Supplemental: Improving Inference of Genetic Architecture and Selection with African Genomes

项目摘要 迫切需要在小而多样的队列中进行种群基因组研究--允许 遗传学家对任何人类群体的疾病/表型的遗传决定因素进行表征。 最近提出了各种新的复杂性状定位方法，用于内婚制或 混杂种群。然而，这些方法的发展往往带有特定的欧洲血统。 考虑到的案例研究(例如，在哈特人和撒丁岛人中)和对替代队列的应用介绍 特别挑战，特别是在非洲大陆和非洲裔美国人群体中。 我的实验室专门研究非洲的基因组多样性，我有超过13年的经验 在南部非洲发展队列收藏。来检验关于遗传结构的假说 在非洲群体中的多基因选择模式，我关注的是高度可遗传的、容易测量的性状 [例如身高、皮肤色素沉着]作为识别基因-表型关联的模式系统。 例如，我们已经证明，非洲人的色素沉着的多源性要复杂得多。 而不是欧洲人。虽然实地工作是我实验室研究计划的核心，但它也提供了一个至关重要的 为其他研究小组提供基因组资源。南部非洲人，像科桑人一样，含有基因 在其他地方很少观察到的变异及其不寻常的连锁不平衡模式可能 用于对因果变量进行精细映射。这笔赠款的成果将包括：1)收集DNA，维护 为我们的实验室提供野外地点和南部非洲人口的基本基因组特征 和合作者；2)估计南部非洲人的重组率和突变模式 深厚的家系；3)使用皮肤色素沉着和身高作为模型来理解 不同群体间的基因-表型关联。

Project Summary There is a pressing need for population genomic research in small, diverse cohorts -- allowing geneticists to characterize the genetic determinants of disease/phenotype for any human community. A variety of new complex trait mapping methods have been recently proposed for endogamous or admixed populations. However, these methods were often developed with specific European-descent case-studies in mind (e.g. in Hutterites, Sardinians) and application to alternative cohorts introduces special challenges, especially in continental African and African-American populations. My lab specializes in African genomic diversity and I have over 13 years experience developing cohort collections in southern Africa. To test hypotheses about genetic architecture and polygenic selection patterns in African cohorts, I focus on highly heritable, easily measured traits [e.g. height, skin pigmentation] as model systems for identifying genotype-phenotype associations. We have shown, for example, that the polygenicity of pigmentation is far more complex in Africans than in Europeans. While field work is central to my lab's research program, it also provides a crucial genomic resource for other research groups. Southern Africans, like the KhoeSan, contain genetic variants which are rarely observed elsewhere and their unusual patterns of linkage disequilbrium can be used to fine-map causal variants. Outcomes of this grant will include: 1) collect DNA, maintain field sites and characterize fundamental genomic features of southern African populations for our lab and collaborators; 2) estimate recombination rates and mutational patterns in southern Africans using deep pedigrees; 3) use skin pigmentation and height as models for understanding the portability of genotype-phenotype associations across populations.