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Here, we contrasted RNAseq-based gene expression profiling of laboratory-resistant (FUMOZ) and susceptible (FANG) strains of the major malaria vector Anopheles funestus. Cytochrome P450 genes were the predominant over-expressed detoxification genes in FUMOZ, with high expression of the duplicated CYP6P9a (fold-change of 82.23 vs FANG) and CYP6P9b (FC 11.15). Other over-expressed P450s belonged to the same cluster of P450s corresponding to the resistance to pyrethroid 1 (rp1) quantitative trait loci (QTL) on chromosome 2R. Several Epsilon class glutathione S-transferases were also over-expressed in FUMOZ, as was the ATP-binding cassette transporter AFUN019220 (ABCA) which also exhibited between-strain alternative splicing events at exon 7. Significant differences in single-nucleotide polymorphism frequencies between strains occurred in resistance QTLs rp1 (CYP6P9a\/b and CYP6AA1), rp2 on chromosome 2L (CYP6Z1, CYP6M7, and CYP6Z3), and rp3 on chromosome 3R (CYP9J5, CYP9J4, and CYP9J3). Differences were also detected in CYP4G17 and CYP4G16 genes on the X chromosome, both of which are associated with cuticular resistance in Anopheles gambiae. A close analysis of nonsynonymous diversity at the CYP6P9a\/b loci revealed a drastic loss of diversity in FUMOZ with only a single polymorphism and 2 haplotypes vs 18 substitutions and 8 haplotypes in FANG. By contrast, a lowly expressed cytochrome P450 (CYP4C36) did not exhibit diversity differences between strains. We also detected the known pyrethroid resistance conferring amino acid change N384S in CYP6P9b. This study further elucidates the molecular bases of resistance in An. funestus, informing strategies to better manage widespread resistance across Africa.<\/jats:p>","DOI":"10.1093\/g3journal\/jkab352","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T08:14:01Z","timestamp":1633767241000},"source":"Crossref","is-referenced-by-count":33,"title":["RNAseq-based gene expression profiling of the\n                    <i>Anopheles funestus<\/i>\n                    pyrethroid-resistant strain FUMOZ highlights the predominant role of the duplicated\n                    <i>CYP6P9a\/b<\/i>\n                    cytochrome P450s"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-3673","authenticated-orcid":false,"given":"Charles S","family":"Wondji","sequence":"first","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"},{"name":"LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9, P.O. Box 1359, Cameroon"},{"name":"Entomology Unit, International Institute of Tropical Agriculture (IITA), Yaound\u00e9, P.O. Box 2008, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3358-4949","authenticated-orcid":false,"given":"Jack","family":"Hearn","sequence":"additional","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Irving","sequence":"additional","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murielle J","family":"Wondji","sequence":"additional","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"},{"name":"LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9, P.O. Box 1359, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Weedall","sequence":"additional","affiliation":[{"name":"School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"2022013117310735900_jkab352-B1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2583.2008.00776.x","article-title":"Over expression of a cytochrome P450 (CYP6P9) in a major African malaria vector, Anopheles funestus, resistant to pyrethroids","volume":"17","author":"Amenya","year":"2008","journal-title":"Insect Mol Biol"},{"key":"2022013117310735900_jkab352-B2","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count 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