AUG 20, 2014 08:00 AM PDT

Exploring Complex Structural Genomic Variation using Next-Gen Sequencing

C.E. CREDITS: CEU
Speakers
  • Assistant Professor, Department of Computational Medicine & Bioinformatics, Assistant Professor, Department of Human Genetics, University of Michigan
    Biography
      Ryan Mills is an Assistant Professor in Computational Medicine & Bioinformatics and Human Genetics at the University of Michigan. After receiving his PhD in 2006 at Georgia Tech, he worked as an NRSA Postdoctoral Fellow at Emory University where he helped produce some of the first published genome-wide maps of insertion/deletion (indel) variation in human populations and develop technologies to derive their genotypes using microarrays. As a Research Associate at Harvard Medical School, he expanded the scope of his work into the mapping of larger structural and copy number variation as part of the 1000 Genomes and other projects. His current research is focused on developing methods for the identification, resolution and analysis of complex and repetitive genomic rearrangements consisting of multiple breakpoints that are the result of overlapping or co-occurring structural changes to the genome. He is also exploring the prevalence of such variation in the context of brain somatic mosaicism in neuropsychiatric disorders.

    Abstract:

    Structural variants (SVs), defined as the deletion, duplication, insertion, inversion or translocation of genomic regions, are both a major source of genetic diversity in human populations and are also directly responsible for the pathogenesis of numerous diseases. Many studies have been conducted in the past decade to discover and analyze SVs, however these have predominantly focused on unbalanced (copy number variant) events involving only one or two breakpoints. In contrast, more complex rearrangements resulting from co-occurring or overlapping events involving three or more breakpoints have received considerably less attention or have been incorrectly interpreted. In this presentation, I will outline a strategy we have developed to accurately identify and resolve these events. Our method first identifies regions of the genome suspected to involve a complex event and then delineates putative breakpoints using aberrant sequence alignments. The resulting segments are then iteratively rearranged in a randomized fashion and scored against expected models of sequence characteristics to infer the underlying architecture of these variants. I will discuss the application our algorithm to well-characterized genomes and the comparison of our results to identified complex events in these samples. We believe our approach represents a significant advancement towards resolving these complex chromosomal structural rearrangements and furthering our understanding of their mechanistic origins and functional impact.

    Learning Objectives:

    • Differentiate between types of structural genomic rearrangements
    • Apply strategies for using sequence data to identify genetic variation

    Show Resources
    You May Also Like
    MAY 03, 2018 11:00 AM PDT
    MAY 03, 2018 11:00 AM PDT
    DATE: May 3, 2018TIME: 11:00AM PDT, 2:00PM EDTWhile stress is one of the leading causes of neuropsychiatric disorders, the molecular underpinnings of how stress induces alterations in b...
    MAY 22, 2018 08:00 AM PDT
    C.E. CREDITS
    MAY 22, 2018 08:00 AM PDT
    DATE: May 22, 2018TIME: 08:00AM PDT The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that...
    MAY 24, 2018 09:30 AM PDT
    C.E. CREDITS
    MAY 24, 2018 09:30 AM PDT
    DATE: May 24, 2018 TIME: 9:30PM PDT The current gold standard in in vitro pre-clinical cancer treatment screening remain cell lines,...
    AUG 15, 2018 08:00 AM PDT
    C.E. CREDITS
    AUG 15, 2018 08:00 AM PDT
    DATE: August 15, 2018TIME: 08:00AM PDT, 11:00AM EDTThe failure of current chemotherapeutic strategies in the fight against cancer can be largely attributed to the occurrence of drug res...
    APR 27, 2018 10:00 AM PDT
    C.E. CREDITS
    APR 27, 2018 10:00 AM PDT
    DATE: April 27, 2018TIME: 10:00am PST, 1:00pm ESTGlioblastoma (GBM) and Medulloblastoma (MB) are the most common adult and paediatric brain tumours, both of which can have devastating c...
    MAY 02, 2018 08:00 AM PDT
    C.E. CREDITS
    MAY 02, 2018 08:00 AM PDT
    Immunohistochemistry protocols, which utilize antibodies to visualize proteins in tissue sections, have many steps that need optimized to prevent non-specific background effects, artifacts, o...
    Loading Comments...