Mapping of Two Quantitative Trait Loci (QTL) for Blood Pressure (BP) on Rat Chromosome (CHR.) 2 Using Congenic Strains by Telemetry
We previously mapped a BP QTL on rat Chr. 2 near the Na,K-ATPase (Atp1a1) locus in two congenic strains. In the strain, S.MNS-Adh/D2Mit5, the Dahl salt sensitive (S) Chr. region, which was replaced by that of the Milan normotensive (MNS) strain, was quite large (roughly 80 cM). Now, we made 6 substrains from the original S.MNS-Adh/D2Mit5 strain, and then measured BP by telemetry for two (and will continue to measure for the rest) substrains. These two substrains do not contain overlapping chromosome regions. One, S.MNS-D2Mit6/D2Rat166 (S.MNS1), encompasses the angiotensin receptor AT1B (Agtr1b) and the other substrain, S.MNS-D2Mit9/Camk2d(S.MNS2) includes Atp1a1. Both substrains showed a significant (p<0.0001) effect in reducing the mean arterial pressure (MAP) in mmHg (see graph). This proves the presence of a QTL around Agtr1b. The BP effects of these QTL from the two separate substrains appeared to exceed those of the same number of QTL combined in one strain. This implies that these individual QTL on the same chromosome interact epistatically with one another.