Although thousands of candidate genes are linked to autism, many function together in just a few common pathways, according to a network analysis published in the June issue of PLoS Genetics¹. 

Duplications or deletions of regions of a chromosome, or copy number variations (CNVs), are more common in people who have autism than in controls. Many of the genes within these CNVs may be involved in the disorder.

In the new study, researchers looked closely at the genes within 262 CNVs that arose spontaneously, or de novo,in 181 people with autism. De novo mutations are more likely to be harmful than those that are inherited. 

To identify the function of the genes within these CNVs, the researchers looked at the features of more than 5,000 mouse models, each of which lacks the mouse version of one of the genes.

Overall, the products of 59 of these genes function at neuronal junctions, or synapses, in mice, study found. This is more than would be expected based on chance alone.

The researchers also identified another 144 genes encompassed by the autism-linked CNVs whose protein products interact directly with those 59 proteins. They then built a map showing the links between all 203 proteins and another 22 previously implicated in autism.    

These proteins all form a tightly interconnected network, the study found. On average, three of the genes are altered in each of the people in the study, suggesting that multiple hits to this network may lead to autism.

Interestingly, if only one of the network genes is altered in an individual with autism, that gene is highly connected — with three times as many partners as the genes affected in people with multiple hits. 

The researchers also found that the genes that are duplicated in people with autism tend to code for proteins that drive activities in the cell, whereas those that are deleted tend to hold things in check. 

References:

1: Noh H.J. et al. PLoS Genet. 9, e1003523 (2013) PubMed