The applicant proposes to identify the quantitative trait loci (QTL) controlling blood pressure in the rat. This will be done by (a) identifying genetic markers that cosegregate with blood pressure in the rat; (b) developing linkage maps at a resolution of 5-10 cM for the rat chromosomal regions involved in order to obtain a crude localization of the blood pressure QTL by interval mapping; (c) producing congenic strains for each low-blood pressure-QTL allele on the genetic background of the inbred Dahl salt-sensitive hypertensive rat; (d) developing rat linkage maps at a resolution of 1-2 cM for QTL- containing chromosomal regions; (e) refining the genetic mapping of blood pressure QTL by substituting progressively smaller and smaller regions of chromosome containing the low-blood pressure QTL allele on the S rat genetic background; and (f) ultimately preparing physical maps for at least one such QTL region and attempting positional cloning. These proposed studies are deemed important because they may identify genetic markers that can be used to study essential hypertension in humans, and will provide congenic strains which can serve as new animal models for hypertension research in which the effects of individual QTLs on blood pressure regulation can be determined.
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