Send to

Choose Destination
Am J Hum Genet. 2016 Sep 1;99(3):555-566. doi: 10.1016/j.ajhg.2016.06.032. Epub 2016 Aug 25.

DNA Methylation Profiling of Uniparental Disomy Subjects Provides a Map of Parental Epigenetic Bias in the Human Genome.

Author information

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Medicine, UCSF MC2552, 1700 4th Street, Byers Hall Suite 503C, San Francisco, CA 94158, USA.
New York Genome Center, 101 Avenue of the Americas, 7th Floor, New York, NY 10013, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Departments of Pathology, Genetics and Computer Science, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Genetic Medicine and Development, University of Geneva Medical School, 9th Floor, 1 rue Michel-Servet, 1211 Geneva, Switzerland.
Department of Human Genetics, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands.
Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Emory Genetics Laboratory, Emory University, Atlanta, GA 30033, USA.
Institute of Human Genetics, University Hospital, RWTH, 52074 Aachen, Germany.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia.
Department of Genetics and Cell Biology, Research Institute GROW, Faculty of Health, Medicine and Life Sciences, Maastricht University, PO Box 5800, Maastricht AZ 6202, the Netherlands.
Laboratorio di Citogenetica, Istituto G. Gaslini, 16148 Genova, Italy.
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104, USA.
CHU Nantes, Service de Génétique Médicale, Institut de Biologie, 9 quai Moncousu, 44093 Nantes, France; INSERM, UMR 957, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Nantes 44035, France.
Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Kollegiengasse 10, 07743 Jena, Germany.
Wessex Regional Genetics Laboratory Salisbury District Hospital, Salisbury, Wiltshire SO2 8BJ, UK.
National Institute for Health Research Biomedical Research Centre, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Division of Cytogenetics, LabCorp, Center for Molecular Biology and Pathology, Research Triangle Park, NC 27709, USA.
Department of Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
J.C. Self Research Institute, Greenwood Genetic Center, Greenwood, SC 29646, USA.
Institute of Medical Genetics, University of Zurich, 8603 Schwerzenbach, Switzerland.
Division of Medical Genetics, Lucile Salter Packard Children's Hospital, 300 Pasteur Drive, Boswell Building A097, Stanford, CA 94304, USA.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:


Genomic imprinting is a mechanism in which gene expression varies depending on parental origin. Imprinting occurs through differential epigenetic marks on the two parental alleles, with most imprinted loci marked by the presence of differentially methylated regions (DMRs). To identify sites of parental epigenetic bias, here we have profiled DNA methylation patterns in a cohort of 57 individuals with uniparental disomy (UPD) for 19 different chromosomes, defining imprinted DMRs as sites where the maternal and paternal methylation levels diverge significantly from the biparental mean. Using this approach we identified 77 DMRs, including nearly all those described in previous studies, in addition to 34 DMRs not previously reported. These include a DMR at TUBGCP5 within the recurrent 15q11.2 microdeletion region, suggesting potential parent-of-origin effects associated with this genomic disorder. We also observed a modest parental bias in DNA methylation levels at every CpG analyzed across ∼1.9 Mb of the 15q11-q13 Prader-Willi/Angelman syndrome region, demonstrating that the influence of imprinting is not limited to individual regulatory elements such as CpG islands, but can extend across entire chromosomal domains. Using RNA-seq data, we detected signatures consistent with imprinted expression associated with nine novel DMRs. Finally, using a population sample of 4,004 blood methylomes, we define patterns of epigenetic variation at DMRs, identifying rare individuals with global gain or loss of methylation across multiple imprinted loci. Our data provide a detailed map of parental epigenetic bias in the human genome, providing insights into potential parent-of-origin effects.


15q11.2; Angelman syndrome; Prader-Willi syndrome; genomic imprinting; uniparental disomy

[Available on 2017-03-01]
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center