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The African Genome Variation Project shapes medical genetics in Africa

2014; Nature Portfolio; Volume: 517; Issue: 7534 Linguagem: Inglês

10.1038/nature13997

1476-4687

Deepti Gurdasani, Tommy Carstensen, Fasil Tekola‐Ayele, Luca Pagani, Ioanna Tachmazidou, Konstantinos Hatzikotoulas, Savita Karthikeyan, Louise Iles, Martin Pollard, Ananyo Choudhury, Graham R. S. Ritchie, Yali Xue, Jennifer L. Asimit, Rebecca N. Nsubuga, Elizabeth Young, Cristina Pomilla, Katja Kivinen, Kirk A. Rockett, Anatoli Kamali, Ayo P. Doumatey, Gershim Asiki, Janet Seeley, Fatoumatta Sisay-Joof, Muminatou Jallow, Stephen Tollman, Ephrem Mekonnen, Rosemary Ekong, Tamiru Oljira, Neil Bradman, Kalifa Bojang, Michèle Ramsay, Adebowale Adeyemo, Endashaw Bekele, Ayesha A. Motala, Shane A. Norris, Fraser Pirie, Pontiano Kaleebu, Dominic Kwiatkowski, Chris Tyler‐Smith, Charles N. Rotimi, Eleftheria Zeggini, Manjinder S. Sandhu,

Genetic diversity and population structure

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.