Schizophrenia is a very serious but one of the most misunderstood and mistreated mental health conditions in the world, which affects the person’s thinking, feelings, and behavior. It traditionally results in a mix of hallucinations, delusions, and a disorganized mental state. Hallucinations, in this case, often include, but aren’t limited to, hearing voices, which others cannot, and this is followed by believing in things that aren’t exactly in line with reality.
We know for a fact that there is a genetic component to schizophrenia development, however, until now, only the theory of germline mutation was accounted for. This was to say that a mutation of a reproductive cell before fertilization, no matter if male or female, could, in specific cases after zygote formation, result in a schizophrenia predisposition. New research points in a bit different direction regarding genetic mutations, specifically somatic mosaic mutations.
Somatic mosaicism means we would find two genetically distinct cell populations within an individual as a result of a postzygotic mutational process. This type of mutation can vary in results based on its size, ranging from single cell to entire chromosomes, and has been previously linked to disease.
In this case, the schizophrenia patients showed an increased count of somatic variants in open chromatin (genetic information matter), mainly increased mosaic CpG transversions (CpG is where a cytosine nucleotide is usually followed in sequence by a guanine nucleotide). The transversion means that instead of cytosine and guanine, we see in sequence two guanine nucleotides. We also see T>G mutations (instead of thymine nucleotide, there is guanine) at transcription factor binding sites (the place where enzymes bind and start the process of DNA to RNA transcription) overlapping open chromatin. We don’t see this pathology in the controls of this research.
Some of these mutated variants have the ability to alter gene expression, including the schizophrenia risk genes, as well as genes involved in neurodevelopment, which are the main reason these mutations could be linked to both indirect or direct involvement in schizophrenia progression. Because of these findings, further research on this topic could really shed light on the mechanism of this disease and also raise more awareness about it around the world.
Resources:
Eduardo A. Maury et al. (2024) Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes.
mayoclinic.org Schizophrenia
pmc.ncbi.nlm.nih.gov Somatic Mosaicism in the Human Genome
sciencedirect.com CpG Site
Comentários