Germ-cell-specific transcriptome analysis illuminates the chromatin and ubiquitin pathway in autism spectrum disorders.
Broken gene-control systems in parents' sperm and eggs may pass autism risk to kids.
01Research in Context
What this study did
Scientists looked at mouse sperm and egg cells to find genes linked to autism.
They checked which genes were turned on or off in these germ cells.
The team focused on two cell systems: chromatin remodeling and the ubiquitin-proteasome pathway.
What they found
Both systems were broken in the germ cells of autism-model mice.
These broken systems may pass autism risk from parent to child before birth.
The study points to new biomarkers we might test for in future families.
How this fits with other research
Xie et al. (2021) found a single autism risk gene in Chinese children. Furukawa et al. (2023) now shows whole gene networks that matter, not just one gene.
Taşkıran et al. (2021) used whole-exome sequencing to find gene problems in kids with intellectual disability. The new mouse work adds why those gene changes lead to autism.
Arcebido et al. (2025) showed only a large share of autism patients get genetic tests. Sawako's findings give us more reasons to test parents, not just kids.
Why it matters
You may soon add germ-cell biomarker tests to your autism work-ups. Ask families about genetic counseling before pregnancy. Track this research for future parent-screening tools you can use in clinic.
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02At a glance
03Original abstract
Accumulating epidemiological studies have suggested a positive association between advanced paternal age at conception and the increased risk of neurodevelopmental outcomes such as autism spectrum disorder (ASD) in their children. Recent biological studies using human sperm have identified increased de novo mutations in aged fathers, and hyper- or hypomethylation has been identified in the sperm from aged rodents. Dysregulation of DNA methylation in sperm may explain the transgenerational effects on the pathogenesis of ASD. However, compared to these epigenetic changes in the sperm of aged males, the effects of inherited predisposition from germ cells are largely unknown. Here, we use single-cell transcriptome data sets from 13 cell lines, including 12 ASD-associated CNVs models and control, that are performed neural differentiation from mouse embryonic stem cells. This study performed comprehensive bioinformatic analyses such as gene ontology (GO), network, pathway, and upstream regulator analyses. Through these analyses, we identify several susceptible pathways, such as chromatin and ubiquitin, in addition to translational and oxidative phosphorylation. Our results suggest that dysregulation of epigenetic chromosome remodeling and ubiquitin-proteasome pathway in the germ cell is a possible modulator for subsequent differentiated cells, sperm, and egg, as a risk factor for the neurodevelopmental disorder.
Autism research : official journal of the International Society for Autism Research, 2023 · doi:10.1002/aur.2939