Distribution and functional impact of DNA copy number variation in the rat

被引：165

作者：

Guryev, Victor ^{[1
]}

Saar, Kathrin ^{[2
]}

Adamovic, Tatjana ^{[3
]}

Verheul, Mark ^{[1
]}

Van Heesch, Sebastiaan A. A. C. ^{[1
]}

Cook, Stuart ^{[4
,5
]}

Pravenec, Michal ^{[6
,7
]}

Aitman, Timothy ^{[4
]}

Jacob, Howard ^{[3
]}

Shull, James D. ^{[8
]}

Hubner, Norbert ^{[2
]}

Cuppen, Edwin ^{[1
]}

机构：

[1] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[2] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

[3] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA

[4] Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, MRC, London W12 0NN, England

[5] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England

[6] Acad Sci Czech Republ, Inst Physiol, CR-14220 Prague, Czech Republic

[7] Charles Univ Prague, Inst Biol & Med Genet, Fac Med 1, Prague 12800 2, Czech Republic

[8] Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 05期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ng.141

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The abundance and dynamics of copy number variants ( CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.

引用

页码：538 / 545

页数：8

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