Mood-related disorders rank among the top ten causes of disability worldwide, yet the genes driving these conditions have remained difficult to pinpoint.
Researchers at Linköping University approached this challenge by exploiting an unexpected advantage: domestication. When animals are domesticated, many behavioral and physiological traits change, and one of the earliest and most consistent shifts is a reduction in anxiety-like behavior. By comparing domestic chickens with their wild ancestors, the team aimed to identify genetic variants that influence anxiety.
“Domestication offers a unique opportunity to locate genes that influence anxiety by contrasting domestic birds with their wild relatives,” explains Dominic Wright, the study’s lead author, with findings now published in the journal Genetics.
The research combined classic genetic mapping with gene expression analysis. Scientists created an advanced intercross by breeding domestic chickens with Red Junglefowl (the wild ancestor) for multiple generations. They then measured anxiety-related behavior using an open field test — a standard assay that quantifies how an animal responds to a novel, open environment.
Quantitative trait locus (QTL) analysis across 572 birds identified chromosomal regions linked to variation in anxiety-related behavior. To narrow down candidate genes within these regions, the team measured gene expression in the hypothalamus, a brain region critical for stress and emotion regulation, in over 120 individuals and performed expression QTL (eQTL) analysis. This combined genetical genomics approach allowed the researchers to identify ten genes likely to influence anxiety-related traits in these birds.
To evaluate whether these candidate genes have relevance beyond chickens, the researchers cross-referenced their findings with existing datasets in mice and humans. In a mouse heterogeneous stock dataset that used open field behavior as a phenotype, four of the candidate genes showed meaningful associations with anxiety-related traits. In human genome-wide association study (GWAS) datasets for bipolar disorder, major depressive disorder, and schizophrenia, three of the candidate genes also showed associations, suggesting potential translational relevance.
These cross-species associations suggest a surprising conservation of genetic influences on anxiety: some of the same genes implicated in chicken anxiety behavior appear to play roles in mammalian anxiety and in human psychiatric conditions. “Our results indicate that chickens can serve as an effective genomic model to dissect the genetic architecture of anxiety,” says Dr. Wright. Using domestication as a natural experiment allows researchers to pinpoint genetic changes linked to reduced fear and anxiety that occurred during the domestication process.
Source: Linköping University
Image Source: The image is credited to Linköping University
Original Research: Abstract for “Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior” by Martin Johnsson, Michael J. Williams, Per Jensen, and Dominic Wright in Genetics. Published online January 5 2016 doi:10.1534/genetics.116.179010
Abstract
Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior
This study applies a large-scale genetical genomics framework in chicken brains to identify genes that influence anxiety-like behavior measured in an open field test. Using an advanced intercross between domestic chickens and Red Junglefowl, the authors performed QTL mapping in 572 individuals and eQTL analysis in 129 hypothalamus samples. Integrating behavioral QTLs with expression QTLs enabled the identification of ten putative quantitative trait genes that contribute to anxiety-related variation. To test cross-species relevance, these candidate genes were evaluated in a mouse heterogeneous stock dataset for open field anxiety and in human GWAS datasets for bipolar disorder, major depressive disorder, and schizophrenia. The analyses revealed associations for several candidates in both mouse and human data, supporting the idea that at least some genetic contributors to anxiety are conserved across vertebrates. The study highlights chickens as a valuable and underused model organism for genetic dissection of behavior and for generating hypotheses that may inform studies of human psychiatric disorders.
“Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior” by Martin Johnsson, Michael J. Williams, Per Jensen, and Dominic Wright in Genetics. Published online January 5 2016 doi:10.1534/genetics.116.179010