A comprehensive whole genome sequence scan for positive selection in southern Africa

对南部非洲进行全面的全基因组序列扫描以进行正选择

• 批准号: 10732789
• 负责人: Caitlin Uren
• 金额: $ 9.74万
• 依托单位: STELLENBOSCH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-21 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10732789
• 关键词: Address; Admixture; Africa; African; African ancestry; Area; Asian population; Biological; Botswana; Catalogs; Censuses; Cholera; Climate; Collection; Color; Dairy Products; Data; Data Set; Diabetes Mellitus; Disease; Environment; European; Eye Color; Food; Future; Genes; Genetic Variation; Genome; Geography; Gluten; HIV; Hair Color; Haplotypes; Health; Height; Historical Demography; Home; Human; Human Genome; Individual; Malaria; Mentors; Methods; Modeling; Modernization; Namibia; National Human Genome Research Institute; Native-Born; Natural Selections; Pathway interactions; Pattern; Persons; Phase; Phenotype; Population; Probability; Process; Resources; Role; Sample Size; Scanning; Shapes; Signal Transduction; Skin Pigmentation; South Africa; South African; Southeastern Asia; Southern Africa; Statistical Methods; Testing; Training; Translational Research; Tuberculosis; Variant; Work; Zambia; design; disease phenotype; disorder risk; genome sequencing; genome wide association study; genomic data; genomic locus; human disease; improved; in silico; insight; machine learning framework; migration; novel; population genetic structure; pressure; statistics; trait; translational potential; whole genome

PROJECT SUMMARY An African origin for modern humans and the vast genetic diversity in the region is irrefutable. Within Africa, southern Africa is home to the some of the oldest and most diverse extant human populations world-wide. These populations, the KhoeSan, reside predominantly in the north-western parts of South Africa and throughout Namibia and Botswana. In previous work (PMID 27474727), I and two of my mentors showed that fine-scale genetic population structure between these KhoeSan populations reflects ecogeographical boundaries. In addition to this unique KhoeSan ancestry, populations in southern Africa have been shaped by numerous migrations from within Africa (e.g. Bantu-speaking peoples) and outside Africa (notably European and Asian populations). Thus, the patterns of diversity observed in this area is unique with no comparable regions elsewhere in the world. These southern African populations went on to further adapt to their new environment which was plagued by disease, resource limitations and harsh climates. The role of positive selection in this adaption, remains unknown. Using one of the largest whole genome sequencing dataset collections encompassing numerous southern African populations, we aim to: 1) scan these datasets for signals of positive selection and 2) evaluate the functional, biological and potentially translational implications of these signals. This project will be the largest and most comprehensive single study of natural selection on the African continent. The methods developed in this study will inform future scans for natural selection in heterogenous, admixed African populations. Furthermore, the findings will provide insights into how adaptation to the environment has shaped human genomes and in turn, various phenotypes in this unique part of Africa - these results could be informative to all populations with African ancestry.

项目摘要 现代人类的非洲起源和该地区巨大的遗传多样性是无可辩驳的。之内 非洲，南部非洲是世界范围内一些最古老，最多样化的人类人口的所在地。 这些人口，khoesan，主要居住在南非西北部和整个地区 纳米比亚和博茨瓦纳。在以前的工作（PMID 27474727）中，我和我的两名导师表明了细尺度 这些Khoesan人群之间的遗传种群结构反映了生态地理边界。在 除了这个独特的Khoesan血统外，南部非洲的人口已被无数 从非洲境内（例如讲班图语的民族）和非洲以外的迁移（尤其是欧洲和亚洲人 人口）。因此，在该领域观察到的多样性模式是唯一的，没有可比的区域 世界其他地方。这些南部非洲人口继续适应了他们的新环境 疾病，资源限制和恶劣的环境困扰。积极选择在这方面的作用 适应，仍然未知。 使用最大的整个基因组测序数据集集合之一 南部非洲人口，我们的目标是：1）扫描这些数据集以获取肯定选择的信号和2）评估 这些信号的功能，生物学和潜在的翻译意义。这个项目将是最大的 以及最全面的非洲大陆自然选择研究。在 这项研究将为未来的扫描扫描，以在非洲掺杂的非洲人群中自然选择。 此外，这些发现将提供有关适应环境如何影响人类的见解 基因组和非洲这个独特部分的各种表型反过来 - 这些结果可能对所有人都是有益的 非洲血统的人口。