Grant: Doctoral Research Award - Hypertension Prevention

Hypertension is a disease with increasing frequency in western as well as in transition-economy countries. As many genetic and environmental factors participate and interact in the development of hypertension, the identification of genes involved in altered blood pressure regulation is rather complicated. New genome-wide scanning methodologies enable the detection of larger-sized variability in genomes such as Copy Number Variant (CNV) which represents change (gain or loss) in copy number of DNA fragments of at least 1 KB compared to the reference genome, often resulting in an increase or decrease of the gene product. Although DNA copy number variation phenomenon has been known for a long time, it has only recently been reported to be widely present in the human genome, potentially accounting for important source of variation in genomic components of complex traits like blood pressure. Some CNVs have already been shown to be involved in disease such as Parkinson, Alzheimer, autism or HIV-1 infection susceptibility. The present study aims to investigate, using Affymetrix DNA Mapping arrays, genome-wide characteristics of CNVs in unique set of 75 French-Canadian families (from Saguenay-Lac St-Jean region of Quebec) affected by hypertension. In combination with available data on hundreds of rigorously acquired blood pressure, body composition and metabolic traits and complete annotation of the ancestry back to 17th century, we plan to identify CNVs linked to or associated with hypertension and related metabolic abnormalities and conferring risk for or protection from this disease. Hence, this project will contribute to elucidate the role of CNVs as hereditary component of hypertension, and, for the first time, to analyze in depth their familial transmission in uniquely disposed cohorts. The identification of pathogenic CNVs will help to elaborate tools for early diagnosis and targeted prevention strategies.