Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.
Abstract
Resistance to antimalarial drugs, and in particular to the artemisinin derivatives and their partner drugs, threatens recent progress toward regional malaria elimination and eventual global malaria eradication. Population-level studies utilizing whole-genome sequencing approaches have facilitated the identification of regions of the parasite genome associated with both clinical and in vitro drug-resistance phenotypes. However, the biological relevance of genes identified in these analyses and the establishment of a causal relationship between genotype and phenotype requires functional characterization. Here we examined data from population genomic and transcriptomic studies in the context of data generated from recent functional studies, using a new population genetic approach designed to identify potential favored mutations within the region of a selective sweep (iSAFE). We identified several genes functioning in pathways now known to be associated with artemisinin resistance that were supported in early population genomic studies, as well as potential new drug targets/pathways for further validation and consideration for treatment of artemisinin-resistant Plasmodium falciparum. In addition, we establish the utility of iSAFE i...Continue Reading
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Antimalarial Agents
Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.
Antimalarial Agents (ASM)
Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.