Study completed by Mt. Sinai researchers and the Autism Sequencing Consortium examined several types of rare, genetic differences in more than 14,000 DNA samples from parents, affected children, and unrelated individuals – by far the largest number to date – to dramatically expand the list of genes identified with autism spectrum disorder (ASD).
Small differences in as many as a thousand genes contribute to risk for autism.
Brain machinery for communication, transcription, regulation implicated
– Genes underlying the neural machinery for shaping communication between brain cells, gene expression, and its regulation by environment emerged as conferring the most risk.
– Rare glitches in 107 genes confer relatively higher risk.
– Among 2270 trios of patients and their parents, 13.8% carried such mutations.
20x More Likely in Boys
Such anomalies have a much higher impact on risk than most of the more than 1000 genes that the researchers estimate are likely involved in autism. By comparing types of mutations found in girls versus boys – who have much higher rates of autism – the researchers pinpointed mutations that confer more than a 20-fold increase in risk in boys.
The new study was also the first to compare the rate of different classes of mutations between girls with ASD and boys with ASD. Feminine genetics somehow protect girls from ASD, so comparing mutations between girls and boys enabled the authors to estimate the risk associated with different kinds of mutations. Using this approach, the study authors found mutations that came with a more than 20-fold increase in risk for autism.
Other variations linked to autism by the study were in genes that govern synapses, the spaces between nerve cells in pathways that “decide” whether signals travel onward. Nerve cells must be able to execute well-timed maneuvers, such as allowing charged particles to build up or rush out of them, to pass on nerve signals normally. A third set of genes linked to risk by the study regulate basic steps that turn genes into proteins. For a protein to be built based on genetic code, the code must be translated into related molecules (transcription) and cut up and rebuilt (spliced) into the core instructions for protein building.
Hopefully this study can help in preventative and treatment measures.
Synaptic transcriptional and chromatin genes disrupted in autism
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2014 Oct 29. doi: 10.1038/nature13772. [Epub ahead of print]