title: Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome.
abstract: 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.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mu
authors.forename: Philip
authors.initials: P
authors.lastname: Awadalla
authors.forename: Junhui
authors.initials: J
authors.lastname: Duan
authors.forename: Kate M
authors.initials: KM
authors.lastname: McGee
authors.forename: Jon
authors.initials: J
authors.lastname: Keebler
authors.forename: Karl
authors.initials: K
authors.lastname: Seydel
authors.forename: Gilean A T
authors.initials: GA
authors.lastname: McVean
authors.forename: Xin-zhuan
authors.initials: XZ
authors.lastname: Su
mesh_terms: 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*
chemical_list: D000953:Antigens, Protozoan; D007106:Immune Sera; D017780:Malaria Vaccines