GENETIC MAPPING OF ATHEROSCLEROSIS PHENOTYPES

项目1的目标是绘制影响基因的图谱 与发育相关的数量表型 圣安东尼奥的墨西哥裔美国家庭中的动脉粥样硬化 家庭心脏研究。一项基因组搜索，利用10厘米的长度 391个短串联重复标记的图谱分布于 基因组，将被用于确定染色体位置 在当前资助期内检测到的六个主要基因(基因 影响高密度脂蛋白-C、低密度脂蛋白-C、载脂蛋白AI、载脂蛋白B、SHBG和DHEAS)。 对于尚未发现主要基因的脂蛋白表型 一旦检测到，将寻找主要基因效应的证据。这个 基因组搜索将集中在显示出 基于兄弟姐妹关系的方差中存在连锁的初步证据 项目2中的组件筛选测试。如果得到保证，分析 将被扩展以包括这些区域中的其他DNA标记。 遗传效应对颈动脉和纤溶表型的影响 使用从750名家庭成员召回的数据进行量化。饱满 系谱方差成分分析以及基于外显度的分析 将在基因组搜索中使用方法来确定 影响这些表型的基因的染色体位置。 对于给出连锁暗示证据的DNA标记， 分析将扩展到包括这些标记的其他标记 区域，利用多点方法。为了改进遗传模型， 强化证据联动，减少虚假证据 正性、GxE相互作用及多效性和上位性效应 主要基因将被量化。寡基因分析将得到加强 链接信号，并进一步减少误报，以及 不平衡分析将改善基因定位 影响定量心脑血管疾病危险因素。基因定位于 项目1将指导分子候选基因的选择 项目2中的研究。这些分析将为未来奠定基础 努力识别主要基因并了解其功能。

The objective of Project 1 is to map genes that influence quantitative phenotypes related to the development of atherosclerosis in Mexican American families in the San Antonio Family Heart Study. A genomic search, utilizing a 10 centimorgan map of 391 short tandem repeat markers distributed throughout the genome, will be conducted to determine the chromosomal locations of six major genes detected during the current grant period (gene influencing HDL-C,LDL-C, apoAI, apoB, SHBG, and DHEAS). For lipoprotein phenotypes for which no major genes have yet been detected, evidence for major gene effects will be sought. The genomic search will focus on chromosomal regions that show preliminary evidence for linkage in sibship based variance component screening tests in Project 2. If warranted, the analyses will be expand to include additional DNA markers in these regions. Genetic effects on carotid and fibrinolysis phenotypes will be quantified using data from a recall of 750 family members. Full pedigree variance component analysis as well as penetrance-based methods will be used in a genomic search to determine the chromosomal locations of genes that influence these phenotypes. For DNA markers that give suggestive evidence of linkage, analyses will be expanded to include additional markers in these regions, utilizing multipoint methods. To improve genetic models, strengthen evidence for linkage, and reduce the number of false positives, gxE interactions and pleiotropic and epistatic effects of major genes will be quantified. Oligogenic analysis will strengthen linkage signals and further reduce false positives, and disequilibrium analysis will improve localization of genes influencing quantitative CVD risk factors. Genes localized in Project 1 will guide the selection of candidate genes for molecular studies in Project 2. These analyses will set the stage for future efforts to identify the major genes and understand their functions.