Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt"
Year: 2019
Type: article
Study design: Observational Study
Abstract: Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects populations with intense malaria exposure, in the so called "eBL belt" in sub-Saharan Africa. However, the effects of intense malaria exposure and sub-Saharan populations' genetic histories remain poorly explored. To determine if historical migrations and intense malaria exposure have shaped the genetic composition of the eBL belt populations, we genotyped ~4.3 million SNPs in 1,708 individuals from Ghana and Northern Uganda, located on opposite sides of eBL belt and with ≥ 7 months/year of intense malaria exposure and published evidence of high incidence of BL. Among 35 Ghanaian tribes, we showed a predominantly West-Central African ancestry and genomic footprints of gene flow from Gambian and East African populations. In Uganda, the North West population showed a predominantly Nilotic ancestry, and the North Central population was a mixture of Nilotic and Southern Bantu ancestry, while the Southwest Ugandan population showed a predominant Southern Bantu ancestry. Our results support the hypothesis of diverse ancestral origins of the Ugandan, Kenyan and Tanzanian Great Lakes African populations, reflecting a confluence of Nilotic, Cushitic and Bantu migrations in the last 3000 years. Natural selection analyses suggest, for the first time, a strong positive selection signal in the ATP2B4 gene (rs10900588) in Northern Ugandan populations. These findings provide important baseline genomic data to facilitate disease association studies, including of eBL, in eBL belt populations.
Source: PLoS Genetics
Authors: Mateus H. Gouveia, Andrew W. Bergen, Victor Borda, Kelly Nunes, Thiago P. Leal, Martin D. Ogwang, Edward D. Yeboah, James E. Mensah, Tobias Kinyera, Isaac Otim, Hadijah Nabalende, Ismail D. Legason, Sununguko Wata Mpoloka, Gaonyadiwe George Mokone, Patrick Kerchan, Kishor Bhatia, Steven J. Reynolds, Richard B. Birtwum, Andrew A. Adjei, Yao Tettey, Evelyn Tay, Robert Hoover, Ruth M. Pfeiffer, Robert J. Biggar, James J. Goedert, Ludmila Prokunina-Olsson, Michael Dean, Meredith Yeager, M. Fernanda Lima-Costa, Ann W. Hsing, Sarah A. Tishkoff, Stephen J. Chanock, Eduardo Tarazona-Santos, Sam M. Mbulaiteye
Institutions: Universidade Federal de Minas Gerais, National Institutes of Health, Fundação Oswaldo Cruz, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Universidade de São Paulo, African Field Epidemiology Network, University of Ghana, University of Botswana, National Institute of Allergy and Infectious Diseases, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), Stanford Cancer Institute, Stanford University, University of Pennsylvania
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,350
Funders: U.S. Department of Health and Human Services, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Universidade Federal de Minas Gerais, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Awards: G1131822963, G1164920944, G1645577398, G168645203, G2047198652, G233101189, G237172224, G2480940925, G2848099663, G3138332842, Integrative Genomic Analyses of Human Evolution and Adaptation in Africa, G5747877973, Integrative Genomics of Body Size and Metabolism in Ethnically Diverse Africans, G6284412508, G6404751656, G655501369, G6832470332, G7585116665, G8262246763, G8501068810, Theoretical Population Genetics, G9000010462, G9000048784, G9000138908, G9000234425, G9000335224
OpenAlex ID: W2921086355