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Cytogenetics and FISH characterization of marker. a QFQ banding of the normal chromosome X (right) and the marker (left). b RBA banding shows the inactivation of the marker (arrow) c FISH analysis with the specific probe for Xp11.1-q11.1 alpha-satellite (DXZ1, red signals) on the normal chromosome X and the marker (arrow). d FISH analysis with b167P23 BAC probe (Xp11.22, red signals) on the normal chromosome X and the marker (arrow). e FISH analysis with b217H1 BAC probe (Xq13.2–21.1, red signals) on the normal chromosome X and the marker (arrow). f FISH analysis with the specific probe for Xp/Yp telomere (DXYS129, red signals) on the normal chromosome X and the marker (arrow). g FISH analysis with the probe for common telomeric sequences (TTAGGG, red signals) on all chromosomes. The arrow indicates the marker. h Schematic representation of marker chromosome structure
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Background
Neocentromeres are rare and considered chromosomal aberrations, because a non-centromeric region evolves in an active centromere by mutation. The literature reported several structural anomalies of X chromosome and they influence the female reproductive capacity or are associated to Turner syndrome in the presence of monosomy X cell line...
Contexts in source publication
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... in the anomalous one. The X mono- somy was observed in eight colonies and the presence of marker chromosome in other five different colonies deriv- ing from four independent cultures. It was possible to recognize the marker morphology as a double apparently complete chromosome X, probably an isochromosome, sized more than chromosome 1 (Fig. ...
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... unusual aspect was represented by the presence of an active centromere (AC, primary constriction) in the middle of the marker, at the union of the two Xp arms, where usually the telomeric regions are located. X inacti- vation study by means of RBA banding evidenced that the marker was inactive in all analysed cells (Fig. ...
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... centromeric X alpha-satellite probe (DXZ1) showed an intense positive signal in the middle of the chromosome (new AC) and other two positive regions equally distant from the new centromere in the canon- ical position (Fig. 1c). These two centromeres were inactive (ICs) as indicated by the presence of two distinct signals, one for each ...
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... BAC probes mapped in Xp11.22 (b167P23) and Xq13.2-21.1 (b217H1) an Xp paracentric inversion involving the entire p arm was identified (Fig. 1d, e, and h). In fact, the two hybridization signals for the 167P23 BAC probe were located at both sites of the AC instead near the ICs (Fig. 1d, ...
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... BAC probes mapped in Xp11.22 (b167P23) and Xq13.2-21.1 (b217H1) an Xp paracentric inversion involving the entire p arm was identified (Fig. 1d, e, and h). In fact, the two hybridization signals for the 167P23 BAC probe were located at both sites of the AC instead near the ICs (Fig. 1d, ...
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... specific Xp telomere probe (DXYS129) showed two hybridization signals localized near the two ICs (Fig. 1f) confirming the Xp inversion. The common telomeric sequences (TTAGGG) were evidenced in 4 different posi- tions: 2 in correspondence of Xq telomeres and 2 next to the ICs (Fig. 1g, ...
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... specific Xp telomere probe (DXYS129) showed two hybridization signals localized near the two ICs (Fig. 1f) confirming the Xp inversion. The common telomeric sequences (TTAGGG) were evidenced in 4 different posi- tions: 2 in correspondence of Xq telomeres and 2 next to the ICs (Fig. 1g, ...
Citations
... Beyond Xi deletions, amplifications of large regions of X chromosomes have been associated with several diseases and syndromes [16,37,38], and the duplication of the Xa has been found in BRCA cell lines [39]. We selected TCGA-BRCA samples from the Xi-unaltered group (710 tumour samples; Diagram S1) and performed hierarchical clustering by the X-chromosome allele-specific copy number of the Xa. ...
... This scenario would be anticipated to correspond with higher X-linked gene expression, as we will go on to explore. Beyond Xi deletions, amplifications of large regions of X chromosomes have been associated with several diseases and syndromes [16,37,38], and the duplication of the Xa has been found in BRCA cell lines [39]. We selected TCGA-BRCA samples from the Xiunaltered group (710 tumour samples; Diagram S1) and performed hierarchical clustering by the X-chromosome allele-specific copy number of the Xa. ...
Ubiquitous to normal female human somatic cells, X-chromosome inactivation (XCI) tightly regulates the transcriptional silencing of a single X chromosome from each pair. Some genes escape XCI, including crucial tumour suppressors. Cancer susceptibility can be influenced by the variability in the genes that escape XCI. The mechanisms of XCI dysregulation remain poorly understood in complex diseases, including cancer. Using publicly available breast cancer next-generation sequencing data, we show that the status of the major tumour suppressor TP53 from Chromosome 17 is highly associated with the genomic integrity of the inactive X (Xi) and the active X (Xa) chromosomes. Our quantification of XCI and XCI escape demonstrates that aberrant XCI is linked to poor survival. We derived prognostic gene expression signatures associated with either large deletions of Xi; large amplifications of Xa; or abnormal X-methylation. Our findings expose a novel insight into female cancer risks, beyond those associated with the standard molecular subtypes.
... The structural or numerical abnormality of X chromosome causes TS (4). The phenotypes of TS are very heterogeneous depending on the type of abnormality (12). The most common feature is short stature, which is found in 95% of patients, especially in patients with 46,X,i(Xq). ...
Turner Syndrome (TS) is a genetic disorder caused by total or partial loss of an X chromosome. The isochromosome X (i(X)) is a known variant of TS, however, double i(X) is a very rare variant, reported very few times in the literature. We report on a rare case of TS with double i(X). This is an 11-year-old female patient , addressed to the medical genetics consultation for short stature and facial features suggestive of TS. We performed a constitutional postnatal karyotype from a peripheral blood sample, with lymphocyte culture, and an R band analysis, performed on 70 metaphases. Metaphases analysis in our patient identified the presence of three cell populations: 45,X[22]/46,X,i(X)(q10)[30]/47,X,i(X)(q10),i(X)(q10) [18]. The first has total chromosome X monosomy, the second with a normal X chromosome and one isochromosome of the long arm of the other X chromosome and the third with a normal X chromosome and two isochromosomes of the long arm of the X chromosome. A control cell culture was performed from a second blood sample of the patient and confirmed the abnormality. This paper will discuss this case in comparison with other rare cases described, as well as the formation of the double isochromosome, based on the literature.
... Of the 2 previously described X-autosome translocations in the horse, one was balanced and reciprocal [64,X,t(1p;Xp)(1q;Xq); Bugno-Poniewierska et al., 2018] and the other unbalanced [64,X,der(X),t(Xq;l5q)] with Xp deletion and trisomy ECA15 [Power, 1987]. Some of the few complex X chromosome rearrangements described in humans share elements with the presented equine case, but at the same time, are also different [Haltrich et al., 2015;Villa et al., 2017;Peterson et al., 2018]. Unfortunately, as we did not have access to additional tissue samples, it was not possible to study this case for chromatin features, replication patterns, or methylation to determine the functional status of the der and its centromeres. ...
Complex structural X chromosome abnormalities are rare in humans and animals, and not recurrent. Yet, each case provides a fascinating opportunity to evaluate X chromosome content and functional status in relation to the effect on the phenotype. Here, we report the first equine case of a complex unbalanced X-autosome rearrangement in a healthy but short in stature Thoroughbred mare. Studies of about 200 cells by chromosome banding and FISH revealed an abnormal 2n = 63,X,der(X;16) karyotype with a large dicentric derivative chromosome (der). The der was comprised of normal Xp material, a palindromic duplication of Xq12q21, and a translocation of chromosome 16 to the inverted Xq12q21 segment by the centromere, whereas the distal Xq22q29 was deleted from the der. Microsatellite genotyping determined a paternal origin of the der. While there was no option to experimentally investigate the status of X chromosome inactivation (XCI), the observed mild phenotype of this case suggested the following scenario to retain an almost normal genetic balance: active normal X, inactivated X-portion of the der, but without XCI spreading into the translocated chromosome 16. Cases like this present unique resources to acquire information about species-specific features of X regulation and the role of X-linked genes in development, health, and disease.
