Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii
Abstract Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40693-0 |
| _version_ | 1827710266666647552 |
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| author | Eric R. Lucas Sanjay C. Nagi Alexander Egyir-Yawson John Essandoh Samuel Dadzie Joseph Chabi Luc S. Djogbénou Adandé A. Medjigbodo Constant V. Edi Guillaume K. Kétoh Benjamin G. Koudou Arjen E. Van’t Hof Emily J. Rippon Dimitra Pipini Nicholas J. Harding Naomi A. Dyer Louise T. Cerdeira Chris S. Clarkson Dominic P. Kwiatkowski Alistair Miles Martin J. Donnelly David Weetman |
| author_facet | Eric R. Lucas Sanjay C. Nagi Alexander Egyir-Yawson John Essandoh Samuel Dadzie Joseph Chabi Luc S. Djogbénou Adandé A. Medjigbodo Constant V. Edi Guillaume K. Kétoh Benjamin G. Koudou Arjen E. Van’t Hof Emily J. Rippon Dimitra Pipini Nicholas J. Harding Naomi A. Dyer Louise T. Cerdeira Chris S. Clarkson Dominic P. Kwiatkowski Alistair Miles Martin J. Donnelly David Weetman |
| author_sort | Eric R. Lucas |
| collection | DOAJ |
| description | Abstract Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods. |
| first_indexed | 2024-03-10T17:35:39Z |
| format | Article |
| id | doaj.art-89a3cd77c3ef4159b9624a62ccb60c14 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:35:39Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-89a3cd77c3ef4159b9624a62ccb60c142023-11-20T09:52:57ZengNature PortfolioNature Communications2041-17232023-08-0114111110.1038/s41467-023-40693-0Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzziiEric R. Lucas0Sanjay C. Nagi1Alexander Egyir-Yawson2John Essandoh3Samuel Dadzie4Joseph Chabi5Luc S. Djogbénou6Adandé A. Medjigbodo7Constant V. Edi8Guillaume K. Kétoh9Benjamin G. Koudou10Arjen E. Van’t Hof11Emily J. Rippon12Dimitra Pipini13Nicholas J. Harding14Naomi A. Dyer15Louise T. Cerdeira16Chris S. Clarkson17Dominic P. Kwiatkowski18Alistair Miles19Martin J. Donnelly20David Weetman21Department of Vector Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology, Liverpool School of Tropical MedicineDepartment of Biomedical Sciences, University of Cape CoastDepartment of Biomedical Sciences, University of Cape CoastDepartment of Parasitology, Noguchi Memorial Institute for Medical Research, University of GhanaDepartment of Parasitology, Noguchi Memorial Institute for Medical Research, University of GhanaTropical Infectious Diseases Research Centre (TIDRC), Université d’Abomey-Calavi (UAC)Tropical Infectious Diseases Research Centre (TIDRC), Université d’Abomey-Calavi (UAC)Centre Suisse de Recherches Scientifiques en Côte d’IvoireLaboratory of Ecology and Ecotoxicology, Department of Zoology, Faculty of Sciences, Université de LoméCentre Suisse de Recherches Scientifiques en Côte d’IvoireDepartment of Vector Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology, Liverpool School of Tropical MedicineBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of OxfordDepartment of Vector Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology, Liverpool School of Tropical MedicineWellcome Sanger Institute, HinxtonWellcome Sanger Institute, HinxtonWellcome Sanger Institute, HinxtonDepartment of Vector Biology, Liverpool School of Tropical MedicineDepartment of Vector Biology, Liverpool School of Tropical MedicineAbstract Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods.https://doi.org/10.1038/s41467-023-40693-0 |
| spellingShingle | Eric R. Lucas Sanjay C. Nagi Alexander Egyir-Yawson John Essandoh Samuel Dadzie Joseph Chabi Luc S. Djogbénou Adandé A. Medjigbodo Constant V. Edi Guillaume K. Kétoh Benjamin G. Koudou Arjen E. Van’t Hof Emily J. Rippon Dimitra Pipini Nicholas J. Harding Naomi A. Dyer Louise T. Cerdeira Chris S. Clarkson Dominic P. Kwiatkowski Alistair Miles Martin J. Donnelly David Weetman Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii Nature Communications |
| title | Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii |
| title_full | Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii |
| title_fullStr | Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii |
| title_full_unstemmed | Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii |
| title_short | Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii |
| title_sort | genome wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in anopheles gambiae and anopheles coluzzii |
| url | https://doi.org/10.1038/s41467-023-40693-0 |
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