GENETIC ANALYSIS OF LIPOPROTEIN PHENOTYPES

动脉粥样硬化发展的主要危险因素之一是 血清中脂蛋白的浓度。 遗传因素的知识 影响这一危险因素的因素对于理解 动脉粥样硬化的病因学 本提案的总体目标是寻求 影响脂蛋白表型的遗传因素 动脉粥样硬化狒狒 狒狒是一个很好的动物模型， 动脉粥样硬化，因为它的生理，病理生理， 生化特征与人类相似。 我将推导出 来自几个数据来源的脂蛋白表型（即，血清 胆固醇浓度，脂蛋白谱， 聚丙烯酰胺梯度凝胶电泳和高压液相 色谱法），可在790只纯种狒狒上获得。 那我就 使用两种初步方法对这些表型进行遗传分析 遗传分析、亲缘关系方差检验和结构化探索性数据 分析，以及一种复杂的分离分析方法，PAP。 我也要 进行计算机模拟，以经验性地估计这些 方法，开发用于人类谱系数据，数据来自 在人类疾病的动物模型中常见的谱系结构。

One of the major risk factors for the development of atherosclerosis is the concentration of lipoproteins in serum. Knowledge of the genetic factors that influence this risk factor is importnat for the understanding of the etiology of atherosclerosis. The overall aim of this proposal is to seek genetic factors influencing lipoprotein phenotypes in an animal model for atherosclerosis, the baboon. The baboon is an excellent animal model for atherosclerosis because its physiological, pathophysiological, and biochemical characteristics are similar to those of humans. I will derive lipoprotein phenotypes from several sources of data (i.e., serum cholesterol concentrations, lipoprotein profiles obtained from polyacrylamide gradient gel electrophoresis and high-pressure liquid chromatography), that are available on 790 pedigreed baboons. Then I will perform genetic analyses on these phenotypes using two preliminary methods of genetic analysis, sibship variance tests and Structured Exploratory Data Analysis, and one method of complex segregation analysis, PAP. I also will perform computer simulations to empirically estimate the power of these methods, which were developed for use on human pedigree data, on data from pedigree structures that are common in animal models of human disease.