MOLECULAR GENETICS OF ATHEROSCLEROSIS

项目2的总体目标是执行全基因组搜索以 识别和定位影响定量测量的基因 墨西哥裔美国人的动脉粥样硬化、非胰岛素依赖型糖尿病和肥胖 家人。项目2的重点是本地化 在当前资助期内发现的主要基因， 在许多情况下，占变异30%或更多的主基因 在这些量化指标中。在项目2中，1400个家庭中的每个家庭 成员将输入391多路短串联重复 (Str)等位基因的间隔约为10 cM。 初始统计筛选将使用基于兄弟姐妹关系的 用于识别可能的关联的方差分量法 数量表型。当初步证据表明存在关联时 检测到(p<0.05)，项目1(动脉粥样硬化特征)和 项目3(NIDDM和肥胖特征)将执行更广泛的 连锁分析。当获得有关联的提示性证据时 (LOD大于1.9)，项目2将键入附加近距离 染色体区域中的标记，用于后续的多点 连锁和配对不平衡分析更精确地 定位影响量化风险因素的基因。人类基因 将查阅图谱以确定候选基因是否 位于该染色体区域，这样的基因将被 进行分子分析以确定结构和 等位基因效应背后的功能差异。

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.