Novel Splice-Driven Mechanisms of Human Genetic Diseases Unveiled by Long-Read RNA-Sequencing-Presentation

Video Transcription

Video Summary

The 2025 ACMG Education Webinar Series titled "Translating Genes into Health" featured discussions on the integration of long-read sequencing into genetics research and clinical diagnostics. The webinar aimed to educate on the complexities of genetic variant interpretation, particularly focusing on splicing and isoform diversity. Participants were encouraged to engage with questions related to alternative splicing’s consideration in clinical settings.<br /><br />Speakers included Dr. Gloria Chainman from the University of Virginia, who discussed long-read proteogenomics, and Dr. Pete Castaldi from Harvard Medical School, who explored splice variants in COPD using long-read sequencing. Dr. Paola Justine Rodriguez from the University of Florida highlighted differential isoform usage in schizophrenia, while Dr. Mina Wrighton from University College London shared insights on transcriptomic data's role in neurodegenerative diseases. Dr. Colette Felton from UC Santa Cruz presented on RNA alterations in cancer using long-read sequencing.<br /><br />Key discussions focused on the importance of a comprehensive understanding of transcriptomes in disease analysis, emphasizing the need for high-quality sequencing to elucidate complex splicing events and their clinical implications. The faculty stressed the significance of an accurate transcriptomic map for advancing genomic medicine, particularly in developing RNA-targeting therapies. They acknowledged challenges in variant interpretation based on existing transcript models and emphasized the ongoing evolution of standards for clinical genetic testing. The webinar concluded with an extended Q&A session, highlighting interest in optimizing long-read sequencing for clinical utility and addressing various aspects of genomic research, including non-coding variant prioritization and the impact of transcript diversity on therapeutic strategies.

Keywords

ACMG Education Webinar Series

Translating Genes into Health

long-read sequencing

genetic variant interpretation

splicing

isoform diversity

clinical diagnostics

alternative splicing

proteogenomics

COPD

schizophrenia

neurodegenerative diseases

RNA alterations

transcriptomic data

genomic medicine