As for most other mammals, coat color in cattle depends on the ratio of eumelanin (black/brown pigment) and pheomelanin (red/yellow pigment), though few of the genes and mutations that affect pigmentation of bovine skin have been characterized at the molecular level. Wild-type coloration in cattle, as observed in the Jersey and Brown Swiss breeds, is reddish-brown to brownish-black, with a tan muzzle ring, and darker pigment at the head, neck, and feet. Alleles for the Extension (E) and Agouti (A) loci have been identified in cattle, though the genes controlling blaze, brockling, color-side, and brindle pigmentation patterns remain uncharacterized. Mutations in some of the genes are thought to be associated with phenotypes other than coat color, including milk yield, sterility, and immunodeficiency (Seo et al., 2007).
Figure 1. Coat color categories for scoring Charolais X Holstein cattle (Gutiérrez-Gil et al., 2007).
Charolais, Dexter, Highland, Galloway, and Simmental cattle exhibit a lightening of the base color, defined by the Extension locus; in pale dun Dexter cattle, the lightening is controlled by the TYRP1 gene, whereas in Highland cattle the dilution is caused by our friend from previous posts, the SILV/PMEL17 gene. The background color of Charolais cattle is entirely due to pheomelanin (e/e), yet these animals have the most extreme dilution phenotype, and have a uniform white coat. Kühn and Weikard (2007) reported that dilution of eumelanin in an F2 Holstein x Charolais population was associated with a region on bovine chromosome 5 that includes the SILV gene, and Gutiérrez-Gil and colleagues (2007) also used an F2 Holstein x Charolais population, to identify gene(s) responsible for dilution of pheomelanin.
The authors used a reference second generation population of 273 F2 individuals, 77 Charolais reciprocal backcrosses (CB1), and 86 Holstein reciprocal backcrosses (HB1), to score coat color according to the five categories shown above, and inferred the Dc (dilution) locus genotype. These animals, and the original purebred Charolais sires and Holstein dams, were genotyped at the Extension locus (melanocortin receptor 1). All the Charolais sires were found to be e/e, and 90% of the Holstein dams were EE. Linkage analysis revealed an association for three combined dilution-related traits (Quantitative-Dilution, Quantitative-Black, Quantitative-Red) on chromosome 5; two copies of the Holstein allele and the animal was scored as Black or Dark-Red, two copies of the Charolais allele and the animal was scored as White, and heterozygotes were scored as Grey or Light-Red (and perhaps a few as White).
Figure 2. Top panel: Calves scored as Light-Red, Black, and Grey coat colors. Bottom panel: Two calves scored as White (completely diluted phenotypes), though one is discordant for the SILV c.64A>G genotype.
The SILV/PMEL17 gene was included in the confidence interval for the significant associations, and a mutation in the first exon, at position 64 (c.64A>G), is found exclusively in Charolais cattle. Therefore, the researchers genotyped this mutation in their reference population, and found that animals carrying two copies of the “Charolais” allele (A) exhibited complete dilution, while animals with one copy of the “A” allele showed partial dilution. They then included the putative Dc locus, based solely on phenotypic color score, in the linkage analysis, which placed Dc in the same interval as SILV. The few discordant individuals in this study were attributed either to phenotypic coat color mis-scoring, or to the influence of other minor loci on coat color. In the other mammals I’ve discussed, the SILV gene appeared to have an effect on eumelanin, but not pheomelanin, whereas in cattle, both pigments are affected by mutations in exon 1 (Charolais cattle in this paper, and a deletion in Highland cattle, Berryere et al. 2007). The authors conclude that the SILV c.64A>G mutation is the likely cause for the distinctive white coat of Charolais cattle.
Kühn, C. and Weikard, R. (2007). An investigation into the genetic background of coat colour dilution in a Charolais x German Holstein F2 resource population. Animal Genetics 38, 109-113.
Seo, K., Mohanty, T.R., Choi, T., and Hwang, I. (2007). Biology of epidermal and hair pigmentation in cattle: a mini-review. Vet. Dermatol. 18, 392-400.
GutiÃ©rrez-Gil, B., Wiener, P., Williams, J.L. (2007). Genetic effects on coat colour in cattle: dilution of eumelanin and phaeomelanin pigments in an F2-Backcross Charolais Ã— Holstein population. BMC Genetics, 8(1), 56. DOI: 10.1186/1471-2156-8-56