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Broad Scientists Use Targeted and Global Approach in Malaria Studies

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Though not the most glamorous of research organisms, the malarial parasite — in particular Plasmodium falciparum, the most common one — is a significant public health concern. According to the World Health Organization, 1 million people die each year from malaria. The Broad Institute's project is using genome-wide and targeted SNP genotyping to get a handle on the parasitic organism to learn about malaria and, ultimately, improve public health.

Three years into the project, the group led by Dyann Wirth and Daniel Hartl is peering at the malaria genome on a genome-wide scale to see what impact natural selection has on the organism, and also on a more targeted basis to find molecular barcodes for different strains of the disease-causing parasite.

"The genome-wide approach is great for … studying what natural selection is doing in the malaria genome," says the Broad's Daniel Neafsey, who spoke about the project at Cold Spring Harbor's Biology of Genomes meeting in May. By doing linkage-based disequilibrium studies, Neafsey and his colleagues have found regions of the malaria genome that are under strong natural selection. They are now searching for the causes of that pressure, which could be coming from anti-malarial drugs or even from the human immune system.

The focused SNP genotyping part of the project is aimed at creating a molecular barcode to identify which strain of malaria is infecting a patient. "Since it's based on 24 different high-frequency SNPs, it can very quickly distinguish even two very similar strains from the same population," Neafsey says. The team is trying to design the molecular barcode assay so that it can be used easily in the field. The group uses TaqMan SNP assays, which are simpler than array hybridizations and require less DNA. The assays, Neafsey says, will help clinicians differentiate a resurgence from reinfection and possibly identify novel occurrences of drug resistance in patients, allowing clinicians to act immediately.

The project is not limited to just the parasite and patient, but is also looking at diversity in the third part of the malaria trifecta, the mosquito. Eventually, Neafsey says, the team wants to look at associations among the genomes and see which parts of the P. falciparum genome are co-evolving with the mosquito vector and which are co-evolving with the human host. "It's a very complicated triangle of interactions here," he says.

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