Mood-based disorders are one of the top-ten causes of disability worldwide. However the genes underpinning these disorders have proven to be remarkably elusive.
To try and identify such genes, researchers at Linköping University have used the process of domestication to help shed light on the problem. Domestication has led to a huge raft of changes, but one of the earliest to occur was a decrease in anxiety behaviour.
“Domestication therefore offers a unique opportunity to find the genes responsible for anxiety, by comparing domestic birds with their wild ancestors,” says Dominic Wright, the lead researcher of the study now being published in the Genetics journal.
By crossing wild with domestic chickens for multiple generations in a genetic mapping experiment, then measuring a form of anxiety behaviour, gene regions affecting anxiety were identified.
Gene expression in a specific region of the brain, the hypothalamus, was then measured in over 120 individuals, and used to examine the genetic regions more closely, allowing the identification of ten genes affecting variation in anxiety behaviour in these birds.
By then using these genes as the basis for further investigation, additional datasets in humans and mice were then interrogated. Not only were significant associations for these genes found in mice also assayed in an open field arena, but links were also found for some of these genes in humans affected by schizophrenia and bipolar disorder.
“These results point to the same genes affecting anxiety in animals as diverse as chickens and humans. It also demonstrates that chickens may make an excellent model for the genetic basis of anxiety,” says Dr. Wright.
About this genetics and schizophrenia research
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
Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior
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 large-scale 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.
“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