Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior

Abstract

The identification of genetic variants responsible for behavioral variation is an enduring goal in biology, with wide-scale ramifications, ranging from medical research to evolutionary theory on personality syndromes. Here, we use for the first time a largescale genetical genomics analysis in the brains of chickens to identify genes affecting anxiety as measured by an open field test. We combine quantitative trait locus (QTL) analysis in 572 individuals and expression QTL (eQTL) analysis in 129 individuals from an advanced intercross between domestic chickens and Red Junglefowl. We identify 10 putative quantitative trait genes affecting anxiety behavior. These genes were tested for an association in the mouse Heterogeneous Stock anxiety (open field) data set and human GWAS data sets for bipolar disorder, major depressive disorder, and schizophrenia. Although comparisons between species are complex, associations were observed for four of the candidate genes in mice and three of the candidate genes in humans. Using a multimodel approach we have therefore identified a number of putative quantitative trait genes affecting anxiety behavior, principally in chickens but also with some potentially translational effects as well. This study demonstrates that chickens are an excellent model organism for the genetic dissection of behavior.

Genetics and genomics of social behaviour in a chicken model

“…Correlations between the two trials were found to be extremely significant (see supplementary figure 1), indicating that the tests were strongly repeatable. A high degree of correlation was found between the social reinstatement behaviour reported here, and the open field behaviour that was also recorded for these animals (and reported in (J OHNSSON et al 2016)), with 123 of the 224 pairwise correlation comparisons (these pairwise correlations were both within- and between-tests) being significant (using a 1% significance threshold, see supplementary figure 1).…”

“…in the F 8 . 129 of the 572 F 8 were used in an eQTL experiment, with the hypothalamus/thalamus dissected out at 212 days of age, RNA extracted and run individually on a 135k probe microarray (see (J OHNSSON et al 2016)). For further details on feed and housing see (J OHNSSON et al 2012b).…”

“…In the behavioural QTL analysis batch, sex and arena were always included in the model as fixed effects, whilst body weight was included as a covariate. A Principal Component Analysis (PCA) of the first ten Principal Components (PCs) of the genotypic data were fitted to account for population substructure (see Johnsson et al(J OHNSSON et al 2016) for details), with all significant PCs retained in the final model. A sex-interaction effect was added, where significant, to account for a particular QTL varying between the sexes.…”

“…The study presented here continues from this using an advanced intercross (AIL) to generate small confidence intervals for mapping (D ARVASI 1998). This AIL has already been used to identify genes affecting anxiety-related behaviour in an open field test (Johnsson et al 2016), however here we expand this to look at sociality. It was performed in three distinct phases.…”

Newborn chicks show inherited variability in early social predispositions for hen-like stimuli

“…Understanding the genetic basis of predispositions for animacy cues and its individual variability, might have a crucial importance for translational studies on developmental pathologies, such as Autism Spectrum Disorders42. The use of chicks as system model is particularly suitable not only for the ease of handling and controlling precocial special species until the moment of test and for the established parallels between human newborns and chicks1, but also for the mounting evidence on the neurobiological basis of spontaneous predispositions7184344 and the availability of genomic tools45464748 and controlled populations with segregating variation1647.…”