MAR 20, 2014 01:00 PM PDT

The role of high throughput sequencing in the research and diagnosis of neurodegenerative disorders

Presented At Neuroscience
  • Director of Next-Gen Sequencing Laboratory Laboratory of Personalized Genomic Medicine, Associate Professor, Columbia University
      Peter L. Nagy is a biochemist and a physician, board certified in anatomic and molecular genetic pathology.
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      <br />Dr. Nagy's research focuses on the role of transcriptional processing in the pathogenesis of neurodegenerative disorders. He developed S. pombe and M. musculus models for Ataxia-Oculomotor-Apraxia type 2 (AOA2) caused by mutations in the human ortholog of the yeast RNA helicase Sen1, Senataxin (SETX). Using these models they are working to define the pathomechanism of SETX mediated neurodegenerative disorders. They are also investigating the pathogenesis of ALS caused by C9orf72 expansions and search for novel ALS causing or modifying genetic variants.&nbsp;
      In Dr. Nagy's research, he combines the tools of classical biochemistry and genetics with genomics, most importantly next-gen sequencing for mutation discovery, transcriptome analysis and the identification of novel protein RNA interactions.
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      <br />His clinical interest is the development and use of genome-scale sequencing assays in the clinical diagnosis of constitutional disorders and cancer such as :
      <br />&nbsp;&nbsp;&nbsp; * Mitochondrial Genome Sequencing Test
      <br />&nbsp;&nbsp;&nbsp; * Columbia Combined Genetic Panel (1300 genes most commonly associated with genetic disorders)
      <br />&nbsp;&nbsp;&nbsp; * Whole Exome Sequencing Tests for Constitutional Disorders and Cancer.
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    Using high throughput next-generation sequencing to simultaneously search large number of genes for pathogenic mutations has numerous advantages. It decreases the pressure to narrow the differential diagnosis for diseases with overlapping phenotypes, can identify entirely new causative private mutations when no good candidate genes are available, and shorten the patients diagnostic odyssey. The Laboratory of Personalized Genomic Medicine at Columbia University started offering mitochondrial genome, partial and whole exome sequencing for clinical diagnostic purposes in January 2013. In my talk I will highlight the effectiveness of next-gen sequencing in diagnosing neurological and neurodegenerative conditions. Furthermore I will discuss the use of next-gen sequencing technologies to evaluate transcriptional and translational changes that might define these conditions in cell culture and animal model systems. Finally, I will propose some practical steps that would improve the effectiveness of next-gen sequencing diagnosis of neurodegenerative disorders and present my view of the near future based on the technologies that are available or will soon become available.

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