| Title: |
Interplay of the Genetic Variants and Allele Specific Methylation in the Context of a Single Human Genome Study |
| Authors: |
Maria D. Voronina; Olga V. Zayakina; Kseniia A. Deinichenko; Olga Sergeevna Shingalieva; Olga Y. Tsimmer; Darya A. Tarasova; Pavel Alekseevich Grebnev; Ekaterina A. Snigir; Sergey I. Mitrofanov; Vladimir S. Yudin; Anton A. Keskinov; Sergey M. Yudin; Dmitry V. Svetlichnyy; Veronika I. Skvortsova |
| Source: |
International Journal of Molecular Sciences ; Volume 26 ; Issue 19 ; Pages: 9641 |
| Publisher Information: |
Multidisciplinary Digital Publishing Institute |
| Publication Year: |
2025 |
| Collection: |
MDPI Open Access Publishing |
| Subject Terms: |
allele-specific methylation; cis-regulation; epigenetics |
| Description: |
The methylation of CpG sites with 5mC mark is a dynamic epigenetic modification. However, the relationship between the methylation and the surrounding genomic sequence context remains poorly explored. Investigation of the allele methylation provides an opportunity to decipher the interplay between differences in the primary DNA sequence and epigenetic variation. Here, we performed high-coverage long-read whole-genome direct DNA sequencing of one individual using Oxford Nanopore technology. We also used Illumina whole-genome sequencing of the parental genomes in order to identify allele-specific methylation sites with a trio-binning approach. We have compared the results of the haplotype-specific methylation detection and revealed that trio binning outperformed other approaches that do not take into account parental information. Also, we analysed the cis-regulatory effects of the genomic variations for influence on CpG methylation. To this end, we have used available Deep Learning models trained on the primary DNA sequence to score the cis-regulatory potential of the genomic loci. We evaluated the functional role of the allele-specific epigenetic changes with respect to gene expression using long-read Nanopore RNA sequencing. Our analysis revealed that the frequency of SNVs near allele-specific methylation positions is approximately four times higher compared to the biallelic methylation positions. In addition, we identified that allele-specific methylation sites are more conserved and enriched at the chromatin states corresponding to bivalent promoters and enhancers. Together, these findings suggest that significant impact on methylation can be encoded in the DNA sequence context. In order to elucidate the effect of the SNVs around sites of allele-specific methylation, we applied the Deep Learning model for detection of the cis-regulatory modules and estimated the impact that a genomic variant brings with respect to changes to the regulatory activity of a DNA loci. We revealed higher cis-regulatory impact ... |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms26199641 |
| DOI: |
10.3390/ijms26199641 |
| Availability: |
https://doi.org/10.3390/ijms26199641 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.73226EB4 |
| Database: |
BASE |