@article{95be5127fa2445dcaf0d1c98e0e94ea6,
title = "Distribution and functional impact of DNA copy number variation in the rat",
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.",
keywords = "Animals, Chromosomes/genetics, Computational Biology, DNA/genetics, Disease Models, Animal, Gene Expression, Genetic Diseases, Inborn/genetics, Genome, Humans, Nucleic Acid Hybridization, Quantitative Trait Loci, Rats/genetics, Rats, Inbred Strains",
author = "Victor Guryev and Kathrin Saar and Tatjana Adamovic and Mark Verheul and {van Heesch}, {Sebastiaan A A C} and Stuart Cook and Michal Pravenec and Timothy Aitman and Howard Jacob and Shull, {James D} and Norbert Hubner and Edwin Cuppen",
note = "Funding Information: We thank S. Kurz for technical assistance. This work was supported by the award {\textquoteleft}{\textquoteleft}Exploiting natural and induced genetic variation in the laboratory rat{\textquoteright}{\textquoteright} to E.C. from the European Heads of Research Councils and European Science Foundation EURYI (European Young Investigator) Award scheme; the EURATools integrated project funded by the Sixth Framework Programme of the European Union; grants from the Ministry of Education of the Czech Republic and support from the Howard Hughes Medical Institute to M.P.; support from the British Heart Foundation and the UK Department of Health to S.C.; and US National Institutes of Health grant CA77876 to J.D.S.",
year = "2008",
month = may,
doi = "10.1038/ng.141",
language = "English",
volume = "40",
pages = "538--45",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",
}