NCM 2023 Houston: Potential personalized diagnosis and treatment of autism spectrum disorder in the era of long-read sequencing

Autism Spectrum Disorder (ASD) is the most common childhood developmental disability, affecting 1 in 58 Canadian school-aged children. Despite extensive study, causal variants and molecular diagnosis remain elusive due to the heterogeneity of both the phenotype, as well as the genetic landscape associated with phenotype, which includes both inherited and de novo mutations. Currently, diagnosis is complex and behaviourally based, oftentimes occurring years after the ideal 1-2 years age. Structural variants are large and complex genomic variants which likely have underrepresented contribution to ASD. Methylation patterns associated with imprinting regions and ASD genes remain largely unexplored for their contribution to ASD. Long-read sequencing (LRS) is optimal for the comprehensive interrogation of each affected individuals’ genome for variants of clinical importance, particularly of structural variants, tandem repeats, and methylation variability. This project uses LRS integrated with phenotypic data for earlier, individualized diagnosis and treatment of ASD.