Letter abstract
Nature Genetics 40, 1004 - 1009 (2008)
Published online: 20 July 2008 | doi:10.1038/ng.185
A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse
Gerli Rosengren Pielberg1, Anna Golovko1,12, Elisabeth Sundström2,12, Ino Curik3, Johan Lennartsson4, Monika H Seltenhammer5, Thomas Druml6, Matthew Binns7, Carolyn Fitzsimmons1, Gabriella Lindgren2, Kaj Sandberg2, Roswitha Baumung6, Monika Vetterlein8, Sara Strömberg9, Manfred Grabherr10, Claire Wade10,11, Kerstin Lindblad-Toh1,10, Fredrik Pontén9, Carl-Henrik Heldin4, Johann Sölkner6 & Leif Andersson1,2
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.
- Department of Medical Biochemistry and Microbiology, Uppsala University, Box 597, SE-751 24 Uppsala, Sweden.
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-751 24 Uppsala, Sweden.
- Animal Science Department, Faculty of Agriculture, University of Zagreb, HR-10000 Zagreb, Croatia.
- Ludwig Institute of Cancer Research, Uppsala University, Box 595, SE-751 24 Uppsala, Sweden.
- Department of Clinical Surgery and Ophthalmology, University of Veterinary Medicine, A-1200 Vienna, Austria.
- Department of Sustainable Agricultural Systems, University of Natural Resources and Applied Life Sciences, Vienna, A-1180 Vienna, Austria.
- Royal Veterinary College, Royal College Street, London, NW1 0TU, UK.
- Centre for Anatomy and Cell Biology, Department of Cell Biology and Ultrastructure Research, Medical University of Vienna, A-1080 Vienna, Austria.
- Department of Genetics and Pathology, Rudbeck laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
- Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
- Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
- These authors contributed equally to this work.
Correspondence to: Leif Andersson1,2 e-mail: leif.andersson@imbim.uu.se
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinomaNature Genetics Letter (01 Jul 2008)
Identification of Pigment Cell Antigens Defined by Vitiligo AntibodiesJournal of Investigative Dermatology Original Article
Relation Between the Incidence and Level of Pigment Cell Antibodies and Disease Activity in VitiligoJournal of Investigative Dermatology Commentary
MELANOMA IN SINCLAIR SWINE: A NEW ANIMAL MODELJournal of Investigative Dermatology Original Article
See all 6 matches for Research
