A few years ago very few people were studying copy number variants (CNV) and no one really knew the extent to which they existed in our DNA. Over the course of the past two years, CNVs have emerged as increasingly associated with psychiatric conditions, including autism (see 2007 Spontaneous Mutations). Now, three independent reports published almost simultaneously in early 2008 offered additional insight into the possible role of CNV in autism spectrum disorders.
Like other human genetic variations, these submicroscopic insertions and deletions in the genome could be benign, posing no threat to the health of individuals carrying them, or could lead to abnormal gene expression or protein function implicated in diseases. Several studies have now reported increased overall frequency of CNVs in individuals affected by autism when compared to controls, but given autism's heterogeneity and the newness of the CNV field, very little is known about the frequency of any specific CNVs in relation to autism.
Research groups from Toronto, Chicago and Boston found that CNV in a specific region of chromosome 16 are associated with about 1-2 percent of the autism cases. This chromosomal region (16p11) contains about 25 genes, several of which appear to be involved in brain function and neurodevelopment, and individuals with deletions in this region are more likely to develop autism. While in a few rare individuals the presence of Ch16p11 CNV is not associated with autism, their overall absence from multiple independent control populations and the replication of the finding by three laboratories using different study groups strongly support its role as a genetic risk factor for autism.
The identification of Ch16p11 CNV and others like it have important implications for autism diagnosis and treatment. Individuals screened positive for this CNV may be considered at risk for autism, but like hypertension, diabetes, and other complex diseases, the risk associated with this genetic anomaly may be modulated by the environment as well as changed through appropriate intervention. Since genetic risk factors can be identified very early in life, our knowledge of them may help us mitigate the severity of autism.
Kumar RA, et al. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet. 2008 Feb 15;17(4):628-38. Epub 2007 Dec 21.
Marshall CR, et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008 Feb;82(2):477-88. Epub 2008 Jan 17.
Weiss LA, et al.; Autism Consortium. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008 Feb 14;358(7):667-75. Epub 2008 Jan 9.