Research links genetics, autism

Researchers have come one step closer to unraveling the genetic origins of autism.

A study examining the relationship between genetic abnormalities and autism, which appeared online on Oct. 9, is slated for later publication in the journal “Molecular Psychiatry.” Yale School of Medicine psychiatry resident Daniel Moreno De Luca, the study’s lead author, said the researchers were interested in a particular kind of autism-related genetic abnormality called Copy Number Variant, or CNV. CNV abnormalities display increased amounts of DNA and are distinct from genetic mutations, which show a deficiency of DNA, he said.

“There are many different genetic causes for autism,” he said. “Some places in the human genome are more predisposed to it.”

De Luca said the additional Yale authors of the project, Stephan J. Sanders GRD ’17, A. Jeremy Willsey GRD ’16 and Matthew State GRD ’01, looked for CNVs in three large databases — the Simons Simplex Collection, the Autism Genome Research Exchange and the Autism Genome Project. From these databases, the project team monitored 30,000 documented cases of neurological patients and also observed a controlled population of 13,000. CNVs were found to be more common in the population of neurological patients than in the controlled population, indicating that CNVs were correlated with autism, De Luca said.

Willsey, a graduate student working towards his Ph.D. in genetics, said the researchers also observed factors affecting the prevalence of autism among siblings — genetically and environmentally matched siblings showed different probabilities of developing the disease. He added that the Simons Foundation’s database provided the researchers with a record of 2,650 “simplex families,” which consist of two parents, one offspring with autism and another unaffected by the disease.

The study has laid out a clear path to finding the genes central to autism, Willsey said, as nobody had previously categorized these mutations as carrying risks for the disease.

“We have to take these genes and say what’s actually happening in autism,” he said. “That’s the next step.”

De Luca said the research provides statistical evidence suggesting that CNVs have clinical relevance in detecting autism. He added that he would like to continue observing mutations and CNVs in patients and that he is currently participating in a sequencing project that observes each DNA base pair.

Andrew Timberlake ’11 GRD ’18 MED ’19 said the CNV research exemplifies the vast resources and established collaborations that make Yale ideal for biomedical research.

“Autism spectrum disorders are among the most poorly understood,” Timberlake said. “These findings contribute to a greater understanding of the genetic etiology of such disorders, which will hopefully lead to more efficient diagnosis and clinical management.”

All the sequencing conducted for the project was performed at the Yale Center for Genomic Analysis, located on West Campus, Willsey said.


  • pete

    “CNV abnormalities display increased amounts of DNA and are distinct from genetic mutations, which show a deficiency of DNA, he said.”

    This has to be a misinterpretation of what De Luca said, because CNVs can be either duplications or deletions, and mutations can be insertions, deletions, or substitutions.

  • annemdachel

    The message in this article is that autism is some genetic disorder since there is no mention of what the environmental factors might be.

    In the 1970s, the autism rate was one in every 10,000 kids and almost no one knew anyone with autism. That changed when the definition was broadened in 1994 to include other behaviors doctors were seeing in children. At that point the numbers exploded.

    1995 1:500

    2001 1:250

    2004 1:166

    2007 1:150

    2009 1:110

    2012 1:88

    How could genetics possibly explain why the numbers continue to increase? Autism is now an epidemic and there’s never been a purely genetic epidemic in human history.

    How bad do the number have to get before we address autism as a national health emergency?

    Anne Dachel, Media editor: Age of Autism

    • yalengineer

      Oh dear, the AoA folk have arrived to the YDN.

  • annemdachel

    In truth, autism now affects one in every 88 children, one in every 54 boys and no official can tell us why. There’s nothing a mainstream doctor can tell a new mom whose baby was born healthy and is developing normally so that that child doesn’t also regress and end up with an autism diagnosis. A once rare disorder is now so common that everyone knows someone (probably lots of people) with an affected child. In the face of all this, experts continue to waste millions of dollars in genetic research and refuse to look at the kids who were healthy and suddenly lost learned skills and developed autism. What triggered their autism? No one seems interested in finding out, especially when parents say that their children were fine until they received their routine vaccinations.

    Anne Dachel, Media editor: Age of Autism

  • cycle3man

    Do it ever cross your mind that autism was for all intensive purposes non existant 40 or 50 or so years ago, 1 in 10000, no one really can verify. If this scourge is genetic how come 1 in 88 are struck today. I guess as long as someone is willing to fund genetic investigation you will continue these dead end studies. You’ll keep on keepin’ on the gravy train. You ought to be ashamed.

    How’s about switching gears or splitting the funds and with half the funding start looking for environmental causes of this scourge!!!!

  • Yankeegirl1

    I agree with Anne Dachel. There has been a staggering 78% increase in autism since 2002. With numbers like 1 in 88 children and 1 in 54 boys in the US diagnosed with autism, it stands to reason that there is a significant environmental piece to this. Stressors (toxins) are triggering expression of these genetic variants in what otherwise could be typically developing children. Variants alone are not the cause autism. Variants + environmental stressors/insults to the immune system may= expression of a disorder or chronic disease be it autism or a variety of other chronic conditions. We could have a sensitive subpopulation of children whose immune system are very sensitive to stressors/ toxins in the environment. Many autism parents feel there is a sensitive subset of kids that exist but who are not being recognized or properly screened in infancy as “at risk” – these variants confirm that and it is these babies should be screened prior to any insults to their immune system. When is comes to autism, the whole picture not just genetic piece should be considered here.

  • threewithautism

    I have three kids on the autism spectrum and recently found out that they all have an 11Q22 microduplication. We’re in a database but so far haven’t found others out there with the same abnormality. I hear that 11th chromosome abnormalities can contribute to autism, though…

  • The Anti-Yale

    Link to “Cooking Our Sperm: The Autism Conundrum”