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Radial Arrangement of Chromosome Territories in Human Cell Nuclei: A Computer Model Approach Based on Gene Density Indicates a Probabilistic Global Positioning Code

G. Kreth ^*, J. Finsterle ^*, J. von Hase ^*, M. Cremer  and C. Cremer ^* 

^* Kirchhoff Institute for Physics, and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany; and Department Biology II, University of Munich and Institute of Human Genetics, Technical University, Munich, Germany

Correspondence: Address reprint requests to G. Kreth, Kirchhoff Institute for Physics, INF 227, D-69120 Heidelberg, Germany. E-mail: gkreth{at}kip.uni-heidelberg.de.

Numerous investigations in the last years focused on chromosome arrangements in interphase nuclei. Recent experiments concerning the radial positioning of chromosomes in the nuclear volume of human and primate lymphocyte cells suggest a relationship between the gene density of a chromosome territory (CT) and its distance to the nuclear center. To relate chromosome positioning and gene density in a quantitative way, computer simulations of whole human cell nuclear genomes of normal karyotype were performed on the basis of the spherical 1 Mbp chromatin domain model and the latest data about sequence length and gene density of chromosomes. Three different basic assumptions about the initial distribution of chromosomes were used: a statistical, a deterministic, and a probabilistic initial distribution. After a simulated decondensation in early G1, a comparison of the radial distributions of simulated and experimentally obtained data for CTs Nos. 12, 18, 19, and 20 was made. It was shown that the experimentally observed distributions can be fitted better assuming an initial probabilistic distribution. This supports the concept of a probabilistic global gene positioning code depending on CT sequence length and gene density.

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