Coat colour, extension

Phene ID

2042

Name

Coat colour, extension

Phene Name

Black/red coat colour; Haplotype HBR; Haplotype HHR

OMIA ID

1199

Species ID

9913

Characterised

Yes

Characterised Year

1995

For information relating to Bos indicus cattle see: OMIA 001199-9915 : Coat colour, extension in Bos indicus

As summarised by Lawlor et al. (2014), "Dominant inheritance of black over red hair color was suggested by Barrington and Pearson (1906), and later proven through a designed experiment by Lloyd-Jones and Evvard (1916) at Iowa State University". As summarised by Hauser et al. (2002), "The order of dominance is ED > E + > e (Lawlor et al., 2014; Olson, 1999). Cattle that are e/e are red and ED /− are typically black, as ED is the dominant allele and eumelanin is permanently produced. Individuals with the genotypes E +/E + and E +/e can be of any colour as E + acts as a neutral allele and normal activity of the melanocortin‐1 receptor is assumed so that both types of pigment are produced simultaneously in different parts of the body ... (Klungland et al., 1995)".

By cloning and sequencing the most likely comparative candidate gene (based on similar phenotypes in mice), Klungland et al. (1995) obtained molecular evidence for three alleles at the MSHR locus in Norwegian and Icelandic cattle. The wild-type allele (E+) encodes the normal functional receptor for MSH. The E^D allele contains a missense mutation, changing the 99th amino acid from leucine to proline (p.Leu99Pro). The resultant MSHR molecule is constitutively expressed, i.e. it is expressed without the need for MSH binding. This results in continuously high levels of tyrosinase, and hence production of eumelanin (black coat colour). The e allele contains a single base deletion (a frameshift mutation; c.772delG; p.Tyr155X) which gives rise to a non-functional receptor, and hence to low levels of tyrosinase, resulting in production of phaeomelanin (red coat colour). Because one copy of the E^D allele is sufficient to produce functional MSHR molecules and hence to produce black coat colour, this allele is dominant, while the e allele is recessive. Thus black is dominant to red. As expected, the coat colour associated with wild-type (E+) allele varies, depending, among other things, on the level of MSH produced. 
Joerg et al. (1996) extended these results by showing that red coat colour in Friesians is due to the same deletion (c.772delG; p.Tyr155X) in the MSHR gene, which is now known as MC1R.
Olsen (1999) reported that the ancestral MC1R allele designated as E+ has been reported in various breeds of cattle. Rouzaud et al. (2000): "A new allele, named E1, was found in either homozygous (E1/E1) or heterozygous (E1/E) individuals in Aubrac and Gasconne breeds. This allele displayed a 4 amino acid duplication (12 nucleotides) located within the third cytoplasmic loop of the receptor, a region known to interact with G proteins."
Hauser et al. (2022) summarise that "in addition to the three bovine E alleles mentioned above, two further protein‐changing MC1R variants, denoted Ed1 and Ed2 , have been identified in cattle, but neither for the p.Arg223Trp nor for the p.Gly220_Arg223dup variant can a clear influence on the base colour be demonstrated so far (Graphodatskaya et al., 2002; Kriegesmann et al., 2001; Rouzaud et al., 2000)."
Matsumoto et al. (2020) reported a (missense) variant (c.871G>A; p.(A291T)) that may account for the red coat colour of the Kumamoto sub‐breed of Japanese Brown cattle. More investigation is required before this variant can be added to the OMIA list.
Hauser et al. (2022) “performed a genome-wide allelic association study with black, red and wild-coloured cattle of three Alpine cattle breeds (Eringer, Evolèner and Valdostana), revealing a single significant association signal close to the MC1R gene. [The authors] … searched for candidate causative variants by sequencing the entire coding sequence and identified two novel protein-changing variants. [The authors] … propose designating the mutant alleles at MC1R:c.424C>T as ev1 and at MC1R:c.263G>A as ev2 . Both affect conserved amino acid residues in functionally important transmembrane domains (p.Arg142Cys and p.Ser88Asn). Both alleles segregate predominantly in the Swiss Evolèner breed. They occur in other European cattle breeds ... as well. [The authors] … observed almost perfect association between the MC1R genotypes and the coat colour phenotype in a cohort of 513 black, red and wild-coloured cattle. Animals carrying two copies of MC1R loss-of-function alleles or that were compound heterozygous for e, ev1 , or ev2 have a red to dark red (chestnut-like red) coat colour.”