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

Journal article

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.

Authors: Kreutz, R; Hübner, N; James, MR; Bihoreau, M; Gauguier, D

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 92
• Issue: 19
• Pages: 8778-8782
• Publication date: 1995-09-01
• DOI: 10.1073/pnas.92.19.8778
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Chromosome Mapping; Female; Rats, Inbred WKY; Selection, Genetic; Rats, Inbred SHR; Base Sequence; Male; Genetic Markers; Animals; Rats; Molecular Sequence Data; Genetic Linkage; Crosses, Genetic; Hypertension; Meiosis; Genotype; Phenotype