GENETIC DETERMINANTS OF HIGH BLOOD PRESSURE

高血压的遗传决定因素

• 批准号: 2771440
• 负责人: JEAN-MARC LALOUEL
• 金额: $ 52.11万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-05 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2771440
• 关键词: angiotensinogen; cooperative study; disease /disorder classification; disease /disorder proneness /risk; epidemiology; essential hypertension; family genetics; genetic mapping; genetic markers; genetic polymorphism; genome; genotype; human genetic material tag; human subject; linkage mapping; molecular genetics; polymerase chain reaction; single strand conformation polymorphism

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.

HyperGEN分子遗传学实验室将进行标记研究