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

Sammanfattning

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.

Publicerad i

Nature Genetics
2008, volym: 40, nummer: 8, sidor: 1004-1009
Utgivare: NATURE PUBLISHING GROUP

SLU författare

• Golovko, Anna

  • Uppsala universitet

• Sundström, Elisabeth

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Lindgren, Gabriella

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Sandberg, Kaj

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Andersson, Leif

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    
  • Uppsala universitet

UKÄ forskningsämne

Husdjursvetenskap
Veterinärmedicin

Publikationens identifierare

• DOI: https://doi.org/10.1038/ng.185

Permanent länk till denna sida (URI)

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