5′UTR Variant in KIT Associated With White Spotting in Horses

• Published in: Journal of equine veterinary science 2023-08, Vol.127, p.104563, Article 104563
• Main Authors: McFadden, Aiden, Martin, Katie, Foster, Gabriel, Vierra, Micaela, Lundquist, Erica W., Everts, Robin E., Martin, Erik, Volz, Erin, McLoone, Kaitlyn, Brooks, Samantha A., Lafayette, Christa
• Format: Article
• Language: English
• Subjects: Depigmentation; Genetics; Horse; Mutation
• ISSN: 0737-0806
• DOI: 10.1016/j.jevs.2023.104563

•Mutations in untranslated regions can affect gene expression.•Mutations in KIT are associated with increased degimentation in many mammals.•A mutation in KIT's 5′ untranslated region is associated with depigmentation in horses. Mutations in KIT, a gene that influences melanoblast migration and pigmentation, often result in mammalian white spotting. As of February 2023, over 30 KIT variants associated with white spotting were documented in Equus caballus (horse). Here we report an association of increased white spotting on the skin and coat with a variant in the 5′UTR of KIT (rs1149701677: g.79,618,649A>C). Horses possessing at least one alternate allele demonstrate phenotypic characteristics similar to other KIT mutations: clear borders around unpigmented regions on the body, face, and limbs. Using a quantitative measure of depigmentation, we observed an average white score of 10.70 among individuals with rs1149701677, while the average score of the control, homozygous reference sample was 2.23 (P = 1.892e-11, n = 109, t-test). The rs1149701677 site has a cross-species conservation score of 3.4, one of the highest scores across the KIT 5′UTR, implying regulatory importance for this site. Ensembl also predicted a “moderately impactful” functional effect for the rs1149701677 variant. We propose that this single nucleotide variant likely alters the regulation of KIT, which in turn may disrupt melanoblast migration causing an increase in white spotting on the coat. Alternatively, the rs1149701677 variant may be in linkage with another nearby variant with an as-yet-undiscovered functional impact. We propose to term this new allele “Holiday White” or W35 based on conventional nomenclature.