Chickens Reveal Genetic Links to Anxiety

Chicken genes are grouped into much smaller linkage blocks than mammalian genomes are, allowing researchers to pinpoint genome regions associated with a trait, such as anxious behavior.
Chicken genes are grouped into much smaller linkage blocks than mammalian genomes are, allowing researchers to pinpoint genome regions associated with a trait, such as anxious behavior.

The genetics of anxious chickens may shed light on anxiety in humans, according to research published in Genetics.

By cross-breeding White Leghorn chickens (less anxious domesticated chickens) with red junglefowl (more anxious wild chickens), the researchers have identified specific genes related to anxiety in the chickens that are also associated with anxiety in mice and with schizophrenia or bipolar disorder in humans.

These results demonstrate the potential of chickens to serve as a powerful model for understanding the genetics underlying human behavior.

“By necessity, human genetic studies of behavior often focus only on susceptibility to a mental health disorder. But what about more subtle differences in behavior? For example, what makes one person a little more anxious than others? And what makes someone else a little bolder?” said study leader Dominic Wright of Linköping University in Sweden. “Animal models like the chicken allow us to address challenging questions like these using controlled breeding experiments.”

Chickens are a good model for observing anxiety because of the wild anxious vs domesticated non-anxious temperaments that have been bred after thousands of years. Chicken genes are also grouped into much smaller linkage blocks than mammalian genomes are, allowing researchers to pinpoint genome regions associated with a trait, such as anxiety behavior.

To search for genes that contribute to anxiety behaviors, the researchers first crossed White Leghorn chickens with red junglefowl to create a population of hybrids. They then put the hybrids through an open field test in which they observed their activity in a brightly-lit, featureless space the chickens had never seen before. More anxious birds either stayed frozen with fear or rapidly darted around, avoiding the center of the test arena. Less anxious birds traversed the whole area at a less erratic pace.

The researchers then compared the birds' behavior with their genome data and identified 15 regions of the genome that contributed to their behavioral variation. The team next narrowed the search by examining gene activity in the hypothalamus, a region of the brain involved in regulating anxiety. This narrowed the search to 10 gene candidates for which heritable genetic differences were correlated with anxiety behaviors.

Of the 10 candidate genes, 6 had known functions involving behavior or brain function (for example, ADAM10 is needed for proper brain formation during development, for protection against brain amyloid plaques that form in some neurodegenerative diseases, and also influences learning and memory).

The researchers then tested whether these genes also influenced anxiety behavior in mice and humans. Four of the genes identified in the chickens were also associated with anxiety in mice, while 3 were associated with schizophrenia or bipolar disorder in large human genomic studies.

Although anxiety behaviors were not directly measured in humans, the researchers argue that these other disorders may reveal links to anxiety. A large number of people with bipolar disorder also have diagnosed anxiety disorders, and complex overlaps may also exist between anxiety behaviors and schizophrenia.

“Though we can't yet prove these genes have equivalent functions in chicken and humans, the data certainly raises the intriguing possibility that genes controlling variation in behavior can be remarkably conserved between a whole variety of species,” said Dr Wright in a statement. “Understanding the genetics underlying the chicken results may provide fundamental insights into animal behavior, including normal behavioral variation in humans.”

Reference

Johnsson M, Williams MJ, Jensen P, Wright D. Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior. Genetics. 2016; doi:10.1534/genetics.115.179010.

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