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Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. 2010
Jianbing Mu, and
Rachel A Myers, and
Hongying Jiang, and
Shengfa Liu, and
Stacy Ricklefs, and
Michael Waisberg, and
Kesinee Chotivanich, and
Polrat Wilairatana, and
Srivicha Krudsood, and
Nicholas J White, and
Rachanee Udomsangpetch, and
Liwang Cui, and
May Ho, and
Fengzhen Ou, and
Haibo Li, and
Jianping Song, and
Guoqiao Li, and
Xinhua Wang, and
Suon Seila, and
Sreng Sokunthea, and
Duong Socheat, and
Daniel E Sturdevant, and
Stephen F Porcella, and
Rick M Fairhurst, and
Thomas E Wellems, and
Philip Awadalla, and
Xin-zhuan Su
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. jmu@niaid.nih.gov
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 approximately 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.
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