Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia by Miotto Olivo, Almagro-Garcia Jacob, Manske Magnus, Macinnis Bronwyn, Campino Susana, Rockett Kirk A, Amaratunga Chanaki, Lim Pharath, Suon Seila, Sreng Sokunthea, Anderson Jennifer M, Duong Socheat, Nguon Chea, Chuor Char Meng, Saunders David, Se Youry, Lon Chantap, Fukuda Mark M, Amenga-Etego Lucas, Hodgson Abraham V O, Asoala Victor, Imwong Mallika, Takala-Harrison Shannon, Nosten François, Su Xin-Zhuan, Ringwald Pascal, Ariey Frédéric, Dolecek Christiane, Hien Tran Tinh, Boni Maciej F, Thai Cao Quang, Amambua-Ngwa Alfred, Conway David J, Djimdé Abdoulaye A, Doumbo Ogobara K, Zongo Issaka, Ouedraogo Jean-Bosco, Alcock Daniel, Drury Eleanor, Auburn Sarah, Koch Oliver, Sanders Mandy, Hubbart Christina, Maslen Gareth, Ruano-Rubio Valentin, Jyothi Dushyanth, Miles Alistair, O'Brien John, Gamble Chris, Oyola Samuel O, Rayner Julian C, Newbold Chris I, Berriman Matthew, Spencer Chris C A, McVean Gilean, Day Nicholas P, White Nicholas J, Bethell Delia, Dondorp Arjen M, Plowe Christopher V, Fairhurst Rick M, Kwiatkowski Dominic P in Nature genetics (2013). PubMed

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.

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