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. © 2012 Macmillan Publishers Limited. All rights reserved.

Authors: Manske, M; Manske, M; Miotto, O; Miotto, O; Campino, S

• Journal: Nature
• Volume: 487
• Issue: 7407
• Pages: 375-379
• Publication date: 2012-07-19
• DOI: 10.1038/nature11174
• EISSN: 1476-4687
• ISSN: 0028-0836