Copy numbers count for autism

Mind image: Autism is characterized by a triad of impairments to social behaviour, communication and imagination. One school of thought claims that individuals with autism lack a ‘theory of mind’, implying that they don’t have a concept of themselves and other people as distinct, thinking personalities with their own beliefs, desires, etc. (Photo: N.H. Gross.) Autism, a neurodevelopmental disorder defined by the triad of impairments affecting social behaviour, communication, and imagination, has apparently become tenfold more prevalent in the last four decades (Curr. Biol. (2002), 12, R42). There is clear evidence for genetic causation but, of the around 80 genes that have been linked to autism or to the more widely defined autistic spectrum disorders (ASDs), none accounts for a large proportion of cases, and none has a clearly established causation mechanism as yet. Only in the relatively rare cases where autism is a side effect of a chromosomal aberration, such as fragile X syndrome, can the causes be pinned down with some certainty (J.C. Darnell et al. Cell (2011), 146, 247–261). Since 2007, several studies have found evidence suggesting that rare copy number variations (CNVs) are linked to ASDs. Genome sequencing has shown that CNVs, typically involving the duplication or deletion of more than 1,000 DNA nucleotides, are quite common in the human genome, and those that are widespread in the population are believed to be harmless, although genome studies of cancer cells have also detected CNVs that are under suspicion of causing or helping the cancer. Researchers have estimated that the genomes of any two unrelated people will differ with respect to copy number in around 0.4% of the total number of nucleotides. In 2010, the Autism Genome Project Consortium reported that in a sample of nearly 1,000 people with ASDs, compared with a group of matched controls, there was a significantly higher burden of rare CNVs involving functional genes. The researchers conclude that CNVs are likely to play a role in causing autism and other ASDs (Nature (2010), 466, 368–372).