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| Status |
Public on Apr 05, 2012 |
| Title |
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression (1) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.
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| Overall design |
For analysis of gene expression in primary cultured human dermal fibroblasts, 5.0 μg of total RNA from three biologically independent replicates was extracted from two SIOD (SD8 and SD60) and a control skin fibroblast cell lines, labeled and hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays.
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| Contributor(s) |
Boerkoel CF, Baradaran-Heravi A |
| Citation(s) |
22378147 |
| |
| Submission date |
Feb 03, 2012 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Alireza Baradaran-Heravi |
| E-mail(s) |
abara@cfri.ca
|
| Organization name |
UBC
|
| Department |
Medical Genetics
|
| Street address |
950 West 28th Avenue, Room 218
|
| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 4H4 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (7)
|
| GSM870404 |
Control human skin fibroblasts- biological replicate 1 |
| GSM870405 |
Control human skin fibroblasts- biological replicate 2 |
| GSM870406 |
Control human skin fibroblasts- biological replicate 3 |
| GSM870407 |
SD8 skin fibroblasts- biological replicate 1 |
| GSM870408 |
SD8 skin fibroblasts- biological replicate 2 |
| GSM870409 |
SD60 skin fibroblasts- biological replicate 1 |
| GSM870410 |
SD60 skin fibroblasts- biological replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE35554 |
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression |
|
| Relations |
| BioProject |
PRJNA156079 |
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