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Journal of Heredity Advance Access originally published online on April 27, 2005
Journal of Heredity 2005 96(4):289-301; doi:10.1093/jhered/esi066
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Published by Oxford University Press 2005.

Tyrosinase and Tyrosinase Related Protein 1 Alleles Specify Domestic Cat Coat Color Phenotypes of the albino and brown Loci

A. Schmidt-Küntzel, E. Eizirik, S. J. O'Brien, and M. Menotti-Raymond

From the Basic Research Program, SAIC-Frederick, NCI Frederick, Frederick, MD 21702 and Genetics Department, George Washington University, Washington, DC (Schmidt-Küntzel); Laboratory of Genomic Diversity, NCI Frederick, Frederick, MD (Eizirik, O'Brien, and Menotti-Raymond); and Faculdade de Biociências, PUCRS, Porto Alegre, RS 90619-900, Brazil (Eizirik)

Address correspondence to A. Schmidt-Küntzel at the NCI address above, or e-mail: aschmidt{at}ncifcrf.gov.

The genes encoding enzymes of the tyrosinase family are strong candidates for coat color variation in mammals. To investigate their influence in domestic cat coat color, we determined the complete nucleotide coding sequence of the domestic cat genes tyrosinase (TYR)—a plausible candidate gene for the albino (C) locus, and tyrosinase related protein 1 (TYRP1)—a candidate gene for the brown (B) locus. Sequence variants between individuals exhibiting variation in pigmentation were submitted to association studies. In TYR, two nonsynonymous substitutions encoding TYR-G301R and TYR-G227W were associated with the siamese and burmese phenotypes of the albino locus, respectively. TYRP1 was mapped on chromosome D4 within 5 cM of a highly polymorphic microsatellite, previously found to be fixed in a cat breed selected for the chocolate (b) allele of the B locus, which reinforced TYRP1 as a candidate gene for the B locus in the domestic cat. Two DNA polymorphisms, one leading to a TYRP1-A3G substitution in the signal peptide and another to an in-frame insertion TYRP1-421ins17/18 caused by a donor splice site mutation in intron 6, were associated with the chocolate (b) allele. A premature UAG stop codon at position 100 of TYRP1 was associated with a second allele of the B locus, cinnamon (bl). The results provide very strong evidence that the specific nucleotide variants of feline TYR (chromosome D1) are causative of the siamese (cs) and burmese (cb) alleles of the albino locus, as well as nucleotide variants of TYRP1 (chromosome D4) as specifying the chocolate (b) and cinnamon (bl) alleles of the B locus.


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