The Utility and limitations of Diagnostic Transcriptome RNA Sequencing in Mendelian Disorders OnDemand-The Utility and limitations of Diagnostic Transcriptome RNA Sequencing in Mendelian Disorders

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Video Summary

The webinar titled "Utility and Limitations of Diagnostic Transcriptome RNA Sequencing and Mendelian Disorders" began with administrative details such as disclosures, accreditation, and instructions on how to submit questions. Dr. Pengfei Liu from Baylor College of Medicine led the session, sharing his team's experiences with using RNA sequencing (RNA-seq) to diagnose Mendelian disorders. Highlighting the central dogma of molecular biology, he emphasized the diagnostic potential of RNA-seq when DNA sequencing alone is inconclusive.<br /><br />Dr. Liu presented three case studies demonstrating RNA-seq applications. The first showcased how RNA-seq clarified a previously ambiguous genetic variant in a patient with intellectual disabilities. The second illustrated RNA-seq's capability to detect missed diagnoses from DNA analysis, offering insights into how gene expression variability can affect clinical outcomes. The third explored RNA-seq's role in understanding disease mechanisms beyond mere diagnosis.<br /><br />Dr. Liu also discussed transitioning RNA-seq from research to clinical practice, including defining benchmarks and quality controls. He emphasized the necessity of combining agnostic transcriptome-wide analysis with targeted approaches that consider DNA sequencing results.<br /><br />Addressing the challenges of tissue-specific gene expression, Dr. Liu explored the utility of techniques like CRISPR activation, ultra-deep sequencing, and induced neuron differentiation in improving detection rates for poorly expressed genes in clinically accessible tissues.<br /><br />In summary, while RNA-seq shows great promise for enhancing genetic diagnosis, especially for complex Mendelian disorders, its clinical implementation requires careful consideration of tissue specificity, depth of sequencing, and sophisticated bioinformatics tools. The session concluded with a call for continued research and better integration of these methods into clinical diagnostics.

Keywords

RNA sequencing

Mendelian disorders

genetic diagnosis

transcriptome

clinical practice

gene expression

CRISPR activation

bioinformatics

tissue specificity

case studies