title: How can we identify parasite genes that underlie antimalarial drug resistance?
abstract: This article outlines genome-scale approaches that can be used to identify mutations in malaria (Plasmodium) parasites that underlie drug resistance and contribute to treatment failure. These approaches include genetic mapping by linkage or genome-wide association studies, drug selection and characterization of resistant mutants, and the identification of genome regions under strong recent selection. While these genomic approaches can identify candidate resistance loci, genetic manipulation is needed to demonstrate causality. We therefore also describe the growing arsenal of available transfection approaches for direct incrimination of mutations suspected to play a role in resistance. Our intention is both to review past progress and highlight promising approaches for future investigations.
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245, USA. tanderso@sfbrgenetics.org
authors.forename: Tim
authors.initials: T
authors.lastname: Anderson
authors.forename: Standwell
authors.initials: S
authors.lastname: Nkhoma
authors.forename: Andrea
authors.initials: A
authors.lastname: Ecker
authors.forename: David
authors.initials: D
authors.lastname: Fidock
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics*; D017125:Genes, Protozoan; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D009154:Mutation; D010961:Plasmodium / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000962:Antimalarials