News

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterised by impairments in social interaction, in communication and by the occurrence of repetitive or stereotype behaviour. The prevalence of ASD among children is currently estimated to be around 1 in 100 in the UK (see National Autistic Society website ) and US (see Centers for Disease Control and Prevention website ).

Autism spectrum disorders are known to be highly heritable (see previous news), although they are multi-factorial conditions that arise from complex interactions between multiple genetic and environmental factors. The genetic basis for ASD is not well understood, but recent research has implicated some specific genetic variants, including rare de novo germline mutations or copy number variations (see previous news ) and more common mutations. From an etiological point of view, autism is a genetically heterogeneous spectrum of disorders, meaning that patients with autism can have different underlying genetic causes.

Earlier this year, a combined analysis of a series of genome-wide association studies (GWAs) found significant association with autism for a single SNP located between two known genes on chromosome 5p14 (see previous news ). Now the Harvard-based Autism Consortium has published a new GWA [Weiss LA et al. (2009) Nature. 261(7265):802-8] .

The study was conducted using half a million genome-wide SNPs in a common set of 1,031 multiplex autism families (that is, families with multiple autistic children), and identified two novel regions of linkage, 6q27 and 20p13, although only the latter formally exceeded the threshold for genome-wide significance. Though initial analysis did not yield significant associations, subsequent genotyping in additional families revealed a SNP on chromosome 5p15 which was significantly associated with autism. The locus of the SNP was found to be between two known genes, the expression of one being reduced in the brains of autistic patients. However, the researchers observed no association at locus 5p14 as found in the earlier GWA study.

Comment: The genetic basis of autism spectrum disorders remains unclear, including the relative contributions of rare mutations with major effects and multiple common mutations with individually minor effects. Recent GWA studies are providing further evidence of the involvement of several genes which may interact with each other and with environmental factors to cause autism. However, achieving a clear picture of the elusive and apparently highly complex genetic and environmental etiology of ASD is likely to remain a long way off.