The HyperGEN Molecular Genetics Laboratory will perform the marker studies required for linkage analysis and tests of association, proceeding through the following steps: (1) markers will be generated for a series of up to 20 candidate genes of particular significance in blood pressure regulation; (2) preliminary experiments will establish the specifics of a large-scale genotyping strategy by a unique, automated deep-multiplexing technology; (3) reference marker frequencies needed for linkage analysis will be determined in random controls; the candidate genes will be examined for genetic linkage in three series of hypertensive siblings: (4) a pre-existing Utah sample set including 245 sibling pairs, and (5) two series of HyperGEN 'severe' hypertensive siblings (1,400 subjects generating 1,000 sibling pairs); (6) thereafter, a genome-wide linkage search involving 240 markers will be performed in these two HyperGEN series; (7) assuming that linkage is found and confirmed for up to 5 loci, their possible contribution to milder forms of hypertension will be tested in two HyperGEN samples; (8) of these 5 loci, it is assumed that 3 known genes will become the focus of a systematic search for molecular variants in a collection of 100 random controls of each ethnic group, followed by case-control comparisons between hypertensive probands and normotensive controls; (9) for any marker exhibiting significant association, genotyping will be extended to all relatives and random controls for the purpose of multivariate genetic and epidemiological studies.
Showing the most recent 10 out of 89 publications
