The focus of this dissertation work is twofold. First, this work aims to examine the origin of feline longhair and the distribution of causative mutations in pedigreed and random bred cat populations in order to gain insight on cat domestication and the development of pedigreed breeds. Second, this work expands the current genomic resources available to the feline research community by generating a 15,000Rad radiation hybrid (RH) panel for high-resolution mapping of the cat genome. Longhair in the domestic cat is an economically important trait, and is one of the few phenotypic traits that separate the domestic cat from wildcats. The gene responsible for longhair has been identified as fibroblast growth factor 5 (FGF5), and several polymorphisms within the gene have been identified; however, the impact and distribution of each polymorphism has not been established. In order to establish which polymorphisms are causative and the frequencies of each polymorphism within pedigreed cats, 646 pedigreed cats representing 11 longhaired breeds, 15 shorthaired breeds, five breeds that segregate for hair length, and two hairless breeds were genotyped for all mutations within FGF5. This work indicates four mutations as causative: c.475A>C, which is present in all longhaired breeds and likely the most ancestral mutation; c.365insT, which is present in Ragdolls, Siberians, and the Don Sphynx; c.474delT, which has been identified in Ragdolls, American Curls, Japanese Bobtails, Turkish Angoras, and Munchkins; and c.406C>T, the least frequent causative mutation, found primarily in the Norwegian Forest Cat. As the c.475A>C mutation is likely the ancestral longhair mutation, over 900 random bred cats from 24 worldwide populations were genotyped to elucidate the frequency of the longhair mutation throughout the world. Additionally, three non-causative SNPs were also assayed, and 10 haplotypes could be inferred from the genotyping data. Two common haplotypes were identified, one conferring longhair (LH-1) and one conferring shorthair (SH-1); interestingly, LH-1 does not appear to be directly derived from SH-1, but rather from the less common haplotype SH-2. Analysis of haplotype frequencies throughout the world indicate that SH-2 is the most common haplotype in Iran, suggesting that feline longhair arose from an ancient population of cats in this region. Finally, to expand the resources available for genomic research in the domestic cat, a 15,000 Rad RH panel was developed. The panel consists of 154 clone lines, and each line was assayed with 39 microsatellite markers. The full panel has an estimated retention frequency (RF) of 20.86%. The clone lines were also interrogated with a quantitative PCR assay (Q-PCR) in order to obtain a global measure of donor DNA per line; on average, the panel contains approximately 3.7% donor DNA. This work both advances understanding of the origins of the domestic cat and provides a useful tool for the assembly and analysis of the cat genome.
|Advisor:||Lyons, Leslie A.|
|Commitee:||Delany, Mary E., Sharp, Frank R.|
|School:||University of California, Davis|
|School Location:||United States -- California|
|Source:||DAI-B 72/05, Dissertation Abstracts International|
|Subjects:||Genetics, Veterinary services|
|Keywords:||Domestic cat, Domestication, Fgf5, Longhair, Radiation hybrid panel|
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