In other species: dog , domestic cat , ass (donkey) , Arabian camel , goat , water buffalo

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 172800 (trait) , 164920 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: no

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Variable degree of white spotting ranging from tiny white spots up to completely white animals. The absence of pigment is caused by the absence of skin melanocytes ("leucism, leucistic"), not by failure in the biochemical reactions required for pigment synthesis.

Species-specific name: Hereford pattern or white headed, as well as spotting

Species-specific symbol: SH, s

Species-specific description: 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).

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

Mapping: Milia et al. (2024): "The 1000 Bull Genomes Project generated a substantial amount of short-read sequencing data for three breeds (Simmental, Hereford, and Braunvieh) included in our pangenome. Two of these breeds exhibit white heads, while one has a colored head. Signature of selection analyses using these short-read sequencing-derived variants revealed a strong selective sweep near KIT in both white-headed breeds .... . This finding corroborates previous mapping attempts and suggests a shared genetic origin of the white-headed phenotype (Fontanesi et al., 2010; Qanbari et al., 2014; Whitacre, 2014)."

Molecular basis: 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." 

Breeds: Brown Swiss (Cattle) (VBO_0000166), Hereford (Cattle) (VBO_0000232), Simmental (Cattle) (VBO_0000380).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: