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Title: Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs
Authors: 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
Duong Socheat
Daniel E. Sturdevant
Stephen F. Porcella
Rick M. Fairhurst
Thomas E. Wellems
Philip Awadalla
Xin Zhuan Su
National Institute of Allergy and Infectious Diseases
University of Montreal
North Carolina State University
Xiamen University
National Institutes of Health, Bethesda
Mahidol University
Pennsylvania State University
University of Calgary
Research Center for Qinghao
Guangzhou University of Traditional Chinese Medicine
National Center for Parasitology, Entomology and Malaria Control
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Mar-2010
Citation: Nature Genetics. Vol.42, No.3 (2010), 268-271
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. © 2010 Nature America, Inc. All rights reserved.
ISSN: 15461718
Appears in Collections:Scopus 2006-2010

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