New study identifies distinct gray alleles contributing to the difference in the rate of depigmentation and melanoma risk in horses
A newly published study led by Dr. Leif Andersson and colleagues at Uppsala University in collaboration with researchers at the UC Davis Veterinary Genetics Laboratory (VGL) discovered the existence of two different Gray alleles, one of which is associated with fast graying and increased risk for melanoma.
Graying in horses is a dominant trait where a horse that is fully pigmented at birth undergoes progressive graying, loss of pigment, with age. The initial cause of graying in horses was reported as a 4.6 kb duplication in the Syntaxin 17 (STX17) gene. This duplication had also been linked to an increased incidence of melanoma. However, this recent study showed that the speed of graying and melanoma risk are influenced by the number of copies of this 4.6 kb sequence, indicating the existence of two different alleles responsible for graying in horses: G2, which consists of a duplication that leads to slow graying, and G3, which is a triplication that results in fast graying and increased risk for melanoma.
The study showed that horses with no duplications (G1/G1) did not gray and had the lowest incidence of melanoma. Horses with one copy of G3 (G1/G3) showed fast graying and increased incidence of melanoma, whereas the fastest graying and highest incidence of melanoma was seen in horses that were homozygous for G3 (G3/G3). Horses with the G2 allele, whether heterozygous (G1/G2) or homozygous (G2/G2) showed low incidence of melanoma, similar to horses with no duplications (G1/G1).
Some horses, the ones that will eventually become white, begin to grow gray eyelashes and hairs at the base of the tail within the first week after birth," Dr. Andersson said. "A horse that is 'slow graying' will typically not show signs of gray until it is 5 to 7 years old. Horses that are 'fast graying' are more likely to develop melanomas, whereas we don't see an elevated risk in horses that are 'slow graying'."
Using data generated at the VGL, researchers also investigated the breed distribution of the two gray alleles and found that the G3 allele is much more prevalent across horse breeds. This may be the result of strong selection for the all-white phenotype that is distinct from other causes of white spotting patterns in horses. The slow graying G2 allele was specifically identified in 8 different breeds: Andalusian, Connemara Pony, Miniature Horse, Mangalarga Marchador, Mustang, Quarter Horse, Tennessee Walking Horse, and Welsh Pony.
This is an exciting finding”, notes Dr. Rebecca Bellone, director of the VGL and collaborator of the study, “as we now understand why some horses gray faster than others and now, in those breeds with the G2 allele, breeders have the ability to select for a slow greying phenotype with a lower risk of melanoma.”
Given this finding, the VGL has updated the Gray test to report copy number and both the G2 and G3 alleles. The VGL will continue to report the non-gray allele as N (this is the G1 in the publication) but will follow allele nomenclature for G2 and G3 when it is resolvable by testing.
For more on copy number and the meaning of these updated results please visit https://vgl.ucdavis.edu/test/gray