Epigenetic Influences upon Autism Spectrum Disorder

Abstract

Epigenetic alterations underlying the neurodevelopmental aspects of Autism Spectrum Disorders (ASD) are emerging as important risk factors for disease pathogenesis. These influences present the case that gene expressions may sustain alterations at higher levels of complexity than modifications in the DNA sequence. Part-and-parcel and central to this notion, the phenomenon involves essential environmental impacting upon the gametes before conception. Genomic imprinting may be described as a process of silencing genes through DNA methylation with major effects upon placental biology, brain and functional development and the etiopathogenesis of neuropsychiatric disorders. It offers an epigenetic phenomenon through which some genes may be expressed in a manner that presents parent-of-originspecificity and may be viewed as an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins. If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed. If the allele from the mother is imprinted, then only the allele from the father is expressed. Forms of genomic imprinting have been demonstrated in fungi, plants and mammals with over 150 imprinted in laboratory rodents [1,2]. Through forces of epigenetics, environmental factors, such as endocrine-disrupting agents and mental stress in early life, can alter epigenetic status and gene expression. In this regard, the epigenome, especially in the context of DNA methylation, provides a critical gene expression regulatory mechanism through which the normal and the pathologically anomalous brain development may proceed. Genomic imprinting and other epigenetic mechanisms involving environmental pressures have been found exert consequences and impinge on offspring neurodevelopment and the aberrant development of autism spectrum disorders [3]. ASDs offer an instance of the life-long existing disorders, such as attention-deficit hyperactivity disorder (AHDH), with a high level of heritability and complex conditions genetically, and despite several highly penetrant mutations in multiple genes being identified, these account for the etiology of less than one third of cases. The disorder is characterized by an impaired social communication profile and often repetitive, stereotyped behavior with evidence of regional brain dysconnectivity.