Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.
Manske, Magnus 1,2,*; Miotto, Olivo 2,3,*; Campino, Susana 1,2; Auburn, Sarah 1,2,4; Almagro-Garcia, Jacob 1,2,5; Maslen, Gareth 1,2; O'Brien, Jack 2,5; Djimde, Abdoulaye 6; Doumbo, Ogobara 6; Zongo, Issaka 7; Ouedraogo, Jean-Bosco 7; Michon, Pascal 8; Mueller, Ivo 8; Siba, Peter 8; Nzila, Alexis 9; Borrmann, Steffen 9; Kiara, Steven M. 9; Marsh, Kevin 9; Jiang, Hongying 10; Su, Xin-Zhuan 10; Amaratunga, Chanaki 10; Fairhurst, Rick 10; Socheat, Duong 11; Nosten, Francois 3,12,13; Imwong, Mallika 14; White, Nicholas J. 3,13; Sanders, Mandy 1; Anastasi, Elisa 1; Alcock, Dan 1; Drury, Eleanor 1; Oyola, Samuel 1; Quail, Michael A. 1; Turner, Daniel J. 1; Ruano-Rubio, Valentin 1,2,5; Jyothi, Dushyanth 1,2; Amenga-Etego, Lucas 2,5,15; Hubbart, Christina 5; Jeffreys, Anna 5; Rowlands, Kate 5; Sutherland, Colin 16; Roper, Cally 16; Mangano, Valentina 17; Modiano, David 17; Tan, John C. 18; Ferdig, Michael T. 18; Amambua-Ngwa, Alfred 19; Conway, David J. 16,19; Takala-Harrison, Shannon 20; Plowe, Christopher V. 20; Rayner, Julian C. 1; Rockett, Kirk A. 1,2,5; Clark, Taane G. 1,2,16; Newbold, Chris I. 1,2,21; Berriman, Matthew 1; MacInnis, Bronwyn 1,2; Kwiatkowski, Dominic P. 1,2,5
[Letter]
Nature.
487(7407):375-379, July 19, 2012.
(Format: HTML, PDF)
: 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 1,2. 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.
(C) 2012 Nature Publishing Group
