De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.

De novo structural variants in ASD patients more frequently disrupt neuronal regulatory interactions than in unaffected siblings, highlighting a potential genetic mechanism.

• Why it matters: Understanding how structural variants affect genome organization is crucial for uncovering genetic causes of autism spectrum disorder, yet experimental testing is costly and slow.
• What they did: A computational scoring method was developed and implemented in SuPreMo-Akita to predict how hundreds of de novo SVs impact chromatin contacts, focusing on regulatory regions in neuronal genes.
• The result: The approach identified and validated candidate variants disrupting ASD-related regulatory interactions, supporting disrupted genome folding as a contributing factor in some ASD cases and offering a strategy for prioritizing regulatory variants.