Complete genome searches for quantitative trait loci controlling blood pressure and related traits in four segregating populations derived from Dahl hypertensive rats

The Dahl salt-sensitive rat is one of the principal animal models of heredi tary hypertension. Genome-wide searches were undertaken to detect quantitat ive trait loci (QTLs) that influence blood pressure, cardiac mass, and body weight in four F-2 populations derived from Dahl salt-sensitive rats and d ifferent inbred normotensive control strains of rat. We detected three QTLs associated with one or more of the phenotypes, using a stringent statistic al criterion for linkage (p < 0.00003). These included a novel QTL linked t o blood pressure on rat Chromosome (Chr) 12, and another QTL on rat Chr 3 l inked to body weight. A QTL on rat Chr 10 for which linkage to blood pressu re has been described in other crosses was found to be a principal determin ant of blood pressure and cardiac mass in some but not all of the crosses e xamined here. Three other regions showed evidence of linkage to these pheno types with a less stringent statistical criterion of linkage at QTLs previo usly reported in other studies. As part of our study, microsatellite marker s have been developed for three candidate genes for investigation in hypert ension, and the genes have been localized by linkage mapping. These are: th e rat Gs alpha subunit (Gnas) gene, the alpha-1B adrenergic receptor (Adra1 b), and the Na+, K+-ATPase beta2 subunit (Atp1b2) gene.