title: Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs.
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 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.
authors.affiliation: 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
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mu
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Myers
authors.forename: Hongying
authors.initials: H
authors.lastname: Jiang
authors.forename: Shengfa
authors.initials: S
authors.lastname: Liu
authors.forename: Stacy
authors.initials: S
authors.lastname: Ricklefs
authors.forename: Michael
authors.initials: M
authors.lastname: Waisberg
authors.forename: Kesinee
authors.initials: K
authors.lastname: Chotivanich
authors.forename: Polrat
authors.initials: P
authors.lastname: Wilairatana
authors.forename: Srivicha
authors.initials: S
authors.lastname: Krudsood
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Rachanee
authors.initials: R
authors.lastname: Udomsangpetch
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
authors.forename: May
authors.initials: M
authors.lastname: Ho
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Ou
authors.forename: Haibo
authors.initials: H
authors.lastname: Li
authors.forename: Jianping
authors.initials: J
authors.lastname: Song
authors.forename: Guoqiao
authors.initials: G
authors.lastname: Li
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.forename: Suon
authors.initials: S
authors.lastname: Seila
authors.forename: Sreng
authors.initials: S
authors.lastname: Sokunthea
authors.forename: Duong
authors.initials: D
authors.lastname: Socheat
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wellems
authors.forename: Philip
authors.initials: P
authors.lastname: Awadalla
authors.forename: Xin-zhuan
authors.initials: XZ
authors.lastname: Su
mesh_terms: D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002874:Chromosome Mapping; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization / Q000379:methods; D016054:DNA, Protozoan / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005843:Geography; D020128:Inhibitory Concentration 50; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000235:genetics*; D011995:Recombination, Genetic / Q000187:drug effects; D012641:Selection, Genetic / Q000187:drug effects
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan