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| Status |
Public on Feb 20, 2014 |
| Title |
Blood expression profiles of fragile X premutation carriers identify genes involved in neurodegenerative and infertility phenotypes [FXTAS] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Fragile X premutation carriers (fXPC) of the CGG expansion in the 5’-UTR of the fragile X mental retardation 1 (FMR1) gene are at high risk of Fragile X Tremor/Ataxia Syndrome (FXTAS), and females might undergo Premature Ovarian Failure (POF1). We have evaluated the peripheral blood gene expression profiles of fXPC and detected a strong deregulation of genes enriched in FXTAS-relevant biological pathways, including inflammation, and neuronal homeostasis and survival. More than 30% of differentially expressed correspond to long non-coding RNAs (lncRNAs). Several deregulated genes (CASP3, DFFA, APP, AKT1, COX6C, COX7B, SOD1, RNF10, HDAC5, ATXN7, ATXN3 and EAP1) were validated in brain samples of a mouse model of FXTAS and in neuronal cells expressing the expanded FMR1 5’-UTR. One of the validated genes is the early at menopause 1 (EAP1) gene. We confirmed the EAP1 deregulation both in male and female fXPC. Down-regulation was stronger in female fXPC with POF1 compared with female fXPC without POF1. Increased levels of FMR1 mRNA were detected in all brain areas of the CGG-KI mouse model. EAP1 was significantly downregulated in the brainstem and cerebellum of the KI mouse, suggesting that EAP1 levels in certain brain areas could contribute to POF in this model. All together, these results suggest that gene expression profiling in blood of fXPC reflects changes in the brain transcriptome that may underlie neuropathological aspects in FXTAS and of POF.
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| Overall design |
In the study presented here, we have 5 control samples plus one biological replicate and 9 patients with CGG expansions in the 5'UTR of the FMR1 gene (being premutation carriers)
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| Contributor(s) |
Mateu-Huertas E, Rodriguez-Revenga L, Alvarez-Mora MI, Willemsen R, Milá M, Martí E, Estivill X |
| Citation(s) |
24418349 |
| |
| Submission date |
Jul 15, 2013 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Elisabet Mateu Huertas |
| E-mail(s) |
elisabet.mateu@crg.es
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| Organization name |
Center for Genomic Regulation
|
| Department |
Bioinformatics and Genomics
|
| Lab |
Xavier Estivill
|
| Street address |
Dr. Aiguader, 88
|
| City |
Barcelona |
| State/province |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (1) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE48903 |
Blood expression profiles of fragile X premutation carriers identify genes involved in neurodegenerative and infertility phenotypes |
|
| Relations |
| BioProject |
PRJNA212067 |
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