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

项目摘要 迫切需要在小规模、多样化的群体中进行人口基因组研究， 遗传学家描述任何人类社区疾病/表型的遗传决定因素。 最近提出了各种新的复杂性状定位方法，用于内婚或 混合种群然而，这些方法往往是与特定的欧洲血统， 考虑到案例研究（例如，在赫特人，撒丁岛）和应用到替代队列介绍 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， 在南部非洲发展群组收集。为了验证关于遗传结构的假设， 在非洲群体中的多基因选择模式，我专注于高度遗传，易于测量的性状 [e.g.身高，皮肤色素沉着]作为模型系统，用于识别基因型-表型关联。 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 比欧洲人。虽然野外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 其他研究小组的基因组资源。南部非洲人，如KhoeSan人， 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， 用于精细绘制因果变异。这项赠款的成果将包括：1）收集DNA， 实地考察，并为我们的实验室描述南部非洲人群的基本基因组特征 和合作者; 2）估计重组率和突变模式在南部非洲使用 深谱系; 3）使用皮肤色素沉着和身高作为模型，以了解便携性 基因型-表型的相关性。

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.