Complete genome searches for quantitative trait loci controlling blood pressure and related traits in four segregating populations derived from Dahl hypertensive rats |
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Authors: | Norihiro Kato Gina Hyne Marie-Therese Bihoreau Dominique Gauguier G Mark Lathrop John P Rapp |
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Institution: | (1) The Wellcome Trust Centre for Human Genetics, University of Oxford, Windmill Road, Oxford, OX3 7BN, UK, GB;(2) Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, Ohio 43699-0008, USA, US |
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Abstract: | The Dahl salt-sensitive rat is one of the principal animal models of hereditary hypertension. Genome-wide searches were undertaken
to detect quantitative trait loci (QTLs) that influence blood pressure, cardiac mass, and body weight in four F2 populations derived from Dahl salt-sensitive rats and different inbred normotensive control strains of rat. We detected three
QTLs associated with one or more of the phenotypes, using a stringent statistical criterion for linkage (p < 0.00003). These included a novel QTL linked to blood pressure on rat Chromosome (Chr) 12, and another QTL on rat Chr 3
linked to body weight. A QTL on rat Chr 10 for which linkage to blood pressure has been described in other crosses was found
to be a principal determinant of blood pressure and cardiac mass in some but not all of the crosses examined here. Three other
regions showed evidence of linkage to these phenotypes with a less stringent statistical criterion of linkage at QTLs previously
reported in other studies. As part of our study, microsatellite markers have been developed for three candidate genes for
investigation in hypertension, and the genes have been localized by linkage mapping. These are: the rat Gs alpha subunit (Gnas) gene, the alpha-1B adrenergic receptor (Adra1b), and the Na+, K+-ATPase beta2 subunit (Atp1b2) gene.
Received: 29 June 1998 / Accepted: 30 October 1998 |
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