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| Status |
Public on Dec 31, 2012 |
| Title |
Dosage imbalance of NMD genes is associated with intellectual disability |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Nonsense-mediated mRNA decay (NMD) functions to degrade transcripts bearing premature stop codon (PTC) and is a crucial regulator of gene expression. NMD and the UPF3B gene have been implicated as the cause of various forms of intellectual disability (ID) and other neurological symptoms. Here, we reports three patients with global developmental delay carrying hemizygous deletions of the UPF2 gene, another important member of the NMD pathway and direct interacting partner of UPF3B.
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| Overall design |
Using RNA-SEQ on lymphoblastoid cells from UPF2 deletion patients, we identified 1009 differently expressed genes (DEGs). 38% of these DEGs overlapped with DEGs identified in UPF3B patients. More importantly, 95% of all DEGs in either UPF2 or UPF3B patients share the same trend of de-regulation. This demonstrates that the transcriptome deregulation in these two patient groups is similar and that UPF2 should be considered as a new candidate gene for ID in man. We expanded our inq`uiries and performed a comprehensive search for copy number variations (CNVs) encompassing all NMD genes in cohorts of ID patients and controls. We found that UPF2, UPF3A, Y14, SMG6 and EIF4A3 are frequently deleted and/or duplicated in ID patients. These CNVs are likely to be the root of the problems or to act as predisposing factors. Our results suggest that dosage imbalance of NMD factors is associated with ID and further emphasize the importance of NMD in normal learning and memory processes.
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| Contributor(s) |
Nguyen LS, Kim HG, Mokry J, Huang L, Wilkinson MF, Schaffer L, Gecz J |
| Citation(s) |
23376982 |
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| Submission date |
Jan 30, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Jozef Gecz |
| Organization name |
SA Pathology
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| Department |
Genetics Medicine
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| Lab |
Neurogenetics
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| Street address |
72 King William Rd
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| City |
North Adelaide |
| State/province |
South Australia |
| ZIP/Postal code |
5006 |
| Country |
Australia |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (2) |
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| Relations |
| SRA |
SRP010647 |
| BioProject |
PRJNA152581 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35420_Aligned_File_Description.txt.gz |
547 b |
(ftp)(http) |
TXT |
| GSE35420_RAW.tar |
720.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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