Mike Gandal, MD, PhD
Hetznecker Associate Professor of Psychiatry
Department of Psychiatry
Perelman School of Medicine
University of Pennsylvania

Department of Genetics

Isoform regulation in the developing human brain informs mechanisms of neuropsychiatric disorders

Hosted by:  Dr. Joe Dougherty
In-person only:  Connor Auditorium (FLTC)

Talk abstract:  Large-scale genetic studies have now identified hundreds of common and rare variants associated with neurodevelopmental and psychiatric disorders. However, interpretation of the biological functional impact and pathogenicity of these variants remains a critical obstacle hindering clinical translation. To address this challenge, we have developed a large-scale functional genomic atlas of human brain development, integrating genotype and RNA-sequencing based gene expression measures in >650 developing human brains. In parallel, we have performed high depth long-read sequencing in a subset of samples to capture the full complexity of alternative splicing and isoform diversity. Leveraging this resource has enabled prioritization of previously hidden candidate molecular mechanisms underlying genetic risk for autism spectrum disorders and schizophrenia, with a substantial fraction acting through dysregulation of alternative splicing.