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Faucon, Frederic, Dusfour, Isabelle, Gaude, Thierry, Navratil, Vincent, Boyer, Frederic, Chandre, Fabrice, Sirisopa, Patcharawan, Thanispong, Kanutcharee, Juntarajumnong, Waraporn, Poupardin, Rodolphe, Chareonviriyaphap, Theeraphap, Girod, Romain, Corbel, Vincent, Reynaud, Stephane and David, Jean-Philippe (2015) 'Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegyptiby deep targeted sequencing'. Genome Research, Vol 25, Issue 9, pp. 1347-1359.
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Abstract
The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.
| Item Type: | Article |
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| Additional Information: | Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.189225.115. |
| Subjects: | QU Biochemistry > Genetics > QU 460 Genomics. Proteomics QU Biochemistry > Genetics > QU 550 Genetic techniques. PCR. Chromosome mapping QX Parasitology > Insects. Other Parasites > QX 525 Aedes QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control WC Communicable Diseases > Virus Diseases > Infectious Mononucleosis. Arbovirus Infections > WC 528 Dengue |
| Faculty: Department: | Biological Sciences > Vector Biology Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1101/gr.189225.115 |
| Depositing User: | Lynn Roberts-Maloney |
| Date Deposited: | 23 Oct 2015 10:35 |
| Last Modified: | 06 Feb 2018 13:10 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/5372 |
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