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.
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.
Authors: M C Bonaglia; R Giorda; G Poggi; M E Raggi; E Rossi; A Baroncini; S Giglio; R Borgatti; O Zuffardi Journal: Eur J Hum Genet Date: 2000-08 Impact factor: 4.246
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Authors: Alexsandro Dos Santos; Francine Campagnari; Ana Cristina Victorino Krepischi; Maria de Lourdes Ribeiro Câmara; Rita de Cássia E de Arruda Brasil; Ligia Vieira; Angela M Vianna-Morgante; Paulo A Otto; Peter L Pearson; Carla Rosenberg Journal: Chromosome Res Date: 2018-05-12 Impact factor: 5.239
Authors: P J Hulick; K M Noonan; S Kulkarni; D J Donovan; M Listewnik; C Ihm; J M Stoler; S Weremowicz Journal: Cytogenet Genome Res Date: 2010-01-06 Impact factor: 1.636