Skip to main content
Log in

Delineation of complex chromosomal rearrangements: evidence for increased complexity

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

There is an assumption of parsimony with regard to the number of chromosomes involved in rearrangements and to the number of breaks within those chromosomes. Highly complex chromosome rearrangements are thought to be relatively rare, with the risk for phenotypic abnormalities increasing as the number of chromosomes and chromosomal breaks involved in the rearrangement increases. We report here five cases of de novo complex chromosome rearrangements, each with a minimum of four breaks. Deletions were found in four cases, and in at least one case, a number of genes or potential genes might have been disrupted. This study highlights the importance of the detailed delineation of complex rearrangements, beginning with high-resolution chromosome analysis, and emphasizes the utility of fluorescence in situ hybridization in combination with the data available from the Human Genome Project as a means to delineate such rearrangements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Astbury C, Christ LA, Aughton, DJ, Cassidy SB, Kumar A, Eichler EE, Schwartz S (2004) Detection of cryptic deletions in de novo “balanced” chromosome rearrangements: further evidence for their role in phenotypic abnormalities. Genet Med (in press)

  • Barbour VM, Tufarelli C, Sharpe JA, Smith ZE, Ayyub H, Heinlein CA, Sloane-Stanley J, Indrak K, Wood WG, Higgs DR (2000) Alpha-thalassemia resulting from a negative chromosomal position effect. Blood 96:800–807

    CAS  PubMed  Google Scholar 

  • Brook-Carter PT, Peral B, Ward CJ, Thompson P, Hughes J, Maheshwar MM, Nellist M, Gamble V, Harris PC, Sampson JR (1994) Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease—a contiguous gene syndrome. Nat Genet 8:328–332

    CAS  PubMed  Google Scholar 

  • Brown J, Horsley SW, Jung C, Saracoglu K, Janssen B, Brough M, Daschner M, Beedgen B, Kerkhoffs G, Eils R, Harris PC, Jauch A, Kearney L (2000) Identification of a subtle t(16;19)(p13.3;p13.3) in an infant with multiple congenital abnormalities using a 12-colour multiplex FISH telomere assay, M-TEL. Eur J Hum Genet 8:903–910

    CAS  PubMed  Google Scholar 

  • Callen DF, Eyre H, McDonnell S, Schuffenhauer S, Bhalla K (2002) A complex rearrangement involving simultaneous translocation and inversion is associated with a change in chromatin compaction. Chromosoma 111:170–175

    CAS  PubMed  Google Scholar 

  • Cody JD, Ghidoni PD, DuPont BR, Hale DE, Hilsenbeck SG, Stratton RF, Hoffman DS, Muller S, Schaub RL, Leach RJ, Kaye CI (1999) Congenital anomalies and anthropometry of 42 individuals with deletions of chromosome 18q. Am J Med Gen 85:455–462

    Article  CAS  Google Scholar 

  • Crolla JA, Heyningen V van (2002) Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia. Am J Hum Genet 71:1138–1149

    Article  CAS  PubMed  Google Scholar 

  • Eussen BH, Bartalini G, Bakker L, Balestri P, Di Lucca C, Van Hemel JO, Dauwerse H, Ouweland AM van den, Ris-Stalpers C, Verhoef S, Halley DJ, Fois A (2000) An unbalanced submicroscopic translocation t(8;16)(q24.3;p13.3)pat associated with tuberous sclerosis complex, adult polycystic kidney disease, and hypomelanosis of Ito. J Med Genet 37:287–291

    Article  CAS  PubMed  Google Scholar 

  • Fantes J, Redeker B, Breen M, Boyle S, Brown J, Fletcher J, Jones S, Bickmore W, Fukushima Y, Mannens M, Danes S, Heyningen V Van, Hanson I (1995) Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype. Hum Mol Genet 4:415–422

    CAS  PubMed  Google Scholar 

  • Glaser B, Rossier E, Barbi G, Chiaie LD, Blank C, Vogel W, Kehrer-Sawatzki H (2003) Molecular cytogenetic analysis of a constitutional de novo interstitial deletion of chromosome 12p in a boy with developmental delay and congenital anomalies. Am J Med Genet 116:66–70

    Article  Google Scholar 

  • Horsley SW, Daniels RJ, Anguita E, Raynham HA, Peden JF, Villegas A, Vickers MA, Green S, Waye JS, Chui DH, Ayyub H, MacCarthy AB, Buckle VJ, Gibbons RJ, Kearney L, Higgs DR (2001) Monosomy for the most telomeric, gene-rich region of the short arm of human chromosome 16 causes minimal phenotypic effects. Eur J Hum Genet 9:217–225

    Article  CAS  PubMed  Google Scholar 

  • Kaiser-Rogers KA, Rao KW, Michaelis RC, Lese CM, Powell CM (2000) Usefulness and limitations of FISH to characterize partially cryptic complex chromosome rearrangements. Am J Med Genet 95:28–35

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Becker LA, Depinet TW, Haren JM, Kurtz CL, Robin NH, Cassidy SB, Wolff DJ, Schwartz S (1998) Molecular characterization and delineation of subtle deletions in de novo “balanced” chromosomal rearrangements. Hum Genet 103:173–178

    PubMed  Google Scholar 

  • Kleczkowska A, Fryns JP, Berghe H van den (1987) Pericentric inversions in man: personal experience and review of the literature. Hum Genet 75:333–338

    Google Scholar 

  • Madan K, Nieuwint AW, Bever Y van (1997) Recombination in a balanced complex translocation of a mother leading to a balanced reciprocal translocation in the child. Review of 60 cases of balanced complex translocations. Hum Genet 99:806–815

    Google Scholar 

  • Neitzel H (1986) A routine method for the establishment of permanent growing lymphobastoid cell lines. Hum Genet 73:320–326

    CAS  PubMed  Google Scholar 

  • Peschka B, Leygraaf J, Hansmann D, Hansmann M, Schrock E, Ried T, Engels H, Schwanitz G, Schubert R (1999) Analysis of a de novo complex chromosome rearrangement involving chromosomes 4, 11, 12 and 13 and eight breakpoints by conventional cytogenetic, fluorescence in situ hybridization and spectral karyotyping. Prenat Diagn 19:1143–1149

    Article  CAS  PubMed  Google Scholar 

  • Pinkel D, Straume T, Gray JW (1986) Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci USA 83:2934–2938

    CAS  PubMed  Google Scholar 

  • Rothlisberger B, Kotzot D, Brecevic L, Koehler M, Balmer D, Binkert F, Schinzel A (1999) Recombinant balanced and unbalanced translocations as a consequence of a balanced complex chromosomal rearrangement involving eight breakpoints in four chromosomes. Eur J Hum Genet 7:873–883

    CAS  PubMed  Google Scholar 

  • Seabright M (1971) A rapid banding technique for human chromosomes. Lancet II:971–972

    Google Scholar 

  • Sutherland HF, Wadey R, McKie JM, Taylor C, Atif U, Johnstone KA, Halford S, Kim UJ, Goodship, J, Baldini A, Scambler PJ (1996) Identification of a novel transcript disrupted by a balanced translocation associated with DiGeorge syndrome. Am J Hum Genet 59:23–31

    CAS  PubMed  Google Scholar 

  • Yunis J (1976) High resolution of human chromosomes. Science 191:1268–1270

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge Michele Eichenmiller and Cassy Gulden for technical assistance with the BAC preparations, Bobbi Sundman for the lymphoblast cell lines, the Blood Group for their excellence with the high-resolution chromosomes, and Steve Nagy for his slides. We thank Dr. John Crolla for his generous gift of the 11p13 cosmids and Dr. Evan Eichler for the BACs from the human BAC filter library (RPC1-11).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stuart Schwartz.

Additional information

Electronic database information: URLs for the data in this article are as follows:

http://genomics.roswellpark.org/human/overview.html

http://genome.ucsc.edu

http://www.lanl.gov

Rights and permissions

Reprints and permissions

About this article

Cite this article

Astbury, C., Christ, L.A., Aughton, D.J. et al. Delineation of complex chromosomal rearrangements: evidence for increased complexity. Hum Genet 114, 448–457 (2004). https://doi.org/10.1007/s00439-003-1079-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-003-1079-1

Keywords

Navigation