Unraveling the genetic architecture of autism
Researchers have identified that topologically associated domains (TADs), fundamental units of 3D nuclear organization, play a crucial role in autism risk. Furthermore, they uncovered that de novo mutations in promoter regions of TADs containing known ASD genes are associated with ASD risk, suggesting a link through the 3D structure of the genome.
Validation of these findings was achieved using CRISPR-Cas9 to introduce de novo promoter variants into human induced pluripotent stem cells. The study’s senior author, Atsushi Takata (RIKEN Center for Brain Science, Tokyo, Japan), highlighted the importance of looking beyond ASD-related genes in genetic risk assessments for autism, emphasizing the need to focus on entire TADs containing ASD-related genes.