Co-expression Profiling of Autism Genes in the Mouse Brain

Menashe, I., Grange, P., Larsen, E. C., Banerjee-Basu, S., Mitra, P. P. (2013) Co-expression Profiling of Autism Genes in the Mouse Brain. PLoS Computational Biology, 9 (7). ISSN 1553734X

[img]
Preview
PDF (Paper)
Mitra PLoS Comp Biol 2013.pdf - Published Version

Download (1705Kb) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/23935468
DOI: 10.1371/journal.pcbi.1003128

Abstract

Autism spectrum disorder (ASD) is one of the most prevalent and highly heritable neurodevelopmental disorders in humans. There is significant evidence that the onset and severity of ASD is governed in part by complex genetic mechanisms affecting the normal development of the brain. To date, a number of genes have been associated with ASD. However, the temporal and spatial co-expression of these genes in the brain remain unclear. To address this issue, we examined the co-expression network of 26 autism genes from AutDB (http://mindspec.org/autdb.html), in the framework of 3,041 genes whose expression energies have the highest correlation between the coronal and sagittal images from the Allen Mouse Brain Atlas database (http://mouse.brain-map.org). These data were derived from in situ hybridization experiments conducted on male, 56-day old C57BL/6J mice co-registered to the Allen Reference Atlas, and were used to generate a normalized co-expression matrix indicating the cosine similarity between expression vectors of genes in this database. The network formed by the autism-associated genes showed a higher degree of co-expression connectivity than seen for the other genes in this dataset (Kolmogorov–Smirnov P = 5×10−28). Using Monte Carlo simulations, we identified two cliques of co-expressed genes that were significantly enriched with autism genes (A Bonferroni corrected P<0.05). Genes in both these cliques were significantly over-expressed in the cerebellar cortex (P = 1×10−5) suggesting possible implication of this brain region in autism. In conclusion, our study provides a detailed profiling of co-expression patterns of autism genes in the mouse brain, and suggests specific brain regions and new candidate genes that could be involved in autism etiology.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
diseases & disorders > mental disorders > personality disorders > autism
organs, tissues, organelles, cell types and functions > organs types and functions > brain
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Mitra lab
Depositing User: Matt Covey
Date Deposited: 16 Aug 2013 19:06
Last Modified: 16 Aug 2013 19:06
PMCID: PMC3723491
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28538

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving