Malaria Functional Genomics and Beyond

With the completion and near completion of many malaria parasite genomesequencing projects, efforts are now being directed toward a better understanding of gene functions and discovery of vaccine and drug targets. Novel biologic pathways present in the parasite have been identified through homology searches and inter- and intra-species comparison of the parasite genome. Genetic mapping approaches, including linkage and population association analyses, have provided valuable insights into parasite evolution, virulence, drug resistance, and immune invasion. Genome-wide searches for loci under various selection pressures have lead to discovery of parasite genetic loci or genes playing a role in drug resistance or encoding for protective antigens. In addition, the Plasmodium falciparum genome sequence provides the basis for the development of various microarrays to monitor gene expression and to detect nucleotide substitution and deletion/amplification, for genome-wide profiling of the parasite proteome, and for investigation of epigenetic regulation of gene expression such as chromatin modification, and nucleosome position. In this brief review, we will highlight some recent advances and studies in characterizing gene function and related phenotype in P. falciparum that were made possible by the genome sequence, particularly the development of a genome-wide diversity map and various high-throughput genotyping methods for genome-wide association studies.

Keywords: Malaria, microarray, genome diversity, SNP, recombination, comparative genomics.