Reference database helps narrow list of mutations suspected in ASD
Comparing list of suspect de novo mutations to ExAC reference exomes helps researchers refine the set of mutations thought to play a role in neurodevelopmental disorders
By Veronica Meade-Kelly
Credit: Image by Broad Communications/iStockPhoto
Autism spectrum disorder (ASD) is a group of complex conditions that can be heritable, or can stem from de novo mutations (single-letter alterations in the genetic code that are not inherited). While genetic sequencing studies have, in recent years, turned up many de novo mutations suspected of being associated with ASD, it has been unclear which of those mutations actually contribute to risk for the disorder.
The team, which was led by senior author Mark Daly and first author Jack Kosmicki, found that roughly one third of the de novo mutations previously associated with ASD, intellectual disability, or developmental delay are, in fact, found in the general population and thus do not contribute to neurodevelopmental risk. Eliminating these suspect mutations from subsequent analyses is helping to paint a clearer picture of genetic contributions to ASD. The work also shows the value of using large reference databases like ExAC to evaluate the potential pathogenicity of candidate mutations, even in complex diseases.