Division of Molecular Genetics, Center for Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
Kobe Motomachi Yume Clinic, Kobe, Japan.
Hum Genet. 2023 Oct;142(10):1451-1460. doi: 10.1007/s00439-023-02591-9. Epub 2023 Aug 24.
Constitutional complex chromosomal rearrangements (CCRs) are rare cytogenetic aberrations arising in the germline via an unknown mechanism. Here we analyzed the breakpoint junctions of microscopically three-way or more complex translocations using comprehensive genomic and epigenomic analyses. All of these translocation junctions showed submicroscopic genomic complexity reminiscent of chromothripsis. The breakpoints were clustered within small genomic domains with junctions showing microhomology or microinsertions. Notably, all of the de novo cases were of paternal origin. The breakpoint distributions corresponded specifically to the ATAC-seq (assay for transposase-accessible chromatin with sequencing) read data peak of mature sperm and not to other chromatin markers or tissues. We propose that DNA breaks in CCRs may develop in an accessible region of densely packaged chromatin during post-meiotic spermiogenesis.
染色体结构重排（CCRs）是一种罕见的细胞遗传学异常，其在生殖细胞中通过未知机制产生。在此，我们通过全面的基因组和表观基因组分析，研究了显微镜下三向或更多向复杂易位的断点连接。所有这些易位连接都显示出类似于染色体重排的亚微观基因组复杂性。这些断点聚集在具有微同源性或微插入的小基因组区域内。值得注意的是，所有的新发病例均来自父本。断点分布与成熟精子的 ATAC-seq（转座酶可及染色质测序）读数数据峰相对应，而与其他染色质标记或组织无关。我们提出，CCR 中的 DNA 断裂可能发生在减数后精子发生过程中致密包装染色质的可及区域。
