Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene
Abstract PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) is predominantly expressed in the brain, and regulation of this gene links to neuroprotective effects against tau and Aβ-induced toxicity. Here we studied a (GCC)-repeat spanning the core promoter and 5′ UTR of this gene in 300 h...
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| Format: | Article |
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Nature Portfolio
2021-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-99932-3 |
| _version_ | 1819143374144274432 |
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| author | Safoura Khamse Zahra Jafarian Ali Bozorgmehr Mostafa Tavakoli Hossein Afshar Maryam Keshavarz Razieh Moayedi Mina Ohadi |
| author_facet | Safoura Khamse Zahra Jafarian Ali Bozorgmehr Mostafa Tavakoli Hossein Afshar Maryam Keshavarz Razieh Moayedi Mina Ohadi |
| author_sort | Safoura Khamse |
| collection | DOAJ |
| description | Abstract PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) is predominantly expressed in the brain, and regulation of this gene links to neuroprotective effects against tau and Aβ-induced toxicity. Here we studied a (GCC)-repeat spanning the core promoter and 5′ UTR of this gene in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also implemented several models to study the impact of this repeat on the three-dimensional (3D) structure of DNA. While the PRKACB (GCC)-repeat was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In all examined models, the (GCC)7 and its periodicals had the least range of divergence variation on the 3D structure of DNA in comparison to the 8-repeat periodicals and several hypothetical repeat lengths. A similar inert effect on the 3D structure was not detected in other classes of short tandem repeats (STRs) such as GA and CA repeats. In conclusion, we report monomorphism of a long (GCC)-repeat in the PRKACB gene in human, its inert effect on DNA structure, and enriched divergence in late-onset NCD. This is the first indication of natural selection for a monomorphic (GCC)-repeat, which probably evolved to function as an “epigenetic knob”, without changing the regional DNA structure. |
| first_indexed | 2024-12-22T12:25:13Z |
| format | Article |
| id | doaj.art-fe4862c020ce4923bb49f141af07f819 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-22T12:25:13Z |
| publishDate | 2021-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fe4862c020ce4923bb49f141af07f8192022-12-21T18:25:50ZengNature PortfolioScientific Reports2045-23222021-10-011111910.1038/s41598-021-99932-3Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB geneSafoura Khamse0Zahra Jafarian1Ali Bozorgmehr2Mostafa Tavakoli3Hossein Afshar4Maryam Keshavarz5Razieh Moayedi6Mina Ohadi7Iranian Research Center on Aging, University of Social Welfare and Rehabilitation SciencesIranian Research Center on Aging, University of Social Welfare and Rehabilitation SciencesResearch Center for Addiction and Risky Behaviors, Iran University of Medical SciencesDepartment of Applied Mathematics, Faculty of Mathematical Sciences, Ferdowsi University of MashhadIranian Research Center on Aging, University of Social Welfare and Rehabilitation SciencesTranslational Biogerontology, German Center for Neurodegenerative Diseases (Deutsches Zentrum Fur Neurodegenerative Erkrankungen, (DZNE))Department of Economics, Vrije Universiteit AmsterdamIranian Research Center on Aging, University of Social Welfare and Rehabilitation SciencesAbstract PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) is predominantly expressed in the brain, and regulation of this gene links to neuroprotective effects against tau and Aβ-induced toxicity. Here we studied a (GCC)-repeat spanning the core promoter and 5′ UTR of this gene in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also implemented several models to study the impact of this repeat on the three-dimensional (3D) structure of DNA. While the PRKACB (GCC)-repeat was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In all examined models, the (GCC)7 and its periodicals had the least range of divergence variation on the 3D structure of DNA in comparison to the 8-repeat periodicals and several hypothetical repeat lengths. A similar inert effect on the 3D structure was not detected in other classes of short tandem repeats (STRs) such as GA and CA repeats. In conclusion, we report monomorphism of a long (GCC)-repeat in the PRKACB gene in human, its inert effect on DNA structure, and enriched divergence in late-onset NCD. This is the first indication of natural selection for a monomorphic (GCC)-repeat, which probably evolved to function as an “epigenetic knob”, without changing the regional DNA structure.https://doi.org/10.1038/s41598-021-99932-3 |
| spellingShingle | Safoura Khamse Zahra Jafarian Ali Bozorgmehr Mostafa Tavakoli Hossein Afshar Maryam Keshavarz Razieh Moayedi Mina Ohadi Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene Scientific Reports |
| title | Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene |
| title_full | Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene |
| title_fullStr | Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene |
| title_full_unstemmed | Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene |
| title_short | Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene |
| title_sort | novel implications of a strictly monomorphic gcc repeat in the human prkacb gene |
| url | https://doi.org/10.1038/s41598-021-99932-3 |
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