Abstract
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.
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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.
Burgess SM, Kleckner N (1999) Collisions between yeast chromosomal loci in vivo are governed by three layers of organization. Genes Dev 13: 1871-1883.
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.
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.
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.
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.
Craig JM, Bickmore WA (1994) The distribution of CpG islands in mammalian chromosomes. Nat Genet 7: 376-382.
Cremer C, Munkel C, Granzow M et al. (1996) Nuclear architecture and the induction of chromosomal aberrations. Mutat Res 366: 97-116.
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.
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.
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.
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.
International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409: 860-921.
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.
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.
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.
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.
Kurahashi H, Emanuel BS (2001) Long AT-rich palindromes and the constitutional t(11;22) breakpoint. Hum Mol Genet. 10: 2605-2617.
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.
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.
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.
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.
Parada LA, McQueen PG, Munson PJ, Misteli T (2002) Conservation of relative chromosome positioning in normal and cancer cells. Curr Biol 12: 1692-1697.
Richardson C, Jasin M (2000) Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 405: 697-700.
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.
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.
Savage JRK (1996) Insights into sites. Mutation Res 366: 81-95.
Savage JRK (2000) Proximity matters. Science 290: 62-63.
Sullivan BA, Wolff DJ, Schwartz S (1994) Analysis of centromeric activity in Robertsonian translocations: implications for a functional acrocentric hierarchy. Chromosoma 103: 459-467.
Venter JC, Adams MD, Myers EW et al. (2001) The sequence of the human genome. Science 291: 1304-1351.
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.
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Bickmore, W.A., Teague, P. Influences of chromosome size, gene density and nuclear position on the frequency of constitutional translocations in the human population. Chromosome Res 10, 707–715 (2002). https://doi.org/10.1023/A:1021589031769
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DOI: https://doi.org/10.1023/A:1021589031769