TORONTO -- In a lab at the Hospital for Sick Children in Toronto, scientists went on a hunt through the DNA of some 10,000 families -- many whom have children with autism.
Through this research, they identified something they call 鈥済enetic wrinkles鈥� in DNA itself, a breakthrough they believe could explain why some individuals find themselves on the autistic spectrum.
The hope is that this could be an important new clue into how to diagnose autism spectrum disorder (ASD) early, or even treat it.
Dr. Stephen Scherer, co-author of the study released Monday and director of the Centre for Applied Genomics at SickKids, told 麻豆传媒 the new discovery is 鈥渞eally quite exciting.鈥�
鈥淚t unveils a whole new class of genes that we didn't know (were) involved in autism before,鈥� he said.
鈥淲e do know that they're involved in brain function but we don't know how they fit into the jigsaw puzzle.鈥�
Current research estimates that genetic factors should be found in anywhere from 50 to 90 per cent of individuals with ASD.
Scientists already know of about 100 genes that play a role in the development of autism, but these genes only explain less than 20 per cent of cases.
In order to delve further into these genetic components, researchers had to 鈥渄evelop new methodologies,鈥� Scherer said.
Ryan Yuen, the team leader for this new study, rose to the challenge.
Nine years ago, he developed a 鈥渘ew computational approach,鈥� according to Scherer, which allowed him to search for specific characteristics within DNA itself, and compare patterns found within individuals with autism to their parents or 鈥渙ther controls in the population.鈥�
Now they鈥檝e discovered that sections of DNA from parents sometimes get doubled -- or, in some cases, tripled -- in their children.
These are called tandem repeat expansions.
鈥淭andem repeats are nucleotides, which are the building blocks of DNA, repeated adjacently, two or more times,鈥� Yuen told 麻豆传媒. 鈥淭hey're like DNA wrinkles.鈥�
When these wrinkled strands of DNA are replicated, the repeat can grow longer, which is why a tandem repeat present in a parent鈥檚 DNA could be expanded from parent to child.
The larger these wrinkles are, the more likely that they could interfere with gene function.
Tandem repeats had been studied before individually, but it was difficult, as they had to be searched for in one gene at a time. Since there can be a million tandem repeats in the genome, according to a press release from SickKids, locating the tandem repeats that actually contribute to ASD 鈥渨ould be like looking for a needle in a haystack.鈥�
鈥淚n this study we pioneered a method that can effectively search and analyze terabytes of whole genome sequencing data for tandem repeat expansions,鈥� Yuen told 麻豆传媒.
鈥淢any of the genes linked to [these] repeats [were] never thought to be involved in autism before.鈥�
Some of the new genes identified included those 鈥渋nvolved in the nervous system,鈥� he said. And the location of the tandem repeat expansion within the DNA itself was associated with 鈥渃ertain characteristics and behaviours such as IQ and life skills,鈥� the press release said.
鈥淭his really is a game changer for autism, and genomic research,鈥� Yuen said. 鈥淚t opens up new opportunities in precision diagnostics and medicine.鈥�
Another way of thinking about these anomalies within the DNA, Scherer said, is as music.
鈥淥ne of the really interesting findings that was made in this study was there's identified to be about a million different sites across the vast expanse of the human genome that have the ability to expand and also contract,鈥� he said. 鈥淭hese are these repeat regions that we've mentioned.
鈥淎nd I think the way we think about this is the DNA in these regions is kind of like an accordion. If they stretch out to a certain extent, 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鈥檚 a different [鈥 song that's played.鈥�
Scherer said that in the almost two decades he鈥檚 been studying the autism spectrum, 鈥渢his is the most exciting advance we've had in 15 years.鈥�
The discovery may lead to improved genetic tests, a boon for families and individuals with autism who want a key question answered: Why?
Yuen believes this research will 鈥渋mpact thousands of families,鈥� and will allow scientists to provide countless individuals with autism a clear explanation for their autism by looking at their genes.
鈥淎nd all of the individuals with autism can also have serious medical conditions,鈥� he added. 鈥淪o identifying [these] new tandem repeat expansions to paste into the genome and find out [鈥 the other [genes] involved can provide crucial information for the families and the health care providers.鈥�
Kristen Ellison, who lives in Cobourg, Ontario, is tentatively excited about the study.
Her son, Carter, is nine years old, and on the autism spectrum. He was diagnosed when he was only two years old.
鈥淲e're in the infancy of this research and so realistically, I don't know if it's gonna have an impact, right away,鈥� she told 麻豆传媒.
鈥淏ut I hope that one day, these events will have an impact and improve the quality of life for people with autism.鈥�
It鈥檚 a hope that Margaret Spoelstra, Executive Director of Autism Ontario, shares.
鈥淸It鈥檚] not only 鈥榳hy does my child have this鈥�, but also does this information tell us anything that we might be able to do to support our child, or just support their development, their health, their learning,鈥� she told 麻豆传媒.
鈥淚 think that is the ultimate goal in this, is to have a greater understanding and a greater way to support, not to eliminate. That's not the goal. For families [it] is really to see how can we help my son, my daughter, my child, be the very best that they can be.鈥�
According to Scherer, looking at the DNA can assist in informing patients and their families early on what type of autism they have, so they can plan for care.
鈥淭his new discovery actually adds at least 15 or so new groupings of autism,鈥� Scherer said. 鈥淒epending on the type of autism one has, you would see a set of specialty doctors -- neurologists, for example.鈥�
The finding may also help scientists find medication that can target these regions in the DNA itself.
Researchers suspect these genetic wrinkles may play a role in other complex conditions related to the brain -- such as epilepsy and schizophrenia.
鈥淭his method also allows other researchers to apply their own data for further genomic discovery,鈥� Yuen said.
Now that scientists have the tools to identify these wrinkles, they can try to find a way to iron them out.
鈥淭his is a major scientific advance in the understanding of autism and it will change lives,鈥� Scherer said.
鈥淚t may take a little bit of time but we'll get there.鈥�
