Genetic Variants Found that Contribute to the Biology of Autism


While prior research has found several gene mutations that are linked to an increased risk of autism, these variations have only really explained a small percentage of cases. A team of researchers from the Children’s Hospital of Philadelphia took a new approach and found genes that contribute to the disruption of important functional roles in brain development and nerve signaling, which may account for a greater percentage of autism risk.

Gene Disruption Occurs in Processes Affecting Neurological Development

Drs Xiaowu Gai PhD and Peter S. White PhD compared the DNA of 631 children with autism to a control set of 1,775 healthy subjects. The team searched for gene variants called copy number variations (CNV’s) appearing in the genomes of autistic individuals and their families, but not in the healthy controls. They also looked for CNV’s in the genomes of the 1,162 parents of the autistic children.

Unlike changes to single bases in DNA, called single-nucleotide polymorphisms or SNPs, CNV’s are larger alterations in DNA structure, such as missing or repeated stretches of dozens or hundreds of bases in sequence. CNV’s have been implicated in other neuropsychiatric disorders such as schizophrenia and attention-deficit hyperactivity disorder.

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Drs. White and Gai found nearly 400 inherited CNV’s in autism subjects that did not occur in the healthy controls. They repeated their study on a second cohort of 593 autistic subjects, 1109 parents, and 2026 healthy controls. The second study found another set of nearly 400 inherited CNV’s exclusive to the children with autism.

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These gene alterations mostly appear to disrupt genes that affected biological processes relevant to autism, most particularly in affecting synapse function, neurotransmission, and brain development, said Dr. White. Synapses are the contact points at which nerve cells communicate with each other and neurotransmitters are the chemical messengers carrying those signals.

“This suggests to us that there may be many different – possibly even hundreds – of genetic paths to autism,” said Dr. White. “But if those hundreds of genes have similar roles in the nervous system, the end result may lead to the same diagnosis: an autism spectrum disorder.”

Source Reference:
X. Gai et al, “Rare Structural Variation of Synapse and Neurotransmission Genes in Autism,” Molecular Psychiatry, published online March 1, 2011. doi: 10.1038/mp.2011.10