Construction and Application of an Epigenetic Atlas of the Human Heart

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dc.contributor.advisorGreenway, Steven C.
dc.contributor.authorPrasher, Dimple
dc.contributor.committeememberGallo, Marco
dc.contributor.committeememberLong, Quan
dc.date2020-06
dc.date.accessioned2019-12-20T22:51:31Z
dc.date.available2019-12-20T22:51:31Z
dc.date.issued2019-12-19
dc.description.abstractEpigenetic modifications, including DNA methylation, regulate gene expression and contribute to the specialization of cells. Currently, there is limited knowledge of the epigenetic patterns of the human heart. To address this gap, we generated methylation profiles for all distinct regions of the human heart. We hypothesized that unique differentially methylated regions (DMRs) of DNA exist for each cardiac region and that changes in DNA methylation occur in diverse cardiac diseases such as heart failure (HF) and congenital heart disease (CHD). Using healthy cardiac tissues and reduced representation bisulfite sequencing on the Illumina platform, we generated genome-wide methylomes in triplicate for the human right atrium, left atrium, right ventricle, left ventricle, aorta, pulmonary artery, mitral valve, tricuspid valve, aortic valve and pulmonary valve. We also generated methylomes (in triplicate) from the left ventricle of adult patients with HF and children with CHD. DMRs, defined as regions with significantly different mean methylation differences, were identified using the software package Metilene. For each tissue we generated 10-20 million reads covering 8-10 million CpG methylation sites across the genome and identified 5-57 tissue-specific DMRs. We identified 290 unique DMRs in the HF group and 317 in the CHD group. Potential disease-associated genes identified from this analysis included FGFR2, TOM22, HEX3 for HF and ROCK1 and MSX1 for CHD. In conclusion, we have created a DNA methylation atlas of the human heart. This data provides a resource for future studies and may help to identify new disease biomarkers and increase our understanding of cardiac development.en_US
dc.identifier.citationPrasher, D. (2019). Construction and Application of an Epigenetic Atlas of the Human Heart (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/37364
dc.identifier.urihttp://hdl.handle.net/1880/111372
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectDNA methylationen_US
dc.subjecthuman hearten_US
dc.subjectRRBSen_US
dc.subject.classificationBiologyen_US
dc.subject.classificationBioinformaticsen_US
dc.subject.classificationBiology--Molecularen_US
dc.titleConstruction and Application of an Epigenetic Atlas of the Human Hearten_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biologyen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopyfalseen_US
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