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Title: The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background
Authors: Lei Zhu
Jaishree Tripathi
Frances Maureen Rocamora
Olivo Miotto
Rob van der Pluijm
Till S. Voss
Sachel Mok
Dominic P. Kwiatkowski
François Nosten
Nicholas P.J. Day
Nicholas J. White
Arjen M. Dondorp
Zbynek Bozdech
Aung Pyae Phyo
Elizabeth A. Ashley
Frank Smithuis
Khin Lin
Kyaw Myo Tun
M. Abul Faiz
Mayfong Mayxay
Mehul Dhorda
Nguyen Thanh Thuy-Nhien
Paul N. Newton
Sasithon Pukrittayakamee
Tin M. Hlaing
Tran Tinh Hien
Ye Htut
Columbia University Medical Center
University of Oxford
Universitat Basel
Swiss Tropical and Public Health Institute (Swiss TPH)
Mahidol University
Nuffield Department of Clinical Medicine
Wellcome Sanger Institute
Nanyang Technological University
Malaria Research Group and Dev Care Foundation
Mahosot Hospital
Defence Services Medical Research Centre
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry;Physics and Astronomy
Issue Date: 1-Dec-2018
Citation: Nature Communications. Vol.9, No.1 (2018)
Abstract: © 2018, The Author(s). The predisposition of parasites acquiring artemisinin resistance still remains unclear beyond the mutations in Pfk13 gene and modulation of the unfolded protein response pathway. To explore the chain of casualty underlying artemisinin resistance, we reanalyze 773 P. falciparum isolates from TRACI-study integrating TWAS, GWAS, and eQTL analyses. We find the majority of P. falciparum parasites are transcriptomically converged within each geographic site with two broader physiological profiles across the Greater Mekong Subregion (GMS). We report 8720 SNP-expression linkages in the eastern GMS parasites and 4537 in the western. The minimal overlap between them suggests differential gene regulatory networks facilitating parasite adaptations to their unique host environments. Finally, we identify two genetic and physiological backgrounds associating with artemisinin resistance in the GMS, together with a farnesyltransferase protein and a thioredoxin-like protein which may act as vital intermediators linking the Pfk13 C580Y mutation to the prolonged parasite clearance time.
ISSN: 20411723
Appears in Collections:Scopus 2018

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