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Title: Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing
Authors: Magnus Manske
Olivo Miotto
Susana Campino
Sarah Auburn
Jacob Almagro-Garcia
Gareth Maslen
Jack O'Brien
Abdoulaye Djimde
Ogobara Doumbo
Issaka Zongo
Jean Bosco Ouedraogo
Pascal Michon
Ivo Mueller
Peter Siba
Alexis Nzila
Steffen Borrmann
Steven M. Kiara
Kevin Marsh
Hongying Jiang
Xin Zhuan Su
Chanaki Amaratunga
Rick Fairhurst
Duong Socheat
Francois Nosten
Mallika Imwong
Nicholas J. White
Mandy Sanders
Elisa Anastasi
Dan Alcock
Eleanor Drury
Samuel Oyola
Michael A. Quail
Daniel J. Turner
Valentin Ruano-Rubio
Dushyanth Jyothi
Lucas Amenga-Etego
Christina Hubbart
Anna Jeffreys
Kate Rowlands
Colin Sutherland
Cally Roper
Valentina Mangano
David Modiano
John C. Tan
Michael T. Ferdig
Alfred Amambua-Ngwa
David J. Conway
Shannon Takala-Harrison
Christopher V. Plowe
Julian C. Rayner
Kirk A. Rockett
Taane G. Clark
Chris I. Newbold
Matthew Berriman
Bronwyn MacInnis
Dominic P. Kwiatkowski
Wellcome Trust Sanger Institute
University of Oxford
Mahidol University
Menzies School of Health Research
Wellcome Trust Centre for Human Genetics
University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology
Institut de Recherche en Sciences de la Santé
Papua New Guinea Institute of Medical Research
Wellcome Trust Research Laboratories Nairobi
National Institute of Allergy and Infectious Diseases
Cambodia National Malaria Centre
Shoklo Malaria Research Unit
Navrongo Health Centre
London School of Hygiene & Tropical Medicine
Universita degli Studi di Roma La Sapienza
University of Notre Dame
Medical Research Council Laboratories Gambia
University of Maryland, Baltimore
Weatherall Institute of Molecular Medicine
Keywords: Multidisciplinary
Issue Date: 19-Jul-2012
Citation: Nature. Vol.487, No.7407 (2012), 375-379
Abstract: Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.falciparum genome. © 2012 Macmillan Publishers Limited. All rights reserved.
ISSN: 14764687
Appears in Collections:Scopus 2011-2015

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