Distribution and functional impact of DNA copy number variation in the rat. Nat Genet 2008 May;40(5):538-45
Date
04/30/2008Pubmed ID
18443591DOI
10.1038/ng.141Scopus ID
2-s2.0-42649117472 (requires institutional sign-in at Scopus site) 171 CitationsAbstract
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.
Author List
Guryev V, Saar K, Adamovic T, Verheul M, van Heesch SA, Cook S, Pravenec M, Aitman T, Jacob H, Shull JD, Hubner N, Cuppen EMESH terms used to index this publication - Major topics in bold
AnimalsChromosomes
Computational Biology
DNA
Disease Models, Animal
Gene Expression
Genetic Diseases, Inborn
Genome
Humans
Nucleic Acid Hybridization
Quantitative Trait Loci
Rats
Rats, Inbred Strains
