Epigenetics And Autism

New Studies on Autism confirms environmental stress is significant activator for disease

Reviewed 2017

Reviewed 2011

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Layman's Abstract

Growing irrefutable evidence pointing towards Autism being an expression of gene pathways as a result of external influence from outside the body. The ratio of what percentage of external influence verses inherited genetics, is identified by several studies (below) as 90% external, leaving 10% at fault of inherited genetics. The numbers of studies completed and continuing along these lines is staggering, considering that many people still believe it is a result of genetic inheritance.

https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2012/autism-progress.shtml

Post by Former NIMH Director Thomas Insel: Autism Progress

By Thomas Insel on December 26, 2012

Every year the Interagency Autism Coordinating Committee (IACC) updates its Strategic Plan for Autism Spectrum Disorder Research, identifying progress and new opportunities across the range of autism spectrum disorder (ASD) research. Each year this task gets more difficult. In 2012, the speed of progress was so rapid that each draft of the Plan was out of date by the time the IACC reviewed it. The sheer volume of research was overwhelming. According to PubMed, there were over 1,000 ASD papers related to genetics or brain imaging since January 2011 – more than three times the number of papers from the same interval a decade ago.

Abstract

Epigenetics is emerging as one of the most dynamic and vibrant biomedical areas. Multiple lines of evidence confirm that inherited genetic changes alone cannot fully explain all phenotypic characteristics of live organisms, and additional factors, which are not encoded in the DNA sequence, are involved. The contribution of non-genetic factors is perhaps best illustrated by monozygotic twins, which, despite sharing nearly identical DNA sequences, are often discordant for diseases they develop. Even when twins develop the same condition, they may experience different clinical manifestations or clinical onset at different ages. Epigenetic mechanisms explain how a zygote can differentiate into >220 different cell types that form an adult organism and, with rare exceptions, share the same DNA. Increasingly, epigenetic factors emerge, in addition to genetic ones, as important contributors to carcinogenesis. Epigenetic modifications also explain the biological impact of environmental factors, including chemical and dietary compounds, physical agents, pathogens linked to cancer, and social–emotional interactions. Unlike genetic changes, epigenetic changes are reversible, a characteristic that opens unprecedented therapeutic avenues, exemplified by the first epigenetic drugs that were recently approved. Understanding the combined contribution of genetic and epigenetic factors to gene expression will be essential to dissect the biological networks shaping development and disease, and to develop a new array of prophylactic, diagnostic, and therapeutic applications.

© 2012 by National Association of Biology Teachers. All rights reserved. Request permission to photocopy or reproduce article content at the University of California Press’s Rights and Permissions Web site at http://www.ucpressjournals.com/reprintinfo.asp. https://www.jstor.org/stable/ordercopyofstudy

https://www.ncbi.nlm.nih.gov/pmc/articles/EpigeneticFindingsInAutism

"The term epigenetics was first coined in the 1940s by British embryologist and geneticist Conrad Waddington, who described it as: “the interactions of genes with their environment, which bring the phenotype into being” [17]. Our present knowledge enhances this earlier understanding, and epigenetics now evaluates the alteration of DNA transcription via variations in DNA methylation and histone modifications, but without alterations in the DNA sequence. These variants represent the epigenome, which in turn will be reflected in the transcriptome: that portion of the DNA which is being actively transcribed into RNA. However, it is noteworthy to consider that the non-coding RNA represents over 90% of the transcripts in most cells. Regions of DNA that do not code for proteins (i.e., intergenic regions) can be actively transcribed and participate in the genes regulation, and is known as non-coding RNA. Epigenetic factors can impact large-scale “omics”-type cellular processes: transcriptome, RNAome, proteome and metabalome [,]."

Click on this link: to read in more detail:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137275/

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Figure 1.

Epigenetic and genetic alterations of DNA. Epigenetic changes, including methylation and hydroxymethylation of cytosines and other nucleotides, chromatin condensation and opening, and the shortening and lengthening of telomeres, are reversible and thus provide a capacity to rapidly adapt to changes in the environment (lightning bolt). Genetic changes, including DNA substitutions, insertion/deletions (not shown), recombination, and viral integration/transposition, are primarily irreversible. For example, it is rare that a second point mutation exactly reverses a mutation or that a second recombination event occurs at precisely the same location as a previous recombination event. The magnitude of reversibility is shown by the length of the blue arrow.

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Figure 2.

DNA epigenetic modifications and their editors. The 2 best-known DNA modifications are methylation (5m) and hydroxymethylation (5hm). Other nucleotides can be modified, but DNA methylation preferentially occurs on cytosine nucleotides adjacent to guanine nucleotides, a modification catalyzed by DNA methyltransferases (DNMTs). DNA methylation generally silences transcription whereas hydroxymethylation generally activates transcription, although exceptions are now widely known, and seem to be related to the genomic feature (e.g., promoter, intragenic region, 3’ UTR) in which the epigenetic modification is located.

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Figure 3.

The histone code and its modifiers. The basic functional unit of chromatin is the nucleosome, which is composed of 147bp of DNA wrapped tightly around an octamer of histone proteins (H2A, H2B, H3, and H4). Histone tails project from nucleosomes and are subject to posttranslational modifications, including methylation (Me), acetylation (Ac), phosphorylation (P), phosphoacetylation (p-Ac), ubiquitination (Ub), and ADP-ribosylation (ADP-R), in different combinations. Local combinations of differentially modified histone proteins form histone codes. Histone codes enhance or inhibit transcription by recruiting enzymes that catalyze the opening or condensing of chromatin, thus making the DNA more or less accessible to transcription factors and additional regulatory factors that modify transcription. The histone code is edited by an ensemble of enzymatic writers, erasers, and readers. Writers add covalent modifications. Erasers catalyze removal of modifications. Readers recognize and bind specific motifs.