Melanocortin 1 receptor variation in the domestic dog

The melanocortin 1 receptor(Mc1r) is encoded by the Extension locus in many different mammals, where a loss-of function causes exclusive production of red/yellow pheomelanin, and a constitutively activating mutation causes ex clusive production of black/brown eumelanin. In the domestic dog, breeds wi th a wild-type E allele, e.g., the Doberman, can produce either pigment typ e, whereas breeds with the e allele, e.g., the Golden Retriever, produce ex clusively yellow pigment. However, a black coat color in the Newfoundland a nd similar breeds is thought to be caused by an unusual allele of Agouti, w hich encodes the physiologic ligand for the Mc1r. Here we report that the p redicted dog Mc1r is 317 residues in length and 96% identical to the fox Mc 1r. Comparison of the Doberman, Newfoundland, Black Labrador, Yellow Labrad or, Flat-coated Retriever, Irish Setter, and Golden Retriever revealed six sequence variants, of which two, S90G and R306ter, partially correlated wit h a black/brown coal and red/yellow coat, respectively. R306ter was found i n the Yellow Labrador, Golden Retriever, and Irish Setter; the latter two h ad identical haplotypes but differed from the Yellow Labrador at three posi tions other than R306ter. In a larger survey of 194 dogs and 19 breeds, R30 6ter and a red/yellow coat were completely concordant except for the Red Ch ow. These results indicate that the e allele is caused by a common Mc1r los s-of-function mutation that either reoccurred or was subject to gene conver sion during recent evolutionary history, and suggest that the allelic and l ocus relationships for dog coat color genes may be more analogous to those found in other mammals than previously thought.