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GENOME-WIDE ASSOCIATION STUDY REVEALS NEW LOCI ASSOCIATED WITH PYRETHROID RESISTANCE IN AEDES AEGYPTI
Affilliation
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT. USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil.
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT. USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil.
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT. USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil.
Abstract
Genome-wide association studies (GWAS) use genetic polymorphism across the genomes
of individuals with distinct characteristics to identify genotype-phenotype associations. In
mosquitoes, complex traits such as vector competence and insecticide resistance could
benefit fromGWAS. We used the Aedes aegypti 50k SNP chip to genotype populationswith
different levels of pyrethroid resistance from Northern Brazil. Pyrethroids are widely used
worldwide to control mosquitoes and agricultural pests, and their intensive use led to the
selection of resistance phenotypes in many insects including mosquitoes. For Ae. aegypti,
resistance phenotypes are mainly associated with several mutations in the voltage-gated
sodium channel, known as knockdown resistance (kdr). We phenotyped those populations
with the WHO insecticide bioassay using deltamethrin impregnated papers, genotyped the
kdr alleles using qPCR, and determined allele frequencies across the genome using the SNP
chip. We identified single-nucleotide polymorphisms (SNPs) directly associated with
resistance and one epistatic SNP pair. We also observed that the novel SNPs correlated
with the known kdr genotypes, although on different chromosomes or not in close physical
proximity to the voltage gated sodium channel gene. In addition, pairwise comparison of
resistance and susceptible mosquitoes from each population revealed differentiated
genomic regions not associated with pyrethroid resistance. These new bi-allelic markers
can be used to genotype other populations along with kdr alleles to understand their
worldwide distribution. The functional roles of the genes near the newly discovered SNPs
require new studies to determine if they act synergistically with kdr alleles or reduce the
fitness cost of maintaining resistant alleles.
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