This project is the continuation and extension of the human molecular genetics projects of the previous SCOR period. Based on resources and expertise accumulated during its first period, the current project has the following Specific Aims: 1) To expand recruitment of hypertensive and normotensive members from existing and new families with special emphasis on selected populations, i.e., African Americans, inbred populations from Greece, Israel and South Africa, and new probands from an extensive evaluated population of the Cardiology clinic. Linkage and association analyses will be applied to subgroups of these populations as appropriate to subgroups of these populations as appropriate, including case-control studies utilizing the Cardiology clinic patients who have undergone hemodynamic and imaging tests and can be subgrouped by intermediate phenotypes, such as presence or absence of coronary artery disease and left ventricular hypertrophy. 2) To conduct a genome-wide scan in our unique genetic isolates (remote island-dwelling Greeks, Israeli-Arabs and Zulus from Natal) in order to localize susceptibility genes for hypertension. Collaboration with physicians from these areas has already yielded the first batches of clinical data and blood samples. 3) To evaluate a series of single nucleotide polymorphisms (SNPs) in genes with known or suspected relevance to blood pressure regulation or to intermediate cardiovascular phenotypes, comparing cases with controls. 4) To evaluate in our large collection of multi-generation families linkage between hypertension and marker loci suggested by gene mapping in humans and/or QTLs in rodents. Data from our own studies (including the Framingham Study and Projects II and III from this SCOR) as well as updates from the literature will guide the selection of loci. 5) To characterize candidate genes for hypertension in defined narrow chromosomal regions, using both DNA sequencing for genes known to map in a certain region (e.g., 17q) and rapid screening mass- spectroscopy-based SNP detection methods.
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