Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients
AimsAutism 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 l...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Bioinformatics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbinf.2025.1532981/full |
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| author | Nicolina Sciaraffa Daniele Santoni Andrea Li Greci Swonild Ilenia Genovese Claudia Coronnello Walter Arancio |
| author_facet | Nicolina Sciaraffa Daniele Santoni Andrea Li Greci Swonild Ilenia Genovese Claudia Coronnello Walter Arancio |
| author_sort | Nicolina Sciaraffa |
| collection | DOAJ |
| description | AimsAutism 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.MethodsGlobal RS transcription was firstly investigated in postmortem dorsolateral prefrontal cortex of 13 ASD patients and 39 matched controls. Results were validated in independent datasets.ResultsAmnSINE1 was the only RS significantly downregulated in ASD specimens. The role of AmnSINE1 in ASD has been investigated at multiple levels, showing that the 1,416 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.ConclusionOur findings provide preliminary evidence supporting a role for AmnSINE1 in ASD development. |
| format | Article |
| id | doaj-art-e9cc57273958404a89dbbccca9b18315 |
| institution | OA Journals |
| issn | 2673-7647 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioinformatics |
| spelling | doaj-art-e9cc57273958404a89dbbccca9b183152025-08-20T02:08:03ZengFrontiers Media S.A.Frontiers in Bioinformatics2673-76472025-04-01510.3389/fbinf.2025.15329811532981Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patientsNicolina Sciaraffa0Daniele Santoni1Andrea Li Greci2Swonild Ilenia Genovese3Claudia Coronnello4Walter Arancio5Advanced Data Analysis Group, Ri. MED Foundation, Palermo, ItalyInstitute for System Analysis and Computer Science “Antonio Ruberti”, National Research Council of Italy (IASI-CNR), Rome, ItalyAdvanced Data Analysis Group, Ri. MED Foundation, Palermo, ItalyIndependent Researcher, Palermo, ItalyAdvanced Data Analysis Group, Ri. MED Foundation, Palermo, ItalyInstitute for Biomedical Research and Innovation, National Research Council of Italy (IRIB-CNR), Palermo, ItalyAimsAutism 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.MethodsGlobal RS transcription was firstly investigated in postmortem dorsolateral prefrontal cortex of 13 ASD patients and 39 matched controls. Results were validated in independent datasets.ResultsAmnSINE1 was the only RS significantly downregulated in ASD specimens. The role of AmnSINE1 in ASD has been investigated at multiple levels, showing that the 1,416 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.ConclusionOur findings provide preliminary evidence supporting a role for AmnSINE1 in ASD development.https://www.frontiersin.org/articles/10.3389/fbinf.2025.1532981/fullautism spectrum disorderrepetitive sequencesneurogenesismicroRNAembryonic developmentautistic disorder |
| spellingShingle | Nicolina Sciaraffa Daniele Santoni Andrea Li Greci Swonild Ilenia Genovese Claudia Coronnello Walter Arancio Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients Frontiers in Bioinformatics autism spectrum disorder repetitive sequences neurogenesis microRNA embryonic development autistic disorder |
| title | Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients |
| title_full | Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients |
| title_fullStr | Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients |
| title_full_unstemmed | Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients |
| title_short | Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients |
| title_sort | transcripts derived from amnsine1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients |
| topic | autism spectrum disorder repetitive sequences neurogenesis microRNA embryonic development autistic disorder |
| url | https://www.frontiersin.org/articles/10.3389/fbinf.2025.1532981/full |
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