Transcriptomic-informed rare variants in common and rare disease diagnosis
Abstract/Contents
- Abstract
- Rare genetic variants are abundant in the human genome and can have large effects on the expression of proximal genes and downstream risk for common and rare diseases, but are difficult to characterize due to annotation and sample size constraints. In recent years, RNA-sequencing (RNA-seq) has emerged as a useful tool in interpreting the molecular and phenotypic effects of rare variants. Using new methods for data de-noising, summarizing genome-wide burden of large-effect rare variants, and aggregation of a large-scale reference set of pluripotent cells, in this dissertation I present research that extends current applications of RNA-seq in rare and common disease diagnosis. In chapter 2, I present work that assesses the utility of RNA-seq of blood as a diagnostic tool among 94 individuals with undiagnosed rare diseases across 16 diverse disease categories. In chapter 3, I discuss research on mapping rare variant effects in induced pluripotent stem cells (iPSCs) as part of a systematic, expansive analysis of both common and rare variation within the "Integrated iPSC QTL" (i2QTL) consortium. Finally, in chapter 4, I present research on integrating rare, large-effect expression variants to assess the deviation in phenotypes as predicted by polygenic risk scores (PRS)
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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Smail, Craig |
|---|---|
| Degree supervisor | Montgomery, Stephen, 1979- |
| Thesis advisor | Montgomery, Stephen, 1979- |
| Thesis advisor | Pritchard, Jonathan D |
| Thesis advisor | Rivas, Manuel (Manuel A.) |
| Thesis advisor | Tibshirani, Robert |
| Degree committee member | Pritchard, Jonathan D |
| Degree committee member | Rivas, Manuel (Manuel A.) |
| Degree committee member | Tibshirani, Robert |
| Associated with | Stanford University, Program in Biomedical Informatics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Craig Smail |
|---|---|
| Note | Submitted to the Program in Biomedical Informatics |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Craig Smail
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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