Probe of DNA repeats reveals genetic link to schizophrenia

Magnetic resonance imaging (fMRI) and other imaging modalities allow the study of differences in brain function in people diagnosed with schizophrenia. The image shows two brain levels, with areas that are more active in health care than schizophrenia patients shown in orange, while studying fMRI of active memory. Credit: Kim J, Matthews NL, Park S./PLoS One.

Researchers at the Children’s Hospital (SickKids) and the Center for Addiction and Psychiatry (CAMH) have found that repetitive DNA sequencing in genes may contribute to a person’s risk of developing schizophrenia.

Repeated Tandem is a class of DNA sequences where two or more nucleotides, known as DNA building blocks, are replicated next to each other. Sometimes these repetitions can extend over time from one generation to the next. As the repetition sequence expands, the potential for this to disrupt cell function increases.

Repeated tandem is known to contribute to more than 50 conditions, including Huntington’s Disease. Little is known about the role of these repetitive tandem in a complex disease such as schizophrenia, which is influenced by the diversity of different organisms.

Dr. Ryan Yuen, Scientist at Biomedical Engineering & Biomedical Sciences at SickKids, and Dr. Anne Bassett, Senior Scientist at CAMH and the University Health Center, study published May 12, 2022 in Biology It has been found that people with schizophrenia have a higher incidence of recurrent tandem than in normal populations. These recurrences of tandem are closely related to schizophrenia, and are often accompanied by other genetic variants, which are known to be associated with schizophrenia.

As part of the study, the team found that the strains also belong to a genetic family of people with a family history of schizophrenia.

“This is the first time that this extraordinary expansion has been assessed organic matter– falls into schizophrenia. Our findings suggest that tandem remodeling is an important type of disorder that contributes to the risk of schizophrenia, ”Yuen said.

Tandem repetitive expansion contributes to errors in how viruses in the brain communicate

Tandem repetitions are generally found in non-codeing DNA, which means their function is uncertain and can be difficult for researchers to study. The researchers used a new mathematical technique developed by Yuen and his team at SickKids to analyze and identify abnormalities in 257 adult schizophrenia body parts carefully evaluated by the Bassett team. They compared the data with 225 non-geneticists and a population of over 2,500 out of the 1000 Genomes Project, the world’s genetic data.

The study found that tandem repetitive expansion contributes to inactivity at the synapse — where neurons connect and communicate with each other in the brain — perhaps by disrupting their immune system.

The study follows a number of recently published studies identifying other contributors to the risk of schizophrenia — which identified common and secondary regional differences that focused on rare protein diversity .

“We found that the molecule and the recurrent tandem expand to fill the rest of the research we see in the field. Our study helps to fill some gaps in our knowledge and emphasizes the importance of synaptic functions in schizophrenia and complex schizophrenia. and a variety of different genetic variants, ”said Yuen, whose team has previously used this method to link the re-expansion of tandem to Autism.

The findings help to broaden our understanding of the underlying causes of schizophrenia

Bassett said the study provided additional evidence for a well-defined risk factor for schizophrenia and related psychiatric disorders.

Bassett said: “Given the biological chain of schizophrenia, we hope that our research, along with other recent research in the field, could be used to further understand this disease as a mental illness for help reduce illness, ”Bassett said. “These findings are a major step forward for the future of schizophrenia.”

Yuen noted the next reading with the size of the group is needed to further clarify the role that tandem is rarely repeated in nature.

“As we open up more understanding of the root cause of genetics schizophrenia“One day we will be able to move forward with the use of biological hazards to diversify treatment options for patients.”

Mutations related to the expression of genes associated with complex characteristics

Learn more:
Genom-fadi tandem repetitive strain contributes to the risk of schizophrenia, Biology (2022).

Provided by Sick Children’s Hospital

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