A Major Genome Region Underlying Artemisinin Resistance in Malaria

Title
A Major Genome Region Underlying Artemisinin Resistance in Malaria
Authors
Cheeseman, IH; Miller, BA; Nair, S; Nkhoma, S; Tan, A; Tan, JC; Al Saai, S; Phyo, AP; Moo, CL; Lwin, KM; McGready, R; Ashley, E; Imwong, M; Stepniewska, K; Yi, P; Dondorp, AM; Mayxay, M; Newton, PN; White, NJ; Nosten, F; Ferdig, MT; Anderson, TJC
Keywords
PLASMODIUM-FALCIPARUM; POSITIVE SELECTION; HIGH-ALTITUDE; PARASITES; POPULATIONS; ADAPTATION; EVOLUTION; SPREAD
Issue Date
2012
Publisher
SCIENCE
Citation
Science;06-Apr;2012;336;6077
Abstract
Evolving resistance to artemisinin-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10(-6) to 10(-12)) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.
URI
http://hdl.handle.net/11267/2343
ISSN
0036-8075
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5.Mahosot Hospital > Journal articles
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