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- Title
A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse.
- Authors
Pielberg, Gerli Rosengren; Golovko, Anna; Sundström, Elisabeth; Curik, Ino; Lennartsson, Johan; Seltenhammer, Monika H.; Druml, Thomas; Binns, Matthew; Fitzsimmons, Carolyn; Lindgren, Gabriella; Sandberg, Kaj; Baumung, Roswitha; Vetterlein, Monika; Strömberg, Sara; Grabherr, Manfred; Wade, Claire; Lindblad-Toh, Kerstin; Pontén, Fredrik; Heldin, Carl-Henrik; Sölkner, Johann
- Abstract
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.
- Subjects
ANIMAL genetics research; MELANOMA; HORSE diseases; PIGMENTATION disorders; NEUROENDOCRINE tumors; PHENOTYPES; GENETICS; CANCER risk factors
- Publication
Nature Genetics, 2008, Vol 40, Issue 8, p1004
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.185