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Dissection of a quantitative trait locus for genetic hypertension on rat chromosome 10

Item Type:Article
Title:Dissection of a quantitative trait locus for genetic hypertension on rat chromosome 10
Creators Name:Kreutz, R. and Huebner, N. and James, M.R. and Bihoreau, M.T. and Gauguier, D. and Lathrop, G.M. and Ganten, D. and Lindpaintner, K.
Abstract:We have previously identified a locus on rat chromosome 10 as carrying a major hypertension gene, BP/SP-1. The 100:1 odds support interval for this gene extended over a 35-centimorgan (cM) region of the chromosome that included the angiotensin I-converting enzyme (ACE) locus as demonstrated in a cross between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKY-0HD) rat. Here we report on the further characterization of BP/SP-1, using a congenic strain, WKY-1HD. WKY-1HD animals carry a 6-cM chromosomal fragment genotypically identical with SHRSPHD on chromosome 10, 26 cM away from the ACE locus. Higher blood pressures in the WKY-1HD strain compared with the WKY-0HD strain, as well as absence of linkage of the chromosome 10 region to blood pressure in an F2 (WKY-1HD x SHRSPHD) population suggested the existence of a quantitative trait locus, termed BP/SP-1a, that lies within the SHRSP-congenic region in WKY-1HD. Linkage analysis in the F2 (WKY-0HD x SHRSPHD) cross revealed that BP/SP-1a is linked to basal blood pressure, whereas a second locus on chromosome 10, termed BP/SP-1b, that maps closer to the ACE locus cosegregates predominantly with blood pressure after exposure to excess dietary NaCl. Thus, we hypothesize that the previously reported effect of BP/SP-1 represents a composite phenotype that can be dissected into at least two specific components on the basis of linkage data and congenic experimentation. One of the loci identified, BP/SP-1a, represents the most precisely mapped locus affecting blood pressure that has so far been characterized by random-marker genome screening.
Keywords:Base Sequence, Chromosome Mapping, Genetic Crosses, Genetic Linkage, Genetic Markers, Genetic Selection, Genotype, Hypertension, Meiosis, Molecular Sequence Data, Phenotype, Animals, Rats
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:92
Number:19
Page Range:8778-8782
Date:12 September 1995
Official Publication:http://www.pnas.org/content/92/19/8778.abstract
PubMed:View item in PubMed

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