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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.

Original publication

DOI

10.1038/ng1924

Type

Journal article

Journal

Nature genetics

Publication Date

01/2007

Volume

39

Pages

126 - 130

Addresses

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Keywords

Cell-Free System, Animals, Humans, Plasmodium falciparum, Malaria, Falciparum, Immune Sera, Malaria Vaccines, Antigens, Protozoan, Drug Delivery Systems, Chromosome Mapping, Drug Design, Drug Resistance, Genome, Protozoan, Genetic Variation