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Open Access Research article

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

Meaghan J Jones1, Pau Farré2, Lisa M McEwen1, Julia L MacIsaac1, Kim Watt3, Sarah M Neumann1, Eldon Emberly2, Max S Cynader4, Naznin Virji-Babul5* and Michael S Kobor16*

Author Affiliations

1 Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

2 Department of Physics, Simon Fraser University, Burnaby, British Columbia, Canada

3 Department of Psychology, Simon Fraser University, Burnaby, British Columbia, Canada

4 Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

5 Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada

6 Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada

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BMC Medical Genomics 2013, 6:58  doi:10.1186/1755-8794-6-58

Published: 27 December 2013



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.


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.


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.


Overall, our results indicated that both Trisomy 21 and cognitive impairment were associated with distinct patterns of DNA methylation.

Down syndrome; DNA methylation; Cognitive impairment; Aging; Illumina 450k human methylation array