Comprehensive Congenic Coverage Revealing Multiple Blood Pressure Quantitative Trait Loci on Dahl Rat Chromosome 10

Chromosome mapping based on congenic strains can restrict quantitative trait loci (QTLs) for blood pressure (BP) into small intervals that are otherwise indistinguishable in linkage analysis. Also, congenic strains can be created to test a candidate gene to be a BP QTL. Taking full advantage of these features, we produced 10 congenic strains by replacing various segments of chromosome (Chr) 10 of the Dahl salt-sensitive (DSS) rat with those of the Lewis (LEW) rat. These strains were made to systematically cover an entire section of Chr 10. Three of the strains were designed to narrow the intervals that harbor previously mapped QTL1 and QTL2. Two of the strains were designed for the express purpose of testing the QTL candidacy of loci for inducible nitric oxide synthase (Nos2) and angiotensin-converting enzyme (Ace) genes. BPs of these strains were measured by telemetry and compared with those of the DSS rat. Consequently, QTL1 and QTL2 were narrowed to segments of 53.5 and 100.4 centiRays, respectively. A new QTL, QTL3, was found between QTL1 and QTL2. Both Nos2 and Ace have been disqualified as QTLs in the DSS and LEW comparison. Therefore, there are no obvious candidate genes in the segments that harbor these 3 QTLs, which represent genes previously not thought to be involved in BP regulation. These QTLs will likely have an influence on studies of human hypertension because of their homology with the human CHR 17 region in which QTLs for BP have been found.