In other species: Tasmanian devil , common brushtail possum , gray wolf , coyote , dog , red fox , domestic cat , leopard , ass (donkey) , horse , pig , llama , Western roe deer , impala , taurine cattle , goat , sheep , rabbit , tassel-eared squirrel , North American deer mouse , Mongolian gerbil , meadow voles , domestic guinea pig , fallow deer , alpaca , leopard cat , oldfield mouse , Kodkod , Colocolo , Asiatic golden cat , Northern mole vole , Eurasian water mole

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 611742 (trait) , 600201 (gene)

Mendelian trait/disorder: yes

Disease-related: no

Key variant known: yes

Year key variant first reported: 2018

Cross-species summary: This locus, ASIP, encodes the agouti signalling protein, a peptide antagonist of the melanocyte-stimulating hormone receptor (MC1R), which is the product of the extension locus. 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".

Molecular basis: Adopting the comparative candidate gene approach, Almathen et al. (2018) sequenced the ASIP gene in "91 animals from ten Arabian camel populations, that included the four predominant coat color phenotypes observed in the dromedary (light brown, dark brown, black and white)". They identified two variants "a 1-bp deletion (23delT/T) and a SNP (25G/A) in exon 2 of ASIP" that exist as two haplotypes, namely "23delT-25A and 23T-25G". Noting that the "23delT-25A haplotype results in a frame shift mutation, which changes the amino acid sequence and introduces a premature stop codon at position 24", Almathen et al. (2018) reported that this haplotype is associated with black and dark-brown coat colour: "Animals with black and dark-brown coat colors (n = 40, Magaheem and Sofor [populations]) were homozygous for haplotype 23delT-25A, whereas all light-brown and white individuals (n = 51) were homozygous for the 23T-25G haplotype". Alshanbari et al. (2019) "confirmed that the majority [with 4 exceptions] of black dromedaries were homozygous for . . . [the 23delT-25A] frameshift mutation in ASIP exon 2"

Associated gene: