MOLECULAR GENETICS OF ATHEROSCLEROSIS

动脉粥样硬化的分子遗传学

• 批准号: 6448206
• 负责人: JAMES E. HIXSON
• 金额: $ 49.81万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6448206
• 关键词: Mexican Americans; atherosclerosis; blood lipoprotein; cardiovascular disorder epidemiology; clinical research; diabetes mellitus genetics; family genetics; genetic markers; genetic polymorphism; human data; human genetic material tag; linkage mapping; noninsulin dependent diabetes mellitus; nucleic acid repetitive sequence; obesity; phenotype; sequence tagged sites

The overall goal of Project 2 is to perform a genome-wide search to identify and localize genes that affect quantitative measures of atherosclerosis, NIDDM, and obesity in Mexican American families. The particular focus of Project 2 is on localization of major genes that have been detected in the current grant period, major genes that account for 30% or more of the variance in many of these quantitative measures. In Project 2, each of 1,400 family members will be typed for 391 multiplexed short tandem repeat (STR) polymorphisms spaced at approximately 10 cM intervals. An initial statistical screen will be performed using a sibship-based variance component method to identify possible linkage with quantitative phenotypes. When preliminary evidence for linkage is detected (p less than 0.05), Project 1 (atherosclerosis traits) and Project 3 (NIDDM and obesity traits) will perform more extensive linkage analyses. When suggestive evidence for linkage is obtained (lod greater than 1.9), Project 2 will type additional closely spaced markers in the chromosomal region, for subsequent multipoint linkage and gametic disequilibrium analyses to more precisely localize genes affecting quantitative risk factors. The human gene map will be consulted to determine whether candidate genes are located in that chromosomal region, and such genes will be subjected to molecular analyses to determine structural and functional differences that underlie allelic effects.

项目2的总体目标是进行全基因组搜索 识别和定位影响定量度量的基因 墨西哥裔美国人的动脉粥样硬化，NIDDM和肥胖症 家庭。项目2的特别重点是本地化 在当前赠款期内已检测到的主要基因， 占许多差异30％或以上的主要基因 这些定量措施。 在项目2中，每个家庭中的每个 会员将输入391个多路复用短串联重复 （STR）多态性以大约10 cm的间隔间隔。 最初的统计屏幕将使用基于Sibship的屏幕进行 差异组件方法以识别可能的链接 定量表型。 当有联系的初步证据是 检测到（P小于0.05），项目1（动脉粥样硬化特征）和 项目3（NIDDM和肥胖特征）将表现更广泛 链接分析。 当获得联系的暗示证据时 （LOD大于1.9），项目2将键入额外的额外间隔 染色体区域的标记，以进行随后的多点 连锁和配子不平衡分析更精确 定位影响定量危险因素的基因。人类基因 将咨询地图以确定候选基因是否为 位于该染色体区域，此基因将是 进行分子分析以确定结构和 构成等位基因影响的功能差异。