Two Novel Variants in MITF and PAX3 Associated With Splashed White Phenotypes in Horses

• Published in: Journal of equine veterinary science 2023-09, Vol.128, p.104875-104875, Article 104875
• 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; Mutation; Pura Raza Espanola Horses; Splash White 10; Splash White 9
• ISSN: 0737-0806
• DOI: 10.1016/j.jevs.2023.104875

•Splash White 9 and Splash White 10 found in Pura Raza Espanola horses.•Novel Mutations in PAX3 and MITF associated with depigmentation in horses.•Coat color mutations can influence equine health and sentimental value. Mutations causing depigmentation are relatively common in Equus caballus (horse). Over 40 alleles in multiple genes are associated with increased white spotting (as of February 2023). The splashed white phenotype, a coat spotting pattern described as appearing like the horse has been splashed with white paint, was previously associated with variants in the PAX3 and MITF genes. Both genes encode transcription factors known to control melanocyte migration and pigmentation. We report two novel mutations, a stop-gain mutation in PAX3 (XM_005610643.3:c.927C>T, ECA6:11,196,181, EquCab3.0) and a missense mutation in a binding domain of MITF (NM_001163874.1:c.993A>T, ECA16:21,559,940, EquCab3.0), each with a strong association with increased depigmentation in Pura Raza Española horses (P = 1.144E-11, N = 30, P = 4.441E-16, N = 39 respectively). Using a quantitative method to score depigmentation, the PAX3 and MITF mutations were found to have average white scores of 25.50 and 24.45, respectively, compared to the average white coat spotting score of 1.89 in the control set. The functional impact for each mutation was predicted to be moderate to extreme (I-TASSER, SMART, Variant Effect Predictor, SIFT). We propose to designate the MITF mutant allele as Splashed White 9 and the PAX3 mutant allele as Splashed White 10 per convention.