Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Chocolate coated cats: TYRP1 mutations for brown color in domestic cats


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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3


  1. Adalsteinsson S, Bjarnadottir S, Vage DI, Jonmundsson JV (1995) Brown coat color in Icelandic cattle produced by the loci Extension and Agouti. J Hered 86(5), 395–398

  2. Berryere TG, Schmutz SM, Schimpf RJ, Cowan CM, Potter J (2003) TYRP1 is associated with dun coat colour in Dexter cattle or how now brown cow? Anim Genet 34(3), 169–175

  3. CFA (1993) The Cat Fanciers’Association Cat Encyclopedia (New York: Simon & Schuster), pp 128–136

  4. Grahn RA, Biller DS, Young AE, Roe BA, Qin B, et al. (2004) Genetic testing for feline polycystic kidney disease. Anim Genet 35(6), 503–504

  5. Hirobe T, Wakamatsu K, Ito S (1998) Effects of genic substitution at the agouti, brown, albino, dilute, and pink-eyed dilution loci on the proliferation and differentiation of mouse epidermal melanocytes in serum-free culture. Eur J Cell Biol 75(2), 184–191

  6. Jackson IJ (1988) A cDNA encoding tyrosinase-related protein maps to the mouse brown locus. Proc Natl Acad Sci USA 85(12), 4391–4396

  7. Javerzat S, Jackson IJ (1998) White-based brown (TYRP1B-w) is a dominant mutation causing reduced hair pigmentation owing to a chromosomal inversion. Mamm Genome 9(6), 469–471

  8. Jimenez–Cervantes C, Solano F, Kobayashi T, Urabe K, Hearing VJ, et al. (1994) A new enzymatic function in the melanogenic pathway: The 5,6-dihydroxyindole-2-carboxylic acid oxidase activity of tyrosinase-related protein-1 (TYRP1). J Biol Chem 269(27), 17993–18000

  9. Kobayashi T, Urabe K, Winder A, Tsukamoto K, Brewington T, et al. (1994) DHICA oxidase activity of TYRP1 and interactions with other melanogenic enzymes. Pigment Cell Res 7(4), 227–234

  10. Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Nat Acad Sci USA 81(11), 3443–3446

  11. Lyons LA, Laughlin TF, Copeland NG, Jenkins NA, Womack JE, et al. (1997) Comparative anchor tagged sequences (CATS) for integrative mapping of mammalian genomes. Nat Genet 15(1), 47–56

  12. Lyons LA, Imes DL, Rah HC, Grahn RA (2005) Tyrosinase mutations associated with Siamese and Burmese patterns in the domestic cat (Felis catus). Anim Genet (in press) 36:119–26

  13. McPherson JD, Marra M, Hillier L, Waterston RH, Chinwalla A, et al. (2001) A physical map of the human genome. Nature 409(6822), 934–941

  14. Menotti–Raymond M, David VA, Agarwala R, Schaffer AA, Stephens R, et al. (2003a) Radiation hybrid mapping of 304 novel microsatellites in the domestic cat genome. Cytogenet Genome Res 102(1–4), 272–276

  15. Menotti–Raymond M, David VA, Roelke ME, Chen ZQ, Menotti KA, et al. (2003b) Second-generation integrated genetic linkage/radiation hybrid maps of the domestic cat (Felis catus). J Hered 94(1), 95–106

  16. Nicholls AC, Oliver J, McCarron S, Winter GB, Pope FM (1996) Splice site mutation causing deletion of exon 21 sequences from the pro alpha 2(I) chain of type I collagen in a patient with severe dentinogenesis imperfecta but very mild osteogenesis imperfecta. Hum Mutat 7(3), 219–227

  17. O’Neill JP, Rogan PK, Cariello N, Nicklas JA (1998) Mutations that alter RNA splicing of the human HPRT gene: a review of the spectrum. Mutat Res 411(3), 179–214

  18. Rieder S, Taourit S, Mariat D, Langlois B, Guerin G (2001) Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mamm Genome 12(6), 450–455

  19. Robinson R (1977) Genetics for cat breeders, 2nd ed. (New York: Pergamon Press), pp 108–109

  20. Sambrook J, Russell DW (2001) Molecular cloning: A Laboratory Manual, 3rd ed. (New York: Cold Spring Harbor Press), pp 611–1614

  21. Schmutz SM, Berryere TG, Goldfinch AD (2002) TYRP1 and MC1R genotypes and their effects on coat color in dogs. Mamm Genome 13(7), 380–387

  22. Tamate HB, Hirobe T, Wakamatsu K, Ito S, Shibahara S, et al. (1989) Levels of tyrosinase and its mRNA in coat-color mutants of C57BL/10 J congenic mice: effects of genie substitution at the agouti, brown, albino, dilute, and pink-eyed dilution loci. J Exp Zool 250(3), 304–311

  23. Young A, Biller D, Herrgesell E, Roberts H, Lyons L (2005) Feline polycystic kidney disease linkage to the PKD1 region. Mamm Genome 16(1), 59–65

Download references


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.

Author information

Correspondence to Leslie A. Lyons.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation


  • Allelic Series
  • Stop Mutation
  • Oculocutaneous Albinism
  • Brown Variant
  • TYRP1 Gene