Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii

Lucas, Eric ORCID: https://orcid.org/0000-0003-3892-1668, Nagi, Sanjay, Egyir-Yawson, Alexander, Essandoh, John, Dadzie, Sam, Chabi, Joseph, Djogbénou, Luc S., Medjigbodo, Adandé A., Edi, Constant V., Ketoh, Guillaume K., Koudou, Benjamin G., Van't Hof, Arjen, Rippon, Emily, Pipini, Dimitra, Harding, Nicholas J., Dyer, Naomi, Cerdeira, Louise, Clarkson, Chris S., Kwiatkowski, Dominic P., Miles, Alistair, Donnelly, Martin ORCID: https://orcid.org/0000-0001-5218-1497 and Weetman, David ORCID: https://orcid.org/0000-0002-5820-1388 (2023) 'Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii'. Nature Communications, Vol 14, Issue 1, e4946.

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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, multiallelic 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 form the basis for improved surveillance methods.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes QX Parasitology > Insects. Other Parasites > QX 515 Anopheles WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41467-023-40693-0
Depositing User:	Luciene Salas Jennings
Date Deposited:	15 Jun 2023 14:08
Last Modified:	14 Sep 2023 11:00
URI:	https://archive.lstmed.ac.uk/id/eprint/22641

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