Unknown,Transcriptomics,Genomics,Proteomics

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Distinct DNA methylation patterns of cognitive impairment and Trisomy 21 in Down Syndrome

ABSTRACT: 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). While the mechanism underlying these changes is unknown, it has been hypothesized that the presence of the amyloid precursor protein (APP) on chromosome 21 may contribute to the phenotype. Genome-wide DNA methylation abnormalities have been shown in neural tissue of patients with AD, and cells may respond to changes in gene dosage with altered DNA methylation. We therefore examined whole-genome DNA methylation in buccal epithelial cells of adults with DS to determine whether patterns of DNA methylation 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 450K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells. We found 297 CpGs to be differentially methylated between the groups, including 26 genes that were represented by more than one CpG. In addition, we found 331 probes that were correlated with cognitive function including 23 genes represented by more than one probe. We found no enrichment on chromosome 21 and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype. Overall, our results indicate that both Trisomy 21 and cognitive impairment are associated with distinct patterns of DNA methylation. This cohort consist of genomic DNA extracted from 20 buccal swabs, bisulphite converted and hybridized to the Illumina Infinium HumanMethylation450 Beadchip for genome wide DNA methylation profiling.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Kobor

PROVIDER: E-GEOD-50586 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Jones Meaghan J MJ Farré Pau P McEwen Lisa M LM Macisaac Julia L JL Watt Kim K Neumann Sarah M SM Emberly Eldon E Cynader Max S MS Virji-Babul Naznin N Kobor Michael S MS

BMC medical genomics 20131227

<h4>Background</h4>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 p ...[more]

PMID: 24373378

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Distinct DNA methylation patterns of cognitive impairment and Trisomy 21 in Down Syndrome

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

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