威康桑格研究所Thomas M. Keane小组的最新研究揭示了两个小鼠亚种的全基因组组装揭示了端粒和着丝粒的结构多样性。相关论文于2025年10月21日发表于国际顶尖学术期刊《自然—遗传学》杂志上。

在这里，该研究团队提出了两个关键近交系，C57BL/6J和CAST/EiJ的第一个端粒到端粒（T2T）单主题基因组。这些T2T基因组揭示了端粒和着丝粒大小和结构组织的实质性变异性。他们要再加213个参考基因组包含517个蛋白编码基因。课题组研究人员还研究了两个重要但不完整的基因座，即性染色体上的假常染色体区域（PAR）和KRAB锌指蛋白位点。课题组在PAR基因中发现了距离较远的PAR边界位置、不同的片段复制拷贝数和大小以及大量的氨基酸替代突变。

研究人员表示，C57BL/6J基序参考基因组的发表已经有20多年的历史了，它一直是理解哺乳动物疾病生物学的关键催化剂。然而，小鼠参考基因组仍然缺乏端粒和着丝粒，包含281个染色体序列缺口，仅部分代表许多生物医学相关位点。

附：英文原文

Title: Complete genome assemblies of two mouse subspecies reveal structural diversity of telomeres and centromeres

Author: Francis, Bailey A., Gozashti, Landen, Costello, Kevin, Kasahara, Takaoki, Harringmeyer, Olivia S., Lilue, Jingtao, Wu, Tianzhen, Zoltowska, Katarzyna, Helmy, Mohab, Kato, Tadafumi, Czechanski, Anne, Bronner, Iraad. F., Dawson, Emma, Quail, Michael A., Ferguson-Smith, Anne, Reinholdt, Laura, Adams, David J., Keane, Thomas M.

Issue&Volume: 2025-10-21

Abstract: It has been more than 20 years since the publication of the C57BL/6J mouse reference genome, which has been a key catalyst for understanding the biology of mammalian diseases. However, the mouse reference genome still lacks telomeres and centromeres, contains 281 chromosomal sequence gaps and only partially represents many biomedically relevant loci. Here we present the first telomere-to-telomere (T2T) mouse genomes for two key inbred strains, C57BL/6J and CAST/EiJ. These T2T genomes reveal substantial variability in telomere and centromere sizes and structural organization. We thus add an additional 213Mb of new sequence to the reference genome, which contains 517 protein-coding genes. We also examined two important but incomplete loci in the mouse genome—the pseudoautosomal region (PAR) on the sex chromosomes and KRAB zinc-finger protein loci. We identified distant locations of the PAR boundary, different copy numbers and sizes of segmental duplications and a multitude of amino acid substitution mutations in PAR genes.

DOI: 10.1038/s41588-025-02367-z

Source: https://www.nature.com/articles/s41588-025-02367-z