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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • July 19, 2012

Published In

Volume / Issue

  • 487 / 7407

Start / End Page

  • 375 - 379

PubMed ID

  • 22722859

Pubmed Central ID

  • 22722859

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature11174


  • eng

Conference Location

  • England