|
| Status |
Public on Jul 13, 2018 |
| Title |
Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of a disease spectrum with shared clinical, genetic and pathological features. These include near ubiquitous pathological inclusions of the RNA binding protein (RBP) TDP-43, and often the presence of a GGGGCC expansion in the C9ORF72 (C9) gene. Here we show unexpectedly that the signature of hnRNP H sequestration and altered splicing of target transcripts we identified in C9ALS patients (Conlon et al. 2016) also occurs in fully half of 50 post-mortem sporadic, non-C9 ALS/FTD post-mortem brains. Furthermore, and equally surprisingly, these “like-C9” brains also contained correspondingly high amounts of insoluble TDP-43, as well as several other disease-related RBPs, and this correlates with widespread global splicing defects. Finally, we show that the like-C9 sporadic patients, like actual C9ALS patients, were much more likely to have developed FTD. We propose that these unexpected links between C9 and sporadic ALS/FTD define a common mechanism in this disease spectrum.
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| |
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| Overall design |
Differential splicing analysis of Amyotrophic Lateral Sclerosis (ALS) and Control samples
contributor: NYGC ALS Consortium
contributor: The Target ALS Human Postmortem Tissue Core
|
| Web link |
https://www.nygenome.org/als-consortium/
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| |
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| Contributor(s) |
Fagegaltier D, Phatnani H, Agius P |
| Citation(s) |
30003873, 33055097, 35197626, 35197628 |
| |
| Submission date |
Jul 03, 2018 |
| Last update date |
Jun 17, 2024 |
| Contact name |
Delphine Fagegaltier |
| E-mail(s) |
dfagegaltier@nygenome.org
|
| Organization name |
New York Genome Center
|
| Department |
Center for Genomics of Neurodegenerative Disease
|
| Lab |
Hemali Phatnani
|
| Street address |
101 Ave of the Americas
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10013 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (77)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA479536 |
| SRA |
SRP151960 |
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