GWAS pyrethroid-resistant Aedes aegypti

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 from GWAS use.
We used the Ae. aegypti 50k SNP chip to genotype
populations with different levels of pyrethroid resistance from Northern
Brazil. Pyrethroids are widely used worldwide to control mosquitoes and
other 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 the whole genomic
regions with 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, a 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.