Manske M
Miotto O
Campino S
Auburn S
Almagro-Garcia J
Maslen G
O'Brien J
Djimde A
Doumbo O
Zongo I
Ouedraogo JB
Michon P
Mueller I
Siba P
Nzila A
Borrmann S
Kiara SM
Marsh K
Jiang H
Su XZ
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
Nature. 2012;487375-9
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.
