Pigini #ASHG24 Narrowed further with those vars involved in neurological disorders, 529 pathogenic variants, 345 poison exons. Selected genes for targeted validation (about 14). Uses Prime editing, validating variant effect on poison exon splicing.

Paolo Pigini (Mass Gen Hosp MA) #ASHG24 Defining the landscape of poison exon splicing events in the human brain: implications for neurodevelopmental and neurodegenerative disorders

Sangermano #ASHG24 Shows diagram of exon inclusion events (GFP neg), and exon skipping events with GPF pos pools. HTSA = high throughput skipping assay. For 3' or 5' splicing errors, ref seq and var seq as combined libraries, and do RT-PCR and NGS sequence - to see alt splices

Ramadesikan #ASHG24 Showing Firefly plot of GNAS, a tool they developed in-house. An imprinted locus; enrolled in rare disease program. RNAseq shows intron 5 variant - Shows a sashimi plot with differing splicing patterns. Evidence for exon 5 skipping.