Long repetitive DNA can cause schizophrenia

Parallel repeats are a class of DNA sequences in which two or more nucleotides, known as the building blocks of DNA, are repeated adjacent to each other. Sometimes these repeats can expand as they are passed from generation to generation. As a repeat sequence expands, the likelihood that it could disrupt gene function increases.

Parallel repeat expansion is known to cause more than 50 disease conditions, including Huntington’s Disease. Less is known about the role of these tandem repeats in a disorder as complex as schizophrenia, which is influenced by the effects of many variations in different genes.

Led by Dr Ryan Yuen, a scientist in the Genetics & Genome Biology program at SickKids, and Dr Anne Bassett, a senior scientist at CAMH and the University Health Network, a research team led by Dr. Research published recently in Molecular Psychiatry found that individuals with schizophrenia have a large number of rare tandem repeat expansions that are not commonly seen in the general population.

This tandem repeat expansion is located near genes that, and often together with other genetic variants, are known to be associated with schizophrenia.

As part of the study, the team found that the extensions were also present in the genomes of individuals with a family history of schizophrenia.

“This is the first time that these rare repeat expansions have been evaluated genome-wide in schizophrenia. Our findings suggest that tandem repeat expansion is an important type of variation that contributes to schizophrenia risk,” Yuen said.

Parallel repeat expansion contributes to errors in the way neurons in the brain communicate

Parallel repeats are often found in non-coding DNA, which means their function is unclear and they can be difficult for researchers.

The researchers applied a new computational method developed by Yuen and his team at SickKids to search and find rare long repeats across the genomes of 257 adults with mental illness. Schizophrenia was carefully evaluated by Bassett’s team. They compared the data with the genomes of 225 individuals without mental illness as well as with a cohort of more than 2,500 individuals from the 1000 Genomes Project, an international genomic database.

Research shows that tandem repeat dilation contributes to dysfunction at the synapse – where neurons connect and communicate with each other in the brain – potentially by disrupting regulation of their associated genes.

This study follows other recently published studies that have described other factors that contribute to schizophrenia risk – one that identified common regions of variation and the second that focused on rare protein-breaking variant.

“We found that genes with tandem repeat extensions overlap with other discoveries we’re seeing in this area. Our study helps fill some gaps in our knowledge. our study and highlight the important function of synaptic functions in schizophrenia as well as in complex disease According to Yuen, the team previously used a similar approach to link repeat expansion parallel to autism spectrum disorder, said.

Discovery expands understanding of genetic underpinnings of schizophrenia

These findings provide further evidence for a range of potential genetic risks for schizophrenia and related psychiatric disorders, Bassett said.

“Given the biological complexity of schizophrenia, we hope that our findings, combined with other recent studies in the field, can be used,” Bassett said. to improve understanding of this disorder as a brain disease to help navigate the disease. “These findings are a big step forward for the future of schizophrenia research.”

Yuen notes that future studies with larger cohorts are required to better characterize the role of rare tandem repeats in the disease state.

“As we better understand the genetic underpinnings of schizophrenia, we may one day move toward a future in which genetic risk factors can be used to personalize treatments for patients.”

Source: Eurekalert

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