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: 6242559
• 负责人: TRUDY L BURNS
• 金额: $ 18.11万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-28 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6242559
• 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，血压过多（高血压）和体型（肥胖） 与心血管风险增加有关。之间的关联 高血压和肥胖症已经很好地确定 病理生理关系仍然知之甚少。两种高血压 肥胖是多因素表型，其病因显然涉及 主要基因和多基因的影响以及 许多环境因素。在这个项目中，我们的基本目的是 确定与血压确定有关的遗传因素 和身体大小。为了实现这一目标，我们将采用两个不同的研究 设计以识别拟议调查的家庭。 第一个研究设计将涉及对 500个核心家庭，至少有两个来自爱荷华州马斯卡汀的孩子 未选择任何表型。每个参与的父母和孩子 在这些家族中，我们将在20 cm处确定STRP基因座的基因型 整个基因组的间隔。 sib-pair和多点身份 下降分析方法将用于识别具有 对血压和体型的可测量影响。一旦这些基因座是 确定，我们将使用测量的基因型和标记 - 关联方法 分析以估计其对 血压和体型的确定。 第二项研究设计将重点关注来自部落的贝都因人家庭 以色列南部的内盖地区。这个部落一直是 确定是因为有多个患有高血压的家庭成员 和/或肥胖。将在STRP上输入200名受影响的家庭成员 整个基因组的初始网格间隔为20 cm。这 受影响的 - 链接分析方法将用于 确定受影响成员明显更多的遗传基因座 比偶然的预期相似，这表明标记 基因座不是独立于高血压或肥胖的隔离，而是 而是与这些表型有关。 通过专注于这两个特征良好的研究人群，并使用 精心选择的高度多态标记面板，跨越 基因组，我们期望确定一些维持的遗传因素 人群的血压和体型变化（来自 马斯喀丁核家庭数据），主要遗传基因座与 高血压和肥胖症（来自贝都因人部落的分析）。