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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 (3) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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 |
The RNA sequencing libraries were constructed from the liver RNA of 3-4-month Smarcal1del/del and wt female mice (n=3/group) at 20°C and after 1 hour at 39.5°C. These libraries were sequenced using the whole transcriptome shotgun sequencing procedure.
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| Contributor(s) |
Boerkoel CF, Baradaran-Heravi A |
| Citation(s) |
22378147 |
| Submission date |
Feb 03, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Alireza Baradaran-Heravi |
| E-mail(s) |
abara@cfri.ca
|
| Organization name |
UBC
|
| Department |
Medical Genetics
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| Street address |
950 West 28th Avenue, Room 218
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 4H4 |
| Country |
Canada |
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| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (8)
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| GSM871338 |
Smarcal1+/+ liver at 20oC- lane 1 |
| GSM871339 |
Smarcal1+/+ liver at 20oC- lane 2 |
| GSM871343 |
Smarcal1del/del liver at 20oC- lane 1 |
| GSM871344 |
Smarcal1del/del liver at 20oC- lane 2 |
| GSM871345 |
Smarcal1+/+ liver at 39.5oC- lane 1 |
| GSM871346 |
Smarcal1+/+ liver at 39.5oC- lane 2 |
| GSM871347 |
Smarcal1del/del liver at 39.5oC- lane 1 |
| GSM871348 |
Smarcal1del/del liver at 39.5oC- lane 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 |
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| Relations |
| SRA |
SRP010780 |
| BioProject |
PRJNA156083 |
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