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Extra repeats in DNA, half of which have not been previously linked to autism, may account for around 3 percent of the condition’s genetic architecture. This is according to a new study led by Steve Scherer, professor of medicine at the University of Toronto in Canada.

The team of researchers looked at the areas of the genome with tandem repeats. There are the building blocks of DNA, 2 to 20 nucleotides, that are repeated twice or more times in one spot. When passed down from parents to children, these repeats can expand. For example, if a combination is repeated 10 times in a parents’ DNA, it can repeat hundreds of times in the offspring. The more times a repeat expands, the more likely it can disrupt the gene’s function.

Specific repeats have already been associated with autism. 5 percent of people with autism have fragile X syndrome, usually caused by the expansion of a repeat in the FMR1 gene. Less than a quarter of people with autism have a known genetic cause, though, although it is established that the condition is highly heritable.

It has been long suspected that expanded repeats may make up some of autism’s missing heritability. However, there have been no adequate methods or sample sizes to test the theory. Scherer’s new study uses a statistical approach that scans whole genomes to identify differences in rare tandem repeat expansions between people with autism and their siblings.

The team was able to analyze the full genomes of more than 17,000 subjects, which included 5,194 people with autism, 7,535 parents, 1,998 typical siblings, and 2,504 unrelated controls. They identified 2,588 regions that are more expanded in people with autism.

Because these repeats are expanded in 23.3 percent of people with autism, the findings suggest that the repeats contribute up to 2.6% of autism’s genetic influence.

The team identified 57 areas of relevant genes or loci wherein tandem repeats occurred more often in children with autism. According to Scherer, none of these would be detected by exome scans used to screen people for autism gene mutations.

Other genetic variants linked to autism tend to occur only in genes associated with neural function, but Scherer’s study found that the repeats with rare expansions occur more often in genes involved in the nervous, muscular, and cardiovascular systems. The researcher adds that if cardiac genes are associated with autism, it may open avenues for therapeutics.

While the study is successful in associating repeats with autism, it has not been able to identify individual repeats, indicating that larger datasets are needed for further studies. It is also possible that autism’s heritability is caused not by a specific repeat but by having a high overall number of repeats.

Scherer’s team continues to gather more whole genome sequences from people with autism and their families to take the studies further using the same statistical method. He adds that the method can be helpful in studying the role of repeats in other conditions such as Alzheimer’s disease and schizophrenia.

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