Functional genomic dissection of rat blood pressure QTL

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DESCRIPTION (provided by applicant): The purpose of this proposal is to identify the quantitative trait loci (QTL) that control blood pressure (BP) in the Dahl salt sensitive (S) rat. Multiple linkage analyses, each using the S rat as one of the parental strains, has resulted in the identification of at least 16 different QTL on the S rat genome that control blood pressure. The locations of 7 of these QTL on rat chromosomes 1, 2, 3, 5, 7, 9 and 10 have been confirmed and well defined by the construction of congenic rat strains. Each congenic strain contains a genomic segment from a relatively normotensive strain introgressed into the S rat genome and has significantly lower BP compared to the S rat. Congenic strains containing low BP QTL alleles on rat chromosomes 1 and 5 are the major focus for this proposal. These represent a unique research resource, by having their chromosomal locations delimited to precisely defined genomic intervals. Positional cloning of each of these QTL, while desirable, is a slow and laborious process. The overall strategy of this proposal is to couple congenic mapping of these BP QTL with gene expression analysis, thus providing the opportunity to expedite the process of BP QTL identification. We propose to address two questions using two approaches: Question (1) What is the identity of the BP causative gene within a QTL? Question (2) What is its action? Question 1 will be addressed by constructing and using a congenic-interval specific oligonucleotide array to identify differentially expressed genes between S rats and congenic rats. Question 2 will be addressed by using an already available rat genome chip, to identify the genes whose mRNA expression levels are affected by the causative gene.