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New mutations linked to sporadic autism spectrum disorder
| Study: | Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations |
| By: | O'Roak B.J. et al. (16 authors total) |
| In: | Nature Genetics |
| Link: | http://dx.doi.org/doi:10.1038/ng.835 |
Previous studies on autism spectrum disorder (ASD) have suggested that sporadic cases may be caused by new (de novo) mutations, as opposed to inherited mutations. The aim of this study was to identify specific de novo mutations in sporadic ASD cases.
The genomes of families with sporadic ASD (i.e. parents and child) as well as controls were analysed to identify genetic variants unique to sporadic ASD. ArrayCGH was used to identify large copy number variants followed by exome sequencing. Comparison with parental sequences as well as data from the dbSNP database, 1000 Genomes Project and other genome sequences was used to filter out variants not unique to children with ASD.
ArrayCGH did not identify any large de novo copy number changes except in one individual, which was not thought to be causal for ASD. In total 21 de novo changes were identified in individuals with ASD, many within gene coding regions. Eleven mutations were predicted to affect protein function. In four cases the mutations were within genes that have previously been shown to be associated with autism, epilepsy and intellectual disability, suggesting they may be the causal mutations. However, the researchers also identified rare inherited variants that may be linked with autism in these individuals.
New mutations that may be associated with autism can be identified through trio studies. However, inherited variants were also found, suggesting that other genetic factors may impact disease symptoms or severity, and more research is needed to understand how different genetic and environmental factors interact.
Research has shown that autism spectrum disorders have a strong heritable component, however, identification of the genetic factors involved has been difficult (see previous news). This paper contributes to our understanding of the genetic basis of autism, but also highlights the need for a better understanding of the biology as well as the role of environmental factors in order to better understand this multifactorial condition.