Eumelanin is the black pigment in mammalian fur. Eumelanin production is mediated by at least three different enzymes: Tyrosinase (TYR), Dopachrome Tautomerase (DCT), and Tyrosinase Related Protein One (TYRP1). Certain mutations in these genes cause the organism to produce little or no eumelanin and instead the enzyme's substrate becomes the hair's pigment. For example, mutations in the mouse TYRP1 gene result in a brown fur pigment.

Our hypothesis is that mutations in the cat TYRP1 gene will also result in a brown coat color. We are evaluating this hypothesis by comparing the TYRP1 sequence in wild type (black fur) and the allelic variant (brown fur). The TYRP1 gene is composed of eight exons, seven of which are translated in other mammals. We have evaluated six of these exons to date using direct sequencing, and we have located two missense mutations in the third exon. The first mutation causes a lysine to be replaced with an arginine while the second causes a threonine to be exchanged for a methionine. Both of these mutations are drastic enough to potentially cause a conformational change in the protein. To evaluate this, we propose to test unrelated brown cats from several different breeds to determine whether all show one or both of the mutations. If these mutations are found to be the cause of the brown phenotype, then it will be possible to use our research to design tests to determine the carrier status of individual cats. This will eliminate the need for test crosses.