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Clarkson, CS, Miles, A, Harding, NJ, O'Reilly, AO, Weetman, D, Kwiatkowski, D, Donnelly, MJ and Anopheles gambiae 1000 Genomes Consortium, (2021) The genetic architecture of target-site resistance to pyrethroid insecticides in the African malaria vectors Anopheles gambiae and Anopheles coluzzii. Molecular Ecology. ISSN 0962-1083
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Abstract
Resistance to pyrethroid insecticides is a major concern for malaria vector control. Pyrethroids target the voltage-gated sodium channel (VGSC), an essential compo nent of the mosquito nervous system. Substitutions in the amino acid sequence can inducing a resistance phenotype. We use whole-genome sequence data from phase 2 of the Anopheles gambiae 1000 Genomes Project (Ag1000G) to provide a comprehensive account of genetic variation in the Vgsc gene across 13 African countries. In addition to known resistance alleles, we describe 20 other non-synonymous nucleotide substitutions at appreciable population frequency, and map these variants onto a protein model to investigate the likelihood of a pyrethroid resistance phenotypes. Thirteen of these novel alleles were found to occur almost exclusively on haplotypes carrying the known L995F kdr (knock-down resistance allele) and may enhance or compensate for the L995F resistance genotype. A novel mutation I1527T, adjacent to a predicted pyrethroid binding site, was found in tight linkage with V402L substitutions, similar to combinations associated with resistance in other insect species. We also analysed genetic backgrounds carrying resistance alleles, to determine which alleles have experienced recent positive selection, and describe ten distinct haplotype groups carrying known kdr resistance alleles. Five of these groups are observed in more than one country, in one case separated by over 3000 km, providing new information about the potential for the geographical spread of resistance. Our results demonstrate that the molecular basis of target-site pyrethroid resistance in malaria vectors is more complex than previously appreciated, and provide a foundation for the development of new genetic tools for insecticide resistance management.
| Item Type: | Article |
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| Uncontrolled Keywords: | 06 Biological Sciences |
| Subjects: | Q Science > QR Microbiology |
| Divisions: | Biological & Environmental Sciences (from Sep 19) |
| Publisher: | Wiley |
| Related URLs: | |
| Date Deposited: | 22 Feb 2021 12:13 |
| Last Modified: | 04 Sep 2021 05:54 |
| DOI or ID number: | 10.1111/mec.15845 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/14495 |
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