Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.
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.
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, SM; Marsh, K; Jiang, H; Su, X-Z; Amaratunga, C; Fairhurst, R; Socheat, D; Nosten, F; Imwong, M; White, NJ; Sanders, M; Anastasi, E; Alcock, D; Drury, E; Oyola, S; Quail, MA; Turner, DJ; Ruano-Rubio, V; Jyothi, D; Amenga-Etego, L; Hubbart, C; Jeffreys, A; Rowlands, K; Sutherland, C; Roper, C; Mangano, V; Modiano, D; Tan, JC; Ferdig, MT; Amambua-Ngwa, A; Conway, DJ; Takala-Harrison, S; Plowe, CV; Rayner, JC; Rockett, KA; Clark, TG; Newbold, CI; Berriman, M; MacInnis, B; Kwiatkowski, DP
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