Identifying Natural Genetic Modifiers of Apoptosis and Retinal Degeneration

Update Item Information
Publication Type honors thesis
School or College College of Science
Department Biology
Faculty Mentor Clement Y. Chow,
Creator Ong, Elaine
Title Identifying Natural Genetic Modifiers of Apoptosis and Retinal Degeneration
Date 2018
Description Apoptosis, or cell death, is an integral part of many diseases such as neurodegeneration, retinal degeneration, and cancer, yet it is unclear how apoptosis varies among individuals in a population. Retinitis pigmentosa (RP) is a retinal degeneration disease characterized by phenotypic heterogeneity thought to be caused by genetic variation among patients, yet the identity of genetic modifiers remains unknown. A previous study conducted in our lab used the Drosophila Genetic Reference Panel (DGRP) to study the effects of natural genetic variation on a model of RP in which half of the candidate genes identified through an association study were involved in apoptosis, suggesting that variation in apoptosis signaling may contribute to variation in retinal degeneration. I hypothesized that genetic variation in apoptosis pathways might also contribute to variation in not only RP severity, but in many diseases in which outcomes are ultimately a result of cell death. I crossed fly lines overexpressing proteins from the apoptosis pathway, such as p53 and rpr, in the eye discs onto the DGRP strains and followed their effects on degeneration in the adult eye, similar to the RP model described above. I quantified variation in eye size and found extensive phenotypic variation among the DGRP in levels of apoptosis and used an association analysis to identify candidate modifier genes. I identified a number of biologically interesting modifiers, including RunxB, sif, ftz, and CycE which function in transcription, rhodopsin localization, cell migration, cell death, and cell cycle regulation, respectively. I explored the functional consequences of each of these candidates on the p53 model and found that several of them do modify the degeneration phenotype. Identifying natural genetic modifiers of apoptosis may identify modifiers that may be applicable to a number of different degeneration diseases.
Type Text
Publisher University of Utah
Language eng
Rights Management (c) Elaine Ong
Format Medium application/pdf
Permissions Reference URL https://collections.lib.utah.edu/ark:/87278/s6422bw0
ARK ark:/87278/s6s23hmr
Setname ir_htoa
ID 1565304
Reference URL https://collections.lib.utah.edu/ark:/87278/s6s23hmr