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

Journal of Human Genetics volume 68, pages 751–757 (2023)Cite this article

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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.

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Data availability

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to express our gratitude to the patients and their families for their cooperation. We also thank M. Kiyooka and W. Chen for the PacBio sequencing and GeneBay, Inc. for the Nanopore PromethION sequencing.

Funding

This study was supported by JSPS KAKENHI, Grant Numbers 21K07873 (JSPS) and 16H06279 (PAGS).

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Authors and Affiliations

  1. Department of Transfusion Medicine and Cell Processing, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Keiko Shimojima Yamamoto & Hitoshi Kanno

  2. Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Keiko Shimojima Yamamoto, Hitoshi Kanno & Toshiyuki Yamamoto

  3. Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, 173-8610, Japan

    Takeaki Tamura

  4. Division of Gene Medicine, Graduate Scholl of Medical Science, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Takeaki Tamura & Toshiyuki Yamamoto

  5. Department of Medical Genetics, Osaka Women’s and Children’s Hospital, Izumi, 594-1101, Japan

    Nobuhiko Okamoto & Eriko Nishi

  6. Department of Pediatrics, Akita University Graduate School of Medicine, Akita, 010-8543, Japan

    Atsuko Noguchi & Ikuko Takahashi

  7. Department of Pediatrics, Akita Prefectural Center on Development and Disability, Akita, 010-0000, Japan

    Yukio Sawaishi

  8. Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan

    Masaki Shimizu

  9. Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Shizuoka, 411-0801, Japan

    Yohei Minakuchi & Atsushi Toyoda

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  1. Keiko Shimojima Yamamoto
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Contributions

TY designed the study. KSY organized the study and drafted the manuscript. TT, NO, EN, AN, IT, YS, and MS contributed to acquisition of data. YM and AT analyzed the data. HK reviewed the manuscript critically. All authors contributed to the data interpretation. All authors agree to be accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the study are appropriately investigated and resolved.

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Correspondence to Toshiyuki Yamamoto.

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Shimojima Yamamoto, K., Tamura, T., Okamoto, N. et al. Identification of small-sized intrachromosomal segments at the ends of INV–DUP–DEL patterns. J Hum Genet 68, 751–757 (2023). https://doi.org/10.1038/s10038-023-01181-x

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