'Dark Genome' May Hold the Key to Treatment of Mental Illnesses

Pavankumar Kamat

December 24, 2021

Scientists may have discovered important clues to the treatment of mental illnesses such as schizophrenia and bipolar disorder within a recently-evolved region of the so-called 'dark genome', that part of the DNA outside known genes, according to a study published in Molecular Psychiatry.

Presently, there is limited understanding about the function of the dark genome. First author, Chaitanya Erady, Department of Genetics, University of Cambridge, 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."

Researchers at the University of Cambridge and the University of Leicester have discovered that proteins are produced by 248,135 regions of the dark genome, called novel open reading frames (nORFs).

Some of these proteins originating from recently-evolved nORFs could serve as potential diagnostic and therapeutic targets for schizophrenia and bipolar disorder. The findings also provide a plausible explanation as to why schizophrenia and bipolar disorder have a strong heritability.

"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," said senior author, Dr Sudhakaran Prabakaran. "This opens up huge potential for new druggable targets."

The authors believe these newly emerged genomic features of schizophrenia and bipolar disorder became specific to humans during the evolutionary process and remain more susceptible to disruption by environmental factors.

Dr Sudhakaran Prabakaran is a former researcher at the University of Cambridge and the co-founder of NonExomics. Sabine Bahn is a director of Psynova Neurotech Ltd. and Psyomics Ltd. The remaining authors report no competing interests. Cambridge Enterprise Limited, the commercialisation arm of the University of Cambridge, has filed a patent application related to the research.

Erady C, Amin K, Onilogbo TOAE, Tomasik J, Jukes-Jones R, Umrania Y, Bahn S, Prabakaran S. Novel open reading frames in human accelerated regions and transposable elements reveal new leads to understand schizophrenia and bipolar disorder. Mol Psychiatry. 2021 Dec 23. doi: 10.1038/s41380-021-01405-6.

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