In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our ninth item, Copy Number Variations, is from Autism Speaks’ Top 10 Autism Research Events of 2007.
Three studies published in 2007 pointed autism researchers toward the importance not only of mutations within the DNA code of specific genes, but also of variations in the number of copies of genes, known as Copy Number Variations (CNV). Created by submicroscopic deletions or duplications of DNA sequences, recent advances have only now allowed CNV to become routinely detectable, establishing an entirely new avenue of genetic research.
Armed with the latest technology and three different collections of patient DNA, including Autism Speaks’ Autism Genetic Resource Exchange (AGRE), researchers at Cold Spring Harbor scanned the genome for the presence of CNV in autism. In February 2007 they reported that not only do individuals with autism have more CNV than individuals without autism, but that CNV in autism occur more often as “de novo” or spontaneous mutations (mutations not found in the DNA of either parent). They also found that these spontaneous CNV appear to be more common in families with only one child with autism (simplex) than those with multiple affected children (multiplex).
With their data suggesting that genetic mechanisms may be different in different types of autism, the researchers then carefully studied the inheritance pattern of autism in the many families in Autism Speaks’ AGRE and IAN databases. In July they published that they could fit the data to a model in which there are at least two distinct ways that genes may play a role in the development of autism: spontaneous CNV might help to explain autism in simplex families, whereas inherited gene mutations may be at the root of autism spectrum disorders in a greater portion of multiplex families. Such a model is significant because although autism has been thought to have a strong genetic component, so far it has not been shown to be as clearly inherited as other simple genetic disorders.
The team from Cold Spring Harbor has provided a new theory of autism risk that stands to influence how future autism genetic research is conceptualized. Although their results require replication, it also now leads to the question of what causes this increase in spontaneous CNV, opening the door to an exploration of the interplay between genetics and environmental factors. Possible risk factors include age of the parents, specific toxicological factors and accumulated exposures, as well as genetic predisposition.
Update since this story was first run: Improvement in DNA technology since the publication of this first major autism CNV study has meant that new insights into the role of CNV are actively being pursued. The largest and most comprehensive autism CNV study to date was published in April 2009 in the top research journal, Nature. The new study focused on inherited rather than spontaneous CNV, with the researchers finding CNV variations in genes important for neural development [for more details, see http://www.autismspeaks.org/science/science_news/top_ten_autism_research_events_2009_cnv.php]. Researchers in autism are continuing to lead geneticists in other fields with an intense focus on CNV and early recognition of their importance as potential disease risk factors.