A Third MLPH Variant Causing Coat Color Dilution in Dogs.

Samantha L. Van Buren,Jennifer C. Grahn,Alexandra Kehl,James R. Mickelson,Petra Kuehnlein,Jennifer R. Colangelo,Katie M. Minor,Julia Malvick,Robert A. Grahn,Elisabeth Mueller

doi:10.3390/genes11060639

Samantha L. Van Buren, Jennifer C. Grahn + Show 8 more

Open Access

https://doi.org/10.3390/genes11060639

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Abstract

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, the MLPH gene corresponds to the D locus and two variants, c.−22G > A (d1) and c.705G > C (d2), 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 third MLPH variant, (c.667_668insC) (d3), which leads to a frameshift and premature stop codon (p.His223Profs*41). The d3 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 d3 allele contributed to the grey (dilute) phenotype were d1/d3 compound heterozygotes or d3 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.

Highlights

Natural and artificial selection in dogs has led to a myriad of phenotypes with respect to coat coloration and its patterns
Not all dogs that are phenotypically dilute are explained by the two published MLPH dilution variants
The d3 variant was identified at the UC Davis Veterinary Genetics Laboratory, in exon 7 of a phenotypically dilute Italian greyhound, with one copy of d1 and no copies of d2

Summary

Introduction

Natural and artificial selection in dogs has led to a myriad of phenotypes with respect to coat coloration and its patterns. Phaeomelanin (red/yellow) and eumelanin (black/brown), in which physical changes to the pigments themselves, as well as the timing and location of their deposition, contribute to a variety of color phenotypes. One such phenotype, dilution, is found in multiple mammalian and avian species. Melanosome transport, along cortical actin filaments in melanocytes, is regulated by three major proteins: Rab27A (a member of the small GTPase Rab family), the motor protein myosin Va (MYO5A), and melanophilin (MLPH) [1] These three proteins form a functional ternary complex, in which an

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