Understanding the effects of Insecticides using Genome-Wide Association Studies.

Understanding the effects of Insecticides using Genome-Wide Association Studies. Llewellyn Green^1,2, Josh Schmidt^1,2, Bec Smith^1,2, Paul Battlay^1,2, Charles Robin^1,2. 1) Genetics, The University of Melbourne, Melbourne, Victoria, Australia; 2) The Bio21 Institute, Melbourne, Victoria, Australia.

The Drosophila melanogaster Genetic Reference Panel consists of 192 highly inbred lines, 162 of which have had their genomes sequenced [1]. These lines form a living library, where limitless numbers of flies of each genotype can be phenotype for any trait. The genetic variants contributing to the traits can then be identified using genome-wide association methods. We report on three insecticide screens of the DGRP and the experiments we have employed to validate the genes implicated by these screens. Three important perspectives into the genetic basis of insecticide biology arise from these studies. Firstly, we can identify polygenes underlying insecticide resistance and assess them for footprints of positive selection. This allows us to determine environmental exposure of non-target organism to insecticides, and address the debate of the role of polygenes and monogenes in insecticide resistance evolution. Secondly, we can identify genetic variants that affect resistance to new insecticides (specifically those that target the Ryanodine receptor) and thereby help predict the mechanisms of field resistance before it can arise and compromise pest control. Thirdly, we have gained insights into the biological processes that are perturbed by insecticides, which are supposed to have distinct modes of action. Perhaps not surprisingly these include several genes involved in neurogenesis and calcium homeostasis. Among the genes uncovered by these studies is a previously poorly characterized muscle associated, protein-kinase-like gene. We dub this gene knocked-up, as reduced function alleles increased resistance to a DDT-knockdown phenotype. [1]. Mackay et al. (2012) The Drosophila melanogaster Genetic Reference Panel. Nature 482 p173-178.