MOLECULAR GENETICS OF ATHEROSCLEROSIS

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测量的基因， 墨西哥裔美国人的动脉粥样硬化、NIDDM和肥胖 家庭项目2的重点是 在当前资助期内检测到的主要基因， 主要基因，占30%或更多的变异，在许多 这些量化措施。 在项目2中， 成员将被分型为391个多路短串联重复序列 (STR)多态性间隔约10 cM。 将使用基于同胞关系的 方差分量法确定可能的联系 数量表型 当关联的初步证据 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）将进行更广泛的 连锁分析 当获得关联的暗示性证据时 (lod大于1.9），项目2将输入其他密集的 染色体区域中的标记，用于随后的多点 连锁和配子不平衡分析， 定位影响定量风险因子的基因。人类基因 将查阅图谱以确定候选基因是否 位于染色体区域，这些基因将被 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.