Background: Broken chromosomes must acquire new telomeric “caps” to be structurally stable. Chromosome healing can be mediated either by telomerase through neo-telomere synthesis or by telomere capture.
Aim: To unravel the mechanism(s) generating complex chromosomal mosaicisms and healing broken chromosomes.
Methods: G banding, array comparative genomic hybridization (aCGH), fluorescence in-situ hybridisation (FISH) and short tandem repeat analysis (STR) was performed on a girl presenting with mental retardation, facial dysmorphism, urogenital malformations and limb anomalies carrying a complex chromosomal mosaicism.
Results & discussion: The karyotype showed a de novo chromosome rearrangement with two cell lines: one cell line with a deletion 9pter and one cell line carrying an inverted duplication 9p and a non-reciprocal translocation 5pter fragment. aCGH, FISH and STR analysis enabled the deduction of the most likely sequence of events generating this complex mosaic. During embryogenesis, a double-strand break occurred on the paternal chromosome 9. Following mitotic separation of both broken sister chromatids, one acquired a telomere vianeo-telomere formation, while the other generated a dicentric chromosome which underwent breakage during anaphase, giving rise to the del inv dup(9) that was subsequently healed by chromosome 5 telomere capture.
Conclusion: Broken chromosomes can coincidently be rescued by both telomere capture and neo-telomere synthesis.
- aCGH, array comparative genomic hybridisation
- BLAST, basic local alignment search tool
- DSB, double-strand break
- FISH, fluorescence in situ hybridization
- LCRs, low-copy repeats
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Published Online First 15 December 2006
Funding: This work was made possible by grants G.0200.03 from the FWO, OT/O2/40, GOA/2006/12 and Centre of Excellence SymBioSys (Research Council K.U.Leuven EF/05/007), Catholic University of Leuven, and grant (PI020028) from the Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain. Elyes Chabchoub was supported by the Ministry of Higher Education from Tunisia (Scholarship 2005-032/001).
Competing interests: None.
Parental informed consent was obtained for publication of figure 1.