Extensive cytogenetic analysis of a stable dicentric isochromosome 21, idic(21), formed by fusion of the terminal long arms.

The dicentric isochromosome 21 described in this paper was formed by fusion of the terminal parts of the long arms of two chromosomes 21. No interstitial telomeric AGGGTT repeats could be detected at the fusion point, but G-banding, comparative genomic hybridization, and fluorescence in situ hybridization with painting probes for 21qter revealed no loss of other terminal DNA sequences at the fusion point. Thus, only the telomeric repeats seem to have been lost prior to, or as a consequence of, isochromosome formation. Both short arms of the isochromosome were intact with complete NORs, and staining for alpha-satellite DNA showed that the DNA content of the two centromeres was the same. Antibody staining for the centromeric proteins CENP-C and CENP-E and for topoisomerase IIalpha and IIbeta demonstrated that these proteins were localized predominantly or exclusively at the centromere in the primary constriction. A novel functional in situ assay for topoisomerase activity in vivo similarly demonstrated enzyme activity exclusively at the primary constriction centromere.