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<p>Over 400 β-thalassemia mutations show population-differentiated spectra, yet their origins and evolution remain unclear. Focusing on targeted sequencing of 20,222 individuals and 510 β-thalassemia patients in southern China, we identified three major haplotype groups (HG) at the β-globin locus and observed highest haplotype diversity for CD41/42, -50, and HbE among 13 prevalent mutations in 993 carriers. Allele dating suggest these mutations emerged during agricultural expansions in the past 7420 years, represented by CD41/42 arising in mainland China. However, the -50 mutation likely originated on Hainan Island within 3900 years, subsequently spreading to the mainland and experiencing lineage-specific selection. HbE exhibits substantial haplotype heterogeneity in Yunnan, with network analyses indicating bidirectional disseminations between southern China and South/Southeast Asia. We further suggest an ameliorating effect of HG2, associated with elevated hemoglobin and fetal hemoglobin levels. These findings highlight multi-centric origins of β-thalassemia mutations and underscore the evolutionary context shaping their clinical impact.</p>

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Multi-centric origins and gene flow shape the diversity of β-thalassemia mutations in Southern East Asia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • Qianqian Zhang,
  • Jialong Li,
  • Haoyang Huang,
  • Xuan Shang,
  • Yuhua Ye,
  • Wei Zhang,
  • Peng Lin,
  • Yi Gong,
  • Boon-Peng Hoh,
  • Qingming Luo,
  • Tizhen Yan,
  • Xinghua Pan,
  • Mark Stoneking,
  • Shuhua Xu,
  • Xiangmin Xu,
  • Lian Deng

摘要

Over 400 β-thalassemia mutations show population-differentiated spectra, yet their origins and evolution remain unclear. Focusing on targeted sequencing of 20,222 individuals and 510 β-thalassemia patients in southern China, we identified three major haplotype groups (HG) at the β-globin locus and observed highest haplotype diversity for CD41/42, -50, and HbE among 13 prevalent mutations in 993 carriers. Allele dating suggest these mutations emerged during agricultural expansions in the past 7420 years, represented by CD41/42 arising in mainland China. However, the -50 mutation likely originated on Hainan Island within 3900 years, subsequently spreading to the mainland and experiencing lineage-specific selection. HbE exhibits substantial haplotype heterogeneity in Yunnan, with network analyses indicating bidirectional disseminations between southern China and South/Southeast Asia. We further suggest an ameliorating effect of HG2, associated with elevated hemoglobin and fetal hemoglobin levels. These findings highlight multi-centric origins of β-thalassemia mutations and underscore the evolutionary context shaping their clinical impact.