{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/32050"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/32050","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Identification of DNA Methylation Episignatures for Classification and Phenotype/Genotype Correlation in Mendelian Neurodevelopmental Disorders","abstract":"ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of neurodevelopmental disorders. I hypothesized DNA methylation can provide classifications of neurodevelopmental disorders, and identify epigenetic patterns that relate the phenotypic and genotypic variations seen in these patients. Main objectives of this work include 1) determination of syndrome specific episignatures, 2) analysis of domain specific variants and their effects on the methylation profiles and ensuing phenotypes 3) determine effectiveness of episignature assessment in classifying neurodevelopmental disorders in paralogous genes, 4) assessing phenotypic overlap between distinct neurodevelopmental disorders and correlation to their methylation profiles. My thesis demonstrates that these episignatures are robust biomarkers that inform effective methods to diagnose complex neurodevelopmental disorders, and provide evidence of shared functional pathways highlighted by the various genomic and phenotypic contexts episignatures have been derived from.","abstract_html":"ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of neurodevelopmental disorders. I hypothesized DNA methylation can provide classifications of neurodevelopmental disorders, and identify epigenetic patterns that relate the phenotypic and genotypic variations seen in these patients. Main objectives of this work include 1) determination of syndrome specific episignatures, 2) analysis of domain specific variants and their effects on the methylation profiles and ensuing phenotypes 3) determine effectiveness of episignature assessment in classifying neurodevelopmental disorders in paralogous genes, 4) assessing phenotypic overlap between distinct neurodevelopmental disorders and correlation to their methylation profiles. My thesis demonstrates that these episignatures are robust biomarkers that inform effective methods to diagnose complex neurodevelopmental disorders, and provide evidence of shared functional pathways highlighted by the various genomic and phenotypic contexts episignatures have been derived from.","abstract_has_math":false,"creators":["Reilly, John"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Pathology and Laboratory Medicine","degree_department":null,"school":null,"contributors":[],"advisors":["Sadikovic, Bekim"],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-04-19","date_published":"2022-04-19","updated_at":"2026-07-27T21:56:09Z","subjects":["Genetics","Epigenetics","Neurodevelopmental Disorders","DNA Methylation"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/32050","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Sadikovic, Bekim"]},{"key":"dc:creator","label":"Author","values":["Reilly, John"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T19:26:10Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T19:26:10Z"]},{"key":"dc:date.issued","label":"Date","values":["2022-04-19"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pathology and Laboratory Medicine"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Genetics","Epigenetics","Neurodevelopmental Disorders","DNA Methylation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/32050"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of neurodevelopmental disorders. I hypothesized DNA methylation can provide classifications of neurodevelopmental disorders, and identify epigenetic patterns that relate the phenotypic and genotypic variations seen in these patients. Main objectives of this work include 1) determination of syndrome specific episignatures, 2) analysis of domain specific variants and their effects on the methylation profiles and ensuing phenotypes 3) determine effectiveness of episignature assessment in classifying neurodevelopmental disorders in paralogous genes, 4) assessing phenotypic overlap between distinct neurodevelopmental disorders and correlation to their methylation profiles. My thesis demonstrates that these episignatures are robust biomarkers that inform effective methods to diagnose complex neurodevelopmental disorders, and provide evidence of shared functional pathways highlighted by the various genomic and phenotypic contexts episignatures have been derived from."]},{"key":"dc:title","label":"Title","values":["Identification of DNA Methylation Episignatures for Classification and Phenotype/Genotype Correlation in Mendelian Neurodevelopmental Disorders"]}]}],"canonical_facts":{"dc:contributor.advisor":["Sadikovic, Bekim"],"dc:creator":["Reilly, John"],"dc:date.accessioned":["2025-07-10T19:26:10Z"],"dc:date.available":["2025-07-10T19:26:10Z"],"dc:date.issued":["2022-04-19"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). 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EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of neurodevelopmental disorders. I hypothesized DNA methylation can provide classifications of neurodevelopmental disorders, and identify epigenetic patterns that relate the phenotypic and genotypic variations seen in these patients. Main objectives of this work include 1) determination of syndrome specific episignatures, 2) analysis of domain specific variants and their effects on the methylation profiles and ensuing phenotypes 3) determine effectiveness of episignature assessment in classifying neurodevelopmental disorders in paralogous genes, 4) assessing phenotypic overlap between distinct neurodevelopmental disorders and correlation to their methylation profiles. My thesis demonstrates that these episignatures are robust biomarkers that inform effective methods to diagnose complex neurodevelopmental disorders, and provide evidence of shared functional pathways highlighted by the various genomic and phenotypic contexts episignatures have been derived from."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/32050"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Genetics","Epigenetics","Neurodevelopmental Disorders","DNA Methylation"],"dc:title":["Identification of DNA Methylation Episignatures for Classification and Phenotype/Genotype Correlation in Mendelian Neurodevelopmental Disorders"],"dc:type":["thesis"],"thesis:degree_discipline":["Pathology and Laboratory Medicine"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:09Z"}