in vivo RNAi contributes to follow-up of GWAS candidate aggression-related genes

Shorter J, Couch C, Huang W, Carbone MA, Peiffer J, Anholt RR, Mackay TF. Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior. Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):E3555-63. PMID: 26100892.

From the abstract: "Aggression is an evolutionarily conserved complex behavior ... Here, we performed genome-wide association analyses using the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and replicate advanced intercross populations derived from the most and least aggressive DGRP lines. We identified genes that have been previously implicated in aggressive behavior as well as many novel loci ... We used mutations and RNAi knock-down alleles to functionally validate 79% of the candidate genes and 75% of the candidate epistatic interactions tested. Epistasis for aggressive behavior causes cryptic genetic variation in the DGRP that is revealed by changing allele frequencies in the outbred populations derived from extreme DGRP lines. This phenomenon may pertain to other fitness traits and species, with implications for evolution, applied breeding, and human genetics."