Combining genetic crosses and targeted mass sequencing for identifying genomic variations associated with resistance to multiple insecticides in the dengue vector Aedes aegypti

the present study aimed at combining genetic crosses and targeted DNA-seq to identify genomic variations specifically associated with resistance to distinct insecticides in a multi-resistant Ae. aegypti population. After exposure to three insecticides of distinct chemical families (the pyrethroid deltamethrin, the organophosphate fenitrothion and the carbamate bendiocarb), survivors to each insecticide were crossed with a susceptible strain to generate three F2 lines. Each F2 line was then phenotyped with two increasing doses of insecticide and survivors were used to identify CNV and polymorphism variations associated with resistance in hundreds of target genes including all detoxification enzymes and insecticide target proteins. In addition, the capture of thousands of intergenic regions regularly distributed over mosquito genome also allowed crossing up these data with a genome-wide screening of selection signatures associated with resistance.