Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The molecular mechanisms of recombinant chromosome 18 with parental pericentric inversions and a review of the literature

Journal of Human Genetics volume 68, pages 625–634 (2023)Cite this article

Subjects

Abstract

Chromosomal rearrangements mostly result from non-allelic homologous recombination mediated by low-copy repeats (LCRs) or segmental duplications (SDs). Recent studies on recombinant chromosome 18 (rec (18)) have focused on diagnoses and clinical phenotypes. We diagnosed two cases of prenatal rec (18) and identified precise breakpoint intervals using karyotype and chromosomal microarray analyses. We analyzed the distribution characteristics of breakpoint repetitive elements to infer rearrangement mechanisms and reviewed relevant literature to identify genetic trends. Among the 12 families with 25 pregnancies analyzed, 68% rec (18), 24% spontaneous abortions, and 8% normal births were reported. In the 17 rec (18) cases, 65% presented maternal origin and 35% were paternal. Short-arm breakpoints at p11.31 were reported in 10 cases, whereas the long-arm breakpoints were located at q21.3 (6 cases) and q12 (4 cases). Breakpoints of pericentric inversions on chromosome 18 are concentrated in p11.31, q21.3, and q12 regions. Rearrangements at 18p11.31 are non-recurrent events. ALUs, LINE1s, and MIRs were enriched at the breakpoint regions (1.85 to 3.42-fold enrichment over the entire chromosome 18), while SDs and LCRs were absent. ALU subfamilies had sequence identities of 85.94% and 83.01% between two pair breakpoints. Small repetitive elements may mediate recombination-coupled DNA repair processes, facilitating rearrangements on chromosome 18. Maternal inversion carriers are more prone to abnormal recombination in prenatal families with rec (18). Recombinant chromosomes may present preferential segregation during gamete formation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Karyotypes and ideograms of two families.
Fig. 2: Chromosome microarray results.
Fig. 3: Distribution patterns in prenatal cases of rearranged chromosome 18.
Fig. 4: Repetitive elements within and around the breakpoint intervals.

Similar content being viewed by others

Data availability

All relevant data of this study are presented.

References

  1. Martin AO, Simpson JL, Deddish RB, Elias S. Clinical implications of chromosomal inversions. A pericentric inversion in No. 18 segregating in a family ascertained through an abnormal proband. Am J Perinatol. 1983;1:81–8.

    Article  CAS  PubMed  Google Scholar 

  2. Sujansky E, Smith AC, Peakman DC, McConnell TS, Baca P, Robinson A. Familial pericentric inversion of chromosome 8. Am J Med Genet. 1981;10:229–35.

    Article  CAS  PubMed  Google Scholar 

  3. Lee JA, Carvalho CM, Lupski JR. A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders. Cell. 2007;131:1235–47.

    Article  CAS  PubMed  Google Scholar 

  4. Weckselblatt B, Rudd MK. Human structural variation: mechanisms of chromosome rearrangements. Trends Genet. 2015;31:587–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Samonte RV, Eichler EE. Segmental duplications and the evolution of the primate genome. Nat Rev Genet. 2002;3:65–72.

    Article  CAS  PubMed  Google Scholar 

  6. Abdullaev E. Dynamical aspects of the evolution of segmental duplications in the human genome. Berlin: Freie Universität Berlin; 2022. p. 3–33.

  7. Kojima KK. LINEs contribute to the origins of middle bodies of SINEs besides 3’ tails. Genome Biol Evol. 2018;10:370–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lee MJ, Park SH, Shim SH, Moon MJ, Cha DH. Prenatal diagnosis and molecular cytogenetic characterization of partial dup(18q)/del(18p) due to a paternal pericentric inversion 18 in a fetus with multiple anomalies. Taiwan J Obstet Gynecol. 2019;58:318–23.

    Article  PubMed  Google Scholar 

  9. Yu J, Xiaolu C, Jiayan C, Meijiao C, Jian Z, Yunsheng G, et al. Prenatal diagnosis and genetic counseling for two pedigrees with pericentric inversion of chromosome 18. Chin J Perinat Med. 2019;22:127–33.

    Google Scholar 

  10. Shuang C, Dejun L, Chunzhu J, Linlin L. Prenatal diagnosis of a case of 46, XY, rec(18)dup(18q)inv(18)(p11q12). Chin J Med Genet. 2019;36:681–81.

    Google Scholar 

  11. Zamani AG, Acar A, Durakbasi-Dursun G, Yildirim MS, Ceylaner S, Tuncez E. Recurrent proximal 18p monosomy and 18q trisomy in a family due to a pericentric inversion. Am J Med Genet A. 2014;164a:1239–44.

    Article  PubMed  Google Scholar 

  12. Sahin FI, Ozer O, Tarim E, Yilmaz Z. Detection of identical unbalanced karyotype in two consequent fetuses due to a maternal pericentric inversion of chromosome 18. J Obstet Gynaecol. 2012;32:698–700.

    Article  CAS  PubMed  Google Scholar 

  13. Kariminejad A, Kariminejad R, Moshtagh A, Zanganeh M, Kariminejad MH, Neuenschwander S, et al. Pericentric inversion of chromosome 18 in parents leading to a phenotypically normal child with segmental uniparental disomy 18. Eur J Hum Genet. 2011;19:555–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Prabhakara K, Wyandt HE, Huang XL, Prasad KS, Ramadevi AR. Recurrent proximal 18p monosomy and 18q trisomy in a family with a maternal pericentric inversion of chromosome 18. Ann Genet. 2004;47:297–303.

    Article  CAS  PubMed  Google Scholar 

  15. Roberts D, Sweeney E, Walkinshaw S. Congenital cystic adenomatoid malformation of the lung coexisting with recombinant chromosome 18. A case report. Fetal Diagn Ther. 2001;16:65–7.

    Article  CAS  PubMed  Google Scholar 

  16. Leonard NJ, Tomkins DJ, Demianczuk N. Prenatal diagnosis of holoprosencephaly (HPE) in a fetus with a recombinant (18)dup(18q)inv(18)(p11.31q11.2)mat. Prenat Diagn. 2000;20:947–9.

    Article  CAS  PubMed  Google Scholar 

  17. Mohsen-Pour N, Talebi T, Naderi N, Moghadam MH, Maleki M, Kalayinia S. Chromosome 9 Inversion: Pathogenic or Benign? A comprehensive systematic review of all clinical reports. Curr Mol Med. 2022;22:385–400.

  18. Stapley J, Feulner PGD, Johnston SE, Santure AW, Smadja CM. Variation in recombination frequency and distribution across eukaryotes: patterns and processes. Philos Trans R Soc Lond B Biol Sci. 2017;372:20160455.

  19. Liehr T, Weise A, Mrasek K, Ziegler M, Padutsch N, Wilhelm K, et al. Recombinant chromosomes resulting from parental pericentric inversions-two new cases and a review of the literature. Front Genet. 2019;10:1165.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV, Schwartz S, et al. Recent segmental duplications in the human genome. Science. 2002;297:1003–7.

    Article  CAS  PubMed  Google Scholar 

  21. Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, et al. DNA sequence and analysis of human chromosome 18. Nature. 2005;437:551–5.

    Article  CAS  PubMed  Google Scholar 

  22. Startek M, Szafranski P, Gambin T, Campbell IM, Hixson P, Shaw CA, et al. Genome-wide analyses of LINE-LINE-mediated nonallelic homologous recombination. Nucleic Acids Res. 2015;43:2188–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rossetti LC, Goodeve A, Larripa IB, De Brasi CD. Homeologous recombination between AluSx-sequences as a cause of hemophilia. Hum Mutat. 2004;24:440.

    Article  PubMed  Google Scholar 

  24. Weckselblatt B, Hermetz KE, Rudd MK. Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis. Genome Res. 2015;25:937–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gu S, Yuan B, Campbell IM, Beck CR, Carvalho CM, Nagamani SC, et al. Alu-mediated diverse and complex pathogenic copy-number variants within human chromosome 17 at p13.3. Hum Mol Genet. 2015;24:4061–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Carvalho CM, Lupski JR. Mechanisms underlying structural variant formation in genomic disorders. Nat Rev Genet. 2016;17:224–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Vianna-Morgante AM, Nozaki MJ, Ortega CC, Coates V, Yamamura Y. Partial monosomy and partial trisomy 18 in two offspring of carrier of pericentric inversion of chromosome 18. J Med Genet. 1976;13:366–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Anton E, Vidal F, Egozcue J, Blanco J. Genetic reproductive risk in inversion carriers. Fertil Steril. 2006;85:661–6.

    Article  CAS  PubMed  Google Scholar 

  29. Morel F, Laudier B, Guérif F, Couet ML, Royère D, Roux C, et al. Meiotic segregation analysis in spermatozoa of pericentric inversion carriers using fluorescence in-situ hybridization. Hum Reprod. 2007;22:136–41.

    Article  CAS  PubMed  Google Scholar 

  30. Asano T, Ikeuchi T, Shinohara T, Enokido H, Hashimoto K. Partial 18q trisomy and 18p monosomy resulting from a maternal pericentric inversion, inv(18)(p11.2q21.3). Jinrui Idengaku Zasshi. 1991;36:257–65.

    Article  CAS  PubMed  Google Scholar 

  31. Gardner RM, Sutherland GR, Shaffer LG. Chromosome abnormalities and genetic counseling. USA: OUP; 2011.

    Book  Google Scholar 

  32. Turleau C. Monosomy 18p. Orphanet J Rare Dis. 2008;3:4.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wester U, Bondeson ML, Edeby C, Annerén G. Clinical and molecular characterization of individuals with 18p deletion: a genotype-phenotype correlation. Am J Med Genet A. 2006;140:1164–71.

    Article  PubMed  Google Scholar 

  34. Prontera P, Buldrini B, Aiello V, Rogaia D, Mencarelli A, Gruppioni R, et al. Familial pericentric inversion of chromosome 18: intrafamilial variability of the recombinant dup(18q). Genet Couns. 2010;21:91–7.

    CAS  PubMed  Google Scholar 

  35. Vermeulen SJ, Speleman F, Vanransbeeck L, Verspeet J, Menten B, Verschraegen-Spae MR, et al. Familial pericentric inversion of chromosome 18: behavioral abnormalities in patients heterozygous for either the dup(18p)/del(18q) or dup(18q)/del(18p) recombinant chromosome. Eur J Hum Genet. 2005;13:52–8.

    Article  CAS  PubMed  Google Scholar 

  36. Poterico JA, Vásquez F, Chávez-Pastor M, Trubnykova M, Chavesta F, Chirinos J, et al. A peruvian child with 18p-/18q+ syndrome and persistent microscopic hematuria. J Pediatr Genet. 2017;6:258–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liehr T, Kosayakova N, Schröder J, Ziegler M, Kreskowski K, Pohle B, et al. Evidence for correlation of fragile sites and chromosomal breakpoints in carriers of constitutional balanced chromosomal rearrangements. Balk J Med Genet. 2011;14:13–6.

    CAS  Google Scholar 

  38. Durkin SG, Glover TW. Chromosome fragile sites. Annu Rev Genet. 2007;41:169–92.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

All authors have contributed to the work, agree with the presented findings, and the work has not been published before nor is being considered for publication in another journal. We appreciate the contributions of our lab colleagues. Apologies to those whose work we are unable to cite. This research received no external funding.

Author information

Authors and Affiliations

  1. Prenatal Diagnosis Center, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, China

    Lingxi Wang, Yamei Xie, Han Kang & Yong Wu

  2. Department of Eugenics, Meishan Women and Children’s Hospital, Alliance Hospital of West China Second University Hospital, Sichuan University, Meishan, 620000, China

    Bing Dong

Authors
  1. Lingxi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bing Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yamei Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Han Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Design, conceptualization and supervision: LW and BD; methodology: YW, YX, HK, and LW; literature collection, bibliographic search and data curation: LW, BD, and YW; writing—original draft preparation: LW; writing—review and editing: LW; figures, table preparation and proofreading: LW and BD; All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Lingxi Wang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, and approved by Ethics Committee of Chengdu Women’s and Children’s Center Hospital(B2021(19) and Aug. 2021)” for studies involving humans.

Informed consent

Informed consent was obtained from all subjects involved in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Dong, B., Xie, Y. et al. The molecular mechanisms of recombinant chromosome 18 with parental pericentric inversions and a review of the literature. J Hum Genet 68, 625–634 (2023). https://doi.org/10.1038/s10038-023-01157-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s10038-023-01157-x

Search

Advanced search

Quick links