Identification of small-sized intrachromosomal segments at the ends of INV-DUP-DEL patterns

Keiko Shimojima Yamamoto; Takeaki Tamura; Nobuhiko Okamoto; Eriko Nishi; Atsuko Noguchi; Ikuko Takahashi; Yukio Sawaishi; Masaki Shimizu; Hitoshi Kanno; Yohei Minakuchi; Atsushi Toyoda; Toshiyuki Yamamoto

doi:10.1038/s10038-023-01181-x

Identification of small-sized intrachromosomal segments at the ends of INV-DUP-DEL patterns

J Hum Genet. 2023 Nov;68(11):751-757. doi: 10.1038/s10038-023-01181-x. Epub 2023 Jul 10.

Authors

Keiko Shimojima Yamamoto^{1

2}, Takeaki Tamura^{3

4}, Nobuhiko Okamoto⁵, Eriko Nishi⁵, Atsuko Noguchi⁶, Ikuko Takahashi⁶, Yukio Sawaishi⁷, Masaki Shimizu⁸, Hitoshi Kanno^{1

2}, Yohei Minakuchi⁹, Atsushi Toyoda⁹, Toshiyuki Yamamoto^{10

11}

Affiliations

¹ Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
² Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
³ Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, 173-8610, Japan.
⁴ Division of Gene Medicine, Graduate Scholl of Medical Science, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
⁵ Department of Medical Genetics, Osaka Women's and Children's Hospital, Izumi, 594-1101, Japan.
⁶ Department of Pediatrics, Akita University Graduate School of Medicine, Akita, 010-8543, Japan.
⁷ Department of Pediatrics, Akita Prefectural Center on Development and Disability, Akita, 010-0000, Japan.
⁸ Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
⁹ Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Shizuoka, 411-0801, Japan.
¹⁰ Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, 162-8666, Japan. yamamoto.toshiyuki@twmu.ac.jp.
¹¹ Division of Gene Medicine, Graduate Scholl of Medical Science, Tokyo Women's Medical University, Tokyo, 162-8666, Japan. yamamoto.toshiyuki@twmu.ac.jp.

PMID: 37423943
DOI: 10.1038/s10038-023-01181-x

Abstract

The mechanism of chromosomal rearrangement associated with inverted-duplication-deletion (INV-DUP-DEL) pattern formation has been investigated by many researchers, and several possible mechanisms have been proposed. Currently, fold-back and subsequent dicentric chromosome formation has been established as non-recurrent INV-DUP-DEL pattern formation mechanisms. In the present study, we analyzed the breakpoint junctions of INV-DUP-DEL patterns in five patients using long-read whole-genome sequencing and detected 2.2-6.1 kb copy-neutral regions in all five patients. At the end of the INV-DUP-DEL, two patients exhibited chromosomal translocations, which are recognized as telomere capture, and one patient showed direct telomere healing. The remaining two patients had additional small-sized intrachromosomal segments at the end of the derivative chromosomes. These findings have not been previously reported but they may only be explained by the presence of telomere capture breakage. Further investigations are required to better understand the mechanisms underlying this finding.