Haplotype variability in the bovine MITF gene and association with piebaldism in Holstein and Simmental cattle breeds

Abstract

Candidate gene analysis, quantitative trait locus mapping in outbreed and experimental cross-populations and a genomewide association study in Holstein have reported that a few chromosome regions contribute to great variability in the degree of white/black spotting in cattle. In particular, an important region affecting this trait was localized on bovine chromosome 22 in the region containing the microphthalmia-associated transcription factor (MITF) gene. We sequenced a total of 7258 bp of the MITF gene in 40 cattle of different breeds, including 20 animals from spotted breeds (10 Italian Holstein and 10 Italian Simmental) and 20 animals from solid coloured breeds (10 Italian Brown and 10 Reggiana), and identified 17 single nucleotide polymorphisms (SNPs). The allele frequencies of one polymorphism (g.32386957A>T) were clearly different between spotted (A = 0.875; T = 0.125) and non-spotted breeds (A = 0.125; T = 0.875) (P = 8.2E-12). This result was confirmed by genotyping additional animals of these four breeds (P < 1.0E-20). A total of 21 different haplotypes were inferred from the sequenced animals. Considering similarities among haplotypes, spotted and non-spotted groups of cattle showed significant differences in their haplotype distribution (P = 0.001), which was further supported by the analysis of molecular variance (amova) of two genotyped SNPs in an enlarged sample of cattle. Variability in the MITF gene clearly explained the differences between spotted and non-spotted phenotypes but, at the same time, it is evident that this gene is not the only genetic factor determining piebaldism in Italian Holstein and Italian Simmental cattle breeds.

A complex structural variant at the KIT locus in cattle with the Pinzgauer spotting pattern

“…Besides other unknown genetic factors, different regulatory single nucleotide variants (SNVs) at the MITF gene contribute to the differences between spotted and non‐spotted phenotypes in cattle (Fontanesi et al . ; Jansen et al . ; Hofstetter et al .…”

Genotypes and allele frequencies of buried SNPs in a bovine single‐nucleotide polymorphism array in Japanese Black cattle

“…Oyama et al () recently reported that the incidence of altered black coat colors such as white spotting and white circular shaped coat in Japanese Black cattle was 0.29% to 3.68% respectively (Oyama et al, ). We found an SNP (MITF_2, g.31769189T>A) in the intron of MITF , which was associated with white spotting in Holstein and Simmental cattle (Fontanesi, Scotti, & Russo, ). The homozygotes were 752 individuals and the risk allele frequency was 0.36 (Table ), which is far higher than the incidence of white spotting phenotype in Japanese Black cattle (Oyama et al, ).…”

“…The homozygotes were 752 individuals and the risk allele frequency was 0.36 (Table ), which is far higher than the incidence of white spotting phenotype in Japanese Black cattle (Oyama et al, ). Previous reports showed that the allele might not be the only genetic factor determining piebaldism (Fontanesi et al, ; Ruvinsky, ); thus other determinants might be required to form the white spotting phenotype in Japanese Black cattle.…”

A non‐coding regulatory variant in the 5′‐region of the MITF gene is associated with white‐spotted coat in Brown Swiss cattle

“…Besides other unknown genetic factors, an intronic regulatory single nucleotide variant in bovine MITF contributes to the differences between spotted and non‐spotted phenotypes in Holstein and Simmental cattle (Fontanesi et al . ; Jansen et al . ; OMIA 000214‐9913).…”