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

被引：238

作者：

Pielberg, Gerli Rosengren ^{[1
]}

Golovko, Anna ^{[1
]}

Sundstrom, Elisabeth ^{[2
]}

Curik, Ino ^{[3
]}

Lennartsson, Johan ^{[4
]}

Seltenhammer, Monika H. ^{[5
]}

Druml, Thomas ^{[6
]}

Binns, Matthew ^{[7
]}

Fitzsimmons, Carolyn ^{[1
]}

Lindgren, Gabriella ^{[2
]}

Sandberg, Kaj ^{[2
]}

Baumung, Roswitha ^{[6
]}

Vetterlein, Monika ^{[8
]}

Stromberg, Sara ^{[9
]}

Grabherr, Manfred ^{[10
]}

Wade, Claire ^{[10
,11
]}

Lindblad-Toh, Kerstin ^{[1
,10
]}

Ponten, Fredrik ^{[9
]}

Heldin, Carl-Henrik ^{[4
]}

Soelkner, Johann ^{[6
]}

Andersson, Leif ^{[1
,2
]}

机构：

[1] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75124 Uppsala, Sweden

[2] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75124 Uppsala, Sweden

[3] Univ Zagreb, Dept Anim Sci, Fac Agr, HR-10000 Zagreb, Croatia

[4] Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden

[5] Univ Vet Med, Dept Clin Surg & Ophthalmol, A-1200 Vienna, Austria

[6] Univ Nat Resources & Appl Life Sci, Dept Sustainable Agr Syst, A-1180 Vienna, Austria

[7] Univ London Royal Vet Coll, London NW1 0TU, England

[8] Med Univ Vienna, Dept Cell Biol & Ultrastruct Res, Ctr Anat & Cell Biol, A-1080 Vienna, Austria

[9] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden

[10] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[11] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 08期

关键词：

D O I：

10.1038/ng.185

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1004 / 1009

页数：6

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