DISSECTION OF A QUANTITATIVE TRAIT LOCUS FOR GENETIC-HYPERTENSION ON RAT CHROMOSOME-10

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 (SHRSP(HD)) and the normotensive Wistar-Kyoto (WKY-0(HD)) rat. Here we report on the further characterization of BP/SP-1, using a congenic strain, WKY-1(HD). WKY-1(HD) animals carry a 6-cM chromosomal fragment genotypically identical with SHRSP(HD) on chromosome 10, 26 cM away from the ACE locus. Higher blood pressures in the WKY-1(HD) strain compared with the WKY-0(HD) strain, as well as absence of linkage of the chromosome 10 region to blood pressure in an F-2 (WKY-1(HD) X SHRSP(HD)) population suggested the existence of a quantitative trait locus, termed BP/SP-1a, that lies within the SHRSP-congenic region in WKY-1(HD). Linkage analysis in the F-2 (WKY-0(HD) X SHRSP(HD)) 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.