Improving Inference of Genetic Architecture and Selection with African Genomes

利用非洲基因组改进遗传结构和选择的推断

基本信息

批准号：
10226849
负责人：
Brenna M Henn
金额：
$ 38.4万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-05 至 2024-07-31
项目状态：
已结题

项目摘要

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.

项目概要迫切需要在小型、多样化的群体中进行群体基因组研究——允许遗传学家来描述任何人类群体疾病/表型的遗传决定因素。最近提出了多种新的复杂性状作图方法，用于内婚或混合人群。然而，这些方法通常是由特定的欧洲血统开发的考虑到的案例研究（例如在哈特派、撒丁岛）以及对替代群体的应用介绍了特殊的挑战，尤其是非洲大陆和非裔美国人。我的实验室专门研究非洲基因组多样性，我有超过 13 年的经验在南部非洲开发队列收藏。测试有关遗传结构的假设非洲群体的多基因选择模式，我关注高度遗传、易于测量的性状 [例如。身高、皮肤色素沉着]作为识别基因型-表型关联的模型系统。例如，我们已经证明，非洲人的色素沉着的多基因性要复杂得多比欧洲人。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，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以用于精细映射因果变异。这笔赠款的成果将包括：1）收集 DNA、维护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) 使用以下方法估计南部非洲人的重组率和突变模式深厚的血统； 3）使用皮肤色素沉着和身高作为模型来理解便携性跨人群的基因型-表型关联。