Researchers use DNA sequencing to uncover genes that heighten autism risk

In the largest study of its kind to date, researchers have used DNA sequencing to uncover dozens of genes that heighten the risk for autism. Joseph Buxbaum, Ph.D., Icahn School of Medicine at Mount Sinai, New York City, Mark Daly, Ph.D., Broad Institute of Harvard and MIT, and their colleagues examined more than 14,000 DNA samples from affected children, parents and unrelated people. They identified changes in 107 genes that are likely to contribute to the risk for autism spectrum disorder (ASD) – a jump from the nine genes implicated in earlier studies using these approaches. The findings, reported online October 29, 2014, in Nature, provide a better understanding of some of the genetic and cellular changes in pathways and processes thought to be involved in ASD, and eventually may help lead to potential therapies. ASD, a complex disorder that affects one in 68 children in the United States, frequently affects a person's behavior and ability to interact with others.

The scientists identified variations and mutations in genes in three pathways that are important to normal development. In each case, the changes in these pathways were linked to autism risk. They include:

• Synaptic function. Synapses are the spaces between nerve cells over which brain messages must travel. Mutations in synaptic genes and synapse formation and function can alter these messages.

• Chromatin remodeling. DNA is packaged into chromatin in cells. Changes in this packaging can affect which genes are turned on and off, and the formation of neural connections in the brain.

• Transcription. Instructions embedded in genes must be transcribed, or read, to build proteins, the workhorse of the cell. Transcription mistakes can affect a wide range of important processes in the brain, from controlling gene activity to transmitting messages.