Chromosome Research

, Volume 10, Issue 8, pp 707–715 | Cite as

Influences of chromosome size, gene density and nuclear position on the frequency of constitutional translocations in the human population

  • Wendy A. Bickmore
  • Peter Teague


Translocations are the most frequent chromosome structural aberration in the human population, yet little is known about their aetiology. Here, factors that might influence the occurrence of constitutional translocations in the population are examined. By analysing >10 000 translocations from two large databases of cytogenetic abnormalities, chromosome size is identified as the major determinant of translocation frequency. This probably reflects the large target size for double-strand breakage and repair presented by the largest chromosomes. There is also evidence for selection against translocations that involve breakage through the most gene-dense chromosomes. Lastly, it is suggested that nuclear organization of chromosomes impinges on the frequency of translocations amongst the smallest autosomes.

abnormalities chromosome territories clinical cytogenetics human nuclear organization translocations 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Boyle S, Gilchrist S, Bridger JM, Mahy NL, Ellis JA, Bickmore WA (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10: 211-219.Google Scholar
  2. Burgess SM, Kleckner N (1999) Collisions between yeast chromosomal loci in vivo are governed by three layers of organization. Genes Dev 13: 1871-1883.Google Scholar
  3. Cafourkova A, Lukasova E, Kozubek S et al. (2001) Exchange aberrations among 11 chromosomes of human lymphocytes induced by gamma-rays. Int J Radiat Biol 77: 419-429.Google Scholar
  4. Chubb JR, Boyle S, Perry P, Bickmore WA (2002) Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol 12: 439-445.Google Scholar
  5. Cohen O, Mermet M-A, Demongeot J (2001) HC Forum: a web site based on an international human cytogenetic database. Nucl Acids Res 29: 305-307.Google Scholar
  6. Cornforth MN, Greulich-Bode KM, Loucas BD et al. (2002) Chromosomes are predominantly located randomly with respect to each other in interphase human cells. J Cell Biol 159: 237-244.Google Scholar
  7. Craig JM, Bickmore WA (1994) The distribution of CpG islands in mammalian chromosomes. Nat Genet 7: 376-382.Google Scholar
  8. Cremer C, Munkel C, Granzow M et al. (1996) Nuclear architecture and the induction of chromosomal aberrations. Mutat Res 366: 97-116.Google Scholar
  9. Cremer M, von Hase J, Volm T et al. (2001)Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells. Chromosome Res 9: 541-567.Google Scholar
  10. Denegri M, Moralli D, Rocchi M et al. (2002) Human chromosomes 9, 12, and 15 contain the nucleation sites of stress-induced nuclear bodies. Mol Biol Cell 13: 2069-2079.Google Scholar
  11. Giglio S, Calvari V, Gregato G et al. (2002) Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation. Am J Hum Genet 71: 276-285.Google Scholar
  12. Hazzouri M, Rousseaux S, Mongelard F et al. (2000) Genome organization in the human sperm nucleus studied by FISH and confocal microscopy. Mol Reprod Dev 55: 307-315.Google Scholar
  13. International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409: 860-921.Google Scholar
  14. Jacobs PA, Browne C, Gregson N, Joyce C, White H (1992) Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet 29: 103-108.Google Scholar
  15. Jolly C, Konecny L, Grady DL et al. (2002) In vivo binding of active heat shock transcription factor 1 to human chromosome 9 heterochromatin during stress. J Cell Biol 156: 775-781.Google Scholar
  16. Kozubek S, Lukášová E, Marecková A et al. (1999) The topological organization of chromosomes 9 and 22 in cell nuclei has a determinative role in the induction of t(9,22) translocations and in the pathogenesis of t(9,22) leukemias. Chromosoma 108: 426-435.Google Scholar
  17. Krystosek A (1998) Repositioning of human interphase chromosomes by nucleolar dynamics in the reverse transformation of HT1080 fibrosarcoma cells. Exp Cell Res 241: 202-209.Google Scholar
  18. Kurahashi H, Emanuel BS (2001) Long AT-rich palindromes and the constitutional t(11;22) breakpoint. Hum Mol Genet. 10: 2605-2617.Google Scholar
  19. Lukasova E, Kozubek S, Kozubek M et al. (1999) Chromosomes participating in translocations typical of malignant hemoblastoses are also involved in exchange aberrations induced by fast neutrons. Radiation Res 151: 375-384.Google Scholar
  20. Manuelidis L, Borden J (1988) Reproducible compartmentalization of individual chromosome domains in human CNS cells revealed by in situ hybridization and three dimensional reconstruction. Chromosoma 96: 397-410.Google Scholar
  21. Martínez-López W, Boccardo EM, Folle GA et al. (1998) Intrachromosomal localization of aberration breakpoints induced by neutrons and gamma rays in Chinese hamster ovary cells. Radiat Res 150: 585-592.Google Scholar
  22. Nikiforova MN, Stringer JR, Blough R et al. (2000) Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science 290: 138-141.Google Scholar
  23. Parada LA, McQueen PG, Munson PJ, Misteli T (2002) Conservation of relative chromosome positioning in normal and cancer cells. Curr Biol 12: 1692-1697.Google Scholar
  24. Richardson C, Jasin M (2000) Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 405: 697-700.Google Scholar
  25. Rothkamm K, Kuhne M, Jeggo PA, Lobrich M, (2001) Radiation-induced genomic rearrangements formed by nonhomologous end-joining of DNA double-strand breaks. Cancer Res 61: 3886-3893.Google Scholar
  26. Sachs RK, Chen AM, Brenner DJ (1997) Proximity effects in the production of chromosome aberrations by ionizing radiation. Int J Radiat Biol 71: 1-19.Google Scholar
  27. Savage JRK (1996) Insights into sites. Mutation Res 366: 81-95.Google Scholar
  28. Savage JRK (2000) Proximity matters. Science 290: 62-63.Google Scholar
  29. Sullivan BA, Wolff DJ, Schwartz S (1994) Analysis of centromeric activity in Robertsonian translocations: implications for a functional acrocentric hierarchy. Chromosoma 103: 459-467.Google Scholar
  30. Venter JC, Adams MD, Myers EW et al. (2001) The sequence of the human genome. Science 291: 1304-1351.Google Scholar
  31. Wang P, Zhou R-H, Zou Y, Jackson-Cook CK, Povirk LF (1997) Highly conservative reciprocal translocations formed by apparent joining of exchanged DNA double-strand break ends. Proc Natl Acad Sci USA 94: 12018-12023.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Wendy A. Bickmore
    • 1
  • Peter Teague
    • 1
  1. 1.MRC Human Genetics UnitEdinburghUK; Tel

Personalised recommendations