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

Victor Guryev, Kathrin Saar, Tatjana Adamovic, Mark Verheul, Sebastiaan A A C van Heesch, Stuart Cook, Michal Pravenec, Timothy Aitman, Howard Jacob, James D Shull, Norbert Hubner, Edwin Cuppen

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162 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)538-45
Number of pages8
JournalNature Genetics
Issue number5
Publication statusPublished - May-2008
Externally publishedYes


  • Animals
  • Chromosomes
  • Computational Biology
  • DNA
  • Disease Models, Animal
  • Gene Expression
  • Genetic Diseases, Inborn
  • Genome
  • Humans
  • Nucleic Acid Hybridization
  • Quantitative Trait Loci
  • Rats
  • Rats, Inbred Strains

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