Rare genetic variations implicated in autism

July 2010

Autism spectrum disorders (ASDs) are a group of developmental disorders that are characterised by difficulties in social interaction, communication, and understanding other people’s emotions, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in their cognitive development, which can range from being above average to having marked intellectual disability. Studies of twins and families have shown that these disorders have a strong genetic basis (the disorder is 90% heritable), but the genetic changes responsible are varied and remain largely unknown. Single gene mutations or large rearrangements in chromosomes are responsible for a minority of cases of ASD.  However, stretches of DNA – perhaps including one gene or perhaps including 10–20 genes – can become lost or duplicated in our genomes.  In a new study reported in the journal Nature, the occurrence of these so-called ‘copy number variants’ was analysed in a large cohort of people with ASD using technology that allows analysis of the whole genome.  The study was conducted by the Autism Genome Project Consortium (AGPC) - an international collaboration involving researchers from institutions across the USA, Canada and Europe, including UK researchers at Oxford, Newcastle, Manchester, and the Institute of Psychiatry, London.  At Newcastle Dr Jeremy Parr from the Institute of Neuroscience and Professor Ann le Couteur and Professor Helen McConachie from the Institute of Health and Society were among the international team which compared the incidence of rare copy number variants in 996 people with ASD and 1287 unaffected people, all with European ancestry.  They found that people with ASD had, on average, 19% more copy number variants that disrupted genes than in the control group.  Many of the lost or duplicated DNA chunks occurred in genetic regions already implicated in autism. But they were also found in many new gene regions, suggesting these genes offer new biological pathways that might be involved in autism spectrum disorders.  The results suggest that this type of rare genetic variation accounts for a significant portion of the genetic basis of autism.  In future, the ability to detect genetic features that are strongly associated with ASD may help in the early diagnosis and treatment of this common developmental disorder.

Functional impact of global rare copy number variation in autism spectrum disorders.  Pinto D et al (2010) Nature  466: 368-372 (PubMed abstract: http://www.ncbi.nlm.nih.gov/pubmed/20531469)

published on: 2nd July 2010