Congenic substitution mapping excludes Sa as a candidate gene locus for a blood pressure quantitative trait locus on...

Previously, linkage analysis in several experimental crosses between hypertensive rat strains and their contrasting reference strains have identified a major quantitative trait locus (QTL) for blood pressure on rat chromosome 1 (Chr 1) spanning the Sa gene locus. In this study, we report the further dissection of this Chr 1 blood pressure QTL with congenic substitution mapping. To address whether the Sa gene represents a candidate gene for the Chr 1 blood pressure QTL, congenic strains were developed by introgressing high blood pressure QTL alleles from the stroke-prone spontaneously hypertensive rat (SHRSP) into the normotensive Wistar-Kyoto (WKY-1) reference strain. Congenic animals carrying a chromosomal segment from stroke-prone spontaneously hypertensive rats between genetic markers Mt1pa and D1Rat200 (including the Sa gene locus) show a significant increase in basal systolic and diastolic blood pressure compared with their normotensive Wistar-Kyoto progenitors (P<0.001, respectively), whereas congenic animals carrying a subfragment of this Chr 1 region defined by markers Mt1pa and D1Rat57 (also spanning the Sa gene) do not show elevated basal blood pressure levels (P=0.83 and P=0.9, respectively). Similar results were obtained for NaCl-induced blood pressure values. Thus, the blood pressure QTL on Chr 1 is located centromeric to the Sa gene locus in a region that is syntenic to human chromosome 11p15.4-p15.3. This region excludes the Sa as a blood pressure-elevating candidate gene locus on the basis of congenic substitution mapping approaches.