1. The African Genome Variation Project shapes medical genetics in Africa
- Author
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Gershim Asiki, Fasil Tekola-Ayele, Stephen Tollman, Dominic P. Kwiatkowski, Eleftheria Zeggini, Adebowale Adeyemo, Manjinder S. Sandhu, Luca Pagani, Ayesha A. Motala, Charles N. Rotimi, Deepti Gurdasani, Kalifa Bojang, Tommy Carstensen, Yali Xue, Elizabeth H. Young, Anatoli Kamali, Savita Karthikeyan, Tamiru Oljira, Neil Bradman, Rebecca N. Nsubuga, Katja Kivinen, Muminatou Jallow, Janet Seeley, Fatoumatta Sisay-Joof, Jennifer L. Asimit, Ephrem Mekonnen, Louise Iles, Endashaw Bekele, Graham R. S. Ritchie, Ananyo Choudhury, Pontiano Kaleebu, Rosemary Ekong, Konstantinos Hatzikotoulas, Martin O. Pollard, Fraser J. Pirie, Michèle Ramsay, Shane A. Norris, K Rockett, Ayo P. Doumatey, Cristina Pomilla, Ioanna Tachmazidou, Chris Tyler-Smith, Asimit, Jennifer [0000-0002-4857-2249], Kivinen, Katja [0000-0002-1135-7625], Sandhu, Manjinder [0000-0002-2725-142X], and Apollo - University of Cambridge Repository
- Subjects
medicine.medical_specialty ,Asia ,Genetics, Medical ,Population genetics ,Biology ,Genome variation ,Risk Factors ,Genotype ,Genetic variation ,parasitic diseases ,medicine ,Humans ,Selection, Genetic ,Africa South of the Sahara ,Genetics ,Genetic diversity ,Multidisciplinary ,Genome, Human ,Haplotype ,Genetic Variation ,Genomics ,3. Good health ,Europe ,Evolutionary biology ,Africa ,Medical genetics ,Imputation (genetics) - 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.
- Published
- 2014