Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs

Jianbing Mu, Rachel A. Myers, Hongying Jiang, Shengfa Liu, Stacy Ricklefs, Michael Waisberg, Kesinee Chotivanich, Polrat Wilairatana, Srivicha Krudsood, Nicholas J. White, Rachanee Udomsangpetch, Liwang Cui, May Ho, Fengzhen Ou, Haibo Li, Jianping Song, Guoqiao Li, Xinhua Wang, Suon Seila, Sreng Sokunthea & 7 others Duong Socheat, Daniel E. Sturdevant, Stephen F. Porcella, Rick M. Fairhurst, Thomas E. Wellems, Philip Awadalla, Xin Zhuan Su

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome; screening for genes under selection may suggest potential drug or immune targets. Genome-wide association studies (GWAS) of parasite traits have been hampered by the lack of high-throughput genotyping methods, inadequate knowledge of parasite population history and time-consuming adaptations of parasites to in vitro culture. Here we report the first Plasmodium GWAS, which included 189 culture-adapted P. falciparum parasites genotyped using a custom-built Affymetrix molecular inversion probe 3K malaria panel array with a coverage of 1 SNP per 7 kb. Population structure, variation in recombination rate and loci under recent positive selection were detected. Parasite half-maximum inhibitory concentrations for seven antimalarial drugs were obtained and used in GWAS to identify genes associated with drug responses. This study provides valuable tools and insight into the P. falciparum genome.

Original languageEnglish (US)
Pages (from-to)268-271
Number of pages4
JournalNature Genetics
Volume42
Issue number3
DOIs
StatePublished - Mar 1 2010

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Antimalarials
Plasmodium falciparum
Genetic Recombination
Parasites
Genome
Genome-Wide Association Study
Molecular Probes
Plasmodium
Pharmaceutical Preparations
Population
Genes
Malaria
Single Nucleotide Polymorphism

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Mu, Jianbing ; Myers, Rachel A. ; Jiang, Hongying ; Liu, Shengfa ; Ricklefs, Stacy ; Waisberg, Michael ; Chotivanich, Kesinee ; Wilairatana, Polrat ; Krudsood, Srivicha ; White, Nicholas J. ; Udomsangpetch, Rachanee ; Cui, Liwang ; Ho, May ; Ou, Fengzhen ; Li, Haibo ; Song, Jianping ; Li, Guoqiao ; Wang, Xinhua ; Seila, Suon ; Sokunthea, Sreng ; Socheat, Duong ; Sturdevant, Daniel E. ; Porcella, Stephen F. ; Fairhurst, Rick M. ; Wellems, Thomas E. ; Awadalla, Philip ; Su, Xin Zhuan. / Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. In: Nature Genetics. 2010 ; Vol. 42, No. 3. pp. 268-271.
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Mu, J, Myers, RA, Jiang, H, Liu, S, Ricklefs, S, Waisberg, M, Chotivanich, K, Wilairatana, P, Krudsood, S, White, NJ, Udomsangpetch, R, Cui, L, Ho, M, Ou, F, Li, H, Song, J, Li, G, Wang, X, Seila, S, Sokunthea, S, Socheat, D, Sturdevant, DE, Porcella, SF, Fairhurst, RM, Wellems, TE, Awadalla, P & Su, XZ 2010, 'Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs', Nature Genetics, vol. 42, no. 3, pp. 268-271. https://doi.org/10.1038/ng.528

Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. / Mu, Jianbing; Myers, Rachel A.; Jiang, Hongying; Liu, Shengfa; Ricklefs, Stacy; Waisberg, Michael; Chotivanich, Kesinee; Wilairatana, Polrat; Krudsood, Srivicha; White, Nicholas J.; Udomsangpetch, Rachanee; Cui, Liwang; Ho, May; Ou, Fengzhen; Li, Haibo; Song, Jianping; Li, Guoqiao; Wang, Xinhua; Seila, Suon; Sokunthea, Sreng; Socheat, Duong; Sturdevant, Daniel E.; Porcella, Stephen F.; Fairhurst, Rick M.; Wellems, Thomas E.; Awadalla, Philip; Su, Xin Zhuan.

In: Nature Genetics, Vol. 42, No. 3, 01.03.2010, p. 268-271.

Research output: Contribution to journalArticle

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AU - Liu, Shengfa

AU - Ricklefs, Stacy

AU - Waisberg, Michael

AU - Chotivanich, Kesinee

AU - Wilairatana, Polrat

AU - Krudsood, Srivicha

AU - White, Nicholas J.

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AU - Ho, May

AU - Ou, Fengzhen

AU - Li, Haibo

AU - Song, Jianping

AU - Li, Guoqiao

AU - Wang, Xinhua

AU - Seila, Suon

AU - Sokunthea, Sreng

AU - Socheat, Duong

AU - Sturdevant, Daniel E.

AU - Porcella, Stephen F.

AU - Fairhurst, Rick M.

AU - Wellems, Thomas E.

AU - Awadalla, Philip

AU - Su, Xin Zhuan

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