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Schizophrenia is associated with somatic mutations that occur in utero – ScienceDaily
Schizophrenia, an adult-onset psychiatric disorder, is thought to be caused by a combination of environmental factors and genetics, but the exact cause is still not fully understood.In a study published in a journal cell genomics On July 6, researchers discovered a correlation between schizophrenia and somatic copy number variations. Somatic copy number variation is a type of mutation that occurs after inheritance of genetic material early in development. This study is one of the first to rigorously describe the relationship between non-inherited somatic gene mutations and schizophrenia risk.
“We originally thought of genetics as the study of heredity, but now we know that the mechanisms of heredity go far beyond that,” says researchers at the Howard Hughes Medical Institute. , says lead author Chris Walsh, director of genetics and genomics at Boston Children’s Hospital. “We are looking for mutations that are not inherited from parents.”
Researchers analyzed data for genotypic markers from more than 20,000 blood samples from people with and without schizophrenia, collected from the Psychiatric Genomics Consortium. They finally identified two genes he – NRXN1 and ABCB11 — When interrupted, correlated with cases of schizophrenia in the womb. NRXN1, genes that help transmit signals throughout the brain have been previously associated with schizophrenia. However, this is the first study to link somatic cells rather than genetics. NRXN1 Mutation due to schizophrenia.
Unlike hereditary mutations that are present in all cells of the body, somatic mutations are present only in some cells, based on when and where the mutation occurred. If mutations occur early in development, they are expected to be present in a mosaic pattern throughout the body. Based on this principle, researchers can identify somatic mutations that occur early in development and are present not only in the brain but also in some cells in the blood.
“If a mutation occurs when there are only two cells after fertilization, the mutation will be present in half the cells of the body,” Walsh said. “First he will be present in about a quarter of the cells of the body if it occurs in one of the four cells, and so on.”
The second gene the researchers identified was ABCB11, It is best known to encode liver proteins. “It came out of nowhere for us,” says Eduardo Morley, a student in his MD-PhD program at Harvard-MIT. “Although some studies have linked mutations in this gene to treatment-resistant schizophrenia, it is not strongly associated with schizophrenia per se.”
After further investigation by the team, we found that: ABCB11 It is also expressed in a very specialized subset of neurons that carry dopamine from the brainstem to the cerebral cortex. Most schizophrenia drugs are thought to act on these cells to lower dopamine levels in individuals, which may explain why this gene is associated with treatment resistance.
Next, the team is working to identify other acquired mutations that may be associated with schizophrenia. Given that this study analyzed blood samples, it is important to focus on more brain-specific mutations that were either too subtle to be detected by this analysis or may have occurred recently in the patient’s life. would be In addition, somatic deletions or duplications may be understudied risk factors associated with other diseases.
“This study shows that it is possible to find somatic mutations in adult-onset psychiatric disorders,” Morley said. “This raises the question of what other disorders are controlled by this kind of mutation.”
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