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Title: Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia
Authors: Olivo Miotto
Jacob Almagro-Garcia
Magnus Manske
Bronwyn MacInnis
Susana Campino
Kirk A. Rockett
Chanaki Amaratunga
Pharath Lim
Seila Suon
Sokunthea Sreng
Jennifer M. Anderson
Socheat Duong
Chea Nguon
Char Meng Chuor
David Saunders
Youry Se
Chantap Lon
Mark M. Fukuda
Lucas Amenga-Etego
Abraham V.O. Hodgson
Victor Asoala
Mallika Imwong
Shannon Takala-Harrison
François Nosten
Xin Zhuan Su
Pascal Ringwald
Frédéric Ariey
Christiane Dolecek
Tran Tinh Hien
Maciej F. Boni
Cao Quang Thai
Alfred Amambua-Ngwa
David J. Conway
Abdoulaye A. Djimdé
Ogobara K. Doumbo
Issaka Zongo
Jean Bosco Ouedraogo
Daniel Alcock
Eleanor Drury
Sarah Auburn
Oliver Koch
Mandy Sanders
Christina Hubbart
Gareth Maslen
Valentin Ruano-Rubio
Dushyanth Jyothi
Alistair Miles
John O'Brien
Chris Gamble
Samuel O. Oyola
Julian C. Rayner
Chris I. Newbold
Matthew Berriman
Chris C.A. Spencer
Gilean McVean
Nicholas P. Day
Nicholas J. White
Delia Bethell
Arjen M. Dondorp
Christopher V. Plowe
Rick M. Fairhurst
Dominic P. Kwiatkowski
University of Oxford
Mahidol University
Wellcome Trust Sanger Institute
Wellcome Trust Centre for Human Genetics
National Institute of Allergy and Infectious Diseases
National Center for Parasitology, Entomology and Malaria Control
Armed Forces Research Institute of Medical Sciences, Thailand
Armed Forces Health Surveillance Center
Navrongo Health Research Center
University of Maryland School of Medicine
Shoklo Malaria Research Unit
Organisation Mondiale de la Sante
Institut Pasteur, Paris
Oxford University Clinical Research Unit
Medical Research Council Laboratories Gambia
London School of Hygiene & Tropical Medicine
University of Sciences
Institut de Recherche en Sciences de la Santé
Menzies School of Health Research
Weatherall Institute of Molecular Medicine
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jun-2013
Citation: Nature Genetics. Vol.45, No.6 (2013), 648-655
Abstract: We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination. © 2013 Nature America, Inc. All rights reserved.
ISSN: 15461718
Appears in Collections:Scopus 2011-2015

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