Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Magnus Manske, Olivo Miotto, Susana Campino, Sarah Auburn, Jacob Almagro-Gracia, Gareth Maslen, J O'Brien, Abdoulaye Djimde, Ogobara Doumbo, Issaka Zongo, Jean Ouedraogo, Pascal Michon, Ivo Mueller, Peter Siba, Alexis Nzila, Steffen Borrman, Steven Kiara, Kevin Marsh, Hongying Jiang, Xin-Zhuan SuChanaki Amaratunga, Rick Fairhurst, Duong Socheat, François Nosten, Mallika Imwong, Nicholas J White, Mandy Sanders, Elisa Anastasi, Daniel Alcock, Eleanor Drury, S Oyola, Michael Quail, Daniel Turner, V Ruano-Rubio, D Jyothi, Lucas Amenga-Etego, C Hubbart, A Jeffreys, Kate Rowlands, Colin Sutherland, C Roper, Valentina Mangano, David Modiano, J Tan, M Ferdig, A Amambua-Ngwa, D Conway, Shannon Takala-Harrison, C Plowe, J Rayner, Kirk Rockett, Taane Clark, Christopher Newbold, M Berriman, Bronwyn MacInnis, Dominic Kwiatkowski

    Research output: Contribution to journalArticle

    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.
    Original languageEnglish
    Pages (from-to)375-379
    Number of pages5
    JournalNature
    Volume487
    DOIs
    Publication statusPublished - 19 Jul 2012

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  • Cite this

    Manske, M., Miotto, O., Campino, S., Auburn, S., Almagro-Gracia, J., Maslen, G., O'Brien, J., Djimde, A., Doumbo, O., Zongo, I., Ouedraogo, J., Michon, P., Mueller, I., Siba, P., Nzila, A., Borrman, S., Kiara, S., Marsh, K., Jiang, H., ... Kwiatkowski, D. (2012). Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature, 487, 375-379. https://doi.org/10.1038/nature11174