Scholarlink

<p>The double homeobox 4 gene (<i>DUX4</i>) and its centromeric paralogue, <i>DUX4C</i>, reside in the subtelomeric region of chromosome 4 and have been implicated in facioscapulohumeral muscular dystrophy (FSHD) and cancers. However, the high sequence similarity between these genes, together with the widespread presence of <i>DUX4</i>-like paralogues across the human genome, has hindered accurate genotyping and expression profiling using short-read sequencing. To elucidate the genetic architecture and potential disease-associated functions of <i>DUX4</i> and <i>DUX4C</i>, we first identified two distinct <i>DUX4C</i> haplotypes with expression quantitative trait effects—<i>DUX4C</i>-4qα and <i>DUX4C</i>-4qβ. We then integrated them with known <i>DUX4</i> haplotypes to generate a reference genome, D4Ref-T2T, using long-read sequencing. Haplotype analysis indicated strong linkage disequilibrium between <i>DUX4C</i> and <i>DUX4</i> haplotypes (<i>r</i><sup>2</sup> = 0.86). We further characterized full-length <i>DUX4C</i> mRNA isoforms and established a corresponding transcriptome reference. Applying these resources to breast tumor, FSHD, and lymphoblastoid cell line datasets revealed that <i>DUX4</i> is expressed in both breast tumor and FSHD tissues, whereas <i>DUX4C</i> shows expression only in breast tumors. Differential gene expression and Gene Ontology enrichment analyses further suggested that <i>DUX4C</i> expression is associated with activation of pathways involved in leukocyte differentiation, chemotaxis, and cell migration.</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

A new integrated genetic and transcriptomic approach for investigating DUX4 and DUX4C

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月16日

查看全文
  • Zhaohui Zhuang,
  • Mahoko Takahashi Ueda,
  • Kensuke Yamaguchi,
  • Yuta Kochi

摘要

The double homeobox 4 gene (DUX4) and its centromeric paralogue, DUX4C, reside in the subtelomeric region of chromosome 4 and have been implicated in facioscapulohumeral muscular dystrophy (FSHD) and cancers. However, the high sequence similarity between these genes, together with the widespread presence of DUX4-like paralogues across the human genome, has hindered accurate genotyping and expression profiling using short-read sequencing. To elucidate the genetic architecture and potential disease-associated functions of DUX4 and DUX4C, we first identified two distinct DUX4C haplotypes with expression quantitative trait effects—DUX4C-4qα and DUX4C-4qβ. We then integrated them with known DUX4 haplotypes to generate a reference genome, D4Ref-T2T, using long-read sequencing. Haplotype analysis indicated strong linkage disequilibrium between DUX4C and DUX4 haplotypes (r2 = 0.86). We further characterized full-length DUX4C mRNA isoforms and established a corresponding transcriptome reference. Applying these resources to breast tumor, FSHD, and lymphoblastoid cell line datasets revealed that DUX4 is expressed in both breast tumor and FSHD tissues, whereas DUX4C shows expression only in breast tumors. Differential gene expression and Gene Ontology enrichment analyses further suggested that DUX4C expression is associated with activation of pathways involved in leukocyte differentiation, chemotaxis, and cell migration.