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Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states
While the role of G4 G quadruplex structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915501/ https://www.ncbi.nlm.nih.gov/pubmed/36778288 http://dx.doi.org/10.1101/2023.01.30.526341 |
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author | Neupane, Aryan Chariker, Julia H. Rouchka, Eric C. |
author_facet | Neupane, Aryan Chariker, Julia H. Rouchka, Eric C. |
author_sort | Neupane, Aryan |
collection | PubMed |
description | While the role of G4 G quadruplex structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on alteration of G4 secondary structure. 37,515 G4 SNVs in the COSMIC database and 2,115 in CLINVAR were identified. Of those, 7,236 COSMIC (19.3%) and 416 (18%) of the CLINVAR variants result in G4 loss, while 2,728 (COSMIC) and 112 (CLINVAR) SNVs gain a G4 structure. The gene ontology term “GnRH (Gonadotropin-releasing hormone) secretion” is enriched in 21 genes in this pathway that have a G4 destabilizing SNV. Analysis of mutational patterns in the G4 structure show a higher selective pressure (3-fold) in the coding region on the template strand compared to the non-template strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter and enhancer regions across strands. Using GO and pathway enrichment, genes with SNVs for G4 forming propensity in the coding region are enriched for Regulation of Ras protein signal transduction and Src homology 3 (SH3) domain binding. |
format | Online Article Text |
id | pubmed-9915501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-99155012023-02-11 Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states Neupane, Aryan Chariker, Julia H. Rouchka, Eric C. bioRxiv Article While the role of G4 G quadruplex structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on alteration of G4 secondary structure. 37,515 G4 SNVs in the COSMIC database and 2,115 in CLINVAR were identified. Of those, 7,236 COSMIC (19.3%) and 416 (18%) of the CLINVAR variants result in G4 loss, while 2,728 (COSMIC) and 112 (CLINVAR) SNVs gain a G4 structure. The gene ontology term “GnRH (Gonadotropin-releasing hormone) secretion” is enriched in 21 genes in this pathway that have a G4 destabilizing SNV. Analysis of mutational patterns in the G4 structure show a higher selective pressure (3-fold) in the coding region on the template strand compared to the non-template strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter and enhancer regions across strands. Using GO and pathway enrichment, genes with SNVs for G4 forming propensity in the coding region are enriched for Regulation of Ras protein signal transduction and Src homology 3 (SH3) domain binding. Cold Spring Harbor Laboratory 2023-02-02 /pmc/articles/PMC9915501/ /pubmed/36778288 http://dx.doi.org/10.1101/2023.01.30.526341 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Neupane, Aryan Chariker, Julia H. Rouchka, Eric C. Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states |
title | Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states |
title_full | Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states |
title_fullStr | Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states |
title_full_unstemmed | Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states |
title_short | Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states |
title_sort | analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915501/ https://www.ncbi.nlm.nih.gov/pubmed/36778288 http://dx.doi.org/10.1101/2023.01.30.526341 |
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