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

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

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2001

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: By cloning and sequencing a very likely comparative candidate gene (based on the known molecular basis of the agouti locus in other species), Rieder et al. (2001) identified recessive black in nine breeds as being due "an 11-bp deletion in exon 2 (ADEx2) [of the ASIP gene]. . . . The frameshift initiated by ADEx2 is believed to alter the regular coding sequence, acting as a loss-of-function ASIP mutation." The same authors also state that they consider the deletion to be "between position 2174–2184 on genomic DNA level or at position 191–201, with regard to the start codon, if only exonic sequences are taken into account".

Associated gene: