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Published 28 October 2002. doi:10.1083/jcb.200206009
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© The Rockefeller University Press, 0021-9525/2002/10/237 $5.00
The Journal of Cell Biology, Volume 159, Number 2, 237-244

Article

 Chromosomes are predominantly located randomly with respect to each other in interphase human cells

Michael N. Cornforth1, Karin M. Greulich-Bode2,3, Bradford D. Loucas1, Javier Arsuaga4,5, Mariel Vázquez4, Rainer K. Sachs4, Martina Brückner3, Michael Molls3, Philip Hahnfeldt6, Lynn Hlatky6 and David J. Brenner7

1 Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX 77555
2 Department of Skin Carcinogenesis, German Cancer Research Center, Heidelberg 69120, Germany
3 Department of Radiation Oncology, Technical University of Munich, Munich 81675, Germany
4 Department of Mathematics, University of California, Berkeley, CA 94720
5 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720
6 Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
7 Center for Radiological Research, Columbia University, New York, NY 10032

Address correspondence to David J. Brenner, Center for Radiological Research, Columbia University, 630 W. 168th St., New York, NY 10032. Tel.: (212) 305-9930. Fax: (212) 305-3229. E-mail: djb3{at}columbia.edu

To test quantitatively whether there are systematic chromosome–chromosome associations within human interphase nuclei, interchanges between all possible heterologous pairs of chromosomes were measured with 24-color whole-chromosome painting (multiplex FISH), after damage to interphase lymphocytes by sparsely ionizing radiation in vitro. An excess of interchanges for a specific chromosome pair would indicate spatial proximity between the chromosomes comprising that pair. The experimental design was such that quite small deviations from randomness (extra pairwise interchanges within a group of chromosomes) would be detectable. The only statistically significant chromosome cluster was a group of five chromosomes previously observed to be preferentially located near the center of the nucleus. However, quantitatively, the overall deviation from randomness within the whole genome was small. Thus, whereas some chromosome–chromosome associations are clearly present, at the whole-chromosomal level, the predominant overall pattern appears to be spatially random.

Key Words: nuclear organization; human chromosome clustering; multiplex FISH; chromosome aberrations; proximity


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