Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia

Olivo Miotto, Jacob Almagro-Garcia, Magnus Manske, Bronwyn MacInnis, Susana Campino, Kirk A. Rockett, Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Jennifer M. Anderson, Socheat Duong, Chea Nguon, Char Meng Chuor, David Saunders, Youry Se, Chantap Lon, Mark M. Fukuda, Lucas Amenga-Etego, Abraham V.O. Hodgson & 42 others Victor Asoala, Mallika Imwong, Shannon Takala-Harrison, François Nosten, Xin Zhuan Su, Pascal Ringwald, Frédéric Ariey, Christiane Dolecek, Tran Tinh Hien, Maciej F. Boni, Cao Quang Thai, Alfred Amambua-Ngwa, David J. Conway, Abdoulaye A. Djimdé, Ogobara K. Doumbo, Issaka Zongo, Jean Bosco Ouedraogo, Daniel Alcock, Eleanor Drury, Sarah Auburn, Oliver Koch, Mandy Sanders, Christina Hubbart, Gareth Maslen, Valentin Ruano-Rubio, Dushyanth Jyothi, Alistair Miles, John O'Brien, Chris Gamble, Samuel O. Oyola, Julian C. Rayner, Chris I. Newbold, Matthew Berriman, Chris C.A. Spencer, Gilean McVean, Nicholas P. Day, Nicholas J. White, Delia Bethell, Arjen M. Dondorp, Christopher V. Plowe, Rick M. Fairhurst, Dominic P. Kwiatkowski

Research output: Contribution to journalArticle

256 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)648-655
Number of pages8
JournalNature Genetics
Volume45
Issue number6
DOIs
StatePublished - Jun 1 2013

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Cambodia
Plasmodium falciparum
Population
Parasites
Founder Effect
DNA Mismatch Repair
Population Genetics
Gene Frequency
Codon
Haplotypes
Single Nucleotide Polymorphism
Proteins
Genome
artemisinine

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Miotto, O., Almagro-Garcia, J., Manske, M., MacInnis, B., Campino, S., Rockett, K. A., ... Kwiatkowski, D. P. (2013). Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nature Genetics, 45(6), 648-655. https://doi.org/10.1038/ng.2624
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. / Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. In: Nature Genetics. 2013 ; Vol. 45, No. 6. pp. 648-655.
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Miotto, O, Almagro-Garcia, J, Manske, M, MacInnis, B, Campino, S, Rockett, KA, Amaratunga, C, Lim, P, Suon, S, Sreng, S, Anderson, JM, Duong, S, Nguon, C, Chuor, CM, Saunders, D, Se, Y, Lon, C, Fukuda, MM, Amenga-Etego, L, Hodgson, AVO, Asoala, V, Imwong, M, Takala-Harrison, S, Nosten, F, Su, XZ, Ringwald, P, Ariey, F, Dolecek, C, Hien, TT, Boni, MF, Thai, CQ, Amambua-Ngwa, A, Conway, DJ, Djimdé, AA, Doumbo, OK, Zongo, I, Ouedraogo, JB, Alcock, D, Drury, E, Auburn, S, Koch, O, Sanders, M, Hubbart, C, Maslen, G, Ruano-Rubio, V, Jyothi, D, Miles, A, O'Brien, J, Gamble, C, Oyola, SO, Rayner, JC, Newbold, CI, Berriman, M, Spencer, CCA, McVean, G, Day, NP, White, NJ, Bethell, D, Dondorp, AM, Plowe, CV, Fairhurst, RM & Kwiatkowski, DP 2013, 'Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia', Nature Genetics, vol. 45, no. 6, pp. 648-655. https://doi.org/10.1038/ng.2624

Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. / 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, Vol. 45, No. 6, 01.06.2013, p. 648-655.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia

AU - Miotto, Olivo

AU - Almagro-Garcia, Jacob

AU - Manske, Magnus

AU - MacInnis, Bronwyn

AU - Campino, Susana

AU - Rockett, Kirk A.

AU - Amaratunga, Chanaki

AU - Lim, Pharath

AU - Suon, Seila

AU - Sreng, Sokunthea

AU - Anderson, Jennifer M.

AU - Duong, Socheat

AU - Nguon, Chea

AU - Chuor, Char Meng

AU - Saunders, David

AU - Se, Youry

AU - Lon, Chantap

AU - Fukuda, Mark M.

AU - Amenga-Etego, Lucas

AU - Hodgson, Abraham V.O.

AU - Asoala, Victor

AU - Imwong, Mallika

AU - Takala-Harrison, Shannon

AU - Nosten, François

AU - Su, Xin Zhuan

AU - Ringwald, Pascal

AU - Ariey, Frédéric

AU - Dolecek, Christiane

AU - Hien, Tran Tinh

AU - Boni, Maciej F.

AU - Thai, Cao Quang

AU - Amambua-Ngwa, Alfred

AU - Conway, David J.

AU - Djimdé, Abdoulaye A.

AU - Doumbo, Ogobara K.

AU - Zongo, Issaka

AU - Ouedraogo, Jean Bosco

AU - Alcock, Daniel

AU - Drury, Eleanor

AU - Auburn, Sarah

AU - Koch, Oliver

AU - Sanders, Mandy

AU - Hubbart, Christina

AU - Maslen, Gareth

AU - Ruano-Rubio, Valentin

AU - Jyothi, Dushyanth

AU - Miles, Alistair

AU - O'Brien, John

AU - Gamble, Chris

AU - Oyola, Samuel O.

AU - Rayner, Julian C.

AU - Newbold, Chris I.

AU - Berriman, Matthew

AU - Spencer, Chris C.A.

AU - McVean, Gilean

AU - Day, Nicholas P.

AU - White, Nicholas J.

AU - Bethell, Delia

AU - Dondorp, Arjen M.

AU - Plowe, Christopher V.

AU - Fairhurst, Rick M.

AU - Kwiatkowski, Dominic P.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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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Miotto O, Almagro-Garcia J, Manske M, MacInnis B, Campino S, Rockett KA et al. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nature Genetics. 2013 Jun 1;45(6):648-655. https://doi.org/10.1038/ng.2624