Document Detail


Whole genome survey of copy number variation in the spontaneously hypertensive rat: relationship to quantitative trait loci, gene expression, and blood pressure.
MedLine Citation:
PMID:  20231529     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Copy number variation has emerged recently as an important genetic mechanism leading to phenotypic heterogeneity. The aim of our study was to determine whether copy number variants (CNVs) exist between the spontaneously hypertensive rat (SHR) and its control strain, the Wistar-Kyoto rat, whether these map to quantitative trait loci in the rat and whether CNVs associate with gene expression or blood pressure differences between the 2 strains. We performed a comparative genomic hybridization assay between SHR and Wistar-Kyoto strains using a whole-genome array. In total, 16 CNVs were identified and validated (6 because of a relative loss of copy number in the SHR and 10 because of a relative gain). CNVs were present on rat autosomes 1, 3, 4, 6, 7, 10, 14, and 17 and varied in size from 10.0 kb to 1.6 Mb. Most of these CNVs mapped to chromosomal regions within previously identified quantitative trait loci, including those for blood pressure in the SHR. Transcriptomic experiments confirmed differences in the renal expression of several genes (including Ms4a6a, Ndrg3, Egln1, Cd36, Sema3a, Ugt2b, and Idi21) located in some of the CNVs between SHR and Wistar-Kyoto rats. In F(2) animals derived from an SHRxWistar-Kyoto cross, we also found a significant increase in blood pressure associated with an increase in copy number in the Egln1 gene. Our findings suggest that CNVs may play a role in the susceptibility to hypertension and related traits in the SHR.
Authors:
Fadi J Charchar; Michael Kaiser; Andrew J Bingham; Nina Fotinatos; Fahima Ahmady; Maciej Tomaszewski; Nilesh J Samani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-15
Journal Detail:
Title:  Hypertension     Volume:  55     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-15     Completed Date:  2010-05-28     Revised Date:  2010-05-31    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1231-8     Citation Subset:  IM    
Affiliation:
School of Science and Engineering, University of Ballarat, University Dr, Mt Helen, Ballarat, Australia 3350. f.charchar@ballarat.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / genetics*,  physiology
Chromosome Mapping / methods
DNA / genetics,  isolation & purification
Gene Expression*
Genetic Variation*
Genome-Wide Association Study / methods*
Kidney / physiopathology
Liver / physiopathology
Oligonucleotide Array Sequence Analysis / methods
Polymerase Chain Reaction / methods
Proteins / genetics
Quantitative Trait Loci / genetics*
Rats / genetics
Rats, Inbred SHR / genetics*
Grant Support
ID/Acronym/Agency:
//British Heart Foundation; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Proteins; 0/eglin proteinase inhibitors; 9007-49-2/DNA
Comments/Corrections
Erratum In:
Hypertension. 2010 Jun;55(6):e28

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


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