title: A major genome region underlying artemisinin resistance in malaria.
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.
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Cheeseman
authors.forename: Becky A
authors.initials: BA
authors.lastname: Miller
authors.forename: Shalini
authors.initials: S
authors.lastname: Nair
authors.forename: Standwell
authors.initials: S
authors.lastname: Nkhoma
authors.forename: Asako
authors.initials: A
authors.lastname: Tan
authors.forename: John C
authors.initials: JC
authors.lastname: Tan
authors.forename: Salma
authors.initials: S
authors.lastname: Al Saai
authors.forename: Aung Pyae
authors.initials: AP
authors.lastname: Phyo
authors.forename: Carit Ler
authors.initials: CL
authors.lastname: Moo
authors.forename: Khin Maung
authors.initials: KM
authors.lastname: Lwin
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ashley
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Poravuth
authors.initials: P
authors.lastname: Yi
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.forename: Mayfong
authors.initials: M
authors.lastname: Mayxay
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.forename: Michael T
authors.initials: MT
authors.lastname: Ferdig
authors.forename: Timothy J C
authors.initials: TJ
authors.lastname: Anderson
mesh_terms: D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D002160:Cambodia; D056915:DNA Copy Number Variations; D004351:Drug Resistance / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D018503:Genome, Protozoan; D006239:Haplotypes; D006801:Humans; D007812:Laos; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D018895:Microsatellite Repeats; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics; D012641:Selection, Genetic; D013785:Thailand
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D015800:Protozoan Proteins; C031327:artemisinin