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Early identification of causal genetic variants underlying antimalarial drug resistance could provide robust epidemiological tools for timely public health interventions. Using a novel natural genetics strategy for mapping novel candidate genes we analyzed >75,000 high quality single nucleotide polymorphisms selected from high-resolution whole-genome sequencing data in 27 isolates of Plasmodium falciparum. We identified genetic variants associated with susceptibility to dihydroartemisinin that implicate one region on chromosome 13, a candidate gene on chromosome 1 (PFA0220w, a UBP1 ortholog) and others (PFB0560w, PFB0630c, PFF0445w) with putative roles in protein homeostasis and stress response. There was a strong signal for positive selection on PFA0220w, but not the other candidate loci. Our results demonstrate the power of full-genome sequencing-based association studies for uncovering candidate genes that determine parasite sensitivity to artemisinins. Our study provides a unique reference for the interpretation of results from resistant infections.

Original publication

DOI

10.1038/srep03318

Type

Journal article

Journal

Scientific reports

Publication Date

25/11/2013

Volume

3

Addresses

1] KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya [2] Institute of Microbiology, Magdeburg University School of Medicine, Germany.

Keywords

Humans, Plasmodium falciparum, Malaria, Falciparum, Artemisinins, DNA, Protozoan, Antimalarials, Parasitic Sensitivity Tests, Sequence Analysis, DNA, Base Sequence, Drug Resistance, Polymorphism, Single Nucleotide, Genome, Protozoan, Kenya, High-Throughput Nucleotide Sequencing