Major Cause of Autism: Rare DNA Mutation May Help To Understand


Finding the cause of autism is like trying to put together a huge jigsaw puzzle, according to Anthony Monaco MD PhD of the University of Oxford. He and his team may have found “the edges of the puzzle” – accumulations of rare DNA mutations in genes that affect brain function appear to be a major cause of autism.

The study, a part of the Autism Genome Project Consortium, a collaboration of more than 120 scientists and 50 institutions, used new technology to look for unusual DNA deletions or duplications that are known as copy number variants or CNV’s in over 2000 study participants, 996 who had autism and 1287 who were healthy controls.

Copy number variations may include either missing copies or additional copies of genes. If such variations occur in important genes, such as those involved in development, they could have serious effects.

Although the people with autism didn’t have more CNV’s than people without autism, those with the condition had CNVs that were much more likely to occur in genes that were linked to brain function, especially the growth and maintenance of the synapses through which brain cells communicate with each other.

However, the CNV’s that were implicated in autism weren’t the same in each child. Nearly every child in the study had a unique CNV profile. However the CNV’s were clustered around particular networks of gene pathways that control brain-cell development and function.


"We knew genetics were involved through twin studies and family studies, but the majority of studies focused on common variations in probably a few genes," explained study author Stephen Scherer PhD. "We found dozens, if not hundreds, of genes involved and each autism family may have their own genetic form of autism. The variations are quite rare."

Most of the genetic variants found in the study do not directly cause autism, says study co-investigator Louise Gallagher PhD of Trinity College Dublin, but instead contribute to risk.

Geri Dawson PhD of the advocacy group Autism Speaks says that studies are under way that will link specific sets of CNV’s to certain autism symptoms. One day, parents may be able to use genetic testing that will help physicians choose optimal medical interventions.

“Families want to understand what caused their child’s autism,” says Dawson. “They want to have good information about what that means for family planning, for their next child if they are planning one. They also want to be able to detect autism as early as possible because we know that if we provide early intervention in the first years of life, this can have a huge impact on the outcome of the disorder.”

The Autism Genome Project is currently analyzing another 1,500 families. Organizers want to start the next generation sequencing of the whole genome–searching for new mutations to try to finish the puzzle that is autism.

Source reference:
Scherer S, et al "Functional impact of global rare copy number variation in autism spectrum disorders" Nature 2010; DOI: 10.1038/nature09146.



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