Frequency of Chromosome Healing and Interstitial Telomeres in 40 Cases of Constitutional Abnormalities

Abstract

Human telomeres play a major role in stabilizing chromosome ends and preventing fusions. Chromosomes bearing a broken end are rescued by the acquisition of a new telomeric cap without any subtelomeric sequences being present at the breakpoint, a process referred to as chromosome healing. Conversely, a loss of telomeric function or integrity can lead to the presence of interstitial telomeres at the junction site in translocations or ring chromosomes. In order to determine the frequency at which interstitial telomeres or chromosome healing events are observed in target chromosome abnormalities, we conducted a retrospective FISH study using pan-telomeric and chromosome-specific subtelomeric probes on archival material from 40 cases of terminal deletions, translocations or ring chromosomes. Of the 19 terminal deletions investigated, 17 were negative for the subtelomeric probe specific to the deleted arm despite being positive for the pan-telomeric probe. These 17 cases were thus considered as having been rescued through chromosome healing, suggesting that this process is frequent in terminal deletions. In addition, as 2 of these cases were inherited from a parent bearing the same deletion, chromosomes healed by this process are thus stable through mitosis and meiosis. Regarding the 13 cases of translocations and 8 ring chromosomes, 4 and 2 cases respectively demonstrated pan-telomeric sequences at the interstitial junction point. Furthermore, 2 cases of translocations and 1 ring chromosome had both interstitial pan-telomeres and subtelomeres, whereas 2 other cases of ring chromosomes and 1 case of translocation only showed interstitial subtelomeres. Therefore, interstitial (sub)telomeric sequences in translocations and ring chromosomes are more common than previously thought, as we found a frequency of 43% in this study. Moreover, our results illustrate the necessity of performing FISH with both subtelomeric and pan-telomeric probes when investigating these rearrangements, as the breakpoints can be either in the distal part of the pan-telomeres, or in between the 2 types of sequences.

Distribution of Telomeric DNA Sequences on the X-Radiation-Induced Chromosome Fragments Observed in the Genome of Androgenetic Brook Trout (<b><i>Salvelinus fontinalis</i></b>, Mitchill 1814)

“…Similar telomere-less rings were observed in the genome of androgenetic rainbow trout [Ocalewicz et al, 2004a[Ocalewicz et al, , 2009. Presumably, chromosome fragments with 2 interstitially located telomeric signals were also ring chromosomes as the fusion of a radiation-broken chromosome with the opposite telomeric region has been described previously [Henegariu et al, 1997;Fortin et al, 2009]. However, we do not exclude that some of these fragments might have originated from the brook trout chromosomes with interstitially located telomeric DNA sequences [Ocalewicz et al, 2004b].…”

A Girl with 15q Overgrowth Syndrome and dup(15)(q24q26.3) that Included Telomeric Sequences

“…Actually, interstitial telomeres were found in a 9p duplication [26] but not in 12 terminal duplications involving diverse chromosomes [27]. In contrast, interstitial telomeric and/or subtelomeric sequences have been detected in both triplications alluded to in previous studies [7,8], in a tandem 15q telomeric translocation [28], as well as in 9/21 (43%) translocations and rings concerning chromosomes other than chromosome number 15 [29].…”

Endogenous Hot Spots of De Novo Telomere Addition in the Yeast Genome Contain Proximal Enhancers That Bind Cdc13

“…Endogenous sites of de novo telomere addition can affect genome stability and have been associated with cancer (36) and congenital disorders (37)(38)(39). While S. cerevisiae provides a useful model system to study mechanisms of de novo telomere addition, most studies utilize artificial sequences to stimulate telomere formation.…”