Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya

Steffen Borrmann, Judith Straimer, Leah Mwai, Abdirahman Abdi, Anja Rippert, John Okombo, Steven Muriithi, Philip Sasi, Moses Mosobo Kortok, Brett Lowe, Susana Campino, Samuel Assefa, Sarah Auburn, Magnus Manske, Gareth Maslen, Norbert Peshu, Dominic Kwiatkowski, Kevin Marsh, Alexis Nzila, Taane Clark

Research output: Contribution to journalArticle

8 Downloads (Pure)

Abstract

Early identification of causal genetic variants underlying antimalarial drug resistance could provide robust epidemiological tools for timely public health interventions. Using a novel natural genetics strategy for mapping novel candidate genes we analyzed >75,000 high quality single nucleotide polymorphisms selected from high-resolution whole-genome sequencing data in 27 isolates of Plasmodium falciparum. We identified genetic variants associated with susceptibility to dihydroartemisinin that implicate one region on chromosome 13, a candidate gene on chromosome 1 (PFA0220w, a UBP1 ortholog) and others (PFB0560wPFB0630cPFF0445w) with putative roles in protein homeostasis and stress response. There was a strong signal for positive selection on PFA0220w, but not the other candidate loci. Our results demonstrate the power of full-genome sequencing-based association studies for uncovering candidate genes that determine parasite sensitivity to artemisinins. Our study provides a unique reference for the interpretation of results from resistant infections.
Original languageEnglish
Article number3318
Pages (from-to)1-10
Number of pages10
JournalScientific Reports
Volume3
DOIs
Publication statusPublished - 2013
Externally publishedYes

    Fingerprint

Cite this

Borrmann, S., Straimer, J., Mwai, L., Abdi, A., Rippert, A., Okombo, J., Muriithi, S., Sasi, P., Kortok, M. M., Lowe, B., Campino, S., Assefa, S., Auburn, S., Manske, M., Maslen, G., Peshu, N., Kwiatkowski, D., Marsh, K., Nzila, A., & Clark, T. (2013). Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya. Scientific Reports, 3, 1-10. [3318]. https://doi.org/10.1038/srep03318