Sarah Dada from Canada’s Michael Smith Genome Sequence Center and the University of British Columbia in Canada presented at the Nanopore Community Meeting in Houston. The title of the session is “Potential personalized diagnosis and treatment of autism spectrum disorder in the era of long-read sequencing.” They presented three cases and started by acknowledging the land of their place of work. Dada spoke about Autism Spectrum Disorders (ASD) and how hundreds of genes and variants have been identified. One in fifty Canadian children under seventeen are diagnosed. Long-read sequencing can help sequence repetitive regions and provide phasing of alleles to elucidate tough-to-sequence regions in ASD. Dada worked with clinicians to obtain patient samples. Base calling was performed with Guppy5/Guppy6, and alignment was done with Minimap2. SNP/INDEL calling used Clair3, and structural variants were determined with Sniffles2 and cuteSV. Copy number calling was analyzed with Delly, and Tandem Repeats with Straglr. Nonopolish and Nanomethpase were used for methylation calling. Local assembly of identified breakpoints was performed with Shasta. Analyses were visualized with IGB. Case 1 was a young female with ASD and mild to moderate ID. Long-read identified a unique insertion and inversion. Nanopore sequencing helped further understand the structural variant and its context, determining the allele. Case 2 is a young male with ASD and has self-injury behavior. Sequencing identified an expansion that resulted in a duplication… a very large expansion. Case 3 is a male showing ASD, intellectual disability, and behavioral problems. Sequencing identified a complex duplication. Dada also analyzed the number of tandem repeats of genes in ASD databases. Dada’s work is helping refine our understanding of autism spectrum disorder on a case-by-case basis for personalized diagnosis and treatment.
