Studies are designed to identify genes that cosegregate with hypertension and with phenotypes associated with hypertension (""""""""hypertension associated phenotypes"""""""") in a genetically isolated population with traditionally large families residing in Chicoutimi Saguenay Lac St. Jean, Canada. A genome-wide search and a candidate gene approach will be used and a sib-pair analysis will be carried out using 200 sibs to define hypertension susceptibility loci. We will subdivide the population to further reduce the genetic heterogeneity by including only sib pairs who exhibit both hypertension and hypercholesterolemia. Extensive phenotyping of 200 of these sibs will be carried out to determine loci that influence blood pressure and alterations of physiological functions that may contribute to hypertension. Phenotypic studies will evaluate renal function, renal and peripheral vascular reactivity, insulin sensitivity, and ion transport in erythrocytes. The general linkage analysis will be refined by determining mutations that exist in linkage disequilibrium. Inheritance by descent (IBD) will be determined by studying additional sib pairs from the large family pedigrees (sibs who belong to a family with at least 3 living generations and at least 5 members in 1 generation) to re-analyze mapped phenotypes for their segregation with hypertension.
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