Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome.
One goal in sequencing the Plasmodium falciparum genome, the agent of the most lethal form of malaria, is to discover vaccine and drug targets. However, identifying those targets in a genome in which approximately 60% of genes have unknown functions is an enormous challenge. Because the majority of known malaria antigens and drug-resistant genes are highly polymorphic and under various selective pressures, genome-wide analysis for signatures of selection may lead to discovery of new vaccine and drug candidates. Here we surveyed 3,539 P. falciparum genes ( approximately 65% of the predicted genes) for polymorphisms and identified various highly polymorphic loci and genes, some of which encode new antigens that we confirmed using human immune sera. Our collections of genome-wide SNPs ( approximately 65% nonsynonymous) and polymorphic microsatellites and indels provide a high-resolution map (one marker per approximately 4 kb) for mapping parasite traits and studying parasite populations. In addition, we report new antigens, providing urgently needed vaccine candidates for disease control.
Mu
Jianbing
J
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Awadalla
Philip
P
Duan
Junhui
J
McGee
Kate M
KM
Keebler
Jon
J
Seydel
Karl
K
McVean
Gilean A T
GA
Su
Xin-zhuan
XZ
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000302:isolation & purification* / Q000378:metabolism; D002474:Cell-Free System / Q000378:metabolism; D002874:Chromosome Mapping; D016503:Drug Delivery Systems; D015195:Drug Design; D004351:Drug Resistance / Q000235:genetics; D014644:Genetic Variation; D018503:Genome, Protozoan; D006801:Humans; D007106:Immune Sera / Q000737:chemistry; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*
D000953:Antigens, Protozoan; D007106:Immune Sera; D017780:Malaria Vaccines