A Major Genome Region Underlying Artemisinin Resistance in Malaria

Author:

Cheeseman Ian H.1,Miller Becky A.2,Nair Shalini1,Nkhoma Standwell1,Tan Asako2,Tan John C.2,Al Saai Salma1,Phyo Aung Pyae3,Moo Carit Ler3,Lwin Khin Maung3,McGready Rose345,Ashley Elizabeth345,Imwong Mallika4,Stepniewska Kasia456,Yi Poravuth7,Dondorp Arjen M.45,Mayxay Mayfong8,Newton Paul N.58,White Nicholas J.45,Nosten François345,Ferdig Michael T.2,Anderson Timothy J. C.1

Affiliation:

1. Texas Biomedical Research Institute, San Antonio, TX 78245, USA.

2. The Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.

3. Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand.

4. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

5. Centre for Tropical Medicine, Churchill Hospital, Oxford, UK.

6. Worldwide Antimalarial Resistance Network, Oxford, UK.

7. The National Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.

8. Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People’s Democratic Republic.

Abstract

Narrowing Down Artemisinin Resistance Knowing that antimalarial drug resistance is characterized by selective sweeps and reduced diversity around resistance mutations, Cheeseman et al. (p. 79 ) looked for signatures of selection in a modified genome-wide association study in parasite populations from Cambodia, Laos, and Thailand. Thirty-three regions showed evidence of selection and enrichment of known antimalarial resistance genes. Fine-mapping of parasite samples taken during the past decade narrowed the association down to a 35-kb region of seven genes on chromosome 13 that seemed to explain at least 35% of the observed reduction in parasite clearance rate. However, the absence of strong candidate mutations suggests the involvement of noncoding regulatory mutations.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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