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Nature. 2015 Jan 15;517(7534):327-32. doi: 10.1038/nature13997. Epub 2014 Dec 3.

The African Genome Variation Project shapes medical genetics in Africa.

Author information

1
1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
2
Centre for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, MSC 5635, Bethesda, Maryland 20891-5635, USA.
3
1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
4
Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
5
1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK [3] Department of Archaeology, University of York, King's Manor, York YO1 7EP, UK.
6
Sydney Brenner Institute of Molecular Bioscience (SBIMB), University of the Witwatersrand, The Mount, 9 Jubilee Road, Parktown 2193, Johannesburg, Gauteng, South Africa.
7
1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Vertebrate Genomics, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
8
Medical Research Council/Uganda Virus Research Institute, Plot 51-57 Nakiwogo Road, Uganda.
9
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
10
Medical Research Council Unit, Atlantic Boulevard, SerrekundaPO Box 273, Banjul, The Gambia.
11
1] Medical Research Council/Wits Rural Public Health and Health Transitions Unit, School of Public Health, Education Campus, 27 St Andrew's Road, Parktown 2192, Johannesburg, Gauteng, South Africa [2] INDEPTH Network, 38/40 Mensah Wood Street, East Legon, PO Box KD 213, Kanda, Accra, Ghana.
12
Institute of Biotechnology, Addis Ababa University, Entoto Avenue, Arat Kilo, 16087 Addis Ababa, Ethiopia.
13
Department of Genetics Evolution and Environment, University College, London, Gower Street, London WC1E 6BT, UK.
14
University of Haramaya, Department of Biology, PO Box 138, Dire Dawa, Ethiopia.
15
Henry Stewart Group, 28/30 Little Russell Street, London WC1A 2HN, UK.
16
1] Sydney Brenner Institute of Molecular Bioscience (SBIMB), University of the Witwatersrand, The Mount, 9 Jubilee Road, Parktown 2193, Johannesburg, Gauteng, South Africa [2] Division of Human Genetics, National Health Laboratory Service, C/O Hospital and de Korte Streets, Braamfontein 2000, Johannesburg, South Africa [3] School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Braamfontein 2000, Johannesburg, South Africa.
17
Department of Microbial, Cellular and Molecular Biology, College of Natural Sciences, Arat Kilo Campus, Addis Ababa University, PO Box 1176, Addis Ababa, Ethiopia.
18
Department of Diabetes and Endocrinology, University of KwaZulu-Natal, 719 Umbilo Road, Congella, Durban 4013, South Africa.
19
Department of Paediatrics, University of Witwatersrand, 7 York Road, Parktown 2198, Johannesburg, Gauteng, South Africa.
20
1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.

Abstract

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

PMID:
25470054
PMCID:
PMC4297536
DOI:
10.1038/nature13997
[Indexed for MEDLINE]
Free PMC Article

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