Targeted long-read RNA sequencing and allele-specific gene silencing in cardiovascular disease
Abstract/Contents
- Abstract
- As diagnostic genetic sequencing becomes more prevalent and as new genetic technologies rapidly develop towards clinical applicability, studies of the basic science behind these tools in human samples and model systems are increasingly important. In this dissertation, I explore the current state of cardiovascular precision medicine as it relates to genetics, and describe two experimental research projects that I have conducted over the past five years that focus on the use of gene silencing and sequencing technologies with a therapeutic and diagnostic perspective. The first project uses targeted long-read RNA sequencing to examine the effects of a rare mutation on MYBPC3 splicing in hypertrophic cardiomyopathy (HCM). This project describe new alternative splicing patterns in MYBPC3 that arise as a result of this mutation in a lowly characterized region of the protein, and stands as a case study for the importance of RNA sequencing in clinical settings. The second project examines two methods of allele-specific MYH7 silencing in HCM, using a human induced pluripotent stem cell derived cardiomyocyte (iPSC-CM) model. We use biophysical assays to probe not only the effects of an MYH7 mutation on iPSC-CM contractility, but also how therapeutic silencing may ameliorate disease phenotypes. This experiment finds a dissociation between allele-specificity and phenotypic effect in iPSC-CMs. Both of these projects use genetics to probe the underlying biology of HCM and highlight how genetic technologies, including sequencing and silencing, are poised to play important roles in the clinical cardiovascular world.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Dainis, Alexandra Marie |
|---|---|
| Degree supervisor | Ashley, Euan A |
| Thesis advisor | Ashley, Euan A |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Pruitt, Beth |
| Degree committee member | Bassik, Michael |
| Degree committee member | Fire, Andrew Zachary |
| Degree committee member | Pruitt, Beth |
| Associated with | Stanford University, Department of Genetics. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Alexandra Dainis. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Alexandra Marie Dainis
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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