A Third MLPH Variant Causing Coat Color Dilution in Dogs

Altered melanosome transport in melanocytes, resulting from variants in the melanophilin (MLPH) gene, are associated with inherited forms of coat color dilution in many species. In dogs, theMLPHgene corresponds to the D locus and two variants, c.-22G > A (d(1)) and c.705G > C (d(2)), leading to the dilution of coat color, as described. Here, we describe the independent investigations of dogs whose coat color dilution could not be explained by known variants, and who report a thirdMLPHvariant, (c.667_668insC) (d(3)), which leads to a frameshift and premature stop codon (p.His223Profs*41). The d(3)allele is found at low frequency in multiple dog breeds, as well as in wolves, wolf-dog hybrids, and indigenous dogs. Canids in which the d(3)allele contributed to the grey (dilute) phenotype were d(1)/d(3)compound heterozygotes or d(3)homozygotes, and all non-dilute related dogs had one or two D alleles, consistent with a recessive inheritance. Similar to other loci responsible for coat colors in dogs, this, alongside likely additional allelic heterogeneity at the D locus, or other loci, must be considered when performing and interpreting genetic testing.