Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States
Abstract
:1. Introduction
1.1. Functional Role of G4 Regions
1.2. Mutations within G4 Regions
1.3. Study Motivation
2. Materials and Methods
2.1. Putative and Validated G4 Identification
2.2. Somatic and Germline Variants in G4 Regions
2.3. Identification of SNPs Affecting G4 Formation
2.4. Functional and Transcription Factor Enrichment Analysis
3. Results
3.1. COSMIC Somatic Mutations
3.2. CLINVAR Germline Mutations
3.3. Predicted Change to G4 Stability
3.4. G4 Variants in Transcript Regions
3.5. G4 Variants in Gene Features
3.6. Enrichment Analysis
3.6.1. Gene Ontology
3.6.2. KEGG Metabolic Pathways
3.6.3. INTERPRO Protein Domains
3.6.4. Transcription Factors
3.7. Trinucleotide Context Mutation in the G4 Sequence
3.8. Role of the Location of SNVs in G4s
4. Discussion
4.1. Molecular Mechanisms for Promoting Mutations in G4 Regions
4.2. TERT G4 Mutations
4.3. G4 Mutations Disrupting the Transcription Factor Binding
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type of SNV | Effect of SNV on MFE | Freq | Percentage |
---|---|---|---|
Transition | Destabilized | 8600 | 22.93 |
Transversion | Further stabilized | 6603 | 17.60 |
Transition | No change | 6552 | 17.46 |
Transversion | Destabilized | 6419 | 17.11 |
Transversion | No change | 5509 | 14.68 |
Transition | Further stabilized | 3832 | 10.21 |
SNV | 3′ UTR | 5′ UTR | CDS | CpG Islands | Enhancers | Exon | Intergenic | Intron | lncRNA GENCODE | Promoter |
---|---|---|---|---|---|---|---|---|---|---|
G→A | 34.82 | 31.23 | 39.34 | 27.58 | 19.01 | 35.18 | 27.84 | 26.74 | 28.27 | 26.87 |
G→T | 18.3 | 14.82 | 15.84 | 12.01 | 12.08 | 16.6 | 17.15 | 14.56 | 14.89 | 13.64 |
C→T | 11.13 | 8.24 | 12.19 | 12.23 | 5.68 | 11.35 | 7.94 | 9.06 | 10.46 | 8.89 |
T→G | 12.67 | 16.48 | 8.59 | 16.78 | 29.84 | 11.74 | 18.38 | 19.91 | 18.15 | 18.95 |
A→G | 7.62 | 10.83 | 6.91 | 9.56 | 12.61 | 8 | 11.38 | 11.49 | 9.89 | 10.98 |
G→C | 5.16 | 6.05 | 4.69 | 6.27 | 7.28 | 5.09 | 6.89 | 6.3 | 6.23 | 6.51 |
C→G | 3.66 | 4.85 | 4.47 | 7.69 | 6.75 | 4.33 | 3.47 | 4.59 | 4.56 | 6.34 |
C→A | 2.76 | 2.99 | 4.11 | 3.85 | 1.42 | 3.65 | 1.95 | 2.6 | 2.73 | 3.3 |
T→C | 2.15 | 1.66 | 1.79 | 2 | 2.13 | 1.96 | 1.67 | 2.1 | 2.13 | 2.07 |
T→A | 0.7 | 0.86 | 0.84 | 0.67 | 0.89 | 0.81 | 1.27 | 1 | 1.17 | 0.82 |
A→T | 0.59 | 1.2 | 0.72 | 0.75 | 1.6 | 0.76 | 1.12 | 0.94 | 1 | 0.85 |
A→C | 0.45 | 0.8 | 0.51 | 0.62 | 0.71 | 0.52 | 0.94 | 0.72 | 0.53 | 0.77 |
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Neupane, A.; Chariker, J.H.; Rouchka, E.C. Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States. Genes 2023, 14, 2125. https://doi.org/10.3390/genes14122125
Neupane A, Chariker JH, Rouchka EC. Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States. Genes. 2023; 14(12):2125. https://doi.org/10.3390/genes14122125
Chicago/Turabian StyleNeupane, Aryan, Julia H. Chariker, and Eric C. Rouchka. 2023. "Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States" Genes 14, no. 12: 2125. https://doi.org/10.3390/genes14122125
APA StyleNeupane, A., Chariker, J. H., & Rouchka, E. C. (2023). Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States. Genes, 14(12), 2125. https://doi.org/10.3390/genes14122125