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

Joward J. Jacob, Klaus Lindpaintner, Stephen E. Lincoln, Kenro Kusumi, Ruth K. Bunker, Yi Pei Mao, Detlev Ganten, Victor J. Dzau, Eric S. Lander

Research output: Contribution to journalArticle

634 Scopus citations

Abstract

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, Bp1, 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 angiotensin-converting 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.

Original languageEnglish (US)
Pages (from-to)213-224
Number of pages12
JournalCell
Volume67
Issue number1
DOIs
StatePublished - Oct 4 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Jacob, J. J., Lindpaintner, K., Lincoln, S. E., Kusumi, K., Bunker, R. K., Mao, Y. P., Ganten, D., Dzau, V. J., & Lander, E. S. (1991). Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell, 67(1), 213-224. https://doi.org/10.1016/0092-8674(91)90584-L