Scholarlink

<p>Spinocerebellar ataxia type 36 (SCA36)—caused by a GGCCTG hexanucleotide repeat expansion in the <i>NOP56</i> gene—has traditionally been considered to originate from a founder effect in the Ashida River basin of southern Japan. However, its genetic background remains incompletely understood. In this study, we analyzed five Japanese patients with SCA36 from four unrelated families using long-read sequencing to determine repeat length and reconstruct detailed haplotypes around the <i>NOP56</i> locus. We successfully resolved extended haplotypes ranging from approximately 90 kb to 1.3 Mb. All five individuals shared a 5.3-kb haplotype adjacent to the repeat expansion, while four patients from northern Japan shared a larger haplotype block of at least 95.2 kb. Comparison with seven previously reported Korean SCA36 cases revealed a shared 4.2-kb haplotype, and available data from other populations were concordant within a ~ 2.1-kb core region. Notably, the shared 5.3-kb haplotype is relatively common in the general population, suggesting that the underlying core haplotype may represent a permissive haplotypic background rather than a unique founder haplotype. These findings indicate that SCA36 is unlikely to be explained solely by a regional founder in southern Japan. Instead, a shared permissive haplotypic background may underlie repeat expansion, with large pathogenic expansion arising independently in different populations. This pattern may be consistent with a stepwise process of repeat expansion.</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

Haplotype analysis of spinocerebellar ataxia type 36 suggests a shared permissive core haplotype across populations

  • 期刊论文

  • 发表日期：

    2026年7月1日

查看全文
  • Katsuki Eguchi,
  • Satoko Miyatake,
  • Asako Takei,
  • Hiroaki Yaguchi,
  • Yuki Iida,
  • Shinsuke Hamada,
  • Yoshiko Ito,
  • Sanae Honma,
  • Fumio Moriwaka,
  • Taishi Wada,
  • Takashi Jono,
  • Misako Kunii,
  • Hiroyasu Komiya,
  • Hitaru Kishida,
  • Hiroshi Doi,
  • Fumiaki Tanaka,
  • Naomichi Matsumoto,
  • Ichiro Yabe

摘要

Spinocerebellar ataxia type 36 (SCA36)—caused by a GGCCTG hexanucleotide repeat expansion in the NOP56 gene—has traditionally been considered to originate from a founder effect in the Ashida River basin of southern Japan. However, its genetic background remains incompletely understood. In this study, we analyzed five Japanese patients with SCA36 from four unrelated families using long-read sequencing to determine repeat length and reconstruct detailed haplotypes around the NOP56 locus. We successfully resolved extended haplotypes ranging from approximately 90 kb to 1.3 Mb. All five individuals shared a 5.3-kb haplotype adjacent to the repeat expansion, while four patients from northern Japan shared a larger haplotype block of at least 95.2 kb. Comparison with seven previously reported Korean SCA36 cases revealed a shared 4.2-kb haplotype, and available data from other populations were concordant within a ~ 2.1-kb core region. Notably, the shared 5.3-kb haplotype is relatively common in the general population, suggesting that the underlying core haplotype may represent a permissive haplotypic background rather than a unique founder haplotype. These findings indicate that SCA36 is unlikely to be explained solely by a regional founder in southern Japan. Instead, a shared permissive haplotypic background may underlie repeat expansion, with large pathogenic expansion arising independently in different populations. This pattern may be consistent with a stepwise process of repeat expansion.