Melanocortin 1 receptor variation in the domestic dog

Abstract

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 exclusive production of black/brown eumelanin. In the domestic dog, breeds with a wild-type E allele, e. g., the Doberman, can produce either pigment type, whereas breeds with the e allele, e.g., the Golden Retriever, produce exclusively yellow pigment. However, a black coat color in the Newfoundland and similar breeds is thought to be caused by an unusual allele of Agouti, which encodes the physiologic ligand for the Mc1r. Here we report that the predicted dog Mc1r is 317 residues in length and 96% identical to the fox Mc1r. Comparison of the Doberman, Newfoundland, Black Labrador, Yellow Labrador, Flat-coated Retriever, Irish Setter, and Golden Retriever revealed six sequence variants, of which two, S90G and R306ter, partially correlated with a black/brown coat and red/yellow coat, respectively. R306ter was found in the Yellow Labrador, Golden Retriever, and Irish Setter; the latter two had identical haplotypes but differed from the Yellow Labrador at three positions other than R306ter. In a larger survey of 194 dogs and 19 breeds, R306ter and a red/yellow coat were completely concordant except for the Red Chow. These results indicate that the e allele is caused by a common Mc1r loss-of-function mutation that either reoccurred or was subject to gene conversion during recent evolutionary history, and suggest that the allelic and locus relationships for dog coat color genes may be more analogous to those found in other mammals than previously thought.

Born blonde: a recessive loss‐of‐function mutation in the melanocortin 1 receptor is associated with cream coat coloration inAntarctic fur seals

“…This reduction could be attributed to regulatory elements acting on a unique MC1R haplotype as found in Labradors (Newton et al. 2000), a hypothesis that is consistent with our having found a unique MC1R haplotype in all cream‐colored pups.…”

“…1996; Newton et al. 2000), or a frameshift mutation as in yellow recessive mice (Robbins et al. 1993).…”

“…The cream coat of hypopigmented fur seals is most likely the result of a dilution of pheomelanin, as has been suggested for the hypopigmented Kermode bear and the Labrador breed of domestic dogs (Newton et al. 2000; Ritland et al. 2001).…”

“…It has previously been suggested that the dilution of pheomelanin in cream‐colored dogs might be due to a reduced expression of MC1R in melanocytes compared to dogs with a red coat (Newton et al. 2000). This reduction could be attributed to regulatory elements acting on a unique MC1R haplotype as found in Labradors (Newton et al.…”

“…However, leucism is caused by defects in pigment cell differentiation, whereas the form of hypopigmentation observed in fur seals is characterized by a reduced amount of melanin production which leads to a cream (pheomelanic) phenotype, as also observed in yellow Labradors (Newton et al. 2000). Hypopigmented fur seals have mainly been observed at South Georgia, where around 97% of the extant population currently breeds, as well as in the nearby South Shetland Islands (Bonner 1968; Acevedo et al.…”