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Deciphering Brain Mosaicism with Long-read Sequencing

C.E. Credits: CEU P.A.C.E. CE Florida CE
Speaker
  • Principal investigator, Nationwide Children's Hospital; Assistant Professor of Pediatrics, The Ohio State University College of Medicine
    Biography

      Tracy Bedrosian leads a laboratory in the Institute for Genomic Medicine at Nationwide Children's Hospital. Her group uses single-cell sequencing approaches to understand how brain somatic mutations contribute to neurodevelopmental disorders, including developmental brain malformations, epilepsy, and autism. She also serves as an Assistant Professor of Pediatrics at The Ohio State University.


    Abstract

    Somatic mutations that arise during development are increasingly recognized as contributors to neurodevelopmental disease. One challenge has been to determine how mosaic mutations contribute to cell lineages and affect the function of individual cells, which could have implications for disease manifestation. We integrated high-throughput single-cell 3’-RNA-sequencing with targeted Iso-Seq long-read RNA sequencing on the PacBio Sequel II platform to overlay single-cell genotype with cell-type and gene expression analyses. We applied this strategy to study the contribution of somatic mutations to developmental brain malformations in surgically-resected patient brain tissue.

    Learning objectives:

    1. Understand how long-read sequencing can be useful for haplotype phasing of variants.

    2. Understand how long-read sequencing can be integrated with single-cell 3’-RNA-sequencing.


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