Journal Article

A Major Genome Region Underlying Artemisinin Resistance in Malaria

Yi, Poravuth, Tan, Asako, White, Nicholas J., Miller, Becky A., Nkhoma, Standwell, Tan, John C., Mayxay, Mayfong, Cheeseman, Ian H., Anderson, Timothy J. C., Newton, Paul N., Saai, Salma Al, Lwin, Khin Maung, Imwong, Mallika, Stepniewska, Kasia, Ashley, Elizabeth, Nair, Shalini, Dondorp, Arjen M., Ferdig, Michael T., Phyo, Aung Pyae, Moo, Carit Ler, McGready, Rose, Nosten, François

2012

Overview

Evolving resistance to arte misi ni n-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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Antimalarials - pharmacology / Antimalarials - therapeutic use / artemisinin / Artemisinins / Artemisinins - pharmacology / Artemisinins - therapeutic use / Biodiversity / Biological and medical sciences / Cambodia / Chromosomes / DNA Copy Number Variations / Drug resistance / Drug Resistance - genetics / Evolutionary genetics / Gene Frequency / General aspects / Genetic Association Studies / Genetic loci / genome / Genome, Protozoan / Genomes / Half lives / Haplotypes / Human protozoal diseases / Humans / Individualized Instruction / Infectious diseases / Laos / Malaria / Malaria, Falciparum - drug therapy / Malaria, Falciparum - parasitology / Medical genetics / Medical sciences / Microsatellite Repeats / Mutation / Parasites / Parasitic diseases / Plasmodium falciparum - drug effects / Plasmodium falciparum - genetics / Polymorphism, Single Nucleotide / Protozoal diseases / Protozoan Proteins - genetics / Selection, Genetic / single nucleotide polymorphism / Thailand / Vector-borne diseases