Date of Award
2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biotechnology Science and Engineering
Committee Chair
Paul Wolf
Committee Member
Jerome Baudry
Committee Member
Richard M. Myers
Committee Member
Joseph Ng
Subject(s)
Genomics, Gene mapping, Pancreas--Cancer--Genetic aspects, Dementia--Genetic aspects
Abstract
Genomic technologies are used to analyze genetic information. The work described focused on multiple sequencing applications to evaluate the impact of genetic variation in patients with disease. Whole genome sequencing, RNA-sequencing, and ChIP-sequencing were performed to identify variants, understand gene expression, and determine the differences in chromatin structure that contribute to cellular and organismal phenotypes. My thesis work describes the use of computational tools to analyze genomic data with the goal of understanding acquired genetic and epigenetic variation in cancer as well as inherited variation associated with rare neurological disease. Whole genome sequencing yielded a diagnostic rate of 53 percent in patients with rare disease. In our pancreatic cancer study, I identified genes that are regulated by HDAC1 overexpression and contribute to drug resistance. This work revealed an improved mechanistic understanding of the role of HDAC1 in chemoresistance and nominated GTPase genes as potential therapeutic targets. Both studies show how advancing genomic technologies can be used to study human disease.
Recommended Citation
Wright, Carter, "Regulation of rare genetic variation in human disease" (2023). Dissertations. 271.
https://louis.uah.edu/uah-dissertations/271