GENETIC DETERMINANTS OF HIGH BLOOD PRESSURE

HyperGEN分子遗传学实验室将进行标记研究 进行关联分析和关联测试， 以下步骤：（1）标记将产生一系列高达 20个在血压中具有特殊意义的候选基因 （2）初步实验将建立一个具体的 通过独特的自动化深度多路复用的大规模基因分型策略 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 在三组高血压同胞中检查遗传连锁：（4） 预先存在的犹他州样本集，包括245个同胞对，和（5）两个 HyperGEN“重度”高血压同胞系列（1，400例受试者 产生1，000对兄弟姐妹）;（6）此后，全基因组连锁 将在这两个HyperGEN中进行涉及240个标记物的检索 系列;（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被测试 在两个HyperGEN样品中;（8）在这5个基因座中，假设3个已知的基因座是 基因将成为分子变异系统搜索的焦点 在每个种族组的100个随机对照组中， 高血压先证者与血压正常者的病例对照比较 对照;（9）对于任何表现出显著关联的标记物， 基因分型将扩展到所有亲属和随机对照， 多变量遗传学和流行病学研究的目的。

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.