Scholarlink

Background <p>Variability in disease onset and severity among heterozygous females with X-linked recessive disorders, such as ornithine transcarbamylase (OTC) deficiency, may result from differences in the expression level of the normal allele caused by skewed X-chromosome inactivation (XCI). However, previous studies on the mechanisms of XCI lack relevance to humans. By applying the concept of hypomethylated allele frequency, gene expression can be estimated through DNA methylation analysis of transcriptional regulatory regions, including tissue-/cell-type-specific differentially methylated regions (T-DMRs) and XCI-affected regions.</p> Results <p>In this study, we identified a porcine <i>OTC</i> transcriptional regulatory region that functions both as a T-DMR and XCI-affected differentially methylated region. Furthermore, by distinguishing alleles using a single nucleotide polymorphism, we detected evidence of skewed XCI in female pigs.</p> Conclusions <p>Accordingly, by demonstrating that hypomethylated allele frequency reflects the active X allele, this study provides possible molecular evidence of skewed X inactivation through DNA methylation within the <i>OTC</i> T-DMR.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Simultaneous X-chromosome inactivation and tissue-/cell-type-specific DNA methylation in the transcriptional regulatory region of the X-linked recessive disease gene OTC

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月29日

查看全文
  • Fuko Yamada,
  • Shiori Hinata,
  • Ryohei Shigeta,
  • Hiroshi Nagashima,
  • Kenji Yamatoya,
  • Jun Ohgane

摘要

Background

Variability in disease onset and severity among heterozygous females with X-linked recessive disorders, such as ornithine transcarbamylase (OTC) deficiency, may result from differences in the expression level of the normal allele caused by skewed X-chromosome inactivation (XCI). However, previous studies on the mechanisms of XCI lack relevance to humans. By applying the concept of hypomethylated allele frequency, gene expression can be estimated through DNA methylation analysis of transcriptional regulatory regions, including tissue-/cell-type-specific differentially methylated regions (T-DMRs) and XCI-affected regions.

Results

In this study, we identified a porcine OTC transcriptional regulatory region that functions both as a T-DMR and XCI-affected differentially methylated region. Furthermore, by distinguishing alleles using a single nucleotide polymorphism, we detected evidence of skewed XCI in female pigs.

Conclusions

Accordingly, by demonstrating that hypomethylated allele frequency reflects the active X allele, this study provides possible molecular evidence of skewed X inactivation through DNA methylation within the OTC T-DMR.