Document Detail


Distribution and functional impact of DNA copy number variation in the rat.
MedLine Citation:
PMID:  18443591     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  40     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-02     Completed Date:  2008-05-22     Revised Date:  2008-05-23    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  538-45     Citation Subset:  IM    
Affiliation:
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences & University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
CA77876/CA/NCI NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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