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      Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome.

      Nature genetics
      Animals, Antigens, Protozoan, genetics, isolation & purification, metabolism, Cell-Free System, Chromosome Mapping, Drug Delivery Systems, Drug Design, Drug Resistance, Genetic Variation, Genome, Protozoan, Humans, Immune Sera, chemistry, Malaria Vaccines, immunology, Malaria, Falciparum, parasitology, Plasmodium falciparum

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          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.

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