Population mixture in evolutionary and medical genetics

描述（由申请人提供）：种群间的混合是形成生物学、遗传变异和疾病风险的基本过程。尽管其重要性，分析方法，可用于研究混合物在全基因组范围内是有限的。这使得它成为一个优先发展的方法，可以分析这一历史的大型数据集，现在是实际生成。目前没有任何联邦拨款支持这种方法的发展。该补助金旨在开发研究混合物的方法和软件。目的是：（1）开发基于等位基因频率和单倍型频率差异的混合推断工具。 (2)开发基于混合连锁不平衡和遗传分化数据的混合日期估计工具。 我们预计这笔赠款将在三个方面发挥作用。(a)它将支持开发方法和用户友好的软件，这对进化和医学遗传学很重要。(b)它将支持的工作，将导致相关的见解发现疾病基因在人类群体中最近或古代混合。(c)它将导致对人类历史以及其他生物历史的新见解。 与医学遗传学的联系尤为重要。我们实验室过去对人群进化史的研究与我们对疾病基因图谱的研究交织在一起，我们在这两个领域开发的方法是协同的。特别是，我们利用人类混合的历史来发现新的基因，并了解不同人群疾病风险的变化。我们希望能够通过开发复杂的方法来理解和建模群体混合，从而进一步将进化遗传学和医学遗传学联系起来。

DESCRIPTION (provided by applicant): Mixture between populations is a fundamental process that shapes biology, genetic variation, and the risk for disease. Despite its importance, the analytical methods that are available to study mixture on a genome-wide scale are limited. This makes it a priority to develop methods that can analyze this history in the large data sets that are now practical to generate. No federal grant currently supports the development of such methods. This grant proposes to develop methods and make software available for studying mixture. The Aims are: (1) To develop tools that make inferences about mixture based on allele frequency and haplotype frequency differences. (2) To develop tools that estimate dates of mixture based on admixture linkage disequilibrium and genetic divergence data. We expect that this grant will be of value in three areas. (a) It will support the development of methods and user-friendly software that will be important for evolutionary and medical genetics. (b) It will support work that will result in insights relevant to finding disease genes in human populations that are recently or anciently admixed. (c) It will lead to new insights about human history as well as the history of other organisms. The connection to medical genetics is particularly important. Our laboratory's past work on the evolutionary history of populations has been intertwined with our work on disease gene mapping, and the approaches that we developed in both areas were synergistic. In particular, we have leveraged the history of admixture in human populations to make new gene discoveries and to understand variation in disease risk across populations. We expect to be able to make further connections between evolutionary and medical genetics by developing sophisticated approaches for understanding and modeling population mixture.