Severe hypertension caused by alleles from normotensive Lewis for a quantitative trait locus on chromosome 2

Pursuing fully a suggestion from linkage analysis that there might be a quantitative trait locus (QTL) for blood pressure (BP) in a chromosome (Chr) 2 region of the Dahl salt-sensitive rat (DSS), four congenic strains were made by replacing various fragments of DSS Chr 2 with those of Lewis (LEW). Consequently, a BP QTL was localized to a segment of around 3 cM or near 3 Mb on Chr 2 by comparative congenics. The BP-augmenting alleles of this QTL originated from the LEW rat, a normotensive strain compared with DSS. The dissection of a QTL with such a paradoxical effect illustrated the power of congenics in unearthing a gene hidden in the context of the whole animal system, presumably by interactions with other genes. The locus for the angiotensin II receptor AT-1B (Agtr1b) is not supported as a candidate gene for the QTL because a congenic strain harboring it did not have an effect on BP. There are ∼19 known and unknown genes present in the QTL interval. Among them, no standout candidate genes are reputed ...