Scientists investigating the DNA outside our genes - the 'dark genome' - have discovered recently evolved regions that code for proteins associated with schizophrenia and bipolar disorder.
From:
Cambridge University
December 23, 2021 -- They say these new
proteins can be used as biological indicators to distinguish between the two
conditions, and to identify patients more prone to psychosis or suicide.
Schizophrenia
and bipolar disorder are debilitating mental disorders that are hard to
diagnose and treat. Despite being amongst the most heritable mental health
disorders, very few clues to their cause have been found in the sections of our
DNA known as genes.
The scientists
think that hotspots in the 'dark genome' associated with the disorders may have
evolved because they have beneficial functions in human development, but their
disruption by environmental factors leads to susceptibility to, or development
of, schizophrenia or bipolar disorder.
The results
are published today in the journal Molecular Psychiatry.
"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 Dr Sudhakaran Prabakaran, who
was based in the University of Cambridge's Department of Genetics when he
conducted the research, and is senior author of the report.
He added:
"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."
The
researchers think that these genomic components of schizophrenia and bipolar
disorder are specific to humans -- the newly discovered regions are not found
in the genomes of other vertebrates. It is likely that the regions evolved
quickly in humans as our cognitive abilities developed, but they are easily
disrupted -- resulting in the two conditions.
"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,"
said Chaitanya Erady, a researcher in the University of Cambridge's Department
of Genetics and first author of the study.
She added:
"When we look outside the regions of DNA classed as genes, we see that the
entire human genome has the ability to 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."
The majority
of 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.
Schizophrenia
is a severe, long-term mental health condition that may result in
hallucinations, delusions, and disordered thinking and behaviour, while bipolar
disorder causes extreme mood swings ranging from mania to depression. The
symptoms sometimes make the two disorders difficult to tell apart.
Prabakaran
left his University position earlier this year to create the company
NonExomics, in order to commercialise this and other discoveries. Cambridge
Enterprise, the commercialisation arm of the University of Cambridge, has
assisted NonExomics by licensing the intellectual property. Prabakaran has
raised seed funding to develop new therapeutics that will target the proteins
implicated in schizophrenia and bipolar disorder, and other diseases.
His team has
now discovered 248,000 regions of DNA outside of the regions conventionally
defined as genes, which code for new proteins that are disrupted in disease.
https://www.sciencedaily.com/releases/2021/12/211223225442.htm
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