Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in down syndrome

UBC Faculty Research and Publications

Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in down syndrome Jones, Meaghan J.; Farré, Pau; McEwen, Lisa M.; MacIsaac, Julia L.; Watt, Kim; Neumann, Sarah M.; Emberly, Eldon; Cynader, Max S.; Virji-Babul, Naznin; Kobor, Michael S. (Geneticist)

Abstract

Background: The presence of an extra whole or part of chromosome 21 in people with Down syndrome (DS) is associated with multiple neurological changes, including pathological aging that often meets the criteria for Alzheimer’s Disease (AD). In addition, trisomies have been shown to disrupt normal epigenetic marks across the genome, perhaps in response to changes in gene dosage. We hypothesized that trisomy 21 would result in global epigenetic changes across all participants, and that DS patients with cognitive impairment would show an additional epigenetic signature. Methods We therefore examined whole-genome DNA methylation in buccal epithelial cells of 10 adults with DS and 10 controls to determine whether patterns of DNA methylation were correlated with DS and/or cognitive impairment. In addition we examined DNA methylation at the APP gene itself, to see whether there were changes in DNA methylation in this population. Using the Illumina Infinium 450 K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells. Results We found 3300 CpGs to be differentially methylated between the groups, including 495 CpGs that overlap with clusters of differentially methylated probes. In addition, we found 5 probes that were correlated with cognitive function including two probes in the TSC2 gene that has previously been associated with Alzheimer’s disease pathology. We found no enrichment on chromosome 21 in either case, and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype. Conclusions Overall, our results indicated that both Trisomy 21 and cognitive impairment were associated with distinct patterns of DNA methylation.

Item Metadata

Title	Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in down syndrome
Creator	Jones, Meaghan J.; Farré, Pau; McEwen, Lisa M.; MacIsaac, Julia L.; Watt, Kim; Neumann, Sarah M.; Emberly, Eldon; Cynader, Max S.; Virji-Babul, Naznin; Kobor, Michael S. (Geneticist)
Contributor	Human Early Learning Partnership (Vancouver, B.C.); University of British Columbia. Djavad Mowafaghian Centre for Brain Health; Child and Family Research Institute; University of British Columbia. Centre for Molecular Medicine and Therapeutics
Publisher	BioMed Central
Date Issued	2013-12-27
Description	Background: The presence of an extra whole or part of chromosome 21 in people with Down syndrome (DS) is associated with multiple neurological changes, including pathological aging that often meets the criteria for Alzheimer’s Disease (AD). In addition, trisomies have been shown to disrupt normal epigenetic marks across the genome, perhaps in response to changes in gene dosage. We hypothesized that trisomy 21 would result in global epigenetic changes across all participants, and that DS patients with cognitive impairment would show an additional epigenetic signature. Methods We therefore examined whole-genome DNA methylation in buccal epithelial cells of 10 adults with DS and 10 controls to determine whether patterns of DNA methylation were correlated with DS and/or cognitive impairment. In addition we examined DNA methylation at the APP gene itself, to see whether there were changes in DNA methylation in this population. Using the Illumina Infinium 450 K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells. Results We found 3300 CpGs to be differentially methylated between the groups, including 495 CpGs that overlap with clusters of differentially methylated probes. In addition, we found 5 probes that were correlated with cognitive function including two probes in the TSC2 gene that has previously been associated with Alzheimer’s disease pathology. We found no enrichment on chromosome 21 in either case, and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype. Conclusions Overall, our results indicated that both Trisomy 21 and cognitive impairment were associated with distinct patterns of DNA methylation.
Subject	Down syndrome; DNA methylation; Cognitive impairment; Aging; Illumina 450k human methylation array
Genre	Article
Type	Text
Language	eng
Date Available	2015-12-16
Provider	Vancouver : University of British Columbia Library
Rights	Attribution 4.0 International (CC BY 4.0)
DOI	10.14288/1.0221316
URI	http://hdl.handle.net/2429/55833
Affiliation	Population and Public Health (SPPH), School of; Non UBC; Medicine, Faculty of; Medical Genetics, Department of; Molecular Medicine and Therapeutics, Centre for; Physical Therapy, Department of
Citation	BMC Medical Genomics. 2013 Dec 27;6(1):58
Publisher DOI	10.1186/1755-8794-6-58
Peer Review Status	Reviewed
Scholarly Level	Faculty
Copyright Holder	Jones et al.; licensee BioMed Central Ltd.
Rights URI	http://creativecommons.org/licenses/by/4.0/
Aggregated Source Repository	DSpace

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