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Series GSE74486 Query DataSets for GSE74486
Status Public on Oct 30, 2015
Title Trans-effects of chromosome aneuploidies on DNA methylation patterns: DNA methylation analysis of Down syndrome in human brain tissues and cells
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary 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.
Overall design 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.
Web link
Contributor(s) Mendioroz M, Do C, Jiang X, Liu C, Darbary HK, Lang CF, Lin J, Thomas A, Abu-Amero S, Stanier P, Temkin A, Yale A, Liu M, Li Y, Salas M, Kerkel K, Capone G, Silverman W, Yu E, Moore G, Wegiel J, Tycko B
Citation(s) 26607552
Submission date Oct 29, 2015
Last update date Mar 22, 2019
Contact name Benjamin Tycko
Phone 5519963595
Organization name HUMC
Department Epigenetics
Street address 40 prospect avenue
City hackensack
State/province NJ
ZIP/Postal code 07601
Country USA
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (131)
GSM1921482 genomic DNA from Down syndrome Cerebellum 1
GSM1921483 genomic DNA from Down syndrome Cerebellum 2
GSM1921484 genomic DNA from Down syndrome Cerebellum 3
This SubSeries is part of SuperSeries:
GSE74519 Trans-effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models
BioProject PRJNA300574

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE74486_DS_OXBS_processed_matrix_3.txt.gz 19.7 Mb (ftp)(http) TXT
GSE74486_DS_OXBS_raw_signal_matrix_2.txt.gz 26.7 Mb (ftp)(http) TXT
GSE74486_DS_processed_norm_batch_corrected_filtered_matrix_2.txt.gz 222.4 Mb (ftp)(http) TXT
GSE74486_DS_processed_norm_no_batch_correction_no_filtering_matrix_1.txt.gz 161.5 Mb (ftp)(http) TXT
GSE74486_DS_raw_signal_matrix_1.txt.gz 278.6 Mb (ftp)(http) TXT
GSE74486_RAW.tar 183.1 Mb (http)(custom) TAR
Raw data are available on Series record
Processed data included within Sample table
Processed data are available on Series record

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