Dominant White Mutations – W5, W10, W13, W20, and W22

The KIT gene has crucial function for the development of many cell types, including blood and pigment cells (melanocytes). Mutations that affect normal functioning of the KIT protein often result in lack of melanocytes in the skin and hair follicles, which leads to white patterning in horses known as dominant white.

Dominant white patterns are variable, ranging from extensive face and leg markings with or without minimal sabino-like patterns, including roaning on the belly and/or belly spots, to an all-white horse. Eye color of dominant white horses is typically brown.

A number of different KIT mutations associated with white patterns have been identified in the horse. These include dominant white, Sabino-1, and Tobiano. To date, 34 of these mutations have been characterized as dominant white mutations and can range from alleles that have a minimal impact on coat patterning to those causing an all-white phenotype. Many of the dominant white mutations arose recently and are therefore restricted to specific lines within breeds. The exceptions include W13 and W20. W13 (c. 2807+5G>C) was originally identified in the Quarter Horses but has also been reported in several other breeds including the Australian Miniature Horse, the American Miniature Horse, and the Shetland Pony. W20 (c.2045G>A) has been reported in many breeds. 

W5 (c.2193delG) is found in descendants of the Thoroughbred stallion Puchilingui. W10 (c.1126_1129delGAAC) is found in descendants of the Quarter Horse stallion GQ Santana. W22 (Chr3:79548925-79550822del1898insTATAT) is found in descendants of the Thoroughbred stallion Airdrie Apache.

The majority of the dominant white mutations identified are thought to be detrimental to KIT protein function. When horses have one copy of these mutations they have a reduced number of melanocytes and thus have a white spotting pattern. However, when they have two copies of the mutation (homozygous), it is believed that reduction or absence of KIT signaling occurs, affecting more than just the pigment cells. For example, horses homozygous W5, W10, W13, and W22 are likely embryonic lethal. However, this remains to be confirmed. It is unknown if horses that are compound heterozygotes (two different mutations in the same gene, i.e. W5/W10, W5/W13, W5/22, W10/W13, W10/W22, or W13/W22) are viable, and testing through the VGL has yet to identify horses with these genotypes.

W13 (c. 2807+5G>C) was initially identified in a Quarter Horse X Paso Peruano cross-bred family that had two white horses, and pedigree data in that study determined that the W13 mutation likely arose on the Quarter Horse background. Later, W13 was found to be responsible for the white phenotype in a family of Australian Miniature Horses. A recent study led by VGL director, Dr. Rebecca Bellone, identified 14 all-white American Miniature Horse and one Shetland Pony whose all-white coats were explained by the W13 mutation. All horses were heterozygous for W13 (N/W13) and had pink skin. Genotyping a random sample of 80 American Miniature Horses revealed a W13 allele frequency of 0.0063 (1 N/W13 horse and 79 N/N horses). W13 was not identified in any of 59 randomly selected Shetland Ponies. No W13/W13 homozygous horses have been identified to date, suggesting this may be embryonic lethal.

W20 (c.2045G>A) is a much older mutation and is found in many breeds. This mutation is thought to have a more minor effect on protein function as well as a subtler effect on the amount of white expressed unless in combination with other dominant white alleles (and perhaps other white spotting genes). In combination with other white pattern alleles, W20 has been shown to increase the amount of white patterning, producing an all-white or nearly all-white phenotype. Unlike W5, W10 and W22, the homozygous condition W20/W20 is not lethal.

W22 (Chr3:79548925-79550822del1898insTATAT) occurs on the W20 background, that means that all horses with the W22 mutation also have the W20 mutation. Since the W22 mutation has a greater impact on protein function than W20, the reported allele is W22 even though, technically, both the W20 and W22 variants are present. In the case where a horse inherits a W20 from one parent and a W20 and W22 from the other parent (technically meaning it has two copies of W20 and one copy of W22), it will be reported as a compound heterozygote, W20/W22. Horses with this genotype have been shown to have an all-white phenotype. 

The Veterinary Genetics Laboratory offers tests for W5, W10, W13, W20, and W22 mutations to owners who want to breed horses for dominant white or to determine the genetic status of horses with white patterning.