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| Status |
Public on Apr 08, 2014 |
| Title |
Domains of genomewide gene expression dysregulation in Down syndrome [array] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Trisomy 21 (T21) is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in T21, and to eliminate the noise of the genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for T21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either up- or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins’ fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of DS and wild-type, also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall LADs position was not altered in trisomic cells. However, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results suggest that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome and that GEDDs may therefore contribute to some T21 phenotypes.
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| Overall design |
LaminB1-chromatin interactions in a pair of monozygotic twins discordant for trisomy21
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| Contributor(s) |
Letourneau A, Santoni FA, Bonilla X, Sailani MR, Gonzalez D, Kind J, Chevalier C, Thurman R, Sandstrom RS, Hibaoui Y, Popadin K, Falconnet E, Gagnebin M, Gehrig C, Vannier A, Guipponi M, Farinelli L, Robyr D, Garieri M, Migliavacca E, Borel C, Deutsch S, Feki A, Stamatoyannopoulos JA, Herault Y, van Steensel B, Guigo R, Antonarakis SE |
| Citation(s) |
24740065 |
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| Submission date |
Feb 24, 2014 |
| Last update date |
Mar 24, 2015 |
| Contact name |
Audrey Letourneau |
| E-mail(s) |
audrey.letourneau@unige.ch
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| Organization name |
University of Geneva Medical School
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| Department |
Genetic Medicine and Development
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| Street address |
Rue Michel-Servet 1
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| City |
Geneva |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL10559 |
NimbleGen HD2 Human whole genome custom array 2.1M [090310_LP_til_HX1] |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE55426 |
Domains of genomewide gene expression dysregulation in Down syndrome |
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| Relations |
| BioProject |
PRJNA239210 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE55289_RAW.tar |
507.2 Mb |
(http)(custom) |
TAR (of PAIR, TXT) |
| Processed data included within Sample table |
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