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

Category: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 266300 (trait) , 155555 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: unknown

Considered a defect: no

Year key variant first reported: 2021

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.

Molecular basis: Goud et al. (2021) analysed the Sahiwal MC1R gene and proposed that a missense SNP (c.844C>A; p.(T281N) might be the possible reason for the red coat colour in Sahiwal cattle when compared to black and white-coloured Karan Fries (Bos taurus x Bos indicus) cattle. The authors acknowledged that further molecular studies need to be conducted to validate an association of the variant with red coat colour.

Santana et al. (2021): Gray coat is one of the breed qualifications in Guzerat cattle. The authors report “the birth of a single red individual … as a result of the mating of two gray Guzerat animals. … The primer pair described by Goud et al. (2021) was used for PCR, which amplifies the single exon of the MC1R gene. Sequence analysis permitted the detection of a deletion of one nucleotide whose nitrogenated base is a thymine, at position 311 of the MC1R gene. This deletion causes a change in the reading frame from this point onwards (amino acid 104) and creates a premature stop codon. The predicted protein is smaller, with 155 amino acids compared with the original protein …. "

Breeds: Guzerat (Cattle) (VBO_0000228), Sahiwal (Cattle) (VBO_0000365).

Associated gene: