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Pyrethroids target the voltage\u2010gated 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\u2010genome sequence data from phase 2 of the\n                    <jats:italic>Anopheles gambiae<\/jats:italic>\n                    1000 Genomes Project (Ag1000G) to provide a comprehensive account of genetic variation in the\n                    <jats:italic>Vgsc<\/jats:italic>\n                    gene across 13 African countries. In addition to known resistance alleles, we describe 20 other non\u2010synonymous 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 exclusively on haplotypes carrying the known L995F\n                    <jats:italic>kdr<\/jats:italic>\n                    (knock\u2010down resistance) allele and may enhance or compensate for the L995F resistance genotype. A novel mutation I1527T, adjacent to a predicted pyrethroid\u2010binding site, was found in tight linkage with V402L substitutions, similar to allele 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\n                    <jats:italic>kdr<\/jats:italic>\n                    alleles. Five of these groups are observed in more than one country, in one case separated by over 3000\u00a0km, providing new information about the potential for the geographical spread of resistance. Our results demonstrate that the molecular basis of target\u2010site 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.\n                  <\/jats:p>","DOI":"10.1111\/mec.15845","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T08:18:12Z","timestamp":1613463492000},"page":"5303-5317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["The genetic architecture of target\u2010site resistance to pyrethroid insecticides in the African malaria vectors\n                    <i>Anopheles gambiae<\/i>\n                    and\n                    <i>Anopheles coluzzii<\/i>"],"prefix":"10.1111","volume":"30","author":[{"given":"Chris S.","family":"Clarkson","sequence":"first","affiliation":[{"name":"Wellcome Sanger Institute Cambridge 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