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https://www.arca.fiocruz.br/handle/icict/39721
GENETIC SIGNATURES OF GENE FLOW AND MALARIA-DRIVEN NATURAL SELECTION IN SUB-SAHARAN POPULATIONS OF THE "ENDEMIC BURKITT LYMPHOMA BELT"
Author
Gouveia, Mateus Henrique
Bergen, Andrew W.
Borda, Victor
Nunes, Kelly
Leal, Thiago P.
Ogwang, Martin D.
Yeboah, Edward D.
Mensah, James E.
Kinyera, Tobias
Otim, Isaac
Nabalende, Hadijah
Legason, Ismail D.
Mpoloka, Sununguko Wata
Mokone, Gaonyadiwe George
Kerchan, Patrick
Bhatia, Kishor
Reynolds, Steven J.
Birtwum, Richard B.
Adjei, Andrew A.
Tettey, Yao
Tay, Evelyn
Hoover, Robert
Pfeiffer, Ruth M.
Biggar, Robert J.
Goedert, James J.
Prokunina-Olsson, Ludmila
Dean, Michael
Yeager, Meredith
Costa, Maria Fernanda Furtado Lima
Hsing, Ann W.
Tishkoff, Sarah A.
Chanock, Stephen J.
Santos, Eduardo Tarazona
Mbulaiteye, Sam M.
Bergen, Andrew W.
Borda, Victor
Nunes, Kelly
Leal, Thiago P.
Ogwang, Martin D.
Yeboah, Edward D.
Mensah, James E.
Kinyera, Tobias
Otim, Isaac
Nabalende, Hadijah
Legason, Ismail D.
Mpoloka, Sununguko Wata
Mokone, Gaonyadiwe George
Kerchan, Patrick
Bhatia, Kishor
Reynolds, Steven J.
Birtwum, Richard B.
Adjei, Andrew A.
Tettey, Yao
Tay, Evelyn
Hoover, Robert
Pfeiffer, Ruth M.
Biggar, Robert J.
Goedert, James J.
Prokunina-Olsson, Ludmila
Dean, Michael
Yeager, Meredith
Costa, Maria Fernanda Furtado Lima
Hsing, Ann W.
Tishkoff, Sarah A.
Chanock, Stephen J.
Santos, Eduardo Tarazona
Mbulaiteye, Sam M.
Affilliation
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia. Belo Horizonte, MG, Brasil /Center for Research on Genomics & Global Health, National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia. Belo Horizonte, MG, Brasil.
Universidade de São Paulo. Instituto de Biociências. Departamento de Genética e Biologia Evolutiva. São Paulo, SP, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Departamento de Estatística. Belo Horizonte, MG, Brasil.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
University of Ghana Medical School, Accra, Ghana.
University of Ghana Medical School, Accra, Ghana.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
Department of Biological Sciences. University of Botswana. Gaborone, Botswana.
Department of Biomedical Sciences. University of Botswana School of Medicine. Gaborone, Botswana.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Intramural Research. National Institute of Allergy and Infectious Diseases. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
University of Ghana Medical School. Accra, Ghana.
University of Ghana Medical School. Accra, Ghana.
University of Ghana Medical School. Accra, Ghana.
University of Ghana Medical School. Accra, Ghana.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Laboratory of Translational Genomics. Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. USDepartment of Health and Human Services. Bethesda, Maryland, USA.
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, USA.
Cancer Genomics Research Laboratory. Leidos Biomedical Research. Frederick National Laboratory for Cancer Research. US Department of Health and Human Services. Frederick, Maryland, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Stanford Cancer Institute. Stanford University. Stanford, California, USA.
Department of Genetics and Biology, University of Pennsylvania, Philadelphia, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral. Belo Horizonte, MG, Brasil.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia. Belo Horizonte, MG, Brasil.
Universidade de São Paulo. Instituto de Biociências. Departamento de Genética e Biologia Evolutiva. São Paulo, SP, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Departamento de Estatística. Belo Horizonte, MG, Brasil.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
University of Ghana Medical School, Accra, Ghana.
University of Ghana Medical School, Accra, Ghana.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
Department of Biological Sciences. University of Botswana. Gaborone, Botswana.
Department of Biomedical Sciences. University of Botswana School of Medicine. Gaborone, Botswana.
EMBLEM Study. African Field Epidemiology Network. Kampala, Uganda.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Intramural Research. National Institute of Allergy and Infectious Diseases. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
University of Ghana Medical School. Accra, Ghana.
University of Ghana Medical School. Accra, Ghana.
University of Ghana Medical School. Accra, Ghana.
University of Ghana Medical School. Accra, Ghana.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Laboratory of Translational Genomics. Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. USDepartment of Health and Human Services. Bethesda, Maryland, USA.
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, USA.
Cancer Genomics Research Laboratory. Leidos Biomedical Research. Frederick National Laboratory for Cancer Research. US Department of Health and Human Services. Frederick, Maryland, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Stanford Cancer Institute. Stanford University. Stanford, California, USA.
Department of Genetics and Biology, University of Pennsylvania, Philadelphia, USA.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral. Belo Horizonte, MG, Brasil.
Division of Cancer Epidemiology and Genetics. National Cancer Institute. National Institutes of Health. US Department of Health and Human Services. Bethesda, Maryland, USA.
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.
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