Models of Complex Genetic Systems

描述（由申请人提供）：拟议的研究将在 可用于分析的数学和统计模型 人类和其他人群的基因数据。将特别强调 放在会计模式对个人之间的变化， 不同种群之间的差异。这个项目的总体目标是 研究是开发使用变异模式的方法， 了解人类和其他人群的历史，并协助 努力识别影响遗传疾病的基因。人口的历史 增长、扩散和与其他种群的混合反映在 整个基因组的遗传变异模式。一个人的历史 突变反映在遗传位点的变异模式中， 与这种突变有关。具体目标是：（1）模拟 个体突变导致遗传疾病，以了解在哪里， 以及这些突变的携带者是否具有优势 生存和繁殖，（2）更好地利用非随机关联， 等位基因在不同的遗传基因座（称为连锁不平衡），以定位 导致遗传疾病的基因，（3）模拟自然选择的影响 它的作用是保持遗传基因座的遗传多样性，例如 人类和其他物种的主要组织相容性（MHC）基因座，以及（4） 发展出近亲遗传疾病风险的理论 一个人谁有疾病的遗传基因座的数量影响 疾病以及这些基因座之间的相互作用。数学 本研究所采用的方法主要是概率论方法 和随机过程。尽可能获得分析结果 并将辅以计算机模拟。数据分析方法将 可以用模拟和真实的数据进行检验。计算机程序被发现 将免费提供对数据分析有用的资料。

DESCRIPTION (provided by applicant): The proposed research will be on mathematical and statistical models that can be used to used for the analysis of genetic data in human and other populations. Particular emphasis will be placed on accounting for patterns on variation among individuals within populations and variation among different populations. The overall goal of this research is the development of methods for using patterns of variation to understand the history of human and other populations and to assist with efforts to identify genes affecting genetic diseases. The history of population growth, dispersal and intermixture with other populations is reflected in patterns of genetic variation across the genome. The history of an individual mutation is reflected in patterns of variation at genetic loci that are closely linked to that mutation. The specific goals are (1) to model the history of individual mutations causing genetic diseases in order to understand where and when they arose and whether carriers of those mutations have an advantage survival and reproduction, (2) to make better use of non-random associations of alleles at different genetic loci (called linkage disequilibrium) to locate gene causing genetic diseases, (3) to model the effects of natural selection that acts to maintain genetic diversity at genetic loci such as the loci in the major histocompatibility (MHC) loci in humans and other species, and (4) to develop theories that relate the risk of a genetic disease in close relatives of an individual who has the disease to the number of genetic loci affecting the disease and to the kinds of interactions among those loci. The mathematical methods used in this research will be primarily from the theory of probability and stochastic processes. Analytic results will be obtained whenever possible and will be supplemented by computer simulations. Methods of data analysis will be tested both with simulated and real data. Computer programs that are found to be useful for data analysis will be made freely available.