A Stop-Gain Mutation within MLPH Is Responsible for the Lilac Dilution Observed in Jacob Sheep

Abstract

A coat color dilution, called lilac, was observed within the Jacob sheep breed. This dilution results in sheep appearing gray, where black would normally occur. Pedigree analysis suggested an autosomal recessive inheritance. Whole-genome sequencing of a dilute case, a known carrier, and sixteen non-dilute sheep was used to identify the molecular variant responsible for the coat color change. Through investigation of the genes MLPH, MYO5A, and RAB27A, we discovered a nonsynonymous mutation within MLPH, which appeared to match the reported autosomal recessive nature of the lilac dilution. This mutation (NC_019458.2:g.3451931C>A) results in a premature stop codon being introduced early in the protein (NP_001139743.1:p.Glu14*), likely losing its function. Validation testing of additional lilac Jacob sheep and known carriers, unrelated to the original case, showed a complete concordance between the mutation and the dilution. This stop-gain mutation is likely the causative mutation for dilution within Jacob sheep.

Runs of Homozygosity Detection and Selection Signature Analysis for Local Goat Breeds in Yunnan, China

“…Multiple strong selection signals on chromosome 2 in the breeds of LP, ML, and YL were annotated to the OCA2 gene ( Figure 4 B), known for its association with skin pigmentation [ 44 ]. On chromosome 3 of both ML and GS goats, we identified the MLPH gene ( Figure 4 C), which was characterized as a candidate gene for dilute coat color in some goat breeds [ 45 ]. Additionally, CDKAL1 (FQ) [ 46 ] and POMC (FQ) [ 47 ] were identified as related to weight variation ( Figure 4 D), LIM domain binding 1 ( LDB1 ) and fibroblast growth factor 2 ( FGF2 ) (NL) [ 48 , 49 ] were identified related to high-altitude adaptation ( Table 2 ).…”

Candidate pigmentation genes related to feather color variation in an indigenous chicken breed revealed by whole genome data

“…Deletions have also been found in leaden mice and cat ( Ishida et al, 2006 ). The variations in MLPH gene could cause transport defect melanosomes in melanocytes, resulting in the dilution of coat or plumage colors in cats ( Ishida et al, 2006 ), dogs ( Bauer et al, 2018 ; Drögemüller et al, 2007 ; Van Buren et al, 2020 ), cattle ( Li et al, 2016 ), sheep ( Posbergh et al, 2020 ), rabbits ( Demars et al, 2018 ; Jia et al, 2021 ), and minks ( Cirera et al, 2013 ), as well as Griscelli syndrome type-3 in humans ( Al-Mousa et al, 2016 ; Çağdaş et al, 2012 ; Gironi et al, 2019 ; Jo et al, 2020 ; Ménasché et al, 2005 ). McMurtrie et al reported that RAB17 is an attractive candidate for leaden mice, though failed to identify any RAB17 -coding region mutations, because it was expressed in polarized epithelial cells (E. B.…”

Analysis of MC1R, MITF, TYR, TYRP1, and MLPH Genes Polymorphism in Four Rabbit Breeds with Different Coat Colors

“…An SNP in exon 2 of the TYRP1 gene was found in several rabbit breeds, which led to the early termination of translation of the TYRP1 gene as a strong candidate for the rabbit brown coat color locus [ 14 ]. Variations in the MLPH gene cause melanin transport defects, resulting in dilution of coat colors in cats [ 51 ], dogs [ 52 ], cattle [ 53 ], chickens [ 54 ], sheep [ 55 ], and minks [ 56 ]. In this study, three SNPs (c.693C < G, c.851A < G, c.911G < A) were found in the TB and SW breeds.…”