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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 (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 third MLPH variant, (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.

Leopard complex spotting ( LP), the result of an incompletely dominant mutation in TRPM1, produces a collection of unique depigmentation patterns in the horse. Although the LP mutation allows for expression of the various patterns, other loci are responsible for modification of the extent of white. Pedigree analysis of families segregating for high levels of patterning indicated a single dominant gene, named Pattern-1 ( PATN1), as a major modifier of LP. Linkage analysis in two half-sibling families segregating for PATN1 identified a 15-Mb region on ECA3p that warranted further investigation. Whole transcriptome sequencing of skin samples from horses with and without the PATN1 allele was performed to identify genic SNPs for fine mapping. Two Sequenom assays were utilized to genotype 192 individuals from five LP-carrying breeds. The initial panel highlighted a 1.6-Mb region without a clear candidate gene. In the second round of fine mapping, SNP ECA3:23 658 447T>G in the 3′- UTR of RING finger and WD repeat domain 3 ( RFWD3) reached a significance level of P = 1.063 × 10−39. Sequencing of RFWD3 did not identify any coding polymorphisms specific to PATN1 horses. Genotyping of the RFWD3 3′- UTR SNP in 54 additional LP animals and 327 horses from nine breeds not segregating for LP further supported the association ( P = 4.17 × 10−115). This variant is a strong candidate for PATN1 and may be particularly useful for LP breeders to select for high levels of white patterning. [ABSTRACT FROM AUTHOR]