An area in the human and mouse genome has been found to contain DNA that controls genes involved in anxiety.
The research group led by Professor Alasdair Mackenzie at the University of Aberdeen found a section of non-coding DNA that when removed can increase anxiety. This region of DNA, an enhancer known as BE5.1, is well conserved between humans and mice and controls the BDNF gene. The BDNF gene is known to be involved with key brain processes including survival and growth of neurons, and they found deletion of BE5.1 resulted in increased anxiety in female mice.
'We already know that 95 percent of the genetic differences associated with disease are found outside of protein coding genes. This part of the genome, known as the "non-coding genome" has not been well explored because we previously lacked the tools to do so.' Professor Mackenzie, lead author of the study published in Molecular Psychiatry, said. 'We also know that the non-coding genome contains information in the form of gene switches that tell genes where and when to be turned on. This is important as genes have to be switched on in the right cells and at the right times to ensure good health and when they are not turned on correctly can contribute to conditions like anxiety, depression and addiction.'
CRISPR-based genome editing was used to delete specific areas of the non-coding genome in mice to determine their impact on anxiety, addiction and obesity. Behavioural studies were then used to determine the result of these deletions. Although the team hypothesised an impact on obesity, deletion of the BE5.1 had no significant effect on weight gain and only minimal effects on food intake. The scientists discovered that female mice without BE5.1 demonstrate increased anxiety-like behaviour.
Human genome-wide association studies around the BDNF gene locus have previously identified polymorphisms linked to depression, anxiety and obesity. Using the results from these studies, the scientists found that one allele of a particular polymorphism was associated with anxious feelings that were consistent with the role for BE5.1 in anxiety observed with their mouse model.
First author Dr Andrew McEwan, from the University of Aberdeen, explained: 'To understand the basis of complex human diseases, that includes mental illness and other conditions such as obesity, depression and addiction, it is as important to understand the mechanisms that ensure proper production of proteins in the right cells as it is to understand the proteins themselves. This will only be achieved if we better understand the non-coding genome in health and disease and the function and role of the thousands of enigmatic gene switches that lurk in its depths'.
The team behind the study hopes that the findings will enable further research into drug targets for anxiety, which impacts as many as one in five people according to the Mental Health Foundation.
Sources and References
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Aberdeen scientists identify genetic anxiety 'switch'
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An ancient polymorphic regulatory region within the BDNF gene associated with obesity modulates anxiety-like behaviour in mice and humans
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Aberdeen scientists find anxiety ‘switch’ in DNA
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Research identifies genetic ‘switch’ that can control anxiety
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Genetic 'switch' that controls anxiety discovered in groundbreaking medical research
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