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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结