Researchers in Canada report that expanded tandem DNA repeats—what they dub “genetic wrinkles” in DNA—may play a significant role in autism spectrum disorders (ASD).

Stephen Scherer and his team, including first author Brett Trost, note that while many genes are known to be associated with autism, these genes explain fewer than 20% of cases. A new technique invented by study coauthor Ryan Yuen allowed the researchers to search for specific characteristics within DNA itself and compare patterns found in individuals with ASD to their parents or other controls.

Tandem repeats are nucleotides (building blocks of DNA) repeated next to each other two or more times. Using their new approach to analyze more than 20,000 genomic samples, the team discovered that tandem repeats in parents sometimes are doubled or even tripled in children with ASD, meaning that a tandem repeat present in a parent’s DNA can be expanded in a child. The larger the expansion, the more likely it is that it may alter gene function.

The researchers found that children with ASD were significantly more likely to have rare genic tandem repeat expansions than unaffected siblings. Repeat expansions were seen in 23.3% of children with ASD versus 20.7% of unaffected siblings, indicating that they may be responsible for as much as 2.6% of ASD risk. The expansions appeared to be further enlargements of tandem repeats that were already large in the parents. A number of affected genes were involved in nervous system development, the cardiovascular system, and muscle tissue.

Scherer compares these expansions to the working of an accordion. “If they stretch out to a certain extent,’ he says, “the music that’s played by the DNA or by the instrument has a different tone to it, so the genes are really music here. It’s a different… song that’s played.”

The researchers conclude, “Our findings represent a significant advancement in ASD genetics, as we discovered many genes involved in the tandem repeat expansions that had not been previously identified using conventional genomic analyses.”

“Genome-wide detection of tandem DNA repeats that are expanded in autism,” Brett Trost, Worrawat Engchuan, Charlotte M. Nguyen, Bhooma Thiruvahindrapuram, Egor Dolzhenko, Ian Backstrom, Mila Mirceta, Bahareh A. Mojarad, Yue Yin, Alona Dov, Induja Chandrakumar, Tanya Prasolava, Natalie Shum, Omar Hamdan, Giovanna Pellecchia,Jennifer L. Howe,Joseph Whitney, Eric W. Klee, Saurabh Baheti, David G. Amaral, Evdokia Anagnostou, Mayada Elsabbagh, Bridget A. Fernandez, Ny Hoang, M. E. Suzanne Lewis, Xudong Liu, Calvin Sjaarda, Isabel M. Smith, Peter Szatmari, Lonnie Zwaigenbaum, David Glazer, Dean Hartley, A. Keith Stewart, Michael A. Eberle, Nozomu Sato, Christopher E. Pearson, Stephen W. Scherer, and Ryan K. C. Yuen, Nature, July 27, 2020 (epub prior to print publication). Address: Ryan K. C. Yuen, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, [email protected] sickkids.ca.

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“Breakthrough in autism spectrum research finds genetic ‘wrinkles’ in DNA could be a cause,” Elizabeth St. Philip, Avis Favaro, and Alexandra Mae Jones, CTVnews, July 27, 2020.

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“Individuals with autism more likely to have expanded tandem DNA repeats,” genomeweb.com, July 27, 2020.

This article also appears in Vol. 34, No. 3, 2020, of Autism Research Review International