Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs.
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.
Mu
Jianbing
J
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
Myers
Rachel A
RA
Jiang
Hongying
H
Liu
Shengfa
S
Ricklefs
Stacy
S
Waisberg
Michael
M
Chotivanich
Kesinee
K
Wilairatana
Polrat
P
Krudsood
Srivicha
S
White
Nicholas J
NJ
Udomsangpetch
Rachanee
R
Cui
Liwang
L
Ho
May
M
Ou
Fengzhen
F
Li
Haibo
H
Song
Jianping
J
Li
Guoqiao
G
Wang
Xinhua
X
Seila
Suon
S
Sokunthea
Sreng
S
Socheat
Duong
D
Sturdevant
Daniel E
DE
Porcella
Stephen F
SF
Fairhurst
Rick M
RM
Wellems
Thomas E
TE
Awadalla
Philip
P
Su
Xin-zhuan
XZ
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
D000962:Antimalarials; D016054:DNA, Protozoan