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

TY - JOUR

T1 - Distribution and functional impact of DNA copy number variation in the rat.

AU - Guryev, V.

AU - Saar, K.

AU - Adamovic, T.

AU - Verheul, M.

AU - van Heesch, S.

AU - Cook, S.

AU - Pravenec, M.

AU - Aitman, T.

AU - Jacob, H.

AU - Shull, J.D.

AU - Hubner, N.

AU - Cuppen, E.

N1 - Reporting year: 2008

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1038/ng.141

DO - 10.1038/ng.141

M3 - Article

SN - 1061-4036

VL - 40

SP - 538

EP - 545

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -