Butterfly Effect May Explain Risk for Autism Spectrum Disorder

Author: RIKEN – Contact: riken.jp/en/
Published: 2024/01/27
Peer Reviewed: Yeah – Post type: Experimental study
Table of Contents: SummaryMain articleAbout the Author

Synopsis: The researchers analyzed whole genome sequencing data and found that de novo promoter mutations in TADs containing autism spectrum disorder (ASD) genes were specifically associated with the disease. They examined the genetics of autism spectrum disorder (ASD) by analyzing mutations in the genomes of individuals and their families. The researchers analyzed an extensive data set of more than 5,000 families, making it one of the largest genome-wide studies of ASD in the world to date.

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Main summary

Researchers at the RIKEN Center for Brain Sciences (CBS) examined the genetics of autism spectrum disorder (ASD) by analyzing mutations in the genomes of individuals and their families. They found that a special type of genetic mutation works differently than typical mutations in how it contributes to the condition. Essentially, due to the three-dimensional structure of the genome, mutations can affect neighboring genes that are linked to ASD, which explains why ASD can occur even without direct mutations in ASD-related genes.

ASD is a group of conditions characterized in part by repetitive behaviors and difficulties in social interaction. Although it is hereditary, the genetics of its heritability are complex and only partially understood. Studies have shown that the high degree of heritability cannot be explained simply by looking at the part of the genome that codes for proteins. Rather, the answer could lie in non-coding regions of the genome, particularly promoters, the parts of the genome that ultimately control whether proteins are made or not. The team led by Atsushi Takata of RIKEN CBS examined “de novo” genetic variants (new mutations that are not inherited from parents) in these parts of the genome.

The researchers analyzed an extensive data set of more than 5,000 families, making it one of the largest genome-wide studies of ASD in the world to date. They focused on TADs, three-dimensional structures of the genome that allow interactions between different nearby genes and their regulatory elements. They found that de novo mutations in promoters increased the risk of ASD only when the promoters were located in TADs containing ASD-related genes. Because they are close and on the same TAD, these de novo mutations may affect the expression of ASD-related genes. In this way, the new study explains why mutations can increase the risk of ASD even when they are not located in protein-coding regions or in the promoters that directly control the expression of genes related to ASD.

“Our most important discovery was that de novo mutations in TAD promoter regions containing known ASD genes are associated with ASD risk, and this is likely mediated through interactions in the three-dimensional structure of the genome,” Takata says.

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In this study, researchers analyzed large ASD whole-genome sequencing data and found that de novo promoter mutations in TADs containing ASD genes were specifically associated with the disease. Image credit: RIKEN.

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To confirm this, the researchers edited the DNA of the stem cells using the CRISPR/Cas9 system, making mutations in specific promoters. As expected, they observed that a single genetic change in a promoter caused alterations in an ASD-associated gene within the same TAD. Because numerous genes linked to ASD and neurodevelopment were also affected in the mutant stem cells, Takata likens the process to a genomic “butterfly effect” in which a single mutation deregulates scattered disease-associated genes. in distant regions of the genome.

Takata believes that this finding has implications for the development of new diagnostic and therapeutic strategies.

“At a minimum, when assessing an individual’s risk for ASD, we now know that we should look beyond ASD-related genes when conducting genetic risk assessment and focus on entire TADs that contain ASD-related genes,” Takata explains. “In addition, an intervention that corrects aberrant promoter-enhancer interactions caused by a promoter mutation may also have therapeutic effects on ASD.”

More research involving more families and patients is crucial to better understand the genetic roots of ASD.

“By expanding our research, we will gain a better understanding of the genetic architecture and biology of ASD, leading to clinical management that improves the well-being of affected individuals, their families, and society,” says Takata.

This study appeared in the scientific journal Cell Genomics on January 26, 2024.

Attribution/Source(s):

This peer-reviewed article related to our Autism Facts section was selected for publication by Disabled World editors because of its likely interest to our readers in the disability community. Although content may have been edited for style, clarity, or length, the article “The butterfly effect may explain the risk of autism spectrum disorder” was originally written by RIKEN and published by Disabled-World.com on 01/27/2024. If you require further information or clarification, you can contact RIKEN at riken.jp/en/. Disabled World makes no warranties or representations in connection therewith.

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Permanent link: Butterfly Effect May Explain Risk of Autism Spectrum Disorder

Cite this page (APA): RIKEN. (2024, January 27). The butterfly effect may explain the risk of autism spectrum disorder. Disabled world. Retrieved January 28, 2024 from www.disabled-world.com/health/neurology/autism/butterfly-effect.php

Disabled World provides general information only. The materials presented are never intended to be a substitute for qualified professional medical care. Any third party offers or advertisements do not constitute an endorsement.

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