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DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing
The molecular genetic mechanism of Turner syndrome (TS) still leaves much to be discovered. Methods: TS (45X0) patients and age-matched controls (46XX and 46XY) were selected. The nanopore sequencing combined with trio-whole exome sequencing (trio-WES) were used for the first time to investigate TS....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225209/ https://www.ncbi.nlm.nih.gov/pubmed/35743657 http://dx.doi.org/10.3390/jpm12060872 |
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author | Fan, Xin Zhang, Beibei Fan, Lijun Chen, Jiajia Su, Chang Cao, Bingyan Wei, Liya Qin, Miao Gong, Chunxiu |
author_facet | Fan, Xin Zhang, Beibei Fan, Lijun Chen, Jiajia Su, Chang Cao, Bingyan Wei, Liya Qin, Miao Gong, Chunxiu |
author_sort | Fan, Xin |
collection | PubMed |
description | The molecular genetic mechanism of Turner syndrome (TS) still leaves much to be discovered. Methods: TS (45X0) patients and age-matched controls (46XX and 46XY) were selected. The nanopore sequencing combined with trio-whole exome sequencing (trio-WES) were used for the first time to investigate TS. Results: Thirteen TS (45X0) patients and eight controls were enrolled. Trio-WES analysis did not find any pathogenetic or likely pathogenic variants except X chromosome (chrX) deletion. The average methylation levels and patterns of chrX in 45X0 and 46XY were similar, and significantly higher than in 46XX (p = 2.22 × 10(−16)). Both hyper-methylation and hypo-methylation were detected in the CpG island (CGI), CGI_shore, promoter, genebody, and PAR1-region, while in the transposon element inactivation regions of the chrX and hypermethylation were predominant. A total of 125 differentially methylated genes were identified in 45X0 compared to 46XX, including 8 and 117 hypermethylated and hypomethylated genes, respectively, with the enrichment terms of mitophagy, regulation of DNA-binding transcription factor activity, etc. Conclusions: The results suggest that the methylation profile in patients with TS might be determined by the number of X chromosomes; the patterns of methylation in TS were precisely associated with the maintenance of genomic stability and improvement of gene expression. Differentially methylated genes/pathways might reveal the potential epigenetic modulation and lead to better understanding of TS. |
format | Online Article Text |
id | pubmed-9225209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92252092022-06-24 DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing Fan, Xin Zhang, Beibei Fan, Lijun Chen, Jiajia Su, Chang Cao, Bingyan Wei, Liya Qin, Miao Gong, Chunxiu J Pers Med Article The molecular genetic mechanism of Turner syndrome (TS) still leaves much to be discovered. Methods: TS (45X0) patients and age-matched controls (46XX and 46XY) were selected. The nanopore sequencing combined with trio-whole exome sequencing (trio-WES) were used for the first time to investigate TS. Results: Thirteen TS (45X0) patients and eight controls were enrolled. Trio-WES analysis did not find any pathogenetic or likely pathogenic variants except X chromosome (chrX) deletion. The average methylation levels and patterns of chrX in 45X0 and 46XY were similar, and significantly higher than in 46XX (p = 2.22 × 10(−16)). Both hyper-methylation and hypo-methylation were detected in the CpG island (CGI), CGI_shore, promoter, genebody, and PAR1-region, while in the transposon element inactivation regions of the chrX and hypermethylation were predominant. A total of 125 differentially methylated genes were identified in 45X0 compared to 46XX, including 8 and 117 hypermethylated and hypomethylated genes, respectively, with the enrichment terms of mitophagy, regulation of DNA-binding transcription factor activity, etc. Conclusions: The results suggest that the methylation profile in patients with TS might be determined by the number of X chromosomes; the patterns of methylation in TS were precisely associated with the maintenance of genomic stability and improvement of gene expression. Differentially methylated genes/pathways might reveal the potential epigenetic modulation and lead to better understanding of TS. MDPI 2022-05-26 /pmc/articles/PMC9225209/ /pubmed/35743657 http://dx.doi.org/10.3390/jpm12060872 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fan, Xin Zhang, Beibei Fan, Lijun Chen, Jiajia Su, Chang Cao, Bingyan Wei, Liya Qin, Miao Gong, Chunxiu DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing |
title | DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing |
title_full | DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing |
title_fullStr | DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing |
title_full_unstemmed | DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing |
title_short | DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing |
title_sort | dna hypermethylation and a specific methylation spectrum on the x chromosome in turner syndrome as determined by nanopore sequencing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225209/ https://www.ncbi.nlm.nih.gov/pubmed/35743657 http://dx.doi.org/10.3390/jpm12060872 |
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