Rapid, Field-Deployable Method for Genotyping and Discovery of Single-Nucleotide Polymorphisms Associated with Drug Resistance in Plasmodium falciparum

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Rapid, Field-Deployable Method for Genotyping and Discovery of Single-Nucleotide Polymorphisms Associated with Drug Resistance in Plasmodium falciparum

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dc.contributor.author Daniels, Rachel Fath
dc.contributor.author Ndiaye, Daouda
dc.contributor.author Wall, Mikeal
dc.contributor.author McKinney, Jason
dc.contributor.author Séne, Papa Diogoye
dc.contributor.author Sabeti, Pardis Christine
dc.contributor.author Volkman, Sarah K.
dc.contributor.author Mboup, Souleymane
dc.contributor.author Wirth, Dyann Fergus
dc.date.accessioned 2012-11-13T19:12:02Z
dc.date.issued 2012
dc.identifier.citation Daniels, Rachel, Daouda Ndiaye, Mikeal Wall, Jason McKinney, Papa Diogoye Séne, Pardis Christine Sabeti, Sarah K. Volman, Souleymane Mboup, and Dyann Fergus. 2012. Rapid field-deployable method for genotyping and discovery of single-nucleotide polymorphisms associated with drug resistance in Plasmodium falciparum. Antimicrobial Agents and Chemotherapy Journal 56(6): 2976-2986. en_US
dc.identifier.issn 0066-4804 en_US
dc.identifier.issn 1098-6596 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9894539
dc.description.abstract Despite efforts to reduce malaria morbidity and mortality, drug-resistant parasites continue to evade control strategies. Recently, emphasis has shifted away from control and toward regional elimination and global eradication of malaria. Such a campaign requires tools to monitor genetic changes in the parasite that could compromise the effectiveness of antimalarial drugs and undermine eradication programs. These tools must be fast, sensitive, unambiguous, and cost-effective to offer real-time reports of parasite drug susceptibility status across the globe. We have developed and validated a set of genotyping assays using high-resolution melting (HRM) analysis to detect molecular biomarkers associated with drug resistance across six genes in Plasmodium falciparum. We improved on existing technical approaches by developing refinements and extensions of HRM, including the use of blocked probes (LunaProbes) and the mutant allele amplification bias (MAAB) technique. To validate the sensitivity and accuracy of our assays, we compared our findings to sequencing results in both culture-adapted lines and clinical isolates from Senegal. We demonstrate that our assays (i) identify both known and novel polymorphisms, (ii) detect multiple genotypes indicative of mixed infections, and (iii) distinguish between variants when multiple copies of a locus are present. These rapid and inexpensive assays can track drug resistance and detect emerging mutations in targeted genetic loci in P. falciparum. They pro- vide tools for monitoring molecular changes associated with changes in drug response across populations and for determining whether parasites present after drug treatment are the result of recrudescence or reinfection in clinical settings. en_US
dc.description.sponsorship Organismic and Evolutionary Biology en_US
dc.language.iso en_US en_US
dc.publisher American Society for Microbiology en_US
dc.relation.isversionof doi:10.1128/AAC.05737-11 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pubmed/22430961 en_US
dash.license OAP
dc.subject antimalarials en_US
dc.subject pharmacology en_US
dc.subject drug resistance en_US
dc.subject genetics en_US
dc.subject mutation en_US
dc.subject parasitic sensitivity traits en_US
dc.subject Plasmodium falciparum en_US
dc.subject single nucleotide polymorphism en_US
dc.title Rapid, Field-Deployable Method for Genotyping and Discovery of Single-Nucleotide Polymorphisms Associated with Drug Resistance in Plasmodium falciparum en_US
dc.type Journal Article en_US
dc.description.version Accepted Manuscript en_US
dc.relation.journal Antimicrobial Agents and Chemotherapy Journal en_US
dash.depositing.author Sabeti, Pardis Christine
dc.date.available 2012-11-13T19:12:02Z

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  • FAS Scholarly Articles [7219]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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