Abstract

Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Manske, M. Miotto, O. Campino, S. Auburn, S. Almagro-Garcia, J. Maslen, G. O'Brien, J. Djimde, A. Doumbo, O. Zongo, I. Ouedraogo, J. B. Michon, P. Mueller, I. Siba, P. Nzila, A. Borrmann, S. Kiara, S. M. Marsh, K. Jiang, H. Su, X. Z. Amaratunga, C. Fairhurst, R. Socheat, D. Nosten, F. Imwong, M. White, N. J. Sanders, M. Anastasi, E. Alcock, D. Drury, E. Oyola, S. Quail, M. A. Turner, D. J. Ruano-Rubio, V. Jyothi, D. Amenga-Etego, L. Hubbart, C. Jeffreys, A. Rowlands, K. Sutherland, C. Roper, C. Mangano, V. Modiano, D. Tan, J. C. Ferdig, M. T. Amambua-Ngwa, A. Conway, D. J. Takala-Harrison, S. Plowe, C. V. Rayner, J. C. Rockett, K. A. Clark, T. G. Newbold, C. I. Berriman, M. MacInnis, B. Kwiatkowski, D. P.
Nature. 2012; 487375-9

Permanent descriptor

https://doi.org/10.1038/nature11174

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.