GENETIC DETERMINANTS OF HIGH BLOOD PRESSURE

高血压的遗传决定因素

• 批准号: 2519506
• 负责人: JEAN-MARC LALOUEL
• 金额: $ 45.51万
• 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/2519506
• 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 连锁性分析和关联性测试所需的， 以下步骤：(1)将为一系列最多为 20个对血压有特殊意义的候选基因 法规；(2)初步实验将确定一种 一种独特的、自动化的深度多路复用大规模基因分型策略 (3)连锁分析所需的参考标记频率 将在随机对照中确定；候选基因将是 三个系列高血压同胞的基因连锁检查：(4) 预先存在的犹他州样本集，包括245对兄弟姐妹和(5)两个 HyperGEN严重高血压兄弟姐妹系列(1,400名受试者 产生1,000个兄弟姐妹对)；(6)此后，全基因组连锁 涉及240个标记的搜索将在这两个HyperGEN中执行 序列；(7)假设发现并确认了多达5个基因座的连锁， 他们对轻度高血压的可能贡献将会被测试。 在两个HyperGEN样本中；(8)在这5个基因座中，假设有3个已知 基因将成为系统性寻找分子变异的焦点 在每个种族组的100个随机对照的集合中，随后是 高血压先证者与正常血压患者的病例对照研究 对照；(9)对于表现出显著关联的任何标记， 基因分型将扩大到所有亲属和随机对照 多变量遗传和流行病学研究的目的。