A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse
2008 (English)In: Nature Genetics, ISSN 1061-4036, Vol. 40, no 8, 1004-1009 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 40, no 8, 1004-1009 p.
IdentifiersURN: urn:nbn:se:uu:diva-103700DOI: 10.1038/ng.185ISI: 000258026900018PubMedID: 18641652OAI: oai:DiVA.org:uu-103700DiVA: diva2:218641