(Hypertension. 1996;28:898-906.)
© 1996 American Heart Association, Inc.
Articles |
Quantitative Trait Loci in Genetically Hypertensive Rats
Possible Sex Specificity
Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland (J.S.C., B.J., A.O.D., W.K.L., N.H.A., M.J.B., A.M.D., A.W.K., A.F.D.); the Wellcome Trust Centre for Human Genetics, Oxford, England (M.-T.B.); and the Department of Cardiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (K.L.).
Correspondence to Dr Anna F. Dominiczak, Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, Scotland. E-mail Anna.Dominiczak@clinmed.gla.ac.uk
We performed a total genome screen in an F2 cross derived from the stroke-prone spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat. Blood pressure at baseline and after 1% NaCl was measured by radiotelemetry; other phenotypes included heart rate, motor activity, left ventricle weight to body weight ratio, and vascular smooth muscle cell polyploidy, a measure of vascular hypertrophy. Quantitative trait loci affecting a given phenotype were mapped relative to microsatellite markers by using the MAPMAKER/QTL 1.1 computer package. We identified three blood pressure quantitative trait loci, two on rat chromosome 2 and one on rat chromosome 3. The quantitative trait loci close to genetic markers D2Mgh12 ("suggestive" linkage, with a maximal logarithm of the odds [LOD] score of 3.1) and D3Mgh16 (significant linkage, with a maximal LOD score of 5.6) showed possible sex specificity in the male F2 cohort only. This was confirmed by the likelihood ratio test for the difference in locus effects between the sexes. We also identified a new quantitative trait locus for LV hypertrophy on rat chromosome 14 ("suggestive" linkage, with a maximal LOD score of 3.1). The sex specificity of blood pressure quantitative trait loci will be important in designing congenic strains and substrains for fine genetic mapping and for identifying genes that regulate blood pressure.
Key Words: genes • inbred strains • spontaneously hypertensive rat
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