Ryu Hyunwoo, Han Hyunho, Kim Chuna, Kim Jun
Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
Department of Computer Science and Engineering, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
Nucleic Acids Res. 2025 Jan 11;53(2). doi: 10.1093/nar/gkae1295.
Large genetic variants can be generated via homologous recombination (HR), such as polymerase theta-mediated end joining (TMEJ) or single-strand annealing (SSA). Given that these HR-based mechanisms leave specific genomic signatures, we developed GDBr, a genomic signature interpretation tool for DNA double-strand break repair mechanisms using high-quality genome assemblies. We applied GDBr to a draft human pangenome reference. We found that 78.1% of non-repetitive insertions and deletions and 11.0% of non-repetitive complex substitutions contained specific signatures. Of these, we interpreted that 98.7% and 1.3% of the insertions and deletions were generated via TMEJ and SSA, respectively, and all complex substitutions via TMEJ. Since population-level pangenome datasets are being dramatically accumulated, GDBr can provide mechanistic insights into how variants are formed. GDBr is available on GitHub at https://github.com/Chemical118/GDBr.
大的基因变异可通过同源重组（HR）产生，如聚合酶θ介导的末端连接（TMEJ）或单链退火（SSA）。鉴于这些基于HR的机制会留下特定的基因组特征，我们开发了GDBr，这是一种利用高质量基因组组装对DNA双链断裂修复机制进行基因组特征解读的工具。我们将GDBr应用于人类泛基因组参考草图。我们发现，78.1%的非重复插入和缺失以及11.0%的非重复复杂替换包含特定特征。其中，我们解读为分别有98.7%和1.3%的插入和缺失是通过TMEJ和SSA产生的，而所有复杂替换都是通过TMEJ产生的。由于群体水平的泛基因组数据集正在急剧积累，GDBr可以为变异如何形成提供机制性见解。GDBr可在GitHub上获取，网址为https://github.com/Chemical118/GDBr。
