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.

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