A cis-acting regulatory mutation is causing premature hair greying and susceptibility to melanoma in the horse.
Pielberg, G.R., Golovko, A., Sundström, E., Curik, I., Lennartsson, J., Seltenhammer, M.H., Druml, M., Swanson, K.C., Binns, M., Fitzsimmons, C.J., Lindgren, G., Sandberg, K., Baumung, R., Vetterlein, M., Strömberg, S., Grabherr, M.G., Wade, C., Lindblad-Toh, K., Pontén, F., Heldin, C.-H., Sölkner, J., Andersson, L. (2008). "A cis-acting regulatory mutation is causing premature hair greying and susceptibility to melanoma in the horse.", Nature Genetics, 40(8), pp. 1004-1009. doi : 10.1038/ng.185
In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals.