Polymorphic GGC repeat differentially regulates human reelin gene expression levels
Open accessAbstract
The human gene encoding Reelin (RELN), a pivotal protein in neurodevelopment, includes a polymorphic GGC repeat in its 5' untranslated region (UTR). CHO cells transfected with constructs encompassing the RELN 5'UTR with 4-to-13 GGC repeats upstream of the luciferase reporter gene show declining luciferase activity with increasing GGC repeat number (P < 0.005), as predicted by computer-based simulations. Conversely, RELN 5'UTR sequences boost reporter gene expression above control levels in neuronal SN56 and N2A cell lines, but 12- and 13-repeat alleles still yield 50-60% less luciferase activity compared to the more common 8- and 10-repeat alleles (P < 0.0001). RELN "long" GGC alleles significantly blunt gene expression and may, through this effect, confer vulnerability to human disorders, such as schizophrenia and autism.
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Autism is associated with RELN gene variants yielding reduced Reelin expression in vitro and in vivo, and with PON1 gene variants responsible for lower gene expression and reduced detoxification of some OP compounds.
“At the same time, autism is associated with RELN gene variants yielding reduced Reelin gene expression both in vitro and in vivo, and with PON1 gene variants responsible for lower gene expression and reduced detoxification of some OP compounds [140, 239, 240].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [240]
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Jafarian, Z., Khamse, S., Afshar, H., Khorshid, H. R. K., Delbari, A., & Ohadi, M. (2021) · Research Square · doi:10.21203/rs.3.rs-835509/v1
The human SMAD9 (GCC) repeat links to natural selection and late-onset neurocognitive disorders
Alizadeh, S., Khamse, S., Vafadar, S., Bernhart, S. H., Afshar, H., Vahedi, M., Rezaei, O., Delbari, A., & Ohadi, M. (2024) · Neurological Sciences · doi:10.1007/s10072-024-07637-y
- Authors
- Persico, A. M., Levitt, P., & Pimenta, A. F.
- Affiliations
- Università Campus Bio-Medico (IT)
- Vanderbilt University (US)
- Venue
- Journal of Neural Transmission
- Published
- 2006-04-11
- Volume
- 113
- Issue
- 10
- Pages
- 1373-1382
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W2142056327
- Cited by
- 52
- References
- 52
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 1 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 4 · 2012: 9
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- National Institute of Mental Health (MH45507)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- reelin, RELN gene, 5' untranslated region, gene expression regulation, brain development, schizophrenia, autism spectrum disorder, neuronal cell lines, luciferase reporter
- MeSH terms
- Reelin Protein, Animals, Cell Line, Cricetulus, Fibroblasts, Gene Expression Regulation, Cricetinae, Humans, Nerve Tissue Proteins, Neurons, Polymorphism, Genetic, RNA, Messenger, Serine Endopeptidases, Transfection, Cell Adhesion Molecules, Neuronal, Gene Expression, Extracellular Matrix Proteins, CHO Cells, Genes, Reporter, Trinucleotide Repeats, 5' Untranslated Regions
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