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Title: Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin
Authors: Shannon Takala-Harrison
Taane G. Clark
Christopher G. Jacob
Michael P. Cummings
Olivo Miotto
Arjen M. Dondorpe
Mark M. Fukuda
Francois Nosten
Harald Noedl
Mallika Imwong
Delia Bethell
Youry Se
Chanthap Lon
Stuart D. Tyner
David L. Saunders
Duong Socheat
Frederic Ariey
Aung Pyae Phyo
Peter Starzengruber
Hans Peter Fuehrer
Paul Swoboda
Kasia Stepniewska
Jennifer Flegg
Cesar Arze
Gustavo C. Cerqueira
Joana C. Silva
Stacy M. Ricklefs
Stephen F. Porcella
Robert M. Stephens
Matthew Adams
Leo J. Kenefic
Susana Campino
Sarah Auburn
Bronwyn MacInnis
Dominic P. Kwiatkowskid
Xin Zhuan Su
Nicholas J. White
Pascal Ringwald
Christopher V. Plowe
University of Maryland School of Medicine
London School of Tropical Medicine
University of Maryland
University of Oxford
Mahidol University
Armed Forces Research Institute of Medical Sciences, Thailand
Shoklo Malaria Research Unit
Medizinische Universitat Wien
Armed Forces Research Institute of Medical Sciences
University of Health Sciences
Institut Pasteur, Paris
University of Maryland, Baltimore
National Institutes of Health, Bethesda
Advanced Biomedical Computing Center
Wellcome Trust Sanger Institute
National Institute of Allergy and Infectious Diseases
Organisation Mondiale de la Sante
Keywords: Multidisciplinary
Issue Date: 2-Jan-2013
Citation: Proceedings of the National Academy of Sciences of the United States of America. Vol.110, No.1 (2013), 240-245
Abstract: The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.
ISSN: 10916490
Appears in Collections:Scopus 2011-2015

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