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: 6302398
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6302398
• 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，过高的血压(高血压)和体型(肥胖) 与心血管风险增加有关。两者之间的联系 高血压和肥胖症是公认的，然而， 病理生理学关系仍然知之甚少。两人都有高血压 和肥胖都是多因素表型，其病因显然涉及 主效基因和多基因的效应，以及基因的效应 众多的环境因素。在这个项目中，我们的基本目标是 确定与血压测定有关的遗传因素 和体型。为了实现这一目标，我们将采用两种不同的研究 为拟议的调查确定家庭的设计。 第一项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 对于任何表型都是未选择的。对于每个参与的父代和子代 在这些家系中，我们将确定20 cM的STRP基因座的基因型。 基因组中的间隔时间。兄弟姐妹对和多点身份- 将使用下降分析方法来识别具有 对血压和体型有可测量的影响。一旦这些基因座 鉴定，我们将使用测量的基因型和标记关联方法 分析，以估计它们对 血压和体型的测定。 第二项研究设计将集中在来自一个部落的贝都因家庭 以色列南部的内盖夫地区。这个部落一直是 确定是因为有多个家庭成员患有高血压 和/或肥胖。200名受影响的家庭成员将在STRP上进行打字 在整个基因组20厘米间隔的初始网格中的基因座。这个 将采用连锁分析中的受影响家系成员法 识别受影响成员显著更多的遗传基因座 与预期的相似，这表明标记 基因座并不独立于高血压或肥胖症，但 而是与这些表型有关。 通过关注这两个特征良好的研究群体，并使用 一组精心挑选的高度多态的标记，横跨 基因组，我们希望找出一些维持 人群中的血压和体型变化(来自分析 马斯卡丁核心家族数据)，以及与 高血压和肥胖(来自贝都因部落的分析)。