McCormick, Helen (2017) Measuring inheritance and intrinsic variation in the mouse epigenome. PhD thesis, Victor Chang Cardiac Research Institute & St Vincent's Clinical School, Faculty of Medicine, UNSW.
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Helen McCormick2017 PhD Thesis VCCRI UNSW.pdf Download (44MB) | Preview |
Abstract
Epigenetic variation between individuals can provide a mechanism for phenotypic variation and differences in disease risk. While a proportion of epigenetic variation can be ascribed to genetic factors, epigenetic variation can persist even in the absence of genetic differences and in some cases this variation can be inherited between generations. Only a handful of such loci have so far been identified in animals, but importantly no systematic assessment of the frequency of epigenetic inheritance has been performed. The underlying aim of this work was to determine the extent to which transgenerational epigenetic inheritance occurs in the mammalian genome, with a starting hypothesis that transgenerational epigenetic inheritance is widespread. Genome-wide DNA methylation analysis was performed on two related pedigrees of isogenic mice. Investigations of pedigree-specific epigenomic differences were hampered by batch effects in RRBS data, but a systematic approach to this confounder led to the identification of epigenomic variation across the genome that was specific to each pedigree of the isogenic animals. As this investigation progressed, two other areas came in to focus: gender-specific cytosine methylation differences across autosomal DNA of several tissue types, and the problem of low concordance of results from differential methylation analysis methods. Gender-specific methylation differences are widespread and tissue specific, and a fraction of them appear to be independent of sex-specific hormonal factors. Furthermore, a considerable degree of under-calling was found among differential DNA methylation analysis methods, suggesting that a majority of genuine differentially methylated loci may be going undetected in a range of experimental scenarios.
| Item Type: | Thesis (PhD ) |
|---|---|
| Additional Information: | SUPERVISORS: Cropley, Jennifer, Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW; Giannoulatou, Eleni, Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 17 Apr 2019 01:00 |
| Last Modified: | 17 Apr 2019 01:00 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/832 |
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