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

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.

Published in

Nature Genetics
2008, volume: 40, number: 8, pages: 1004-1009
Publisher: NATURE PUBLISHING GROUP

SLU Authors

• Golovko, Anna

  • Uppsala University

• Sundström, Elisabeth

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Lindgren, Gabriella

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Sandberg, Kaj

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Andersson, Leif

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Uppsala University

UKÄ Subject classification

Animal and Dairy Science
Veterinary Science

Publication identifier

• DOI: https://doi.org/10.1038/ng.185

Permanent link to this page (URI)

https://res.slu.se/id/publ/19755