Exome-wide association study reveals largely distinct gene sets underlying specific resistance to dengue virus types 1 and 3 in < i > Aedes aegypti < /i >

by Laura B. Dickson, Sarah H. Merkling, Mathieu Gautier, Amine Ghozlane, Davy Jiolle, Christophe Paupy, Diego Ayala, Isabelle Moltini-Conclois, Albin Fontaine, Louis Lambrechts Although specific interactions between host and pathogen genotypes have been well documented in invertebrates, the identification of host genes involved in discriminating pathogen genotypes remains a challenge. In the mosquitoAedes aegypti, the main dengue virus (DENV) vector worldwide, statistical associations between host genetic markers and DENV types or strains were previously detected, but the host genes underlying this genetic specificity have not been identified. In particular, it is unknown whether DENV type- or strain-specific resistance relies on allelic variants of the same genes or on distinct gene sets. Here, we investigated the genetic architecture of DENV resistance in a population ofAe.aegypti from Bakoumba, Gabon, which displays a stronger resistance phenotype to DENV type 1 (DENV-1) than to DENV type 3 (DENV-3) infection. Following experimental exposure to either DENV-1 or DENV-3, we sequenced the exomes of large phenotypic pools of mosquitoes that are either resistant or susceptible to each DENV type. Using variation in single-nucleotide polymorphism (SNP) frequencies among the pools, we computed empiricalp values based on average gene scores adjusted for the differences in SNP counts, to identify genes associated with infection in a DENV type-specific manner. Among the top 5% most ...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research