Fontanesi et al. (2012) reported a strong association between an intronic MITF variant and spotted vs non-spotted Italian Holstein and Italian Simmental cattle, explaining that "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." Hofstetter et al. (2019) "hypothesize[d] that rs722765315 [variant g.31908435G>A in MITF] represents the most likely causative variant for the white-spotting phenotype observed in Brown Swiss cattle. Presence of the mutant allele in a heterozygous or homozygous state supports a dominant mode of inheritance with incomplete penetrance and results in a variable extent of coat colour depigmentation." From "the largest GWAS of white spotting to date", conducted on New Zealand cattle (Jersey, Holstein-Friesian and their cross), Jivinji et a. (2019) "extend[ed] those [results] of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes."
Jivanji et al. (2025) investigated white-spotted coat colour in cattle. The authors "report two variants modulating these effects, comprising intronic and long-distance–acting regulatory variants of the MITF [omia.variant:1850] and KIT [omia.variant:1849; see OMIA:001737-9913 for details] genes. [The authors] confirm causality through “Holsteinized” mouse models edited for these alleles and show that these variants are likely responsible for spotting traits ... ." The authors report an epistatic effect between KIT variants for dominant white head (omia.variant:1763) and white spotting (omia.variant:1849) and a non coding MITF SNP (omia.variant:1850; Chr22 g.31651379A>G) resulting in 'splotchy face' in Hereford cross animals, black speckles within patches of white in Holstein Friesian and Jersey cattle, and mottled black 'socks' in Belgian Blue cattle.
