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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 publication

DOI

10.1038/nature11174

Type

Journal article

Journal

Nature

Publication Date

19/07/2012

Volume

487

Pages

375 - 379

Keywords

Alleles, Biodiversity, Genome, Protozoan, Genotype, High-Throughput Nucleotide Sequencing, Humans, Malaria, Falciparum, Phylogeny, Plasmodium falciparum, Polymorphism, Single Nucleotide, Principal Component Analysis