A study published in Nature reports that disruptions to different autism-associated genes can produce similar changes in gene activity. Researchers found that altering any of 18 genes in human neural progenitor cells led to shared effects, including lower expression of other autism-linked genes. They call this pattern “transcriptomic convergence.”
The findings offer a possible explanation for how rare mutations in many genes with different functions can be associated with common biological features of autism. The research team reconstructed a gene regulatory network and identified regulators involved in these effects, including the autism-associated gene CHD8 and the candidate regulator REST.
The study also points to ZFX, an X-linked transcription factor that activates many genes in the network. ZFX is expressed from both the active and inactive X chromosomes in females, and the researchers propose that higher expression in the female brain may help buffer the effects of damaging mutations in other autism-associated genes.
The authors say the results provide a potential molecular explanation for the female protective effect, the observation that autism is diagnosed more often in males and that autistic females tend to carry more autism-related risk alleles. The study proposes a possible role for ZFX, but does not establish it as a treatment target.
Sources: Neuroscience News.