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


ABSTRACT: 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.

SUBMITTER: Manske M 

PROVIDER: S-EPMC3738909 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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

Manske Magnus M   Miotto Olivo O   Campino Susana S   Auburn Sarah S   Almagro-Garcia Jacob J   Maslen Gareth G   O'Brien Jack J   Djimde Abdoulaye A   Doumbo Ogobara O   Zongo Issaka I   Ouedraogo Jean-Bosco JB   Michon Pascal P   Mueller Ivo I   Siba Peter P   Nzila Alexis A   Borrmann Steffen S   Kiara Steven M SM   Marsh Kevin K   Jiang Hongying H   Su Xin-Zhuan XZ   Amaratunga Chanaki C   Fairhurst Rick R   Socheat Duong D   Nosten Francois F   Imwong Mallika M   White Nicholas J NJ   Sanders Mandy M   Anastasi Elisa E   Alcock Dan D   Drury Eleanor E   Oyola Samuel S   Quail Michael A MA   Turner Daniel J DJ   Ruano-Rubio Valentin V   Jyothi Dushyanth D   Amenga-Etego Lucas L   Hubbart Christina C   Jeffreys Anna A   Rowlands Kate K   Sutherland Colin C   Roper Cally C   Mangano Valentina V   Modiano David D   Tan John C JC   Ferdig Michael T MT   Amambua-Ngwa Alfred A   Conway David J DJ   Takala-Harrison Shannon S   Plowe Christopher V CV   Rayner Julian C JC   Rockett Kirk A KA   Clark Taane G TG   Newbold Chris I CI   Berriman Matthew M   MacInnis Bronwyn B   Kwiatkowski Dominic P DP  

Nature 20120701 7407


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 contro  ...[more]

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