biostudies-literatureClarkson CSNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSMedical Research CouncilWellcome Trust5303-5317https://www.ebi.ac.uk/biostudies/studies/S-EPMC9019111biostudies-literatureUnknown30(21)Resistance to pyrethroid insecticides is a major concern for malaria vector control. Pyrethroids target the voltage-gated sodium channel (VGSC), an essential component of the mosquito nervous system. Substitutions in the amino acid sequence can induce 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 pyrethroid resistance phenotypes. Thirteen of these novel alleles were found to occur almost exclusivelyMolecular ecologyThe genetic architecture of target-site resistance to pyrethroid insecticides in the African malaria vectors Anopheles gambiae and Anopheles coluzzii.PMC9019111R01AI116811MR/M006212/1090770/Z/09/ZR01 AI116811MR/P02520X/1G0600718B098051090532/Z/09/Z204911/Z/16/ZHarding NJMiles AKwiatkowski DDonnelly MJAnopheles gambiae 1000 Genomes ConsortiumO'Reilly AOWeetman DClarkson CSfalseThe genetic architecture of target-site resistance to pyrethroid insecticides in the African malaria vectors Anopheles gambiae and Anopheles coluzzii.Resistance to pyrethroid insecticides is a major concern for malaria vector control. Pyrethroids target the voltage-gated sodium channel (VGSC), an essential component of the mosquito nervous system. Substitutions in the amino acid sequence can induce 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 pyrethroid resistance phenotypes. Thirteen of these novel alleles were found to occur almost exclusively2021-01-01T00:00:00Z2021 Nov2026-05-09T23:44:14.569Z2025-04-04T22:14:53.226ZS-EPMC90191113359092610.1111/mec.15845