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Risk factors for autism: translating genomic discoveries into diagnostics

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Abstract

Autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in communication and reciprocal social interaction, and the presence of restricted and repetitive behaviors. The spectrum of autistic features is variable, with severity of symptoms ranging from mild to severe, sometimes with poor clinical outcomes. Twin and family studies indicate a strong genetic basis for ASD susceptibility. Recent progress in defining rare highly penetrant mutations and copy number variations as ASD risk factors has prompted early uptake of these research findings into clinical diagnostics, with microarrays becoming a ‘standard of care’ test for any ASD diagnostic work-up. The ever-changing landscape of the generation of genomic data coupled with the vast heterogeneity in cause and expression of ASDs (further influenced by issues of penetrance, variable expressivity, multigenic inheritance and ascertainment) creates complexity that demands careful consideration of how to apply this knowledge. Here, we discuss the scientific, ethical, policy and communication aspects of translating the new discoveries into clinical and diagnostic tools for promoting the well-being of individuals and families with ASDs.

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Acknowledgments

We thank Janet A. Buchanan for her contributions to all aspects of this manuscript as well as Anath C. Lionel for his technical assistance. Much of the content of this review was drawn from conversations at a meeting called ‘Genetic Risk Factors for Autism: Translating Discoveries into Diagnostics’ held 1–2 September 2010 in Toronto. We wish to thank Andy Shih for initiating and helping to shape the Toronto meeting. The sponsor organizations were Autism Speaks, Autism Speaks Canada, the Canadian Institutes of Health Research (CIHR), Institute of Genetics and Institute of Neurosciences, Mental Health and Addiction, Genome Canada, the Hospital for Sick Children, the Medical Research Council (UK), the National Institute of Child Health and Human Development, NeuroDevNet, the Ontario Genomics Institute, the Ontario Ministry of Research and Innovation, the Robarts Institute (Dr. Robert Hegele-Genome Canada grant), The Centre for Applied Genomics and the University of Toronto McLaughlin Centre. S.W.S. holds the GlaxoSmithKline-CIHR Endowed Chair in Genetics and Genomics at the Hospital for Sick Children and University of Toronto.

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  1. McLaughlin Centre and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, M5G 1L7, Canada

    Stephen W. Scherer

  2. Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada

    Stephen W. Scherer

  3. Autism Speaks and Department of Psychiatry, University of North Carolina, Chapel Hill, 4120 Bioinformatics Building, 130 Mason Farm Road, Campus Box 3366, Chapel Hill, NC, 27599-3366, USA

    Geraldine Dawson

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  1. Stephen W. Scherer
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Correspondence to Stephen W. Scherer.

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Scherer, S.W., Dawson, G. Risk factors for autism: translating genomic discoveries into diagnostics. Hum Genet 130, 123–148 (2011). https://doi.org/10.1007/s00439-011-1037-2

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  • DOI: https://doi.org/10.1007/s00439-011-1037-2

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