Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan 24;13(2):207.
doi: 10.3390/genes13020207.

Mutational Landscape of Autism Spectrum Disorder Brain Tissue

Marc Woodbury-Smith  1 , Sylvia Lamoureux  2 , Ghausia Begum  3 , Nasna Nassir  3 , Hosneara Akter  4 , Darren D O'Rielly  5 , Proton Rahman  5 , Richard F Wintle  2 , Stephen W Scherer  2   6   7 , Mohammed Uddin  3   8
Affiliations

Mutational Landscape of Autism Spectrum Disorder Brain Tissue

Marc Woodbury-Smith et al. Genes (Basel). .

Abstract

Rare post-zygotic mutations in the brain are now known to contribute to several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due to the limited availability of brain tissue, most studies rely on estimates of mosaicism from peripheral samples. In this study, we undertook whole exome sequencing on brain tissue from 26 ASD brain donors from the Harvard Brain Tissue Resource Center (HBTRC) and ascertained the presence of post-zygotic and germline mutations categorized as pathological, including those impacting known ASD-implicated genes. Although quantification did not reveal enrichment for post-zygotic mutations compared with the controls (n = 15), a small number of pathogenic, potentially ASD-implicated mutations were identified, notably in TRAK1 and CLSTN3. Furthermore, germline mutations were identified in the same tissue samples in several key ASD genes, including PTEN, SC1A, CDH13, and CACNA1C. The establishment of tissue resources that are available to the scientific community will facilitate the discovery of new mutations for ASD and other neurodevelopmental disorders.

Keywords: autism spectrum disorder (ASD); brain tissue; exome sequencing; germline; post-zygotic; somatic.

PubMed Disclaimer

Conflict of interest statement

S.W.S. is on the Scientific Advisory Committees of Deep Genomics, Population Bio, and is an Academic Consultant for the King Abdulaziz University. The authors declare no conflict of interest.

References

    1. Woodbury-Smith M., Scherer S.W. Progress in the genetics of autism spectrum disorder. Dev. Med. Child Neurol. 2018;60:445–451. doi: 10.1111/dmcn.13717. - DOI - PubMed
    1. Yuen R.K.C., Merico D., Bookman M., Howe J.L., Thiruvahindrapuram B., Patel R.V., Whitney J., Deflaux N., Bingham J., Wang Z., et al. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat. Neurosci. 2017;20:602–611. doi: 10.1038/nn.4524. - DOI - PMC - PubMed
    1. Zarrei M., Burton C.L., Engchuan W., Young E.J., Higginbotham E.J., MacDonald J.R., Trost B., Chan A.J.S., Walker S., Lamoureux S., et al. A large data resource of genomic copy number variation across neurodevelopmental disorders. NPJ Genom. Med. 2019;4:26. doi: 10.1038/s41525-019-0098-3. - DOI - PMC - PubMed
    1. Trost B., Engchuan W., Nguyen C.M., Thiruvahindrapuram B., Dolzhenko E., Backstrom I., Mirceta M., Mojarad B.A., Yin Y., Dov A., et al. Genome-wide detection of tandem DNA repeats that are expanded in autism. Nature. 2020;586:80–86. doi: 10.1038/s41586-020-2579-z. - DOI - PMC - PubMed
    1. Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. Mol. Autism. 2017;8:21. doi: 10.1186/s13229-017-0137-9. - DOI - PMC - PubMed