Malaria Parasite Sexual Development, Drug Resistance, an

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The Malaria Genomic Unit uses the malaria parasite genome databases and develops new resources to study the mechanism of drug resistance, gene regulation during parasite sexual development, and parasite population diversity and evolution. Building on progress made lasyt year, we have now collected additional single nucleotide polymrphisms (SNPs) from genes on chromosome 1, 2, 4, 5, and 14 (Chromosome 3 was reported last year) of Plasmodium falciparum. To study the evolutionary history and chromosomal haplotypes of the parasite, we have genotyped SNPs on chromosome 3 from a worldwide collection of isolates. We have also finished sequencing the mitochondrial genome from 98 P. falciparum isolates and discovered a recent population expansion in Africa coinciding with mosquito speciation and human population growth. To identify genes that may contribute to drug resistance, we searched for SNPs from 49 putative transporter genes and found that SNPs in 11 of the putative transporters could be associated with the parasite responses to chloroquine and quinine. Another major effort of our lab is to study gene expression and regulation associated with the parasite sexual differentiation. We have identified a gene that may play a key role in gametocyte development using microarray and genetic mapping. Phenotypic changes are being evaluated after genetic knockout of the target gene. We also initiated a pilot project to study genome diversity of another human malaria parasite Plasmodium vivax. Comparison of a ~100 kilo bases DNA segment from five isolates showed that the parasite has highly diverse genome, suggesting a relatively old organism that may present some challenge for disease control.