Genealogical-based inference in statistical genetics

今天观察到的人类基因组的变化是遗传过程的结果，例如突变，随着时间的推移作用于我们祖先的DNA。来自不相关个体的基因样本的“基因谱系”是一棵树，描述了导致这种变异的历史祖先遗传事件和关系。然而，由于时间尺度是数万年的量级，真正的基因谱系无法获知。我对使用遗传标记--可变DNA位点--的信息来推断无关个体之间的谱系关系很感兴趣。我的研究借鉴了统计学和种群遗传学，涉及到发展和传播纳入这些祖先树的统计方法。*我最近开发了一种方法，对可能产生遗传数据样本的系谱树进行概率抽样。我的研究计划的中心目标是增加我开发的家谱抽样方法的实用性和应用。这是通过两个长期目标来实现的。我的研究计划的第一个目标是对抽样方法进行计算改进。第一个改进将使用统计技术来加快采样器的计算时间。第二个改进将扩展采样器以处理丢失的基因数据。*人类遗传学家对发现遗传风险因素的额外能力非常感兴趣。我的研究计划的第二个目标是开发一种新的基于家谱的方法来寻找遗传风险因素，特别是罕见的变异。我将开发和评估统计数据，这些统计数据将疾病状态的相似性与遗传亲缘关系联系起来，通过系谱树来衡量。我开发的抽样方法将被用来处理谱系的不确定性，我将把我的方法与现有的忽略不确定性的方法进行比较。*

The variation observed today in the human genome is a result of genetic processes, such as mutation, acting over time on the DNA of our ancestors. The 'gene genealogy' for a sample of genes from unrelated individuals is a tree describing the historical ancestral genetic events and relationships giving rise to this variation. However, since the time scale is on the order of tens of thousands of years, the true gene genealogy cannot be known. I am interested in using information from genetic markers - variable DNA sites - to infer genealogical relationships between unrelated individuals. My research, which draws on statistics and population genetics, involves the development and dissemination of statistical approaches incorporating these ancestral trees. ****I have recently developed an approach to probabilistically sample genealogical trees that are likely to have given rise to a sample of genetic data. The central goal of my research program is to increase the utility and application of the genealogy sampling approach that I developed. This is accomplished with two long-term objectives. The first objective of my research program is to make computational improvements to the sampling approach. The first improvement will use statistical techniques to speed up the computational time of the sampler. The second improvement will extend the sampler to handle missing genotype data. ****Additional power to discover genetic risk factors is of great interest to human geneticists. The second objective of my research program is to develop a new genealogy-based method for finding genetic risk factors, and in particular rare variants. I will develop and evaluate statistics that relate similarity in disease state to genetic relatedness, as measured by the genealogical tree. The sampling approach that I have developed will be used to handle the uncertainty of the genealogy and I will compare my approach to existing approaches that ignore the uncertainty. ********************************************