title: Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia.
abstract: We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.
authors.affiliation: Medical Research Council MRC Centre for Genomics and Global Health, University of Oxford, Oxford, UK.
authors.forename: Olivo
authors.initials: O
authors.lastname: Miotto
authors.forename: Jacob
authors.initials: J
authors.lastname: Almagro-Garcia
authors.forename: Magnus
authors.initials: M
authors.lastname: Manske
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Macinnis
authors.forename: Susana
authors.initials: S
authors.lastname: Campino
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.forename: Chanaki
authors.initials: C
authors.lastname: Amaratunga
authors.forename: Pharath
authors.initials: P
authors.lastname: Lim
authors.forename: Seila
authors.initials: S
authors.lastname: Suon
authors.forename: Sokunthea
authors.initials: S
authors.lastname: Sreng
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Socheat
authors.initials: S
authors.lastname: Duong
authors.forename: Chea
authors.initials: C
authors.lastname: Nguon
authors.forename: Char Meng
authors.initials: CM
authors.lastname: Chuor
authors.forename: David
authors.initials: D
authors.lastname: Saunders
authors.forename: Youry
authors.initials: Y
authors.lastname: Se
authors.forename: Chantap
authors.initials: C
authors.lastname: Lon
authors.forename: Mark M
authors.initials: MM
authors.lastname: Fukuda
authors.forename: Lucas
authors.initials: L
authors.lastname: Amenga-Etego
authors.forename: Abraham V O
authors.initials: AV
authors.lastname: Hodgson
authors.forename: Victor
authors.initials: V
authors.lastname: Asoala
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Shannon
authors.initials: S
authors.lastname: Takala-Harrison
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.forename: Xin-Zhuan
authors.initials: XZ
authors.lastname: Su
authors.forename: Pascal
authors.initials: P
authors.lastname: Ringwald
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ariey
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Maciej F
authors.initials: MF
authors.lastname: Boni
authors.forename: Cao Quang
authors.initials: CQ
authors.lastname: Thai
authors.forename: Alfred
authors.initials: A
authors.lastname: Amambua-Ngwa
authors.forename: David J
authors.initials: DJ
authors.lastname: Conway
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimdé
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Issaka
authors.initials: I
authors.lastname: Zongo
authors.forename: Jean-Bosco
authors.initials: JB
authors.lastname: Ouedraogo
authors.forename: Daniel
authors.initials: D
authors.lastname: Alcock
authors.forename: Eleanor
authors.initials: E
authors.lastname: Drury
authors.forename: Sarah
authors.initials: S
authors.lastname: Auburn
authors.forename: Oliver
authors.initials: O
authors.lastname: Koch
authors.forename: Mandy
authors.initials: M
authors.lastname: Sanders
authors.forename: Christina
authors.initials: C
authors.lastname: Hubbart
authors.forename: Gareth
authors.initials: G
authors.lastname: Maslen
authors.forename: Valentin
authors.initials: V
authors.lastname: Ruano-Rubio
authors.forename: Dushyanth
authors.initials: D
authors.lastname: Jyothi
authors.forename: Alistair
authors.initials: A
authors.lastname: Miles
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.forename: Chris
authors.initials: C
authors.lastname: Gamble
authors.forename: Samuel O
authors.initials: SO
authors.lastname: Oyola
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.forename: Chris I
authors.initials: CI
authors.lastname: Newbold
authors.forename: Matthew
authors.initials: M
authors.lastname: Berriman
authors.forename: Chris C A
authors.initials: CC
authors.lastname: Spencer
authors.forename: Gilean
authors.initials: G
authors.lastname: McVean
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Day
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Delia
authors.initials: D
authors.lastname: Bethell
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002160:Cambodia / Q000453:epidemiology; D020223:Chromosome Painting; D016000:Cluster Analysis; D004351:Drug Resistance; D018703:Founder Effect; D017125:Genes, Protozoan; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D008957:Models, Genetic; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin