A novel MLPH variant in dogs with coat colour dilution

Coat colour dilution may be the result of altered melanosome transport in melanocytes. Loss-of-function variants in the melanophilin gene (MLPH) cause a recessively inherited form of coat colour dilution in many mammalian and avian species including the dog. MLPH corresponds to the D locus in many domestic animals, and recessive alleles at this locus are frequently denoted with d. In this study, we investigated dilute coloured Chow Chows whose coat colour could not be explained by their genotype at the previously known MLPH:c.-22G>A variant. Whole genome sequencing of such a dilute Chow Chow revealed another variant in the MLPH gene: MLPH:c.705G>C. We propose to designate the corresponding mutant alleles at these two variants d(1) and d(2). We performed an association study in a cohort of 15 dilute and 28 non-dilute Chow Chows. The dilute dogs were all either compound heterozygous d(1)/d(2) or homozygous d(2)/d(2), whereas the non-dilute dogs carried at least one wildtype allele D. The d(2) allele did not occur in 417 dogs from diverse other breeds. However, when we genotyped a Sloughi family, in which a dilute coloured puppy had been born out of non-dilute parents, we again observed perfect co-segregation of the newly discovered d(2) allele with coat colour dilution. Finally, we identified a blue Thai Ridgeback with the d(1)/d(2) genotype. Thus, our data identify the MLPH:c.705G>C as a variant explaining a second canine dilution allele. Although relatively rare overall, this d(2) allele is segregating in at least three dog breeds, Chow Chows, Sloughis and Thai Ridgebacks.