Breakpoints in complex chromosomal rearrangements correspond to transposase-accessible regions of DNA from mature sperm

Takeshi Sugimoto, Hidehito Inagaki, Tasuku Mariya, Rie Kawamura, Mariko Taniguchi-Ikeda, Seiji Mizuno, Yukako Muramatsu, Ikuya Tsuge, Hirofumi Ohashi, Nakamichi Saito, Yuiko Hasegawa, Nobuhiko Ochi, Masatoshi Yamaguchi, Jun Murotsuki, Hiroki Kurahashi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1451-1460
Number of pages10
JournalHuman Genetics
Volume142
Issue number10
DOIs
Publication statusPublished - 10-2023

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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