Canine coat color E locus updates: Identification of a new MC1R variant causing 'sable' coat color in English Cocker Spaniels and a proposed update to the E locus dominance hierarchy

Abstract

The coat color phenotype 'sable' occurs in the English Cocker Spaniel dog breed. It closely resembles other canine color patterns known as domino/grizzle/pied (e^A allele) and grizzle/domino (e^G allele) determined by variants in the melanocortin 1 receptor gene (MC1R; 'extension' or E locus), a key multi-allele regulator of coat color. We examined genetic variation in MC1R, and found one new non-synonymous variant, c.250G>A (p.(Asp84Asn)), consistently associated with the English Cocker Spaniel 'sable' phenotype. We propose calling this newly identified allele e^H and further show that the e^A , e^H and e^G (previously known as E^G ) alleles associate with similar phenotypes in dogs impacting genotypes regulated by beta-defensin 103 gene (CBD103; K locus) and agouti signaling protein gene (ASIP; A locus) in the absence of the E^M and E alleles. This suggests that all three alleles are putative reduced-function variants of the MC1R gene. We propose the revised and updated E locus dominance hierarchy to be E^M > E > e^A /e^H /e^G > e^1-3 .

Keywords: MC1R; canine; coat color; dog; eumelanin; grizzle; pheomelanin; reduced-function variant; sable.