Identification of Loci Interacting with Melanocortin-1 Receptor to Modify Black Coat Color in an F2 Nellore-Angus Population

In cattle, base color is attributed to activity at the melanocortin-1 receptor (MC1R), historically termed the extension locus, with alleles coding for black (ED), red (e), and wild-type (E+). These alleles, in most mammals, are presumed to follow the dominance model ED > E+ > e, although exceptions are often seen. In Bos indicus x Bos taurus F2 cattle, EDE+ heterozygotes observed were discordant with the dominance series for the MC1R alleles and displayed various degrees of reddening on an otherwise predicted black background. The objective of this study was to identify loci modifying black coat color in these individuals. The hypothesis was that degree of reddening was a quantitative trait controlled by multiple genes of small effect. Reddening was classified utilizing photographs for 5 subjective scoring systems and analyzed by general linear model procedures of SAS with fixed effects of sex, sire, family nested within sire, season of photo, and spotted status. Residuals from these models were utilized for interval analyses to identify quantitative trait loci (QTL). Analyses of 19 bovine autosomal chromosomes, identified chromosome-wise suggestive (P < 0.05) and significant (P < 0.01) QTL on bovine chromosomes (BTA) 4, 5, 15, 18, 21, 27, and 29. Unexpectedly, there was evidence of a major gene (F = 67.88) affecting reddening at 71 Mb of BTA 6 (based on build Btau4.0 of the bovine genome sequence) that accounted for 61.1% of the variation in reddening. This QTL coincided closely with a cluster of tyrosine kinase receptor genes (PDGFRA, KIT and KDR). Fitting SNP haplotypes for a 1 Mb region containing all 3 genes and centered on KIT accounted for all the variation attributed to this QTL. These data suggested that one of these 3 genes, or a gene in high linkage disequilibrium with them, was responsible for the majority of variation in degree of reddening. Two recombinants within this region identified PDGFRA as the strongest candidate gene. Functional analyses will be required to verify the role of PDGFRA and its interaction with MC1R to modify black coat color of Bos indicus influenced cattle.