Imbalanced genomic imprinting in brain development: an evolutionary basis for the aetiology of autism

Abstract

We describe a new hypothesis for the development of autism, that it is driven by imbalances in brain development involving enhanced effects of paternally expressed imprinted genes, deficits of effects from maternally expressed genes, or both. This hypothesis is supported by: (1) the strong genomic-imprinting component to the genetic and developmental mechanisms of autism, Angelman syndrome, Rett syndrome and Turner syndrome; (2) the core behavioural features of autism, such as self-focused behaviour, altered social interactions and language, and enhanced spatial and mechanistic cognition and abilities, and (3) the degree to which relevant brain functions and structures are altered in autism and related disorders. The imprinted brain theory of autism has important implications for understanding the genetic, epigenetic, neurological and cognitive bases of autism, as ultimately due to imbalances in the outcomes of intragenomic conflict between effects of maternally vs. paternally expressed genes.