White coat color has been a highly valued trait in horses for at least 2,000 years. Dominant white ( W) is one of several known depigmentation phenotypes in horses. It shows considerable phenotypic variation, ranging from ∼50% depigmented areas up to a completely white coat. In the horse, the four depigmentation phenotypes roan, sabino, tobiano, and dominant white were independently mapped to a chromosomal region on ECA 3 harboring the KIT gene. KIT plays an important role in melanoblast survival during embryonic development. We determined the sequence and genomic organization of the ∼82 kb equine KIT gene. A mutation analysis of all 21 KIT exons in white Franches-Montagnes Horses revealed a nonsense mutation in exon 15 (c.2151C>G, p.Y717X). We analyzed the KIT exons in horses characterized as dominant white from other populations and found three additional candidate causative mutations. Three almost completely white Arabians carried a different nonsense mutation in exon 4 (c.706A>T, p.K236X). Six Camarillo White Horses had a missense mutation in exon 12 (c.1805C>T, p.A602V), and five white Thoroughbreds had yet another missense mutation in exon 13 (c.1960G>A, p.G654R). Our results indicate that the dominant white color in Franches-Montagnes Horses is caused by a nonsense mutation in the KIT gene and that multiple independent mutations within this gene appear to be responsible for dominant white in several other modern horse populations.
White horses have always been highly valued by their human owners. Their important role in history is reflected by their widespread use as heraldic animals (e.g., on the flags of the German states of Lower Saxony and North Rhine-Westphalia). In the Swiss Franches-Montagnes Horse population, a completely white mare named Cigale was born out of solid brown parents in 1957. The white phenotype is inherited as an autosomal dominant trait and all living white Franches-Montagnes Horses are descendants of Cigale. We sequenced the KIT gene in white and solid-colored Franches-Montagnes Horses and found a mutation that inactivates the gene product and thus leads to a lack of pigment-forming cells in the skin of white horses. We then analyzed white horses from other populations and found three additional independent candidate causative mutations in white Thoroughbreds, Arabians, and Camarillo White Horses. The research thus revealed independent mutation events leading to white coat color in different horse populations. Our findings will allow genetic testing and a more precise classification of horses with white coat color.