Brown coat color phenotypes caused by mutations in tyrosinase-related protein-1 (TYRP1) are recognized in many mammals. Brown variations are also recognized in the domestic cat, but the causative mutations are unknown. In cats, Brown, B, has a suggested allelic series, B > b > bl. The B allele is normal wild-type black coloration. Cats with the brown variation genotypes, bb or bbl, are supposedly phenotypically chocolate (aka chestnut) and the light brown genotype, blbl, are supposedly phenotypically cinnamon (aka red). The complete coding sequence of feline TYRP1 and a portion of the 5′ UTR was analyzed by direct sequencing of genomic DNA of wild-type and brown color variant cats. Sixteen single nucleotide polymorphisms (SNPs) were identified. Eight SNPs were in the coding regions, six are silent mutations. Two exon 2 on mutations cause amino acid changes. The C to T nonsense mutation at position 298 causes an arginine at amino acid 100 to be replaced by the opal (UGA) stop codon. This mutation is consistent with the cinnamon phenotype and is the putative light brown, bl, mutation. An intron 6 mutation that potentially disrupts the exon 6 downstream splice-donor recognition site is associated with the chocolate phenotype and is the putative brown, b, mutation. The allelic series was confirmed by segregation and sequence analyses. Three microsatellite makers had significant linkage to the brown phenotype and two for the TYRP1 mutations in a 60-member pedigree. These mutations could be used to identify carriers of brown phenotypes in the domestic cat.
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We appreciate the assistance of the cat breeders from throughout the world for providing samples, cat show managers for allowing the collection of samples at various cat shows, and UC Davis veterinary student Amanda Payne–deVega for collection of random-bred cat samples. Technical assistance for the project was provided by Mark T. Ruhe and Carolyn A. Erdman. Funding for this project was provided to L. A. Lyons from NIH-NCRR R24 RR016094 and a UC Davis faculty research grant and to A. Payne–deVega by the UC Davis School of Veterinary Medicine Students Training in Advanced Research (STAR) program. We acknowledge the National Cancer Institute for allocation of computing time and staff support at the Advanced Biomedical Computing Center of the Frederick Cancer Research and Development Center. The UC Davis feline research colony cats are bred under Animal Care and Use Protocol 10390. Food for the cat colony was gratefully provided by Royal Canin.
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Lyons, L.A., Foe, I.T., Rah, H.C. et al. Chocolate coated cats: TYRP1 mutations for brown color in domestic cats. Mamm Genome 16, 356–366 (2005). https://doi.org/10.1007/s00335-004-2455-4
- Allelic Series
- Stop Mutation
- Oculocutaneous Albinism
- Brown Variant
- TYRP1 Gene