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PLoS Genet. 2019 Mar 8;15(3):e1008027. doi: 10.1371/journal.pgen.1008027. eCollection 2019 Mar.

Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt".

Author information

1
Instituto de Pesquisa René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
2
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
3
Center for Research on Genomics & Global Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, United States of America.
4
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, United States of America.
5
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
6
Department of Statistics, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
7
EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
8
University of Ghana Medical School, Accra, Ghana.
9
Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
10
Department of Biomedical Sciences, University of Botswana School of Medicine, Gaborone, Botswana.
11
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, United States of America.
12
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, United States of America.
13
Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, US Department of Health and Human Services, Frederick, Maryland, United States of America.
14
Stanford Cancer Institute, Stanford University, Stanford, California, United States of America.
15
Department of Genetics and Biology, University of Pennsylvania, Philadelphia, United States of America.

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.

PMID:
30849090
PMCID:
PMC6426263
DOI:
10.1371/journal.pgen.1008027
[Indexed for MEDLINE]
Free PMC Article

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