In other species: Tasmanian devil , common brushtail possum , gray wolf , coyote , dog , red fox , domestic cat , leopard , ass (donkey) , horse , pig , Arabian camel , llama , Western roe deer , impala , taurine cattle , 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

Mode of inheritance: Autosomal

Disease-related: no

Key variant known: yes

Year key variant first reported: 2009

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: Adalsteinsson et al. (1994) hypothesized that there are "10 alleles at the Agouti locus [in goats], with the allele for white or tan color being the top dominant allele, and the nine others codominant. The bottom recessive allele, for nonagouti color, was the 11th allele at this locus. The postulated alleles are white or tan (A^Wt), black mask (A^blm), bezoar (A^bz), badgerface (A^b), grey (A^g), lightbelly (A^lb), swiss markings (A^sm), lateral stripes (A^ls), mahogany (A^mh), red cheek (A^rc), and nonagouti (a)."

Molecular basis: Fontanesi et al. (2009) "confirmed the presence of CNV [copy number variation] affecting a region of less that 100 kb including the ASIP and AHCY genes. In Girgentana and Saanen breeds, this CNV might cause the A^Wt allele, as already suggested for a similar structural mutation in sheep affecting the ASIP and AHCY genes, providing evidence for a recurrent interspecies CNV." Henkel et al. (2019) "confirmed the previously reported [by Fontanesi et al., 2009] triplication and revealed the exact boundaries of the triplication [for the A^Wt allele]. It spans 154,677 bp of the reference genome sequence and comprises the entire coding sequence of the ASIP, AHCY and ITCH genes. The individual copies are arranged in tandem in a head to tail orientation." These same authors also identified the molecular basis of three other alleles, summarising their results for the four alleles as: "Analysis of . . . selective sweeps revealed four different CNVs associated with the white or tan (A^Wt), Swiss markings (A^sm), badgerface (A^b), and the newly proposed peacock allele (A^pc). RNA-seq analyses on skin samples from goats with the different CNV alleles suggest that the identified structural variants lead to an altered expression of ASIP between eumelanistic and pheomelanistic body areas." Henkel et al. (2021): "4 different color varieties of Valais goats were known. Besides Blackneck animals … the brown and white Copperneck goat, the white Capra Sempione, and the greyish Grüenochte comprised the historic Valais goats. The brown pigmentation of Copperneck goats had previously been traced back to an introgression of a mutant TYRP1 allele from Toggenburg goats [OMIA 001249-9925]. In the present study, we identified additional introgression events of distinct ASIP alleles causing the remaining 2 rare coat color patterns within the Valais Blackneck goat breed. We identified the introgression of the AWt allele from Appenzell or Saanen goats in white Capra Sempione goats. Similarly, introgression of the A^pc allele from Peacock goats resulted in the greyish Grüenochte phenotype."

Breeds: Appenzell (Goat) (VBO_0000724), Bezoar (Goat) (VBO_0000733), Chamois Coloured (Goat) (VBO_0000747), Girgentana, Italy (Goat) (VBO_0009647), Grisons Striped (Goat) (VBO_0000771), Peacock Goat (Goat) (VBO_0000818), Saanen (Goat) (VBO_0000827), St Gallen Booted Goat (Goat) (VBO_0000839), Toggenburg (Goat) (VBO_0000846), Valais Blackneck (Goat) (VBO_0000849), Valais Capra Sempione, Valais Copperneck, Valais Grüenochte.
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: