Article abstract
Nature Genetics 40, 538 - 545 (2008)
Published online: 28 April 2008 | doi:10.1038/ng.141
Distribution and functional impact of DNA copy number variation in the rat
Victor Guryev1, Kathrin Saar2, Tatjana Adamovic3, Mark Verheul1, Sebastiaan A A C van Heesch1, Stuart Cook4, Michal Pravenec5,6, Timothy Aitman4, Howard Jacob3, James D Shull7, Norbert Hubner2 & Edwin Cuppen1
Abstract
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.
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences & University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
- Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13092 Berlin, 13125, Germany.
- Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
- Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
- Institute of Physiology, Academy of Sciences of the Czech Republic, 1 Videnska 1083, Prague 14220, Czech Republic.
- Institute of Biology and Medical Genetics, First Medical Faculty, Charles University, Albertov 4, 12800 Prague 2, Czech Republic.
- Department of Genetics, Cell Biology and Anatomy, 985805 University of Nebraska Medical Center, Omaha, Nebraska, 68198-5805, USA.
Correspondence to: Edwin Cuppen1 e-mail: e.cuppen@niob.knaw.nl
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