Chromosome spatial order in human cells: evidence for early origin and faithful propagation |
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Authors: | R G Nagele T Freeman J Fazekas K-M Lee Z Thomson H-Y Lee |
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Institution: | (1) Department of Molecular Biology, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA, US;(2) Department of Biology, Rutgers University, Camden, NJ 08102, USA, US |
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Abstract: | We have investigated the origin and nature of chromosome spatial order in human cells by analyzing and comparing chromosome
distribution patterns of normal cells with cells showing specific chromosome numerical anomalies known to arise early in development.
Results show that all chromosomes in normal diploid cells, triploid cells and in cells exhibiting nondisjunction trisomy 21
are incorporated into a single, radial array (rosette) throughout mitosis. Analysis of cells using fluorescence in situ hybridization,
digital imaging and computer-assisted image analysis suggests that chromosomes within rosettes are segregated into tandemly
linked “haploid sets” containing 23 chromosomes each. In cells exhibiting nondisjunction trisomy 21, the distribution of chromosome
21 homologs in rosettes was such that two of the three homologs were closely juxtaposed, a pattern consistent with our current
understanding of the mechanism of chromosomal nondisjunction. Rosettes of cells derived from triploid individuals contained
chromosomes segregated into three, tandemly linked haploid sets in which chromosome spatial order was preserved, but with
chromosome positional order in one haploid set inverted with respect to the other two sets. The spatial separation of homologs
in triploid cells was chromosome specific, providing evidence that chromosomes occupy preferred positions within the haploid
sets. Since both triploidy and nondisjunction trisomy 21 are chromosome numerical anomalies that arise extremely early in
development (e.g., during meiosis or during the first few mitoses), our results support the idea that normal and abnormal
chromosome distribution patterns in mitotic human cells are established early in development, and are propagated faithfully
by mitosis throughout development and into adult life. Furthermore, our observations suggest that segregation of chromosome
homologs into two haploid sets in normal diploid cells is a remnant of fertilization and, in normal diploid cells, reflects
segregation of maternal and paternal chromosomes.
Received: 19 January 1998; in revised form: 28 May 1998 / Accepted: 30 June 1998 |
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