GENETIC DETERMINANTS OF HGH BLOOD PRESSURE STUDY

我们已经建立了一支经验丰富的调查小组，致力于 定位、识别和评估常见的多态变异 决定血液中个体间差异的基因 血压水平与高血压(EHYT)状态的关系 种族群体：非裔美国人、墨西哥裔美国人和非西班牙裔 白色的。每个合作的调查员负责一项基本的 我们网络的组成部分：Boerwinkle(基因分型和连锁分析)， 费雷尔(基因分型)，哈尼斯(招募墨西哥裔美国人)，哈钦森 (招募非裔美国人)，Sing(分支和预测分析 和数据管理)，以及特纳(招聘非西班牙裔白人和 测量生理变量)。 我们的网络提出了五个具体目标，以本地化和 描述高BP的遗传决定因素。目标1将使用健壮 500对高血压同胞中的同胞对连锁分析 种族群体(总共1,500对兄弟姐妹)定位基因 影响EHYT发生的个体差异。目标 2和3将利用之前收集的BP和中间数据 来自中国的1,488对正常血压兄弟姐妹的预测特征数据 罗切斯特家族心脏研究定位导致EHYT的基因。这个 拟议的连锁分析(目标1-3)将使用广泛的 候选基因和大量的匿名标记 基因组。AIM 4将使用多个双等位基因序列多态性和 连锁基因内的分支分析以确定单倍型 DNA测序以确定候选功能DNA序列 变异导致个体间血压水平和 EHYT状态。目标5将评估候选功能DNA的能力 序列变异预测EHYT在三个种族群体中的状态。

We have established a group of experienced investigators dedicated to localizing, identifying, and evaluating common polymorphic variation in genes involved in determining interindividual differences in blood pressure (BP) levels and essential hypertension (EHYT) status in three racial groups: African-Americans, Mexican-Americans, and Non-Hispanic Whites. Each collaborating investigator is responsible for an essential element of our Network: Boerwinkle (genotyping and linkage analyses), Ferrell (genotyping), Hanis (recruiting Mexican-Americans), Hutchinson (recruiting African-Americans), Sing (cladistic and prediction analyses and data management), and Turner (recruiting Non-Hispanic Whites and measuring physiologic variables). Our Network proposes to carry out five specific aims to localize and characterize the genetic determinants of high BP. Aim 1 will use robust sibling pair linkage methods in 500 hypertensive sibling pairs in each racial group (a total of 1,500 sibling pairs) to localize genes influencing interindividual differences in the occurrence of EHYT. Aims 2 and 3 will take advantage of previously collected BP and intermediate predictor trait data from 1,488 normotensive sibling pairs from the Rochester Family Heart Study to localize genes contributing to EHYT. The proposed linkage analyses (Aims 1-3) will use both an extensive array of candidate genes and a large number of anonymous markers throughout the genome. Aim 4 will use multiple diallelic sequence polymorphisms and cladistic analyses within a linked gene to identify haplotypes for further DNA sequencing in order to identify candidate functional DNA sequence variation contributing to interindividual differences in BP levels and EHYT status. Aim 5 will evaluate the ability of candidate functional DNA sequence variation to predict EHYT status in the three racial groups.