Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene.
5' Untranslated Regions
/ genetics
Alleles
Animals
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
/ genetics
DNA
/ genetics
Gene Regulatory Networks
/ genetics
Genotype
Humans
Microsatellite Repeats
/ genetics
Promoter Regions, Genetic
/ genetics
Sequence Homology
Trinucleotide Repeats
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 10 2021
19 10 2021
Historique:
received:
16
04
2021
accepted:
05
10
2021
entrez:
20
10
2021
pubmed:
21
10
2021
medline:
9
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34667254
doi: 10.1038/s41598-021-99932-3
pii: 10.1038/s41598-021-99932-3
pmc: PMC8526596
doi:
Substances chimiques
5' Untranslated Regions
0
DNA
9007-49-2
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
EC 2.7.11.11
PRKACB protein, human
EC 2.7.11.11
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20629Informations de copyright
© 2021. The Author(s).
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