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: 6273122
• 负责人: TRUDY L BURNS
• 金额: $ 18.84万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-05 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273122
• 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。之间的关联 高血压和肥胖是公认的，然而， 病理生理关系仍然知之甚少。高血压 和肥胖是多因素表型，其病因显然涉及 主基因和多基因的作用，以及 许多环境因素。在这个项目中，我们的基本目标是 确定参与血压测定的遗传因素 和身体大小。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至少有两个孩子的500个核心家庭， 对任何表型都是无意义的。对于每个参与的父母和孩子 在这些家庭中，我们将在20 cM处确定STRP基因座的基因型 在整个基因组中。sib-对和多点标识-by- 分析的下降方法将用于确定基因座， 对血压和体型的影响。一旦这些位点 确定，我们将使用测量基因型和标记关联方法 分析，以估计其影响的大小 测量血压和体型。 第二项研究设计将侧重于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 因为有多名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进行血型鉴定 基因座在整个基因组的20 cM间隔的初始网格中。的 连锁分析的受影响谱系成员方法将用于 确定受影响成员明显更多的遗传位点 与预期的偶然相似，这表明标记物 基因座不是独立于高血压或肥胖的分离，但 而是与这些表型有关。 通过关注这两个特征良好的研究人群，并使用 一组精心挑选的高度多态性的标记， 基因组，我们希望确定一些遗传因素， 血压和身体大小的变化在人群中（从分析 马斯卡廷核家庭数据），和主要的遗传基因座连锁， 高血压和肥胖（来自贝都因部落的分析）。