Genome-wide allele-specific methylation is enriched at gene regulatory regions in a multi-generation pedigree from the Norfolk Island isolate
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Description
<p>Background: Allele-specific methylation (ASM) occurs when DNA methylation patterns exhibit asymmetry among alleles. ASM occurs at imprinted loci, but its presence elsewhere across the human genome is indicative of wider importance in terms of gene regulation and disease risk. Here, we studied ASM by focusing on blood-based DNA collected from 24 subjects comprising a 3-generation pedigree from the Norfolk Island genetic isolate. We applied a genome-wide bisulphite sequencing approach with a genotype-independent ASM calling method to map ASM across the genome. Regions of ASM were then tested for enrichment at gene regulatory regions using Genomic Association Test (GAT) tool. Results: In total, we identified 1.12 M CpGs of which 147,170 (13%) exhibited ASM (P ≤ 0.05). When including contiguous ASM signal spanning ≥ 2 CpGs, this condensed to 12,761 ASM regions (AMRs). These AMRs tagged 79% of known imprinting regions and most (98.1%) co-localised with known single nucleotide variants. Notably, miRNA and lncRNA showed a 3.3- and 1.8-fold enrichment of AMRs, respectively (P < 0.005). Also, the 5′ UTR and start codons each showed a 3.5-fold enrichment of AMRs (P < 0.005). There was also enrichment of AMRs observed at subtelomeric regions of many chromosomes. Five out of 11 large AMRs localised to the protocadherin cluster on chromosome 5. Conclusions: This study shows ASM extends far beyond genomic imprinting in humans and that gene regulatory regions are hotspots for ASM. Future studies of ASM in pedigrees should help to clarify transgenerational inheritance patterns in relation to genotype and disease phenotypes.</p>
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ID Code: | 197592 | ||||||||||||||
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Item Type: | Contribution to Journal (Journal Article) | ||||||||||||||
Refereed: | Yes | ||||||||||||||
ORCID iD: |
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Measurements or Duration: | 10 pages | ||||||||||||||
DOI: | 10.1186/s13072-019-0304-7 | ||||||||||||||
ISSN: | 1756-8935 | ||||||||||||||
Pure ID: | 43571134 | ||||||||||||||
Divisions: | Past > QUT Faculties & Divisions > Faculty of Health Past > Institutes > Institute of Health and Biomedical Innovation Past > QUT Faculties & Divisions > Science & Engineering Faculty |
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Funding Information: | This research was supported by funding from a National Health and Medical Research Council of Australia (NHMRC) Project Grant (APP1058806). It was also supported by infrastructure purchased with Australian Government EIF Super Science Funds as part of the Therapeutic Innovation Australia—Queensland Node project. We would like to acknowledge QUT for providing funding and computational support for this project. Australian Translational Genomics Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology for sequencing (Lisa Anderson, Sharon Song). | ||||||||||||||
Copyright Owner: | The Author(s) 2019 | ||||||||||||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||||||||||||
Deposited On: | 13 Mar 2020 02:22 | ||||||||||||||
Last Modified: | 05 Apr 2024 11:06 |
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