Abstracts (first author)
Neurogenetic networks as substrates for natural variation in olfactory behaviour in Drosophila melanogaster
Appropriate responses to chemical signals are essential for survival and reproduction, and genetic variation that gives rise to phenotypic variation in olfactory behaviour provides a substrate for natural selection. Drosophila melanogaster provides an ideal system to study the genetic basis for natural variation in olfactory behaviour because its olfactory system is well characterized and genetically identical individuals can be reared in controlled environments. The Drosophila melanogaster Genetic Reference Panel (DGRP), a collection of inbred wild-derived lines with fully sequenced genomes enables GWA studies to be performed in a scenario where all variants are known, candidate genes can be functionally tested allowing empirical assessment of the FDR, and outbred populations derived from DGRP lines can be constructed for the analysis of epistasis. GWA analysis together with variance GWA (vGWA) analysis in the DGRP revealed single nucleotide polymorphisms (SNPs) associated with variation in olfactory behaviour. Subsequent extreme QTL mapping using advanced intercross line (AIL) populations derived from lines with opposite extreme behavioural responses revealed additional SNPs. Combined analyses of GWA, vGWA and extreme QTL mapping uncovered a cellular network associated with variation in olfactory behaviour, centered on genes involved with cellular signaling and neural development. Candidate genes and network connectivity were validated through mutational analysis. We show that different elements of the genetic architecture underlying natural variation in olfactory behaviour are revealed in GWA studies and extreme QTL mapping contingent on allele frequencies and context-dependent effects, but they converge on similar cellular processes. Such genetic architecture appears to be a general feature of quantitative traits, is likely to be universal, and has profound implications for the interpretation of human GWA studies and the evolution of complex traits.