Quantitative trait loci in genetically hypertensive rats - Possible sex specificity

被引:111
作者
Clark, JS
Jeffs, B
Davidson, AO
Lee, WK
Anderson, NH
Bihoreau, MT
Brosnan, MJ
Devlin, AM
Kelman, AW
Lindpaintner, K
Dominiczak, AF
机构
[1] UNIV GLASGOW,WESTERN INFIRM,DEPT MED & THERAPEUT,GARDINER INST,GLASGOW G11 6NT,LANARK,SCOTLAND
[2] WELLCOME TRUST CTR HUMAN GENET,OXFORD,ENGLAND
[3] HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT CARDIOL,BOSTON,MA 02115
基金
英国惠康基金;
关键词
genes; inbred strains; spontaneously hypertensive rat;
D O I
10.1161/01.HYP.28.5.898
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
We performed a total genome screen in an Fz 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 F-2 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.
引用
收藏
页码:898 / 906
页数:9
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