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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2024)

Liver cancer is diagnosed yearly in over 800,000 people worldwide. While several gene coding mutations have been found to be associated with this cancer, we lack an understanding of gene regulatory driver mutations that could also lead to liver cancer. Using short sequences, 16 base pairs in length, termed neomers, that are generally absent from the human genome but appear in liver cancer, we identify numerous potential causative gene regulatory mutations in promoters, potential enhancers and 3’UTRs. We identify noncoding neomers that are enriched in numerous patients and are thought to regulate cancer-associated genes. We also characterize specific one kilobase regions in the human genome that are enriched for noncoding neomers that reside near many relevant liver cancer genes. Combined, our study identifies novel mutations in gene regulatory elements that could be key regulators of liver cancer, providing a basis for potential downstream diagnosis and therapeutics.

    Cover page: Utilizing short sequences missing from the genome to identify gene regulatory element mutations associated with liver cancer
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2025)
    The human genome contains millions of copies of retrotransposons that are silenced but many of these copies have potential to become active if mutated, having phenotypic consequences, including disease. However, it is not thoroughly understood how nucleotide changes in retrotransposons affect their jumping activity. Here, we develop a massively parallel jumping assay (MPJA) that tests the jumping potential of thousands of transposons en masse. We generate a nucleotide variant library of four Alu retrotransposons containing 165,087 different haplotypes and test them for their jumping ability using MPJA. We found 66,821 unique jumping haplotypes, allowing us to pinpoint domains and variants vital for transposition. Mapping these variants to the Alu-RNA secondary structure revealed stem-loop features that contribute to jumping potential. Combined, our work provides a high-throughput assay that assesses the ability of retrotransposons to jump and identifies nucleotide changes that have the potential to reactivate them in the human genome.
      Cover page: Massively parallel jumping assay decodes Alu retrotransposition activity.Creative Commons 'BY' version 4.0 license
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