Coat colour, white spotting, KIT-related

Phene ID

4227

Name

Coat colour, white spotting, KIT-related

Phene Name

Hereford pattern or white headed, as well as spotting

OMIA ID

1737

Species ID

9913

Characterised

Yes

Characterised Year

2020

Fontanesi  et al. (2010): "[V]ariation in the white spotting in several cattle breeds is largely influenced by the multiple allelic series at the S locus, which includes at least four alleles (Olson 1999): SH (Hereford pattern), SP (Pinzgauer pattern or lineback), S+ (non-spotted) and s (spotting pattern). The SH allele gives white face, belly, feet and tail, often with a white stripe over the shoulder when homozygous. The SP allele gives pigmented body sides with variable amounts of white appearing along the dorsal and ventral areas extending forward from the tail and rump. The S+ allele gives the non-spotted (solid) phenotype, and is considered to be the wild-type allele, having as example the Angus breed. The spotting pattern allele (s) gives irregular areas of pigmented and white with feet, belly and tail usually white. This spotting pattern is characteristic of the Holstein, among other spotted breeds. Alleles SH and SP appear to be codominant to each other and incompletely dominant over S+. All these three alleles appeared to be completely dominant over the s allele (Olson 1981, 1999).
For SP/Pinzgauer pattern or lineback see: OMIA:001576-9913 : Coat colour, colour-sided in Bos taurus (taurine cattle).

The white-headed phenotype is inherited in a dominant mode of inheritance.

Häfliger et al. (2020): " A Brown Swiss cow showing a piebald pattern resembling colour-sidedness was referred for genetic evaluation. Both parents were normal solid-brown-coloured cattle. The cow was tested negative for the three known DNA variants in KIT, MITF and TWIST2 associated with different depigmentation phenotypes in Brown Swiss cattle. Whole-genome sequencing of the cow was performed and a heterozygous variant affecting the coding sequence of the bovine KIT gene was identified on chromosome 6. The variant is a 40 bp deletion in exon 9, NM_001166484.1:c.1390_1429del, and leads to a frameshift that is predicted to produce a novel 50 amino acid-long C-terminus replacing almost 50% of the wt KIT protein, including the functionally important intracellular tyrosine kinase domain (NP_001159956.1:p.(Asn464AlafsTer50))."
Milia et al. (2024) conducted a pangenome analysis: "Alleles of a segmental duplication upstream of KIT are associated with the characteristic white heads of Simmental and Hereford cattle. ... [T]hree Simmental assemblies contain three copies of a 14.3 kb sequence, which form the bubble. The ARS-UCD1.2 reference genome contains two copies of this segment but misses 1.8 kb and 800 bp of sequence from each copy respectively relative to the full 14.3 kb sequence observed in the Simmental assemblies. The assemblies of the color-headed cattle appear to have only part (~5.5 kb) of one copy of the 14.3 kb sequence, corresponding to a deletion of 20.6 kb relative to the ARS-UCD1.2 reference genome." 
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, see OMIA:000214-9913 for details] and KIT [omia.variant:1849] genes. [The authors] confirm causality through “Holsteinized” mouse models edited for these alleles and show that these variants are likely responsible for spotting traits in other bovine breeds." Animals with ancestrial / solid colour phenotype have an insertion of either 6948-bp (long) or ~6000-bp (intermediate) approximately 114-kbp upstream of KIT exon 1 (NM_001166484.1) compared to the Hereford ARS-UCD1.2 reference genome. "[S]potted breeds appeared to be fixed, or near fixed, for the deletion allele (frequencies ranging from 0.97 to 1). The reverse was true in the most nonspotted breeds, although the deletion did segregate in Jerseys, Red Angus, Gelbvieh, and Bos indicus cattle (frequencies ranging from 0.03 to 0.33 ... ). The intermediate-length allele was observed only in characteristically nonspotted breeds (Limousin, Jersey, Red Angus, Angus, and Gelbvieh) and was the minor allele in all cases (frequencies ranging from 0.08 to 0.25)."