Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39388546.
- Also identified by DOI 10.1126/science.adq1456 and PMC identifier 11490355.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Germline mutations modulate the risk of developing schizophrenia (SCZ). Much less is known about the role of mosaic somatic mutations in the context of SCZ. Deep (239×) whole-genome sequencing (WGS) of brain neurons from 61 SCZ cases and 25 controls postmortem identified mutations occurring during prenatal neurogenesis. SCZ cases showed increased somatic variants in open chromatin, with increased mosaic CpG transversions (CpG>GpG) and T>G mutations at transcription factor binding sites (TFBSs) overlapping open chromatin, a result not seen in controls. Some of these variants alter gene expression, including SCZ risk genes and genes involved in neurodevelopment. Although these mutational processes can reflect a difference in factors indirectly involved in disease, increased somatic mutations at developmental TFBSs could also potentially contribute to SCZ.
Medical subject headings
- Brain
- Mosaicism
- Schizophrenia
- Transcription Factors
- Germ-Line Mutation