Cameron self-injured as a child, but Thomas never did.
Cameron loves the Red Hot Chili Peppers and used to tap out the same tune on the piano over and over, while music doesn’t seem to move Thomas.
Last Friday morning in their Oakville kitchen, Cameron sat expressionless and shook pill bottles repetitively, as Thomas paced, jumped, shouted and smiled, occasionally scarfing Timbits.
Cameron, 20, and Thomas, 14, are brothers. They both have Autism Spectrum Disorder (ASD). They score similarly in the severity of the disorder.
But they don’t seem to experience autism the same way, said their mother, Valerie South.
“Personalities aside, their autism is different.”
A study published Monday and led by Sick Kids’ Stephen Scherer bolsters the intuitions of South and probably many parents like her – and uncovers a surprising new feature of a developmental disorder that now affects 1 in 68 children.
When two siblings are both affected by autism, researchers assume that both kids inherited the same genetic risk factors from their parents. But by sequencing whole genomes from 85 Canadian families with a pair of autistic siblings, Scherer and his colleagues discovered that among the children whose genes told researchers a story about why they had autism, more than two-thirds told a different story than their brother or sister.
“We think that pretty much every child has their own form of autism,” said Scherer, director of the Centre for Applied Genomics at the Hospital for Sick Children.
The study, published in Nature Medicine, is the largest of its kind to date. But the paper marks merely the first wave of a massive scientific effort that will sequence 10,000 whole genomes of people with autism and upload all the data to a cloud-based platform accessible to any scientist in the world.
“We weren’t really able to ask these questions before because our technology wasn’t good enough,” said Scherer. “But now, with this whole genome sequencing, we can do it.”
Scientists already knew that autism is a mixed bag, genetically. Over 100 ASD-linked genetic variations have been discovered, and an individual diagnosed with ASD may have some of those or none. Yet autism also appears to be heritable: parents with one child on the spectrum have a 10 to 20 per cent risk of bearing another.
“Our question was, what is going on in families that have two or more autistic children?” said Scherer.
Most genetic research into autism relies on examining smaller swaths of DNA, but Scherer and his colleagues wanted to look at the entire genome – a much more expensive and time-consuming operation.
Their efforts bore surprising fruit. About 40 per cent of the 85 families had genetic mutations associated with autism. But in nearly 70 per cent of those cases, the two affected siblings did not share the same rare risk factors as each other, and those children tended to differ in their symptoms and behaviours.
“It really throws off standard thinking,” said Brett Abrahams, a professor of genetics at the Albert Einstein College of Medicine at Yeshiva University, who was not involved with the study.
“This is the beginning of much larger efforts that are really going to provide incredible insights and, I think, drive forward treatment.”
In the immediate future, the study suggests that whole genome sequencing may provide dramatically better information to families searching for a diagnosis, or helping making a decision about whether to have another child, compared to more limited genetic tests like microarrays, targeted gene sequencing and exome sequencing.
Ultimately, the hope is to understand the molecular mechanisms of ASD: what exactly is being affected in the brain, and how.
“If I look at the genes that cause heart attack, a lot are involved in creating a plaque, in clotting problems, and it all fits together into one picture,” said Stephan Sanders, a professor at the University of California San Francisco who studies bioinformatics and autism and was also not involved in Monday’s study.
The same is not true of autism. “I sort of get to, ‘Well, it’s something to do with development.’ The hope is that by following these genes we can get to that stage – maybe it won’t be a simple answer, maybe it will to be two or three answers coming together,” said Sanders. “That will provide a target for therapeutics.”
South, in Oakville, plans to enroll her family in Scherer’s study. Her eldest son, Mitchell, 21, is not affected by the disorder. She wants Mitchell to have as much information as possible at his fingertips if he later decides to have children – both insight into their family’s particular genetic quirks but also new discoveries about this frustratingly mysterious disorder that has affected both of Mitchell’s brothers.
“I’d love to spend a minute inside their brains,” says South of Cameron and Thomas. A nurse with a clinical specialty in migraines, South was particularly impressed that the research team in the 10,000 genomes initiative – called the MSSNG project, a collaboration between Sick Kids, Google, and Autism Speaks – are releasing their data openly.
“Substantial progress is being made in understanding the genetic underpinnings of autism,” said Sanders.
“It’s happening very quickly now.”