Whole Genome Sequencing Identifies New Autism Signature

Current genetic tests for autism scan broad portions of the genome for DNA insertions or deletions that have previously been linked to autism. Other tests look for changes in the DNA building blocks of certain genes, but these tests flag only about 10% to 30% of cases.

Autism has genetic roots, but most cases can not be explained by current genetic tests.An analysis of the complete genomes of 2,064 people reveals that multiple genetic variations could contribute to autism. The work suggests that scanning whole genomes may one day be useful for clinical diagnostics.


Scientists at the Howard Hughes Medical Institute (Seattle, WA, USA) and their colleagues sequenced the genomes of 516 autistic children with no family history of autism, and no genetic anomalies detected by current tests. The team also sequenced the genomes of the children's parents and an unaffected sibling equaling 2,064 people in total. They analyzed each family's data, looking for genetic variations that occurred only in children with autism. Genomes were sequenced at the New York Genome Center (NYGC) using 1 μg of DNA, an Illumina polymerase chain reaction (PCR)-free library protocol, and sequencing on the Illumina X Ten platform. The team used the Quick Change Lightning Multi Site-Directed Mutagenesis Kit.

The investigators identified genetic changes that disrupted gene function and led to altered protein production, and genetic deletions too small to see with current tests. They also found changes in areas of the genome that do not contain genes, but are responsible for turning genes on. They compared the number of variations in autistic children's genomes with that of their unaffected siblings and found that children with autism were significantly more likely to have three or more different kinds of genetic variations.

Evan E. Eichler, PhD, the lead author of the study, said, “In five to 10 years, whole genome sequencing could be the most informative tool for autism diagnosis. Children with autism were significantly more likely to have three or more different kinds of genetic variations and that suggests that a combination of sporadic genetic variations could contribute to autism.” The study was published on September 28, 2017, in the journal Cell.

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Howard Hughes Medical Institute