Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human adult postmortem brain tissue from Down syndrome and healthy control subjects

ABSTRACT: Down syndrome (DS) is the result of trisomy chromosome 21 but the mechanisms by which the genotype leads to the characteristic disease phenotype are unclear. We performed a microarray study using human adult brain tissue (dorsolateral prefrontal cortex) from DS subjects and healthy controls to characterise for the first time the human adult Down syndrome brain Experiment Overall Design: RNA extracted from human postmortem brain tissue from adult subjects with Down syndrome and healthy controls was hybridised to Affymetrix HG-U133A GeneChips to identify differentially expressed genes in the disease state.

ORGANISM(S): Homo sapiens

SUBMITTER: Sabine Bahn

PROVIDER: E-GEOD-5390 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiling in the adult Down syndrome brain.

Lockstone H E HE Harris L W LW Swatton J E JE Wayland M T MT Holland A J AJ Bahn S S

Genomics 20071022 6

The mechanisms by which trisomy 21 leads to the characteristic Down syndrome (DS) phenotype are unclear. We used whole genome microarrays to characterize for the first time the transcriptome of human adult brain tissue (dorsolateral prefrontal cortex) from seven DS subjects and eight controls. These data were coanalyzed with a publicly available dataset from fetal DS tissue and functional profiling was performed to identify the biological processes central to DS and those that may be related to ...[more]

PMID: 17950572

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Project description:Background: Trisomy 21 causes Down syndrome (DS), but the mechanisms by which the extra chromosome leads to deficient intellectual and immune function are not well understood. Results: Here, we profile CpG methylation in DS and control cerebral and cerebellar cortex of adults and cerebrum of fetuses. We purify neuronal and non-neuronal nuclei and T-lymphocytes and find biologically relevant genes with DS-specific methylation (DS-DM) in brain cells. Some genes show brain-specific DS-DM, while others show stronger DS-DM in T cells. Both 5-methyl-cytosine and 5-hydroxy-methyl-cytosine contribute to the DS-DM. Thirty percent of genes with DS-DM in adult brain cells also show DS-DM in fetal brains, indicating early onset of these epigenetic changes, and we find early maturation of methylation patterns in DS brain and lymphocytes. Some, but not all, of the DS-DM genes show differential expression. DS-DM preferentially affected CpGs in or near specific transcription factor binding sites, implicating a mechanism involving altered transcription factor binding. Methyl-seq of brain DNA from mouse models with sub-chromosomal duplications mimicking DS reveals partial but significant overlaps with human DS-DM and shows that multiple chromosome 21 genes contribute to the downstream epigenetic effects. Conclusions: These data point to novel biological mechanisms in DS and have general implications for trans effects of chromosomal duplications and aneuploidies on epigenetic patterning. Bisulfite converted DNA from 119 samples from Down syndrome patients and controls were hybridised to the Illumina Infinium 450k Human Methylation Beadchip. In addition, we re-analyzed 6 Down syndrome and 6 control cerebellum DNA samples on the 450K BeadChips using an adaptation of the Illumina probe preparation protocol (TrueMethyl kit; Cambridge Epigenetics, CEGX), in which parallel analyses of bisulfite and oxidative bisulfite DNA for each sample allows assessment of the relative contributions of 5mC and 5hmC to net methylation.

Dataset Information

Transcription profiling of human adult postmortem brain tissue from Down syndrome and healthy control subjects

Publications

Gene expression profiling in the adult Down syndrome brain.

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