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

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 proceedings

  • Nat Genet

altmetric score

  • 13.596

author list (cited authors)

  • Rosengren Pielberg, G., Golovko, A., Sundstrm, E., Curik, I., Lennartsson, J., Seltenhammer, M. H., ... Andersson, L.

citation count

  • 231

complete list of authors

  • Rosengren Pielberg, Gerli||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||Andersson, Leif

publication date

  • August 2008