Scholarlink

<p>Four multi-species conserved sequences (MCSs) are important enhancers which affect α-globin expression. Deletions of MCS can cause α-thalassemia. So far, duplication of MCS has never been reported to account for thalassemia. In this study, an unusual transfusion-dependent case of hemoglobin H disease was identified by whole-genome sequencing, optical genome mapping and longer PCR with special primers, which was caused by a familial 96,620-bp inverted duplication (from MCS-R1 to MCS-R4), inserted between chr16:199348 and 199349 (GRCh37/hg19) within MCSs. The duplication segment included an inverted repeat sequence from chr16:102712 to176193 and one direct repeat sequence from chr16:176208 to 199348. The associated α-thalassemia trait was confirmed to result from disrupted topological chromatin domains using ATAC-seq and the dual‑luciferase reporter assay system. This case presents a new mechanism of α-thalassemia, and may aid our understanding of the effects of enhancers on gene expression and the differential contribution of the four enhancer elements in the human a-globin locus.</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

An unusual transfusion-dependent hemoglobin H disease caused by a novel complex inverted duplication involving the α-globin regulatory elements and α-thalassemia—-SEA deletion

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月12日

查看全文
  • Fan Jiang,
  • Jieying Wu,
  • Manqiu Yang,
  • Xiaojun Chen,
  • Ru Li,
  • Qiuxia Yu,
  • Liandong Zuo,
  • Jianying Zhou,
  • Yongling Zhang,
  • Li Zhen,
  • Xuewei Tang,
  • Ren Zhang,
  • Shiping Chen,
  • Chenyu Wang,
  • Can Liao,
  • Dongzhi Li

摘要

Four multi-species conserved sequences (MCSs) are important enhancers which affect α-globin expression. Deletions of MCS can cause α-thalassemia. So far, duplication of MCS has never been reported to account for thalassemia. In this study, an unusual transfusion-dependent case of hemoglobin H disease was identified by whole-genome sequencing, optical genome mapping and longer PCR with special primers, which was caused by a familial 96,620-bp inverted duplication (from MCS-R1 to MCS-R4), inserted between chr16:199348 and 199349 (GRCh37/hg19) within MCSs. The duplication segment included an inverted repeat sequence from chr16:102712 to176193 and one direct repeat sequence from chr16:176208 to 199348. The associated α-thalassemia trait was confirmed to result from disrupted topological chromatin domains using ATAC-seq and the dual‑luciferase reporter assay system. This case presents a new mechanism of α-thalassemia, and may aid our understanding of the effects of enhancers on gene expression and the differential contribution of the four enhancer elements in the human a-globin locus.