Schizophrenia is an extreme mental illness that impacts how a person thinks, behaves and feels. Individuals with schizophrenia might experience hallucinations, delusions, disordered thinking, and trouble in expressing feelings or feeling enjoyment.
Scientists have discovered a strong connection in between the development of schizophrenia and a rare form of a genetic variant called tandem repeats.
In our cells, DNA functions as a language, producing the special characteristics that make each of us who we are. Tandem repeats take place within DNA when a pattern of one or more nucleotides, the structure blocks of DNA comprised of the chemicals cytosine (C), adenine (A), guanine (G), and thymine (T), is duplicated numerous times in a row. An example of this might be: CAG CAG, in which the series CAG is repeated 3 times.
The University of North Carolina School of Medicine laboratory of Jin Szatkiewicz, Ph.D., associate teacher of genes, and coworkers, have performed one of the most comprehensive examinations of tandem repeats in schizophrenia, utilizing advanced whole-genome sequencing and artificial intelligence strategies. Their research study has shed light on the role of tandem repeats in the advancement of this incapacitating disease.
An image showing a tandem repeat. Credit: Jin Szatkiewicz Lab, UNC School of Medicine
Released in the journal Molecular Psychiatry, the research study reveals that people with schizophrenia had a significantly higher rate of uncommon tandem repeats in their genomes– 7% more than people without schizophrenia. And they observed that the tandem repeats were not randomly situated throughout the genome; they were mostly found in genes essential to brain function and understood to be crucial in schizophrenia, according to previous research studies.
” We believe this discovery opens doors for future functional research studies on the accurate biological mechanism of such variations,” stated Szatkiewicz, who is likewise an adjunct assistant professor of psychiatry. “Understanding the biological cause of schizophrenia will enable future development of diagnostic tests, effective pharmaceuticals, and personalized treatments.”
Tandem repeats generally do not have unfavorable health implications. Based on the location of tandem repeats in the genome and how long they are, they can contribute to illness. Huntingtons illness is caused by a tandem repeat in the HTT gene that has been abnormally expanded. The start of the disease will occur once the sequence of cytosine-adenine-guanine (CAG) repeats more than 36 times on the HTT gene. The longer repeat expansions cause abnormal protein items with a prolonged track of glutamine that is toxic to brain cells. These repeats are acquired and tend to grow longer and longer in successive generations with increasing disease severity or reducing age of start.
In their present study, Szatkiewicz and her group took a look at the whole genomes of 2,100 people to find tandem repeats that looked abnormally long and were rare or distinct. Since all individuals offered access to their medical records, the group was able to compare these rare and long repeat DNA sequence samples from people who had schizophrenia versus samples from people in the study who didnt. This allowed the researchers to figure out which of these tandem repeats may be included with the development of schizophrenia.
Using gene network analysis, the authors of this study demonstrated that genes with unusual tandem repeats discovered in schizophrenia mainly effect synaptic and neuronal signaling functions. In addition, these genes are extremely evolutionarily conserved, suggesting essential biological functions and for that reason the significant effect that tandem repeats may exert.
The UNC School of Medicine researchers then teamed up with researchers from The Hospital for Sick Children in Toronto to see if this increased level of rare tandem variations would also be discovered in another separately collected group of samples. The Szatkiewicz findings were reproduced in the Canadian examination, suggesting that this freshly found link in between tandem repeats and schizophrenia is quite strong.
” We think this is an important research study,” said Szatkiewicz. “Were confident our work sheds significant light on the function of tandem repeat DNA mutations play in the advancement of schizophrenia.”
Referral: “Rare tandem repeat expansions connect with genes involved in synaptic and neuronal signaling functions in schizophrenia” by Jia Wen, Brett Trost, Worrawat Engchuan, Matthew Halvorsen, Linda M. Pallotto, Aleksandra Mitina, NaEshia Ancalade, Martilias Farrell, Ian Backstrom, Keyi Guo, Giovanna Pellecchia, Bhooma Thiruvahindrapuram, Paola Giusti-Rodriguez, Jonathan David Rosen, Yun Li, Hyejung Won, Patrik K. E. Magnusson, Ulf Gyllensten, Anne S. Bassett, Christina M. Hultman, Patrick F. Sullivan, Ryan K. C. Yuen and Jin P. Szatkiewicz, 16 November 2022, Molecular Psychiatry.DOI: 10.1038/ s41380-022-01857-4.
This research study was mainly funded through grants from the National Institute of Mental Health and the SciLifeLab National Project.
Tandem repeats happen within DNA when a pattern of one or more nucleotides, the structure blocks of DNA made up of the chemicals cytosine (C), adenine (A), guanine (G), and thymine (T), is repeated multiple times in a row. Based on the place of tandem repeats in the genome and how long they are, they can contribute to disease. Huntingtons illness is caused by a tandem repeat in the HTT gene that has actually been unusually expanded. In their current study, Szatkiewicz and her team looked at the entire genomes of 2,100 people to discover tandem repeats that looked unusually long and were unique or uncommon. Due to the fact that all individuals provided access to their medical records, the group was able to compare these long and unusual repeat DNA sequence samples from individuals who had schizophrenia versus samples from people in the research study who didnt.