In other species: lorises , coyote , dog , red fox , American black bear , domestic cat , jaguar , ass (donkey) , Przewalski's horse , pig , Arabian camel , reindeer , taurine cattle , indicine cattle (zebu) , goat , sheep , rabbit , Mongolian gerbil , domestic guinea pig , domestic yak , fallow deer , 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

Disease-related: no

Key variant known: yes

Year key variant first reported: 1996

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: Chestnut

Species-specific description: Various theories on the inheritance of horse coat colours have existed for many decades. Since the 1990s, the full force of molecular biology has been brought to bear on this topic. The first results of such work in horses were reported by Marklund et al. (1996) (see below).

Inheritance: The autosomal recessive inheritance of chestnut was first reported by Hurst (1906), soon after the rediscovery of Mendelism. This conclusion was rigorously (and erroneously) opposed by Weldon (1906).

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the very reasonable assumption that chestnut coat colour in horses is due to an allele at the extension locus), Marklund et al. (1996) showed that chestnut coat colour in 12 different breeds is due to a missense mutation in the gene for melanocyte-stimulating hormone receptor (MSHR or MC1R).

Breeds: American Trotter (Horse) (VBO_0000899), Arab (Horse) (VBO_0000905), Belgian Draft (Horse) (VBO_0000915), Black Forest (Horse) (VBO_0017099), Clydesdale (Horse) (VBO_0000934), Freiberger (Horse) (VBO_0000965), Icelandic Horse (Horse) (VBO_0000991), Morgan (Horse) (VBO_0001022), Quarter Horse (Horse) (VBO_0001057), Shetland Pony (Horse) (VBO_0001066), Thoroughbred (Horse) (VBO_0001083), Warmblood (Horse) (VBO_0017483), Welsh Pony (Horse) (VBO_0001091).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: