Whole exome-sequencing studies have identified a large number of mutations associated with significantly increased risk of autism spectrum disorder (ASD).
Published in the journal Nature, three different papers report the findings of hundreds of independent de novo mutations in sporadic (non-inherited) cases of ASD - as identified by exome sequencing. The papers were the work of teams led by Evan Eichler of the University of Washington in Seattle, Mark Daly of the Broad Institute at Harvard and MIT, and Matthew State of Yale University.
The ASD-linked mutations were located widely across the protein-coding areas of the genome, with those that affected brain development being the most apparently harmful. All the papers supported a polygenic model of disease, with contributions from multiple genetic variants likely to contribute to the development of disease in an individual. One suggested that some mutations could confer an increased ASD risk of 5-20 fold.
The paper by Eichler et al. also looked at the source of the new mutations, and found they arose four times more frequently in the father’s sperm cells than the mother’s egg cells, with the probability of mutations rising with increasing paternal age, which could account for the increased risk for ASD observed in the children of older fathers.
Comment: ASD, whilst having a relatively strong genetic component compared with many diseases, is clearly caused by a highly complex and varied combination of genetic factors; Kevin Mitchell of the Smurfit Institute of Genetics at Trinity College Dublin told the Telegraph: "These studies reinforce the fact that autism is not one disorder - not clinically and not genetically either". There are environmental influences to consider, too – research published this week suggests that obesity and diabetes among pregnant mothers increases risk, for instance (see BBC news). There is still a long road ahead for research into ASD.