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理

• 批准号: 10009451
• 负责人: Brenna M Henn
• 金额: $ 38.12万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10009451
• 关键词: African; African American; Biological Models; Case Study; Collection; Communities; Complex; DNA; European; Genetic Determinism; Genetic Recombination; Genome; Genomics; Genotype; Grant; Height; Heritability; Human; Maps; Measures; Methods; Mind; Modeling; Mutation; Namibia; Outcome; Pattern; Phenotype; Pigmentation physiologic function; Population; Research; Resources; Sample Size; Site; Skin Pigmentation; South Africa; Southern Africa; Testing; Work; causal variant; cohort; disease phenotype; experience; genetic architecture; genetic pedigree; genetic selection; genetic variant; hutterite; improved; portability; programs; trait

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.

项目摘要 在小型，多样的人群中迫切需要种群基因组研究 - 允许 遗传学家表征任何人类疾病/表型的遗传决定因素。 最近已经提出了各种新的复杂性状映射方法，以进行内属或 混合种群。但是，这些方法通常是通过特定的欧洲味开发的 考虑案例研究（例如，在Hutterites，Sardinians）和替代人群中的应用介绍 特殊挑战，特别是在非洲和非裔美国大陆人口中。 我的实验室专门从事非洲基因组多样性，我拥有13年以上的经验 在南部非洲开发队列收藏。测试有关遗传结构和的假设 在非洲队列中的多基因选择模式，我专注于高度可遗传的，易于测量的特征 [例如。高度，皮肤色素沉着]作为识别基因型 - 表型关联的模型系统。 例如，我们表明，在非洲人中，色素沉着的多基因更为复杂 比欧洲人。虽然现场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，像Khoesan一样，都包含遗传 很少在其他地方观察到的变体及其异常的连锁不平衡模式可以 用于微图因果变体。这笔赠款的结果将包括：1）收集DNA，维护 现场站点和我们实验室的南部非洲人口的基本基因组特征 和合作者； 2）使用南部非洲人的重组率和突变模式使用 深部族； 3）使用皮肤色素沉着和高度作为了解可移植性的模型 人群之间的基因型 - 表型关联。