MENDELIAN FACTORS UNDERLYING THE DETERMINATION OF BLOOD PRESSURE AND BODY SIZE

决定血压和体型的孟德尔因素

• 批准号: 6110565
• 负责人: TRUDY L BURNS
• 金额: $ 19.94万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110565
• 关键词: Arabs; Israel; caucasian American; clinical research; disease /disorder proneness /risk; familial hypertension; family genetics; genetic polymorphism; genotype; human subject; linkage mapping; molecular genetics; obesity; phenotype; racial /ethnic difference

In humans, excess blood pressure (hypertension) and body size (obesity) are associated with increased cardiovascular risk. The association between hypertension and obesity is well established, however, the pathophysiologic relationship remains poorly understood. Both hypertension and obesity are multifactorial phenotypes whose etiologies clearly involve the effects of major genes and polygenes, as well as the effects of numerous environmental factors. In this project, our basic aim is to identify genetic factors involved in the determination of blood pressure and body size. To accomplish this aim, we will employ two different study designs to identify families for the proposed investigations. The first study design will involve the identification and examination of 500 nuclear families with at least two children from Muscatine, Iowa who are unselected for any phenotype. For each participating parent and child in these families we will determine genotypes for STRP loci at 20 cM intervals throughout the genome. Both sib-pair and multipoint identity-by- descent methods of analysis will be used to identify loci that have measurable effects on blood pressure and body size. Once these loci are identified, we will use measured-genotype and marker-association methods of analysis to estimate the magnitude of their effects on the determination of blood pressure and body size. The second study design will focus on Bedouin families from a tribe in the Negev region in the southern part of Israel. This tribe has been ascertained because there are multiple family members with hypertension and/or obesity. Two hundred affected family members will be typed at STRP loci in an initial grid of 20 cM intervals throughout the genome. The affected-pedigree-member method of linkage analysis will be used to identify genetic loci where affected members are significantly more similar than expected by chance, which is an indication that the marker locus is not segregating independently of hypertension or obesity, but rather is linked to these phenotypes. By focusing on these two well-characterized study populations, and using a carefully selected panel of highly polymorphic markers which spans the genome, we expect to identify some of the genetic factors that maintain blood pressure and body size variation in the population (from analysis of the Muscatine nuclear-family data), and major genetic loci linked to hypertension and obesity (from analysis of the Bedouin tribe).

在人类中，血压过高（高血压）和体型过大（肥胖） 与心血管风险增加有关。之间的关联 高血压和肥胖症已是公认的事实，但 病理生理关系仍知之甚少。既是高血压 肥胖是多因素表型，其病因显然涉及 主基因和多基因的影响，以及 众多的环境因素。在这个项目中，我们的基本目标是 识别参与血压测定的遗传因素 和车身尺寸。为了实现这一目标，我们将采用两种不同的研究 旨在确定拟议调查的家庭。 第一个研究设计将涉及识别和检查 来自爱荷华州马斯卡廷的 500 个至少有两个孩子的核心家庭 未选择任何表型。对于每位参与的家长和孩子 在这些家族中，我们将确定 20 cM 处 STRP 位点的基因型 整个基因组的间隔。同胞对和多点身份识别 将使用下降分析方法来识别具有以下特征的基因座： 对血压和体型的影响可测量。一旦这些基因座 确定后，我们将使用测量基因型和标记关联方法 的分析来估计其影响的程度 血压和身体尺寸的测定。 第二个研究设计将重点关注来自该地区一个部落的贝都因家庭。 以色列南部内盖夫地区。这个部落已经 经查明，家族中有多名高血压患者 和/或肥胖。 STRP 将对 200 名受影响的家庭成员进行分类 整个基因组中间隔 20 cM 的初始网格中的基因座。这 将使用连锁分析的受影响谱系成员方法 确定受影响成员明显更多的遗传位点 与偶然预期的相似，这表明标记 位点的分离并不独立于高血压或肥胖，但是 相反与这些表型有关。 通过关注这两个特征明确的研究人群，并使用 精心挑选的一组高度多态性标记，涵盖 基因组，我们期望识别一些维持的遗传因素 人群中的血压和体型差异（来自分析 马斯卡廷核家族数据），以及与相关的主要遗传位点 高血压和肥胖（来自对贝都因部落的分析）。