Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

• Main 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
• Other Authors: Wellcome Trust Sanger Institute
• Format: Article
• Published: 2018
• Subjects: Multidisciplinary
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/15243
• Institution: Mahidol University

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.