Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism

Abstract

Autism spectrum disorder (ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones. autism spectrum disorder, genetic architecture, genomic disorder, gene mutation, copy number variants, single nucleotide variants, genetic pathways, epigenetic influence, DNA methylation, chromatin remodeling, long non-coding RNAs, environment exposure, immune dysregulation, gastrointestinal microbiota Citation:Yu L, Wu YM, Wu BL. Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism. Sci China Life Sci, 2015, 58: 958-967,

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…Thalidomide Prenatal use also associated with autistic features [134][135][136] The Dexamethasone treatment during pregnancy in mice ( gestational days [16][17][18][19] increases astrocyte density in the adult offspring Substantia nigra and ventral tegmental area in both males and females and increases tyrosine hydroxylase immunoreactivity in these areas in both sexes, but with a more pronounced effect on Tyrosine hydroxylase positive cell density in females [144]. Ethanol Prenatal use associated with autism [135,145] In utero exposure of mouse progeny to alcohol or methamphetamine causes postnatal neurodevelopmental deficits .…”

“…Epigenetic changes have been observed in autism, and these too may be related to environmental agents [12,13] as reported for Bisphenol A and heavy metals (see Table 1) and for flame retardants and other endocrine disruptors, including soy formula and phytoestrogens such as genistein [14][15][16] and also for other nutritional agents such as Vitamin D and folic acid [17][18][19]. However, epigenetics is not the subject of this study, which is limited to the 206 autism-related polymorphic genes reported from gene association studies.…”

Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

“…For example, in males with ASD, attention deficit‐hyperactivity disorder (ADHD) is more prevalent and repetitive behaviors are more severe than females . The manifestation of these deficient behaviors in ASD likely arises from complex interactions between genes and environment that result in improper brain development …”

“…[13][14][15] The manifestation of these deficient behaviors in ASD likely arises from complex interactions between genes and environment that result in improper brain development. [16][17][18]…”

Integrative genomic analyses for identification and prioritization of long non-coding RNAs associated with autism

“…ASD risk genes include hundreds of protein-coding genes most commonly affected by copy number variants (CNVs) which can perturb gene expression; however, each known ASD risk gene only accounts for less than a few percent of ASD cases [2,3]. Most of these ASD risk genes function in several biological pathways, such as synaptic transmission, transcriptional regulation, immune response and chromatin remodeling [4–7].…”