Epigenetics
Epigenetics referes to the study of biological processes that regulate gene transcription within the cell that are heritable mitoticaly and/or meioticaly but that do not involve changes in the DNA sequence. This include regulation of DNA packaging within the nucleus through chromatin remodelling involving histone modifications and chemical changes to the DNA itself such as cytosine methylation.
Within the Faculty of Medicine there are several groups generating large data sets assessing DNA methylation genome-wide utilising both array based platforms and direct sequencing of bisulphite converted DNA. Analysis of DNA methylation variation between individuals in relation to disease state adds an order of magnitude in complexity to genome wide association analysis of DNA sequence variation as methylation values are quantitative rather than binary and vary over time, between tissues and with environmental exposure.
For queries about this topic, contact John Holloway.
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Projects
Identifying factors required for DNA methylation using the imprinting control protein ZFP57
Deborah Mackay (Investigator)
Mutation of ZFP57 in humans is associated with widespread loss of DNA methylation at imprinted genes, and clinical features including congenital anomalies and developmental delay (Mackay et al, 08). This indicates that ZFP57 is required for DNA methylation of imprinted genes necessary for normal development.
We propose to identify the DNA sequences targeted by ZFP57, and its protein cofactors. This work will give insight into the biology of imprinting, indicate mechanisms of disease, and identify novel imprinted genes.
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Imprinting Disorders Finding Out Why
Karen Temple (Investigator)
We are conducting a research project to determine the cause and clinical impact of widespread imprinting aberrations in human development. We are recruiting patients with possible or definite imprinting disorders (due to methylation loss or gain at an imprinted loci)
including Silver Russell syndrome, Transient Neonatal diabetes, Beckwith Wiedemann syndrome, Angelman syndrome Prader Willi syndrome, UPD 14 syndromes and Pseudohypoparathyroidism.
Transgenerational inheritance of allergy in a multi generational cohort
John Holloway (Investigator)
The aim of this project is to determine the vertical transmission of DNA methylation by identification of CpG sites by microarray analysis of 450,000 CpG sites in 252 women of the IoW cohort that are associated with allergic sensitization and testing whether the identified methylation patterns are vertically transmitted to their offspring and whether modifiable environmental conditions during gestation affect DNA methylation.
People
John HollowayProfessor, Medicine (FM)
Karen TempleProfessor, Medicine (FM)
Deborah MackayReader, Medicine (FM)
Matthew HigginsUndergraduate Research Student, Biological Sciences (FNES)