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Nat Genet. 2008 Aug;40(8):1004-9. doi: 10.1038/ng.185. Epub 2008 Jul 20.

A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse.

Author information

1
Department of Medical Biochemistry and Microbiology, Uppsala University, Box 597, SE-751 24 Uppsala, Sweden.

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.

PMID:
18641652
DOI:
10.1038/ng.185
[Indexed for MEDLINE]

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