| Whole genome survey of copy number variation in the spontaneously hypertensive rat: relationship to quantitative trait loci, gene expression, and blood pressure. | |
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MedLine Citation:
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PMID: 20231529 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Fadi J Charchar; Michael Kaiser; Andrew J Bingham; Nina Fotinatos; Fahima Ahmady; Maciej Tomaszewski; Nilesh J Samani |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-15 |
Journal Detail:
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Title: Hypertension Volume: 55 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-15 Completed Date: 2010-05-28 Revised Date: 2010-05-31 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1231-8 Citation Subset: IM |
Affiliation:
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School of Science and Engineering, University of Ballarat, University Dr, Mt Helen, Ballarat, Australia 3350. f.charchar@ballarat.edu.au |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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//British Heart Foundation; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Proteins; 0/eglin proteinase inhibitors; 9007-49-2/DNA |
| Comments/Corrections | |
Erratum In:
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Hypertension. 2010 Jun;55(6):e28 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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