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    Activity and Regulation of L1 Retrotransposons in Human Genomes

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    Author
    Scott, Emma Cecelia
    0000-0001-7854-9982
    Advisor
    Devine, Scott E.
    Date
    2017
    Type
    dissertation
    
    Metadata
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    Abstract
    This dissertation investigates the activity and regulation of endogenous long interspersed element-1 (also known as LINE-1 or L1) mobile elements in normal and cancerous human genomes. L1s are autonomous retrotransposons that constitute ~17% of the human genome; the majority of these elements are no longer active due to truncations or mutations, but a small number of full-length L1 source elements remain capable of mobilizing themselves (via a "copy and paste" mechanism) and pose a huge mutagenic threat to the human genome. Traditionally, transposons were thought to be silenced outside of the germline, but recently frequent somatic activity of L1 in epithelial cancer genomes has been discovered and characterized. Somatic L1 insertions have been identified in many different types of human cancer. This dissertation addresses major unanswered questions in the field. The hypothesis of this study is that tumorigenesis can be initiated by the derepression of endogenous L1 retrotransposons in normal, noncancerous somatic cells. The chapters of this dissertation support this hypothesis by establishing that activity of a hot population-specific full-length L1 source element is capable of causing cancer and beginning to assess the expression of full-length L1 source elements in normal noncancerous tissues. Overall, this dissertation provides important contributions to the field and poses many new questions for further study.
    Description
    University of Maryland, Baltimore. Molecular Medicine. Ph.D. 2017
    Keyword
    cancer genomics
    L1
    LINE-1
    mobile elements
    retrotransposons
    transcriptomics
    Long Interspersed Nucleotide Elements
    Retroelements
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/7055
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