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| Status |
Public on Mar 01, 2016 |
| Title |
Transcriptional consequences of DISC1 knockdown in human neural progenitor cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Background: One of the strongest identified risk factors for major psychiatric illness is a chromosomal translocation directly disrupting the DISC1 gene, which is observed in members of a large Scottish family. Although DISC1 is known to function through a variety of molecular pathways, no global assessment of the molecular consequences of cellular DISC1 perturbation has been carried out to date. Methods: Predicted effects of the t(1;11)(q42;q14) translocation on DISC1 expression were modelled in neural progenitor cells derived from human fetal cortex using RNA interference (RNAi). Downstream effects on the cellular transcriptome were assessed by microarray. The reproducibility of individual gene expression changes was tested in repeat experiments by quantitative PCR.Results: A total of 54 genes were differentially expressed between the DISC1 and control siRNA conditions at a false discovery rate (FDR) ≤ 0.05 in the primary experiment. Differentially expressed genes were significantly over-represented in Gene Ontology terms relating to the cell cycle, but included genes involved in a variety of other functions. Several genes showing reproducible differences in gene expression have been previously implicated in psychiatric disorders. Most consistent gene expression differences were seen for CCND2, MEG3, SPOCK2 and GABRA5.
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| Overall design |
Total RNA extracted from human neural progenitor cells manipulated with either of two siRNAs: control siRNA or siRNA targeting DISC1 . 3 replicates per group. Genome wide transcript levels were then measured using gene expression microarrays.
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| Contributor(s) |
Bray N, Hill M, Jeffries A, Killick R, Buonocore F, Ivanov D, Uwanogho D, Cocks G, Butler O, Stangl D, O’Donovan MC, Williams BP, Price J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Feb 03, 2012 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Matthew James Hill |
| Organization name |
Cardiff University
|
| Street address |
Maindy Road
|
| City |
Cardiff |
| ZIP/Postal code |
CF24 4HQ |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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| Samples (6)
|
| GSM870398 |
human neural progenitor cell line_Control_siRNA_replicate1 |
| GSM870399 |
human neural progenitor cell line_Control_siRNA_replicate2 |
| GSM870400 |
human neural progenitor cell line_Control_siRNA_replicate3 |
| GSM870401 |
human neural progenitor cell line_DISC1_siRNA_replicate1 |
| GSM870402 |
human neural progenitor cell line_DISC1_siRNA_replicate2 |
| GSM870403 |
human neural progenitor cell line_DISC1_siRNA_replicate3 |
|
| Relations |
| BioProject |
PRJNA152283 |
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