Presentation Abstract

Session: Poster Session C Presentations
Abstract Number: LB-2230
Title: Whole genome analysis of directly isolated Plasmodium vivax samples identifies loci under putative selection
Authors: Andrew T. Bright1, Neekesh V. Dharia2, Raul Chuquiyauri1, Joseph M. Vinetz1, Elizabeth A. Winzeler2
1UC San Diego, La Jolla, CA, United States, 2The Scripps Research Institute, La Jolla, CA, United States
Abstract: Plasmodium vivax causes 25-40% of the 400 million cases of malaria each year and is the predominant malaria species in South America and Southeast Asia. Emerging drug resistance in P. vivax is an understudied global health issue and there are recent reports of emerging resistance to primaquine, currently the only licensed drug capable of a radical cure. The recent publication of the P. vivax genome sequence now allows genomics and systems biology approaches to be applied to the parasite, increasing the ability to answer important questions about this neglected human disease. Here we show results of whole genome analysis from patient-derived isolates obtained from around the world. In our analysis we use a whole genome tiling microarray to quickly and accurately identify hundreds of SNPs between field isolates and the Sal1 reference strain. Polymorphisms are then used to identify regions of high linkage disequilibrium, suggested as a hallmark of recently evolved drug resistance, within our Peruvian, Brazilian and Papua New Guinea parasite samples. Our initial genome-wide SNP-based mapping studies have found only a few large linkage disequilibrium blocks throughout the P. vivax genome, indicating loci under selection. These loci are potentially important in drug resistance phenotypes, and one of these loci, located on chromosome 2, contains the P. vivax multidrug resistance associated protein (PvMRP). PvMRP is an ABC transporter and its homolog has been shown to be involved in primaquine drug resistance in P. falciparum. In addition, we have begun molecular studies to further investigate PvMRP’s role in drug resistance in P. vivax. Our initial data suggests that linkage disequilibrium analysis will be successful in identifying loci that underlie drug resistance phenotypes in P. vivax. We are currently in the process of analyzing additional field isolates and adding new study sites to strengthen our conclusions.




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