Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat

HJ Jacob, K Lindpaintner, SE Lincoln, K Kusumi… - Cell, 1991 - cell.com
HJ Jacob, K Lindpaintner, SE Lincoln, K Kusumi, RK Bunker, YP Mao, D Ganten, VJ Dzau…
Cell, 1991cell.com
The stroke-prone spontaneously hypertensive rat (SHRSP) is a well-characterized model for
primary hypertension in humans. High blood pressure in SHRSP shows polygenic
inheritance, but none of the loci responsible have previously been identified. To locate
genes controlling this quantitative trait, we mapped a large collection of DNA polymorphisms
in a cross between SHRSP and the normotensive WKY strain. Here we report strong genetic
evidence that a gene, Bpi, having a major effect on blood pressure maps to rat chromosome …
Summary
The stroke-prone spontaneously hypertensive rat (SHRSP) is a well-characterized model for primary hypertension in humans. High blood pressure in SHRSP shows polygenic inheritance, but none of the loci responsible have previously been identified. To locate genes controlling this quantitative trait, we mapped a large collection of DNA polymorphisms in a cross between SHRSP and the normotensive WKY strain. Here we report strong genetic evidence that a gene, Bpi, having a major effect on blood pressure maps to rat chromosome 10 with a LOD score of 5.10 and is closely linked to the rat gene encoding angiotensinconverting enzyme (ACE), an enzyme that plays a major role in blood pressure homeostasis and is an important target of anti-hypertensive drugs. We also find significant, albeit weaker, linkage to a locus, Bp2, on chromosome 18. We discuss the implications of genetic dissection of quantitative disease-related phenotypes in mammals.
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