Epistasis for head morphology in Drosophila melanogaster

Abstract

Epistasis – gene-gene interaction – is common for mutations with large phenotypic effects in humans and model organisms. Epistasis impacts quantitative genetic models of speciation, response to natural and artificial selection, genetic mapping and personalized medicine. However, the existence and magnitude of epistasis between alleles with small quantitative phenotypic effects is controversial and difficult to assess. Here, we use the Drosophila melanogaster Genetic Reference Panel of sequenced inbred lines to evaluate the magnitude of naturally occurring epistasis modifying the effects of mutations in jing and inv, two transcription factors that have subtle quantitative effects on head morphology as homozygotes. We find significant epistasis for both mutations and performed single marker genome wide association analyses to map candidate modifier variants and loci affecting head morphology. A subset of these loci was significantly enriched for a known genetic interaction network, and mutations of the candidate epistatic modifier loci also affect head morphology.

Perspectives on the Drosophila melanogaster Model for Advances in Toxicological Science

“…The DGRP has been used to identify variants associated with variation in a wide range of morphologic (Özsoy et al., 2021; Zwarts et al., 2015), physiologic (Carbone et al., 2016; Dembeck et al., 2015; Huang et al., 2012; Huang et al., 2020; Jordan et al., 2012; Olivares et al., 2023; Weber et al., 2012; Zhou et al., 2012), and behavioral (Arya et al., 2015; Baker, Carbone, et al., 2021; Chi et al., 2021; Harbison et al., 2013; Harbison et al., 2019; Highfill et al., 2019; Shorter et al., 2015; Spierer et al., 2021; Swarup et al., 2013) phenotypes. Genome‐wide associations seldom reach genome‐wide significance based on Bonferroni corrections for multiple tests.…”

Nrn1 Epistasis With Bdnf and Cacna1c: Mediation Effects on Symptom Severity Through Neuroanatomical Changes in Schizophrenia

“…It has been suggested that such missing heritability could arise, among other factors, from nonlinear molecular interactions, which are not typically explored in classical GWAS models (Zuk et al, 2012). In fact, gene-gene interactions between two or more loci have been extensively studied in animal and cellular models, suggesting that epistatic networks might represent an essential molecular mechanism involved in the modulation of complex traits (Mackay & Moore, 2014;Özsoy et al, 2021). When the collective effect of large-scale genetic interactions is considered in humans, the association with complex traits, such as SZ, becomes more robust and new variants appear (Woo et al, 2017).…”

NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia

“…It has a strong genetic component that is reflected in its high heritability (h 2 = 65-79%) (Hilker interactions, which are not typically explored in classical GWAS models (Zuk et al 2012). In fact, gene-gene interactions between two or more loci have been extensively studied in animal and cellular models, suggesting that epistatic networks might represent an essential molecular mechanism involved in the modulation of complex traits (Mackay and Moore 2014;Özsoy et al 2021). When the collective effect of large-scale genetic interactions is considered in humans, the association with complex traits, such as SZ, becomes more robust and new variants appear (Woo et al 2017).…”