Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene

Autor: Ali Bozorgmehr, Mostafa Tavakoli, Zahra Jafarian, Hossein Afshar, Razieh Moayedi, Maryam Keshavarz, Mina Ohadi, Safoura Khamse
Rok vydání: 2021
Předmět:
Genotype
Evolution
Molecular biology
metabolism [Cyclic AMP-Dependent Protein Kinase Catalytic Subunits]
Science
Protein subunit
genetics [5' Untranslated Regions]
Sequence Homology
genetics [Cyclic AMP-Dependent Protein Kinase Catalytic Subunits]
Biology
Article
chemistry.chemical_compound
Trinucleotide Repeats
Genetics
PRKACB Gene
Animals
Humans
Gene Regulatory Networks
Epigenetics
Promoter Regions
Genetic
Gene
Alleles
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
genetics [DNA]
Multidisciplinary
Promoter
DNA
ultrastructure [Cyclic AMP-Dependent Protein Kinase Catalytic Subunits]
genetics [Microsatellite Repeats]
chemistry
genetics [Gene Regulatory Networks]
genetics [Promoter Regions
Genetic]
genetics [Trinucleotide Repeats]
Medicine
Microsatellite
Structural biology
5' Untranslated Regions
ddc:600
Neuroscience
Microsatellite Repeats
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
Scientific reports 11(1), 20629 (2021). doi:10.1038/s41598-021-99932-3
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-021-99932-3
Popis: 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.
Databáze: OpenAIRE
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