Tyrosinase mutations associated with Siamese and Burmese patterns in the domestic cat (Felis catus)

Abstract

The Siamese cat has a highly recognized coat colour phenotype that expresses pigment at the extremities of the body, such as the ears, tail and paws. This temperature-sensitive colouration causes a 'mask' on the face and the phenotype is commonly referred to as 'pointed'. Burmese is an allelic variant that is less temperature-sensitive, producing more pigment throughout the torso than Siamese. Tyrosinase (TYR) mutations have been suspected to cause these phenotypes because mutations in TYR are associated with similar phenotypes in other species. Linkage and synteny mapping in the cat has indirectly supported TYR as the causative gene for these feline phenotypes. TYR mutations associated with Siamese and Burmese phenotypes are described herein. Over 200 cats were analysed, representing 12 breeds as well as randomly bred cats. The SNP associated with the Siamese phenotype is an exon 2 G > A transition changing glycine to arginine (G302R). The SNP associated with the Burmese phenotype is an exon 1 G > T transversion changing glycine to tryptophan (G227W). The G302R mutation segregated concordantly within a pedigree of Himalayan (pointed) Persians. All cats that had 'pointed' or the Burmese coat colour phenotype were homozygous for the corresponding mutations, respectively, suggesting that these phenotypes are a result of the identified mutations or unidentified mutations that are in linkage disequilibrium. Because the same mutations were identified in different breeds with similar phenotypes, the mutations are likely to be identical by descent rather than multiple mutation events occurring at the same site.

Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs

“…These types of observations, first made by Sewall Wright (1917c) and later by Clarence Cook Little (1957) and A. G. Searle (1968), foreshadowed the field of comparative genomics. Indeed, comparison of genome sequences not only clarified the evolutionary relationships among mammals (and most other organisms), but also provided the tools to identify molecular alterations responsible for the Tyrosinase color series in mice (Kwon et al 1989), cats (Lyons et al 2005;Schmidt-Kuntzel et al 2005), cattle (Schmutz et al 2004), and rabbits (Aigner et al 2000) (although, ironically, not yet in guinea pigs).…”

Skin Pigmentation Genetics for the Clinic

“…Protein expression studies have shown that the 402Q variant encodes a thermolabile enzyme [40] , and in primary melanocyte cultures we have shown that it is retained in the endoplasmic reticulum, hypoglycosylated and preferentially degraded [45] . Interestingly, thermolabile TYR alleles are the basis of the Siamese/Burmese cat coat colours, where pigment appears darkest at the extremities of the body [46] ; this condition is also present in some human albino patients as subtype OCA1B [39] . Recent studies have shown that the TYR genotype is likely to be a significant modifier of other pigmentation gene polymorphisms in human skin, hair and eye colour, and associated with naevus count, though not apparent by body site there is potential for thermal changes in pigmentation of the skin and hair [45] .…”

Génétique de la couleur et de la texture du pelage chez le chat domestique

“…b sont qualifiés de mink et présentent un contraste moyen entre les extrémités et le reste du corps. Leurs yeux sont couleur « aiguemarine » (figure 9) (Lyons et al 2005). …”