Uncovering Molecular Determinants of Pathogenic Non-Coding Structural Variation in Leukemia Genomes

dc.contributor.advisorHon, Gary C.en
dc.contributor.committeeMemberJohnson, Jane E.en
dc.contributor.committeeMemberZhu, Haoen
dc.contributor.committeeMemberXu, Jianen
dc.creatorBotten, Giovanni Angeloen
dc.creator.orcid0000-0001-8054-8030
dc.date.accessioned2023-01-02T21:45:17Z
dc.date.available2023-01-02T21:45:17Z
dc.date.created2022-12
dc.date.issued2022-12-01T06:00:00.000Z
dc.date.submittedDecember 2022
dc.date.updated2023-01-02T21:45:18Z
dc.description.abstractNon-coding structural variants (SVs) can rewire chromatin topologies to cause oncogene activation in cancer genomes, yet the molecular determinants for the transcriptional output mediated by SVs remain poorly understood. Advances in sequencing methodologies are increasing the number of SVs identified yet challenges remain to distinguish non-coding SV cancer drivers from non-functional passenger mutations. Hence, deciphering the regulatory principles governing how SVs, epigenetic landscapes, and 3D genome structure cooperate to control oncogenic transcription will be crucial for understanding the pathogenic potential of non-coding SVs. This dissertation outlines the development and implementation of a novel multimodal strategy to detect non-coding SVs with potential functional consequence and the characterization of an interdependency between genetic and chromatin variation for SV-mediated transcriptional effects. Together, these findings broaden our understanding of the features controlling the transcriptional output of pathogenic non-coding SVs and highlight new opportunities to reprogram gene regulation as epigenetic therapies in human disease.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1356910543
dc.identifier.urihttps://hdl.handle.net/2152.5/10016
dc.language.isoenen
dc.subjectGenomeen
dc.subjectGenome, Humanen
dc.subjectGenomic Structural Variationen
dc.subjectNeoplasmsen
dc.subjectGene Expression Regulationen
dc.titleUncovering Molecular Determinants of Pathogenic Non-Coding Structural Variation in Leukemia Genomesen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineGenetics, Development and Diseaseen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
BOTTEN-PRIMARY-2022.pdf
Size:
5.02 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Plain Text
Description: