Deciphering Brain Mosaicism with Long-read Sequencing

Explore the fascinating world of brain mosaicism and its implications for neurodevelopmental disorders in this 25-minute webinar presented by Dr. Tracy Bedrosian. Delve into the cutting-edge research that combines high-throughput single-cell 3'-RNA-sequencing with targeted Iso-Seq long-read RNA sequencing to uncover how somatic mutations contribute to developmental brain malformations. Learn about the challenges in determining the impact of mosaic mutations on cell lineages and individual cell function, and discover how this innovative approach is applied to surgically-resected patient brain tissue. Gain insights into the types of somatic mutations, malformations of cortical development, and the process of identifying mosaicism in patients. Examine a case study on hemimegalencephaly, focusing on somatic variants in PTEN and their predicted protein effects. Understand the integration of genotype and cell type data, and explore the clinical implications of this research. This webinar offers a comprehensive overview of the latest advancements in deciphering brain mosaicism using long-read sequencing techniques, providing valuable knowledge for researchers and clinicians in the field of neurodevelopmental disorders.

Intro
Overview
Somatic Mosaicism
Brain Somatic Mutations
Types of Somatic Mutations
Malformations of Cortical Development
Identifying mosaicism in patients
Case of Hemimegalencephaly
Somatic variants in PTEN
Predicted protein effects
Variant distribution
Phasing variants
Functional differences
Single-cell 3'-RNA-seq
Integrating long-read sequencing
Integrating genotype and cell type
Variant cells among cell types
Clinical Implications
Summary and Conclusions
Acknowledgments