 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 01, 2011 |
| Title |
Transcriptomic Analysis of Autism Brain Reveals Convergent Molecular Pathology [array data] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Autism spectrum disorder (ASD) is a common, highly heritable neuro-developmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an etiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1/FOX1, and a module enriched for immune genes and glial markers. Using high-throughput RNA-sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in ASD brain. Moreover, using a published autism GWAS dataset, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic etiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.
|
| |
|
| Overall design |
Total RNA was extracted from approximately 100mg of postmortem brain tissue representing Cerebellum (C), Frontal cortex (F), and Temporal cortex (T), from autistic and control individuals.
|
| |
|
| Contributor(s) |
Voineagu I |
| Citation(s) |
21614001 |
| Submission date |
Apr 11, 2011 |
| Last update date |
Mar 20, 2017 |
| Contact name |
Irina Voineagu |
| E-mail(s) |
voineagu@ucla.edu
|
| Organization name |
UCLA
|
| Street address |
695 Chrles E Young Dr
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
|
| Samples (79)
|
|
| Relations |
| BioProject |
PRJNA138969 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28521_RAW.tar |
3.9 Mb |
(http)(custom) |
TAR |
| GSE28521_non-normalized_data.txt.gz |
22.0 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...