Three Novel KIT Polymorphisms Found in Horses with White Coat Color Phenotypes

This paper reports three novel <i>KIT</i> variants likely responsible for previously unexplained white patterning phenotypes observed in three groups of horses. White spots and markings may have substantial consequences on the value and health of domesticated horses. This study aims to elucidate the genetic mechanisms underlying depigmented coat colors to aid in producing prosperous herds. Aligned whole genome sequences were manually screened to identify three polymorphisms in a family of Anglo-Arabian horses (<i>N</i> = 7), a family of Warmblood horses (<i>N</i> = 5), and a single stock-type mare with unexplained white markings. Sanger sequencing confirmed the presence of the variants, and in silico predictive programs were used to predict the functional impacts of each. We propose to term the novel variants <i>W37</i>, <i>W38</i>, and <i>W39</i>, respectively, per convention. The <i>W37</i> polymorphism was always observed in the presence of one <i>W35</i> allele, suggesting complete linkage. All three variants were predicted to alter or remove the <i>KIT</i> protein active domain, repressing typical protein folding and impacting pathways that upregulate pigmentation. The severe predicted impact on biological function suggests that these variants may cause increased white spotting, providing a possible explanation for the depigmentation phenotypes observed in affected individuals.