POSITIONAL CLONING OF BLOOD PRESSURE QTL

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DESCRIPTION (the applicant's description verbatim): Essential hypertension in humans is known to be a complex trait with a genetic component influenced by many genes. The identity of these genes is unknown. To identify these multiple genes controlling blood pressure animal models of genetic hypertension have been developed in the rat. Our overall objective is to use the Dahl-salt-sensitive (S) hypertensive rat to define the genes causing genetic variation in blood pressure. As with all animal model systems it is expected that information obtained in rats will give insight into the human condition. Genetic analysis takes the form of identifying regions of rat chromosomes influencing blood pressure by linkage analysis. The existence of blood pressure quantitative trait loci (QTL) is confirmed by the construction of congenic strains in which a low blood pressure allele is substituted onto the genetic background of the S rat. The congenic chromosomal segment containing the QTL is then progressively reduced by several iterations of congenic strain construction until the region is small enough for positional cloning of the blood pressure causing gene. The latter requires a congenic region of about 0.3 centiMorgans. Physical maps of such a region will be prepared and the entire region will be DNA sequenced. New and known genes in the target region will be identified through the sequence analysis. Candidate genes will be sought based on known or deduced function and/or differences in expression between S rats and the congenic strains. The above analysis is proposed for blood pressure QTL on rat chromosome 1, 5, 7, and 10.