Genetic basis of d3 allele - is a variant of the MLPH gene (melanophilin gene) associated with dilute coat color in dogs. This variant is a single nucleotide insertion, specifically c.667_668insC, which leads to a frameshift and premature stop codon (p.His223Profs*41) causing a truncated melanophilin protein. The d3 allele is inherited in an autosomal recessive manner; affected dogs have two copies of the d3 allele or are compound heterozygotes with d1 or d2 alleles.
Breed Distribution - The d3 allele occurs mainly in breeds such as Chihuahua, Hungarian Pumi, Hungarian Mudi, Italian Greyhound, Pekingese, Shih Tzu, Tibetan Mastiff, Yorkshire Terrier, Shetland Sheepdog, and also found in wolves, wolf-dog hybrids, and indigenous dog populations. This allele appears to be somewhat ancient, persisting at a low frequency in these breeds and populations.
Pathophysiology - The MLPH protein is responsible for transporting melanosomes within melanocytes to the hair shaft, enabling even pigment distribution. The d3 variant leads to defective melanophilin, impairing melanosome transport and resulting in clumped pigment granules, which dilute eumelanin (black pigment) and phaeomelanin (brown/red pigment). This causes the characteristic diluted coat colors such as blue, lilac, cream, and related shades.
Why This Matters to Breeders and Vets - Knowledge of the d3 allele helps breeders predict coat color outcomes more accurately and avoid surprises in litters. It assists in managing breeding to preserve desired dilute coat colors or avoid dilution-related hereditary issues like color dilution alopecia in predisposed breeds. Veterinarians can use this information for diagnosis and advising on coat and skin health issues related to dilution.
