In other species: lorises , coyote , dog , red fox , American black bear , domestic cat , jaguar , ass (donkey) , horse , Przewalski's horse , pig , Arabian camel , reindeer , taurine cattle , indicine cattle (zebu) , goat , sheep , rabbit , Mongolian gerbil , domestic guinea pig , domestic yak , alpaca , gray squirrel , raccoon dog , antarctic fur seal , woolly mammoth , rock pocket mouse , oldfield mouse , lesser earless lizard , Geoffroy's cat , jaguarundi , Colocolo , little striped whiptail , water buffalo , Arctic fox

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 266300 (trait) , 155555 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: no

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: The extension locus encodes the melanocyte-stimulating hormone receptor (MSHR; now known as MC1R). This receptor controls the level of tyrosinase within melanocytes. Tyrosinase is the limiting enzyme involved in synthesis of melanins: high levels of tyrosinase result in the production of eumelanin (dark colour, e.g. brown or black), while low levels result in the production of phaeomelanin (light colour, e.g. red or yellow). When melanocyte-stimulating hormone (MSH) binds to its receptor, the level of tyrosinase is increased, leading to production of eumelanin. The wild-type allele at the extension locus corresponds to a functional MSHR, and hence to dark pigmentation in the presence of MSH. As explained by Schneider et al. (PLoS Genet 10(2): e1004892; 2015), "The most common causes of melanism (black coat) mutations are gain-of-function alterations in MC1R, or loss-of function alterations in ASIP, which encodes Agouti signaling protein, a paracrine signaling molecule that inhibits MC1R signaling". Mutations in MC1R have been associated with white colouring in several species.

Species-specific name: White fallow deer, menil fallow deer

Species-specific description: “The coat colour of fallow deer is highly variable and even white animals can regularly be observed in game farming and in the wild. Affected animals do not show complete albinism but rather some residual pigmentation resembling a very pale beige dilution of coat colour. The eyes and claws of the animals are pigmented” (Reiner et al., 2020). Reissmann et al. (2024) investigated four coat colour phenotypes in the species: brown, black, menile and white.  

Molecular basis: Reiner et al. (2020) conducted whole genome sequencing of one white hind and her brown calf and identified “a variant in the MC1R gene (NM_174108.2:c.143T>C) resulting in an amino acid exchange from leucine to proline at position 48 of the MC1R receptor protein (NP_776533.1:p.L48P)” as a likely cause for the coat colour variation observed in white fallow deer.
Reissmann et al. (2024) investigated four coat colour candidate genes ASIP, MC1R, TYR, and SLC45A2 in fallow deer with brown, black, menil or white coat colour.  The authors confirmed the p.(L48P) variant reported by Reiner et al. (2020) as likely causal variant for white coat colour and identified a p.(G236D) variant as likley causal variant for menil coat colour. Two variants were identified in ASIP as likley causal variants for black coat colour (see OMIA:000201-30532 : Coat colour, agouti in Dama dama (fallow deer) for details).

Genetic testing: “102 samples from 22 white animals and from 80 animals with wildtype coat colour were genotyped” for the NM_174108.2:c.143T>C variant and the “gene test revealed that all animals of the white phenotype were of genotype CC whereas all pigmented animals were of genotype TT or TC. The study showed that 14% of the pigmented (brown or dark pigmented) animals carried the white allele.” (Reiner et al., 2020)

Associated gene: