Researchers begin to map neurogenetic pathway, find new cell is involved in Autism Spectrum.


Researchers from Stanford University have identified a molecular network that comprises many of the genes previously shown to contribute to autism spectrum disorders. The findings provide a map of some of the crucial protein interactions that contribute to autism and will help uncover novel candidate genes for the disease. The opensource study is published in Molecular Systems Biology.

The study of autism disorders is extremely challenging due to the large number of clinical mutations that occur in hundreds of different human genes associated with autism.  The team therefore wanted to see to what extent shared molecular pathways are perturbed by the diverse set of mutations linked to autism in the hope of distilling tractable information that would benefit future studies.

The researchers generated their interactome, the whole set of interactions within a cell, using the BioGrid database of protein and genetic interactions. The team identified a specific module within this interactome that comprises 119 proteins and which shows a very strong enrichment for autism genes.

Gene expression data and genome sequencing were used to identify the protein interaction module with members strongly enriched for known autism genes. The sequencing of the genomes of 25 patients confirmed the involvement of the module in autism; the candidate genes for autism present in the module were also found in a larger group of more than 500 patients that were analyzed by exome sequencing. The expression of genes in the module was examined using the Allen Human Brain Atlas. The researchers revealed the role of the corpus callosum and oligodendrocyte cells in the brain as important contributors to autism spectrum disorders using genome sequencing, RNA sequencing, antibody staining and functional genomic evidence.

The team state that much of today’s research on autism is focused on the study of neurons and now the current study has also revealed that oligodendrocytes are also implicated in this disease.  In the future, the medical community need to study how the interplay between different types of brain cells or different regions of the brain contribute to this disease.

The module the researchers identified which is enriched in autism genes had two distinct components.  One of these components was expressed throughout different regions of the brain. The second component had enhanced molecular expression in the corpus callosum. Both components of the network interacted extensively with each other.

The working hypothesis of the scientists, which is consistent with other recent findings, is that disruptions in parts of the corpus callosum interfere with the circuitry that connects the two hemispheres of the brain. This likely gives rise to the different phenotypes of autism that result due to impairment of signaling between the two halves of the brain.

The team summise that the study highlights the importance of building integrative models to study complex human diseases.  The use of biological networks allowed the group to superimpose clinical mutations for autism onto specific disease-related pathways. This helps finding the needles in the haystack worthy of further investigation and provides a framework to uncover functional models for other diseases.

Source:  EMBO Press

An integrative analysis of the interactome, gene expression and genome sequencing data identifies protein interaction modules implicated in autism spectrum disorders and reveals the corpus callosum as a potential tissue of origin in ASD.  Topological clustering of the human protein‐protein interaction network reveals two modules implicated in ASD, module #2 for chromatin remodeling proteins and transcription factors and #13 for proteins involved in brain function.  Module #13 has dichotomized expression with one sub‐component ubiquitously expressed in the brain, and the other enriched in the corpus callosum.  Module #13 is involved in oligodendrocyte development and axon myelination in the corpus callosum.  This study suggests interhemispheric disconnectivity in the brain as a potential cause underlying autism.  Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.  Snyder et al 2014.

An integrative analysis of the interactome, gene expression and genome sequencing data identifies protein interaction modules implicated in autism spectrum disorders and reveals the corpus callosum as a potential tissue of origin in ASD. Topological clustering of the human protein‐protein interaction network reveals two modules implicated in ASD, module #2 for chromatin remodeling proteins and transcription factors and #13 for proteins involved in brain function. Module #13 has dichotomized expression with one sub‐component ubiquitously expressed in the brain, and the other enriched in the corpus callosum. Module #13 is involved in oligodendrocyte development and axon myelination in the corpus callosum. This study suggests interhemispheric disconnectivity in the brain as a potential cause underlying autism. Integrated systems analysis reveals a molecular network underlying autism spectrum disorders. Snyder et al 2014.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s