Theory, Methods, and Resources for Understanding and Leveraging Spatial Variation in Population Genetic Data

项目摘要 在许多物种中，遗传变异背后的进化过程是由 个体的地理分布以及地理如何影响繁殖和扩散模式。 在人类遗传学中，等位基因频率的地理模式对人类遗传学具有重要的实际意义。 全基因组关联研究，因为它可以与其他空间变化因素产生混淆 有影响力的特质它还与发现罕见的功能丧失变异载体有关。传染 在疾病的传播过程中，新适应性变异的到来和传播是由地理扩散模式介导的。 在这个项目中，我们将开发理论，方法和资源，将明确的地理 成分在第一个研究领域，我们将开发新的理论模型来调查影响 不同的空间采样策略检测有害等位基因，如功能丧失等位基因。 我们还将研究优势等位基因在具有超级传播者和长距离传播者的群体中的传播 扩散，以及基于图形的扩散动力学，在一系列的分析，是相关的， 了解适应性变异在人类传播的病原体中的传播。在第二个研究领域， 我们将扩展一套理解遗传数据空间结构的方法。具体来说，我们希望 建立更准确地捕捉定向和长距离迁移的模型。在第三个研究领域， 我们将继续维护和开发用于可视化等位基因地理分布的资源， 频率.这三个研究领域是协同作用的，理想情况下将有助于促进我们对 包括人类在内的许多物种的遗传变异。

PROJECT SUMMARY Across many species, the evolutionary processes that underlie genetic variation are structured by the geographical distribution of individuals and how geography impacts patterns of reproduction and dispersal. In human genetics, geographic patterning in allele frequencies has important practical consequences for genome-wide association studies, as it can produce a type of confounding with other spatially varying factors impacting traits. It also has relevance for the discovery of rare loss-of-function variant carriers. In infectious disease, the arrival and spread of novel adaptive variants is mediated by geographic dispersal patterns. In this project, we will develop theory, methods, and resources that incorporate an explicitly geographic component. In the first research area, we will develop new theoretical models for investigating the impacts of varying spatial sampling strategies on the detection of deleterious alleles, such as loss-of-function alleles. We will also study the spread of advantageous alleles in populations with super-spreaders and long-distance dispersal, as well as graph-based dispersal dynamics, in a series of analyses that is relevant for understanding the spread of adaptive variants in human-dispersed pathogens. In the second research area, we will expand a set of methods for understanding spatial structure in genetic data. Specifically, we hope to build models that more accurately capture directional and long-distance migration. In the third research area, we will continue to maintain and develop resources for visualizing geographic distributions in allele frequencies. These three research areas are synergistic and ideally will help advance our understanding of genetic variation in numerous species, including humans.