‘Dark Genome’ offers clues to treatment of Schizophrenia and bipolar disorder

The study opens up huge potential for new druggable targets.

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Both Schizophrenia and bipolar disorder are mental disorders that are hard to diagnose and treat. These disorders arise from a combination of environmental and genetic factors.

The sections of our DNA known as genes have provided very few clues about their causes, despite being some of the most heritable mental disorders.

Scientists from Cambridge University set out to explore the dark genome and found several “hotspots” that contain code that produces proteins linked to Schizophrenia and bipolar disorder. These hotspots may have evolved because they have beneficial functions in human development. Their disruption by environmental factors leads to susceptibility to or development of, Schizophrenia or bipolar disorder.

Dr. Sudhakaran Prabakaran, who was based in the University of Cambridge’s Department of Genetics, said, “By scanning through the entire genome, we’ve found regions, not classed as genes in the traditional sense, which create proteins that appear to be associated with schizophrenia and bipolar disorder.”

“This opens up huge potential for new druggable targets. It’s really exciting because nobody has ever looked beyond the genes for clues to understanding and treating these conditions before.”

According to scientists, these genomic components of Schizophrenia and bipolar disorder are specific to humans. However, scientists did not find the newly discovered regions in the genomes of other vertebrates. It means the regions evolved quickly in humans with cognitive abilities.

Chaitanya Brady, a researcher in the University of Cambridge’s Department of Genetics, said, “The traditional definition of a gene is too conservative, and it has diverted scientists away from exploring the function of the rest of the genome.”

“When we look outside the regions of DNA classed as genes, we see that the entire human genome can make proteins, not just the genes. We’ve found new proteins that are involved in biological processes and are dysfunctional in disorders like schizophrenia and bipolar disorder.”

Most currently available drugs are designed to target proteins coded by genes. The new finding helps to explain why Schizophrenia and bipolar disorder are heritable conditions and could provide new targets for future treatments.

Journal Reference:

  1. Brady, C. et al.: ‘Novel open reading frames in human accelerated regions and transposable elements reveal new leads to understand schizophrenia and bipolar disorder’, Molecular Psychiatry, December 2021. DOI: 10.1038/s41380-021-01405-6
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