Pathogenesis of Autism: A Patchwork of Genetic Causes

Abstract

Autism spectrum disorders (ASDs) are relatively infrequent but are devastating developmental conditions characterized by marked deficiencies in social, communicative and other behavioral domains. It has been known for a substantial period of time that these disorders are genetic in nature. However, elucidating the specific mechanisms of these disorders has been difficult. A major reason for such difficulty is the recognized genetic heterogeneity of ASDs. Specifically, many genetic mechanisms related to structural variations in the genome have been reported as possible genetic causes of these disorders. This review briefly exemplifies these genetic mechanisms, presents a concise overview of the evidence for the genetic basis of ASDs and provides an appraisal of the specific structural genetic variants thought to contribute to the pathogenesis of these complex disorders.

Keywords:

• common genetic variants
• copy number variation
• familial risk
• heritability
• rare genetic variants

Financial & competing interests disclosure

The preparation of this article was supported in part by research grants from the US National Institutes of Health (P50 MH81756 to Dr Ami Klin) and from the Autism Speaks Foundation (to Dr Flora Vaccarino). Grantees undertaking such projects are encouraged to express their professional judgment freely. Therefore, this article does not necessarily reflect the position or policies of the National Institutes of Health or the Autism Speaks Foundation, and no official endorsement should be inferred. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgement

Elena L Grigorenko is thankful to Ms Mei Tan for her editorial assistance and to the anonymous reviewers for their critical and helpful comments.

Additional information

Funding

The preparation of this article was supported in part by research grants from the US National Institutes of Health (P50 MH81756 to Dr Ami Klin) and from the Autism Speaks Foundation (to Dr Flora Vaccarino). Grantees undertaking such projects are encouraged to express their professional judgment freely. Therefore, this article does not necessarily reflect the position or policies of the National Institutes of Health or the Autism Speaks Foundation, and no official endorsement should be inferred. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.