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.
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences & University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
authors.forename: Kathrin
authors.initials: K
authors.lastname: Saar
authors.forename: Tatjana
authors.initials: T
authors.lastname: Adamovic
authors.forename: Mark
authors.initials: M
authors.lastname: Verheul
authors.forename: Sebastiaan A A C
authors.initials: SA
authors.lastname: van Heesch
authors.forename: Stuart
authors.initials: S
authors.lastname: Cook
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
authors.forename: Timothy
authors.initials: T
authors.lastname: Aitman
authors.forename: Howard
authors.initials: H
authors.lastname: Jacob
authors.forename: James D
authors.initials: JD
authors.lastname: Shull
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
mesh_terms: D000818:Animals; D002875:Chromosomes / Q000235:genetics; D019295:Computational Biology; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D016678:Genome; D006801:Humans; D009693:Nucleic Acid Hybridization; D040641:Quantitative Trait Loci; D051381:Rats / Q000235:genetics*; D011919:Rats, Inbred Strains
chemical_list: D004247:DNA