Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

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.

• 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
• Journal: Nature (Nature) Vol. 487 Issue 7407 Pg. 375-9 (Jul 19 2012) ISSN: 1476-4687 [Electronic] England
• PMID: 22722859 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Topics

• Alleles
• Biodiversity
• Genome, Protozoan
• Genotype
• High-Throughput Nucleotide Sequencing
• Humans
• Malaria, Falciparum (parasitology)
• Phylogeny
• Plasmodium falciparum (classification, genetics)
• Polymorphism, Single Nucleotide
• Principal Component Analysis