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ORIGINAL RESEARCH article
Front. Bioinform.
Sec. Evolutionary Bioinformatics
Volume 5 - 2025 | doi: 10.3389/fbinf.2025.1532981
This article is part of the Research Topic Evolution of Short Genomic Regions: Discoveries, Methods, and Challenges View all 3 articles
Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients
Provisionally accepted
Nicolina Sciaraffa 1
Daniele Santoni 2
andrea li greci 1
swonild ilenia genovese 3
Claudia Coronnello 1
Walter Arancio 4*- 1 Advanced data Analysis group, Ri.MED Foundation, Palermo, Sicily, Italy
- 2 Institute for System Analysis and Computer Science "Antonio Ruberti", National Research Council (CNR), Roma, Lazio, Italy
- 3 INDEPENDENT, Palermo, Italy
- 4 Institute for Biomedical Research and Innovation, National Research Council (CNR), Roma, Italy
Autism spectrum disorder (ASD) is a brain developmental disability with a not-fully clarified etiogenesis. Current ASD research largely focuses on coding regions of the genome, but up to date much less is known about the contribution of non-coding elements to ASD risk.The non-coding genome is largely made of DNA repetitive sequences (RS). Although RS were considered slightly more than "junk DNA", today RS have a recognized role in almost every aspect of human biology, especially in developing human brain. Our aim was to test if RS transcription may play a role in ASD.Global RS transcription was firstly investigated in postmortem dorsolateral prefrontal cortex of 13 ASD patients and 39 matched controls. Results were validated in independent datasets.AmnSINE1 was the only RS significantly downregulated in ASD specimens.The role of AmnSINE1 in ASD has been investigated at multiple levels, showing that the 1416 genes containing AmnSINE1 are associated with nervous system development and autism susceptibility. This has been confirmed in a different experimental setting, such as in organoid models of the human cerebral cortex, harboring different ASD causative mutations. AmnSINE1 related genes are transcriptionally co-regulated and are involved not only in brain formation but can specifically be involved in ASD development. Looking for a possible direct role of AmnSINE1 non-coding transcripts in ASD, we report that AmnSINE1 transcripts may alter the miRNA regulatory landscape for genes involved in neurogenesis.Our findings provide preliminary evidence supporting a role for AmnSINE1 in ASD development.
Keywords: Autism Spectrum Disorder, Repetitive Sequences, Neurogenesis, MicroRNAs, Embryonic Development, Autistic Disorder, Nervous System
Received: 22 Nov 2024; Accepted: 24 Mar 2025.
Copyright: © 2025 Sciaraffa, Santoni, li greci, genovese, Coronnello and Arancio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Walter Arancio, Institute for Biomedical Research and Innovation, National Research Council (CNR), Roma, Italy
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