ArticlePLoS genetics2011
Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 1 citations in OpenAlex.
- Genetic architecture of artemisinin-resistant Plasmodium falciparum.Nature genetics · 2015Trial
- Genetic diversity of Plasmodium falciparum helical interspersed subtelomeric (phistb) gene in Tanzania and neighboring countries.Malaria journal · 2026Article
- Replication stress increases de novo CNVs across the malaria parasite genome.Nucleic acids research · 2026Article
- Replication stress increases de novo CNVs across the malaria parasite genome.bioRxiv : the preprint server for biology · 2025Article
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- Highly multiplexed molecular inversion probe panel inFrontiers in genetics · 2025Article
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- Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia.Communications medicine · 2024Article
- Genomics reveals heterogeneousmedRxiv : the preprint server for health sciences · 2024Article
- MalariaSED: a deep learning framework to decipher the regulatory contributions of noncoding variants in malaria parasites.Genome biology · 2023Article
- Molecular Profile and the Effectiveness of Antimicrobials Drugs AgainstInfection and drug resistance · 2023Article
- Mechanistic basis for multidrug resistance and collateral drug sensitivity conferred to the malaria parasite by polymorphisms in PfMDR1 and PfCRT.PLoS biology · 2022Article
- Genome-wide SNP analysis ofFrontiers in genetics · 2022Article
- Potential Opportunities and Challenges of Deploying Next Generation Sequencing and CRISPR-Cas Systems to Support Diagnostics and Surveillance Towards Malaria Control and Elimination in Africa.Frontiers in cellular and infection microbiology · 2022Review
- Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2021Article
- Advances and opportunities in malaria population genomics.Nature reviews. Genetics · 2021Review
- Genomic and Genetic Approaches to Studying Antimalarial Drug Resistance and Plasmodium Biology.Trends in parasitology · 2021Review
- Antimalarial Drug Resistance and Implications for the WHO Global Technical Strategy.Current epidemiology reports · 2021Review
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- Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors at 7 institutions in 3 countries.
Funding
Abstract
The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (∼ 1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.