In other species: horse , cattle , meadow voles , red fox , pig , sheep , domestic cat , rabbit , dog , gray wolf , coyote , goat , Eurasian water mole , Northern mole vole , North American deer mouse , alpaca , Asiatic golden cat , leopard cat , ass , impala , Colocolo , Kodkod , Arabian camel , Mongolian gerbil , domestic guinea pig , Western roe deer , llama , oldfield mouse

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 611742 (trait) , 600201 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2012

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".

Inheritance: Robinson (1969, 1970) provided evidence of autosomal recessive inheritance of the melanistic phenotype, based on the breeding records of 439 animals.

Molecular basis: By sequencing the candidate gene ASIP in "wild-type" non-melanistic leopards and melanistic leopards ("black panthers"), Schneider et al. (2012) showed that the "black panther" phenotype is due to a "non-synonymous mutation located in exon 4 (C333A) predicted to introduce a stop codon at amino acid position 111. All 11 analyzed melanistic leopards . . . were homozygous for this mutation, while the wild-type individuals (i.e. bearing a yellowish background coloration with black rosettes; . . .) were either homozygous for the ancestral ‘A’ allele or heterozygous."

Associated gene: