Journal article

Genomic epidemiology of artemisinin resistant malaria

Roberto Amato, Olivo Miotto, Charles J Woodrow, Jacob Almagro-Garcia, Ipsita Sinha, Susana Campino, Daniel Mead, Eleanor Drury, Mihir Kekre, Mandy Sanders, Alfred Amambua-Ngwa, Chanaki Amaratunga, Lucas Amenga-Etego, Voahangy Andrianaranjaka, Tobias Apinjoh, Elizabeth Ashley, Sarah Auburn, Gordon A Awandare, Vito Baraka, Alyssa Barry Show all

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2016

Abstract

The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variation..

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Grants

Awarded by Wellcome Trust


Awarded by Medical Research Council


Awarded by Bill and Melinda Gates Foundation


Awarded by FOGARTY INTERNATIONAL CENTER


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

Wellcome Trust WT Sanger Institute Core Funding, 98051 Roberto Amato Susana Campino Daniel Mead Eleanor Drury Mihir Kekre Mandy Sanders Victoria J Cornelius Rachel Giacomantonio Dawn Muddyman Cinzia Malangone Dushyanth Jyothi Richard D Pearson Julian C Rayner Kirk A Rockett Alistair Miles Heinrich M Manske Jim Stalker Bronwyn MacInnis Dominic P KwiatkowskiWellcome Trust WT Centre for Human Genetics Core Funding, 090532/Z/09/Z Roberto Amato Jacob Almagro-Garcia Victoria J Cornelius Rachel Giacomantonio Christa Henrichs Richard D Pearson Gilean McVean Kirk A Rockett Alistair Miles Paul Vauterin Ben Jeffery Dominic P KwiatkowskiWellcome Trust WT Stategic Award, 90770 Roberto Amato Olivo Miotto Jacob Almagro-Garcia Susana Campino Daniel Mead Eleanor Drury Mihir Kekre Lucas Amenga-Etego Tobias Apinjoh Abdoulaye Djimde Deus Ishengoma Milijaona Randrianarivelojosia Victoria J Cornelius Rachel Giacomantonio Dawn Muddyman Christa Henrichs Cinzia Malangone Dushyanth Jyothi Richard D Pearson Kirk A Rockett Alistair Miles Paul Vauterin Ben Jeffery Heinrich M Manske Jim Stalker Bronwyn MacInnis Dominic P KwiatkowskiMedical Research Council Centre for Genomics and Global Health, G0600718 Roberto Amato Olivo Miotto Jacob Almagro-Garcia Lucas Amenga-Etego Tobias Apinjoh Abdoulaye Djimde Deus Ishengoma Victoria J Cornelius Rachel Giacomantonio Dawn Muddyman Gilean McVean Kirk A Rockett Alistair Miles Paul Vauterin Ben Jeffery Heinrich M Manske Jim Stalker Bronwyn MacInnis Dominic P KwiatkowskiBill and Melinda Gates Foundation Grant OPP1040463 Roberto Amato Olivo Miotto Charles J Woodrow Ipsita Sinha Elizabeth Ashley Nicholas P Day Arjen M Dondorp Mallika Imwong Nicholas J White Dominic P KwiatkowskiWellcome Trust WT Mahidol University Oxford Tropical Medicine Research Programme, 0892375/H/09/Z Olivo Miotto Charles J Woodrow Ipsita Sinha Elizabeth Ashley Nicholas P Day Arjen M Dondorp Caterina I Fanello Mayfong Mayxay Paul N Newton Francois Nosten Nicholas J WhiteNational Institute of Allergy and Infectious Diseases Intramural Research Program Chanaki Amaratunga Rick M Fairhurst Pharath Lim