Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya
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 nucleoti...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2013
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| _version_ | 1797079335695286272 |
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| author | Borrmann, S Straimer, J Mwai, L Abdi, A Rippert, A Okombo, J Muriithi, S Sasi, P Kortok, M Lowe, B Campino, S Assefa, S Auburn, S Manske, M Maslen, G Peshu, N Kwiatkowski, D Marsh, K Nzila, A Clark, T |
| author_facet | Borrmann, S Straimer, J Mwai, L Abdi, A Rippert, A Okombo, J Muriithi, S Sasi, P Kortok, M Lowe, B Campino, S Assefa, S Auburn, S Manske, M Maslen, G Peshu, N Kwiatkowski, D Marsh, K Nzila, A Clark, T |
| author_sort | Borrmann, S |
| collection | OXFORD |
| description | 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 (PFB0560w, PFB0630c, PFF0445w) 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. |
| first_indexed | 2024-03-07T00:44:23Z |
| format | Journal article |
| id | oxford-uuid:841d7598-6aa1-4cfd-b74c-d8a742128e0a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:44:23Z |
| publishDate | 2013 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:841d7598-6aa1-4cfd-b74c-d8a742128e0a2022-03-26T21:49:01ZGenome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in KenyaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:841d7598-6aa1-4cfd-b74c-d8a742128e0aEnglishSymplectic Elements at OxfordSpringer Nature2013Borrmann, SStraimer, JMwai, LAbdi, ARippert, AOkombo, JMuriithi, SSasi, PKortok, MLowe, BCampino, SAssefa, SAuburn, SManske, MMaslen, GPeshu, NKwiatkowski, DMarsh, KNzila, AClark, TEarly 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 (PFB0560w, PFB0630c, PFF0445w) 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. |
| spellingShingle | Borrmann, S Straimer, J Mwai, L Abdi, A Rippert, A Okombo, J Muriithi, S Sasi, P Kortok, M Lowe, B Campino, S Assefa, S Auburn, S Manske, M Maslen, G Peshu, N Kwiatkowski, D Marsh, K Nzila, A Clark, T Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya |
| title | Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya |
| title_full | Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya |
| title_fullStr | Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya |
| title_full_unstemmed | Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya |
| title_short | Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya |
| title_sort | genome wide screen identifies new candidate genes associated with artemisinin susceptibility in plasmodium falciparum in kenya |
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