Thr Pro Ile Leu Lys Leu Met Ala Glu Leu Met Gln Asn Arg     770 775 780 Ser Gln Arg Leu Asn Phe Asp Val Ser Ser Pro Asn Gly Ile Leu Leu 785 790 795 800 Phe Arg Glu Ala Ser Lys Met Ile Cys Thr Tyr Glu Thr Gly Thr Gln                 805 810 815 Ile Leu Ser Leu Gly Ser Leu Ser Lys Asp Gly Ile Tyr Pro Met Lys             820 825 830 Leu Lys Gly Ile Ser Ile Cys Tyr Ser Ala Leu Lys Ser Ala Leu Cys         835 840 845 Gly Asn Tyr Val Ser Phe Gly Val Phe Lys Leu Tyr Gly Asp Asn His     850 855 860 Phe Asp Asn Val Leu Gln Ala Phe Val Lys Met Leu Leu Ser Val Ser 865 870 875 880 His Ser Asp Leu Leu Gln Tyr Arg Lys Leu Ser Gln Ser Tyr Tyr Pro                 885 890 895 Leu Leu Glu Cys Leu Thr Gln Asp His Met Ser Phe Ile Thr Ser Leu             900 905 910 Asp Pro Pro Val Leu Leu Tyr Val Leu Thr Ser Ile Ser Glu Gly Leu         915 920 925 Thr Ala Leu Asp Thr Val Ser Ser Ser Cys Cys Thr Ser Leu Asp     930 935 940 Tyr Ile Val Thr Tyr Leu Phe Lys His Ile Ala Lys Glu Gly Lys Lys 945 950 955 960 Ser Leu Arg Cys Arg Glu Ala Thr Gln Ala Gly Gln Arg Leu Leu His                 965 970 975 Phe Met Gln Gln Asn Pro Glu Val Leu Gln Gln Met Met Ser Val Leu             980 985 990 Met Asn Thr Ile Val Phe Glu Asp Cys Arg Asn Gln Trp Ser Val Ser         995 1000 1005 Arg Pro Leu Leu Gly Leu Ile Leu Leu Asn Glu Lys Tyr Phe Gly Glu    1010 1015 1020 Leu Arg Ala Gly Leu Ile Asn Ser Gln Pro Leu Pro Lys Gln Glu Val 1025 1030 1035 1040 Leu Ala Gln Cys Phe Arg Asn Leu Met Glu Gly Val Glu Gln Asn Leu                1045 1050 1055 Ser Val Lys Asn Arg Asp Arg Phe Thr Gln Asn Leu Ser Val Phe Arg            1060 1065 1070 Arg Asp Met Ala Glu Ala Leu Arg Ser Asp Gly Ser Thr Glu Pro Leu        1075 1080 1085 Asp Met Met Ser    1090 <210> 32 <211> 1849 <212> PRT <213> Bos taurus <400> 32 Met Ala Arg Leu Ala Asp Tyr Phe Ile Val Val Gly Tyr Asp His Glu   1 5 10 15 Lys Pro Gly Ser Gly Ala Gly Leu Gly Lys Ile Ile Gln Arg Phe Pro              20 25 30 Gln Lys Asp Trp Asp Asp Thr Pro Phe Pro Gln Gly Ile Glu Leu Phe          35 40 45 Cys Gln Pro Gly Gly Trp Gln Leu Ser Arg Glu Arg Lys Gln Pro Thr      50 55 60 Phe Val Val Val Leu Thr Asp Ile Asp Ser Asp Arg His Tyr Cys  65 70 75 80 Ser Cys Leu Thr Phe Tyr Glu Ala Glu Ile Asn Leu Gln Gly Thr Lys                  85 90 95 Lys Glu Glu Thr Glu Gly Glu Val Glu Val Ser Gly Leu Ile Gln Pro             100 105 110 Ala Glu Val Phe Ala Pro Lys Ser Leu Val Leu Val Ser Arg Leu Asp         115 120 125 Tyr Pro Glu Ile Phe Arg Ala Cys Leu Gly Leu Ile Tyr Thr Val Tyr     130 135 140 Val Asp Ser Leu Asn Val Ser Leu Glu Ser Leu Ile Ala Asn Leu Cys 145 150 155 160 Ala Cys Leu Val Pro Ala Ala Gly Gly Ser Gln Lys Leu Phe Ser Leu                 165 170 175 Gly Ala Gly Asp Arg Gln Leu Ile Gln Thr Pro Leu His Asp Ser Leu             180 185 190 Pro Val Thr Gly Thr Ser Val Ala Leu Leu Phe Gln Gln Leu Gly Ile         195 200 205 Gln Asn Val Leu Ser Leu Phe Cys Ala Val Leu Thr Glu Asn Lys Val     210 215 220 Leu Phe His Ser Ala Ser Phe Gln Arg Leu Ser Asp Ala Cys Arg Ala 225 230 235 240 Leu Glu Ser Leu Met Phe Pro Leu Lys Tyr Ser Tyr Pro Tyr Ile Pro                 245 250 255 Ile Leu Pro Ala Gln Leu Leu Glu Val Leu Ser Ser Pro Thr Pro Phe             260 265 270 Ile Ile Gly Val His Ser Val Phe Lys Thr Asp Val His Glu Leu Leu         275 280 285 Asp Val Ile Ile Ale Asp Leu Asp Gly Gly Thr Ile Lys Ile Pro Glu     290 295 300 Cys Ile His Leu Ser Ser Leu Pro Glu Pro Leu Leu Gln Gln Thr Gln 305 310 315 320 Ala Ala Leu Ser Leu Ile Leu His Pro Asp Leu Glu Val Ala Asp His                 325 330 335 Ala Phe Pro Pro Arg Thr Ala Leu Ser His Ser Lys Met Leu Asp             340 345 350 Lys Glu Val Arg Ala Val Phe Leu Arg Leu Phe Ala Gln Leu Phe Gln         355 360 365 Gly Tyr Arg Ser Cys Leu Gln Leu Ile Arg Ile His Ala Glu Pro Val     370 375 380 Ile His Phe His Lys Thr Ala Phe Leu Gly Gln Arg Gly Leu Val Glu 385 390 395 400 Asn Asp Phe Leu Thr Lys Val Leu Asn Gly Met Ala Phe Ala Gly Phe                 405 410 415 Val Ser Glu Arg Gly Pro Pro Tyr Arg Ser Cys Asp Leu Phe Asp Glu             420 425 430 Val Val Ala Phe Glu Val Glu Arg Ile Lys Val Glu Glu Asn Asn Pro         435 440 445 Met Lys Met Ile Lys His Val Arg Glu Leu Ala Glu Gln Leu Phe Lys     450 455 460 Asn Glu Asn Pro Asn Pro His Met Ala Phe Gln Lys Val Pro Arg Pro 465 470 475 480 Thr Glu Gly Ser His Leu Arg Val His Ile Leu Pro Phe Pro Lys Ile                 485 490 495 Asn Glu Thr Arg Val Gln Glu Leu Ile Gln Glu Asn Leu Ala Lys Asn             500 505 510 Gln Asn Ala Pro Pro Ala Ser Arg Val Glu Lys Lys Cys Val Val Pro         515 520 525 Ala Gly Pro Pro Val Val Ser Ile Met Asp Lys Val Thr Thr Val Phe     530 535 540 Asn Ser Ala Gln Arg Leu Glu Val Val Arg Asn Cys Ile Ser Phe Ile 545 550 555 560 Phe Glu Asn Lys Thr Leu Glu Thr Glu Lys Thr Leu Pro Ala Ala Leu                 565 570 575 Arg Ala Leu Lys Gly Lys Ala Ala Arg Gln Cys Leu Thr Asp Glu Leu             580 585 590 Gly Leu His Val Gln Gln Asn Arg Ala Ile Leu Asp His Gln Gln Phe         595 600 605 Asp Tyr Ile Ile Arg Met Met Asn Cys Thr Leu Gln Asp Cys Ser Ser     610 615 620 Leu Glu Glu Tyr Asn Ile Ala Ala Leu Leu Pro Leu Thr Ser Ala 625 630 635 640 Phe Tyr Arg Lys Leu Ala Pro Gly Val Ser Gln Phe Ala Tyr Thr Cys                 645 650 655 Val Gln Asp His Pro Ile Trp Thr Asn Gln Gln Phe Trp Glu Thr Thr             660 665 670 Phe Tyr Asn Ala Val Gln Glu Gln Val Arg Ser Leu Tyr Leu Ser Ala         675 680 685 Lys Glu Asp Asn His Ala Leu His Leu Lys Gln Lys Asp Lys Leu Pro     690 695 700 Asp Asp Gln Tyr Gln Glu Lys Thr Ala Met Asp Leu Ala Ala Glu Gln 705 710 715 720 Leu Arg Leu Trp Pro Thr Leu Ser Lys Ser Thr Gln Gln Glu Leu Val                 725 730 735 Gln Arg Glu Glu Ser Thr Val Phe Ser Gln Ala Ile His Phe Ala Asn             740 745 750 Leu Met Val Asn Leu Leu Val Pro Leu Asp Ser Ser Lys Asn Lys Leu         755 760 765 Leu Arg Ala Ser Ala Pro Gly Asp Trp Glu Ser Gly Ser Asn Ser Ile     770 775 780 Val Thr Asn Ser Ale Gly Ser Val Ala Glu Ser Tyr Asp Thr Glu 785 790 795 800 Ser Gly Phe Glu Asp Ser Glu Asn Asn Asp Ile Ala Asn Ser Val Val                 805 810 815 Arg Phe Ile Thr Arg Phe Ile Asp Lys Val Cys Thr Glu Ser Gly Val             820 825 830 Thr Gln Asp His Ile Lys Ser Leu His Cys Met Ile Pro Gly Ile Val         835 840 845 Ala Met His Ile Glu Thr Leu Glu Ala Val His Arg Glu Ser Arg Arg     850 855 860 Leu Pro Pro Ile Gln Lys Pro Lys Ile Leu Arg Pro Ala Leu Leu Pro 865 870 875 880 Gly Glu Glu Ile Val Cys Glu Gly Leu Arg Val Leu Leu Asp Pro Asp                 885 890 895 Gly Arg Glu Glu Ala Thr Gly Gly Leu Leu Gly Gly Pro Gln Leu Leu             900 905 910 Pro Ala Glu Gly Ala Leu Phe Leu Thr Thr Tyr Arg Ile Leu Phe Arg         915 920 925 Gly Thr Pro His Asp Gln Leu Val Gly Glu Gln Thr Val Val Arg Ser     930 935 940 Phe Pro Ile Ala Ser Ile Thr Lys Glu Lys Lys Ile Thr Met Gln Asn 945 950 955 960 Gln Leu Gln Gln Asn Met Gln Glu Gly Leu Gln Val Thr Ser Ala Ser                 965 970 975 Phe Gln Leu Val Lys Val Ala Phe Asp Glu Glu Val Ser Pro Glu Val             980 985 990 Val Glu Val Phe Arg Lys Gln Leu Met Lys Leu Arg Tyr Pro Gln Ser         995 1000 1005 Val Phe Thr Thr Phe Ala Phe Ala Ala Gly Gln Thr Ala Pro Gln Ile    1010 1015 1020 Ile Ser Pro Lys Gln Lys Glu Lys Asn Thr Ser Phe Arg Thr Phe Ser 1025 1030 1035 1040 Lys Thr Ile Val Lys Gly Ala Lys Arg Ala Gly Lys Met Thr Ile Gly                1045 1050 1055 Arg Gln Tyr Leu Leu Lys Arg Arg Thr Gly Thr Ile Val Glu Glu Arg            1060 1065 1070 Val Ser Arg Pro Gly Trp Asn Glu Asp Asp Asp Val Ser Val Ser Asp        1075 1080 1085 Asp Ser Glu Leu Pro Thr Ser Thr Thr Leu Lys Ala Ser Glu Lys Ser    1090 1095 1100 Thr Met Glu Gln Leu Val Glu Lys Ala Cys Phe Arg Asp Tyr Gln Arg 1105 1110 1115 1120 Leu Gly Leu Gly Thr Ile Ser Gly Ser Ser Ser Ser Ser Lys Pro Glu                1125 1130 1135 Tyr Phe Arg Ile Thr Ala Ser Asn Arg Met Tyr Ser Leu Cys Arg Ser            1140 1145 1150 Tyr Pro Gly Leu Leu Val Val Pro Gln Ala Val Gln Asp Ser Ser Leu        1155 1160 1165 Pro Arg Val Ala Arg Cys Tyr Arg His His Arg Leu Pro Val Val Cys    1170 1175 1180 Trp Arg Asn Ser Arg Ser Ser Thr Leu Leu Leu Arg Ser Gly Gly Phe 1185 1190 1195 1200 His Gly Lys Gly Val Val Gly Leu Phe Lys Ser Gln Asn Ser Pro Gln                1205 1210 1215 Ala Ala Pro Thr Ser Ser Leu Glu Ser Ser Ser Ile Glu Gln Glu            1220 1225 1230 Lys Tyr Leu Gln Ala Leu Leu Ser Ala Val Ser Val His Gln Lys Leu        1235 1240 1245 Ser Gly Asn Asn Pro Leu Thr Val Arg Pro Ala Leu Ala Leu Ser Pro    1250 1255 1260 Gly Val Trp Ala Ser Leu Arg Ser Ser Thr Arg Leu Ile Ser Ser Pro 1265 1270 1275 1280 Thr Ser Phe Ile Asp Val Gly Ala Arg Leu Ala Gly Lys Asp His Ser                1285 1290 1295 Thr Ser Phe Ser Asn Ser Thr Tyr Leu Gln Asn Gln Leu Leu Lys Arg            1300 1305 1310 Gln Ala Thr Leu Tyr Ile Phe Gly Glu Lys Ser Gln Leu Arg Asn Phe        1315 1320 1325 Lys Leu Glu Phe Ala Leu Asn Cys Glu Phe Val Pro Val Glu Tyr His    1330 1335 1340 Asp Ile Arg Gln Val Lys Ala Ser Phe Lys Lys Leu Met Arg Ala Cys 1345 1350 1355 1360 Val Pro Ser Ala Ile Pro Thr Asp Ser Glu Val Thr Phe Leu Arg Ala                1365 1370 1375 Leu Gly Asp Ser Glu Trp Phe Pro Gln Leu His Arg Ile Leu Gln Leu            1380 1385 1390 Ala Val Val Ser Glu Val Leu Glu Asn Gly Ser Ser Val Leu Val        1395 1400 1405 Cys Leu Glu Glu Gly Trp Asp Ile Thr Ala Gln Val Thr Ser Leu Val    1410 1415 1420 Gln Leu Leu Ser Asp Pro Phe Tyr Arg Thr Leu Glu Gly Phe Arg Met 1425 1430 1435 1440 Leu Val Glu Lys Glu Trp Leu Ser Phe Gly His Lys Phe Ser Gln Arg                1445 1450 1455 Ser Ser Leu Thr Leu Ser Cys Gln Gly Ser Gly Phe Thr Pro Val Phe            1460 1465 1470 Leu Gln Phe Leu Asp Cys Val His Gln Val His Asn Gln Tyr Pro Thr        1475 1480 1485 Glu Phe Glu Phe Asn Leu Tyr Tyr Leu Lys Phe Leu Ala Phe His Tyr    1490 1495 1500 Val Ser Asn Arg Phe Lys Thr Phe Leu Leu Asp Ser Asp Tyr Glu Arg 1505 1510 1515 1520 Leu Glu His Gly Thr Leu Phe Asp Asp Lys Gly Asp Lys His Ala Lys                1525 1530 1535 Lys Gly Ile Cys Ile Trp Glu Cys Ile Asp Arg Met His Lys Arg Ser            1540 1545 1550 Pro Ile Phe Phe Asn Tyr Leu Tyr Ser Pro Val Glu Ile Glu Ala Leu        1555 1560 1565 Lys Pro Asn Val Asn Val Ser Ser Leu Lys Lys Trp Asp Tyr Tyr Ile    1570 1575 1580 Glu Glu Thr Leu Ser Thr Gly Pro Ser Tyr Asp Trp Met Met Leu Thr 1585 1590 1595 1600 Pro Lys Gln Leu Pro Ser Glu Asp Ser Glu Leu Ala Gly Gly Ala Arg                1605 1610 1615 Pro Gln Ser Gln Arg Arg Thr Val Trp Pro Cys Tyr Asp Asp Val Ser            1620 1625 1630 Cys Ala Gln Pro Asp Ala Leu Thr Ser Leu Phe Ser Glu Ile Glu Arg        1635 1640 1645 Leu Glu His Lys Leu Asn Gln Thr Pro Glu Lys Trp Gln Gln Leu Trp    1650 1655 1660 Glu Arg Val Asn Val Asp Leu Lys Glu Glu Pro Arg Ala Asp His Pro 1665 1670 1675 1680 Gln Arg Tyr Pro Ser Gly Ser Pro Gly Thr Val Ser Thr Asn Leu Pro                1685 1690 1695 Phe Tyr Gln Lys Arg Pro Gln Leu His Leu Pro Asp Ser Asn Leu Ala            1700 1705 1710 Glu Glu Gln Asn Thr Gly Val Ser Ser Ser Gn Val Asp Arg Arg        1715 1720 1725 Ala Ala Thr Leu Tyr Ser Gln Tyr Thr Pro Lys Asn Asp Glu Asn Arg    1730 1735 1740 Ser Phe Glu Gly Thr Leu Tyr Lys Arg Gly Ala Leu Leu Lys Gly Trp 1745 1750 1755 1760 Lys Pro Arg Trp Phe Val Leu Asp Val Thr Lys His Gln Leu Arg Tyr                1765 1770 1775 Tyr Asp Ser Gly Glu Asp Thr Ser Cys Lys Gly His Ile Asp Leu Ala            1780 1785 1790 Glu Val Glu Met Val Ile Pro Ala Gly Pro Ser Met Gly Ala Pro Lys        1795 1800 1805 His Thr Ser Asp Lys Ala Phe Phe Asp Leu Lys Thr Ser Lys Arg Val    1810 1815 1820 Tyr Asn Phe Cys Ala Gln Asp Gly Gln Ser Ala Gln Gln Trp Met Asp 1825 1830 1835 1840 Arg Ile Gln Ser Cys Ile Ser Asp Ala                1845

Claims (5)

A single nucleotide polymorphism (SNP) region of a complementary component 1, r subcomponent-like (C1RL) gene specifically binding to 10-100 consecutive nucleotide sequences comprising a single nucleotide polymorphic site at position 1458 of SEQ ID NO: Lt; RTI ID = 0.0 &gt;N'Dama&lt; / RTI &gt; breed selection kit comprising a primer or a probe.
The kit according to claim 1, wherein the kit is a single nucleotide polymorphism (SNP) region of USH2A (Usher syndrome 2A) gene, a single nucleotide polymorphism site at position 13720 (GenBank SNP database rs110332182)
A single base polymorphism (SNP) region of the ACAD9 (acyl-CoA dehydrogenase family, member 9) gene, a single base polymorphism site at position 1558 (GenBank SNP database rs135578554)
As a single base polymorphism (SNP) region of the AMZ1 (archaelysin family metallopeptidase 1) gene, a single base polymorphism site at the 610th position of the 3rd sequence and a single base polymorphism site at the 340th position (GenBank SNP database rs109821810)
A single nucleotide polymorphism (SNP) region of CDADC1 (cytidine and dCMP deaminase domain containing 1) gene, a single nucleotide polymorphism site at position 1438 (GenBank SNP database rs109691868) of Sequence Listing 4,
A single nucleotide polymorphism (SNP) region of EML1 (echinoderm microtubule associated protein like 1) gene, a single nucleotide polymorphism site at position 1765 of Sequence Listing 5,
A single nucleotide polymorphism (SNP) region of the EOMES (eomesodermin) gene, a single nucleotide polymorphism site at position 763 of SEQ ID NO: 6,
A single nucleotide polymorphism (SNP) region of an opioid binding protein / cell adhesion molecule-like (OPCML) gene, a single nucleotide polymorphism site at position 157 of SEQ ID NO:
A single nucleotide polymorphism (SNP) site of the PIK3C2G (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 gamma) gene, a single nucleotide polymorphism site at position 70 of SEQ ID No. 8, a nucleotide polymorphism site at position 347 (GenBank SNP database rs380908276 ) Single nucleotide polymorphic site,
The single nucleotide polymorphism (SNP) site of the SLIT3 (slit guidance ligand 3) gene, the single nucleotide polymorphic site of the 1814th position (GenBank SNP database rs110101818)
A single nucleotide polymorphism (SNP) region of TIGAR (TP53 induced glycolysis regulatory phosphatase) gene, a single nucleotide polymorphism site at position 272 of SEQ ID NO: 10,
Single base polymorphism (SNP) region of the TPST1 (tyrosylprotein sulfotransferase 1) gene, single nucleotide polymorphism site at position 704 (GenBank SNP database rs383100152) of SEQ ID NO: 11,
The single nucleotide polymorphism (SNP) site of the C1RL (complement component 1, r subcomponent-like) gene, the single nucleotide polymorphism site at position 367 (GenBank SNP database rs207500281) of SEQ ID NO: 12, the 559th position (GenBank SNP database rs208003071 ) And a single nucleotide polymorphic site at position 1344,
Single nucleotide polymorphism (SNP) region of DDX54 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 54) single nucleotide polymorphism site at position 397 of Sequence Listing 13 (GenBank SNP database rs385853893)
A single nucleotide polymorphism (SNP) region of NOX5 (NADPH oxidase, EF-hand calcium binding domain 5) gene, a single nucleotide polymorphism site at position 1015 of SEQ ID No. 14,
A single nucleotide polymorphism site of the 160th position of SEQ ID NO: 15 (GenBank SNP database rs385712825) as the single nucleotide polymorphism (SNP) region of the RANBP17 (RAN binding protein 17) gene, and
A single nucleotide polymorphism (SNP) region of the SET binding factor 2 (SBF2) gene, and at least one single nucleotide polymorphism site selected from the group consisting of a single nucleotide polymorphism site at position 4888 of SEQ ID NO: A sleep apnea resistant N'Dama variety selection kit further comprising a primer or probe that specifically binds to a contiguous nucleotide sequence.
(SNP) site of the C1RL (complemen component 1, r subcomponent-like) gene in the bovine biological sample to provide information necessary for screening of the N'Dama varieties of sleep apnea resistant strains. (SNP) site of the N'Dama variant-specific marker of the present invention.
4. The method according to claim 3, wherein the biological sample is whole blood, plasma or serum.
4. The method according to claim 3, wherein the method is a single nucleotide polymorphism (SNP) region of USH2A (Usher syndrome 2A) gene, a single nucleotide polymorphism site at position 13720 of SEQ ID NO: 1 (GenBank SNP database rs110332182)
A single base polymorphism (SNP) region of the ACAD9 (acyl-CoA dehydrogenase family, member 9) gene, a single base polymorphism site at position 1558 (GenBank SNP database rs135578554)
As a single base polymorphism (SNP) region of the AMZ1 (archaelysin family metallopeptidase 1) gene, a single base polymorphism site at the 610th position of the 3rd sequence and a single base polymorphism site at the 340th position (GenBank SNP database rs109821810)
A single nucleotide polymorphism (SNP) region of CDADC1 (cytidine and dCMP deaminase domain containing 1) gene, a single nucleotide polymorphism site at position 1438 (GenBank SNP database rs109691868) of Sequence Listing 4,
A single nucleotide polymorphism (SNP) region of EML1 (echinoderm microtubule associated protein like 1) gene, a single nucleotide polymorphism site at position 1765 of Sequence Listing 5,
A single nucleotide polymorphism (SNP) region of the EOMES (eomesodermin) gene, a single nucleotide polymorphism site at position 763 of SEQ ID NO: 6,
A single nucleotide polymorphism (SNP) region of an opioid binding protein / cell adhesion molecule-like (OPCML) gene, a single nucleotide polymorphism site at position 157 of SEQ ID NO:
A single nucleotide polymorphism (SNP) site of the PIK3C2G (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 gamma) gene, a single nucleotide polymorphism site at position 70 of SEQ ID No. 8, a nucleotide polymorphism site at position 347 (GenBank SNP database rs380908276 ) Single nucleotide polymorphic site,
The single nucleotide polymorphism (SNP) site of the SLIT3 (slit guidance ligand 3) gene, the single nucleotide polymorphic site of the 1814th position (GenBank SNP database rs110101818)
A single nucleotide polymorphism (SNP) region of TIGAR (TP53 induced glycolysis regulatory phosphatase) gene, a single nucleotide polymorphism site at position 272 of SEQ ID NO: 10,
Single base polymorphism (SNP) region of the TPST1 (tyrosylprotein sulfotransferase 1) gene, single nucleotide polymorphism site at position 704 (GenBank SNP database rs383100152) of SEQ ID NO: 11,
The single nucleotide polymorphism (SNP) site of the C1RL (complement component 1, r subcomponent-like) gene, the single nucleotide polymorphism site at position 367 (GenBank SNP database rs207500281) of SEQ ID NO: 12, the 559th position (GenBank SNP database rs208003071 ) And a single nucleotide polymorphic site at position 1344,
Single nucleotide polymorphism (SNP) region of DDX54 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 54) single nucleotide polymorphism site at position 397 of Sequence Listing 13 (GenBank SNP database rs385853893)
A single nucleotide polymorphism (SNP) region of NOX5 (NADPH oxidase, EF-hand calcium binding domain 5) gene, a single nucleotide polymorphism site at position 1015 of SEQ ID No. 14,
A single nucleotide polymorphism site of the 160th position of SEQ ID NO: 15 (GenBank SNP database rs385712825) as the single nucleotide polymorphism (SNP) region of the RANBP17 (RAN binding protein 17) gene, and
Further comprising the step of detecting at least one single base polymorphism site selected from the group consisting of a single base polymorphism site at position 4888 of SEQ ID NO: 16 sequence as a single nucleotide polymorphism (SNP) region of the SET binding factor 2 (SBF2) Gt; N'Dama &lt; / RTI &gt; variant-specific marker.

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