Telomeric Translocation Research Articles

Molecular characterization of Fusarium resistance from Elymus repens introgressed into bread wheat

A cross was made of Elymus repens onto the wheat cultivar Crocus and BC1 progeny advanced to BC1F7 by single seed descent. Sixteen lines were selected based on agronomic performance and evaluated in an FHB epiphytotic nursery. Eight lines with FHB resistance were selected. Based on GISH analysis, line PI 142-3-1-5 had 42 chromosomes with one pair of chromosomes showing telomeric translocations on both arms. This chromosome was identified as 3D by using SSR markers. An evaluation of lines with single translocations revealed that FHB resistance was contributed by the translocation on the long arm of chromosome 3D. That line has minimal linkage drag and should be amenable to applications inbreeding for disease resistance.

Reconstructing the History of Yeast Genomes

Reconstructing the History of Yeast Genomes

A constitutional telomeric translocation showing meiotic instability

Constitutional telomeric translocations are rare chromosome rearrangements. They are thought to occur as a result of chromosome breakage and subsequent ligation with the telomeric sequence of a different chromosome. Most frequently they occur as de novo events and, depending on the donor chromosome breakpoint, may be associated with an abnormal phenotype. We report a case of an unbalanced translocation involving the long arm of chromosome 15 and the short arm of chromosome 8 [45,XY, der(8)t(8;15)(p23.3;q11.2),-15], diagnosed prenatally; the father carried an unbalanced translocation of the long arm of chromosome 15 and the short arm of chromosome 2 [45,XY,der(2)t(2;15)(p25.3;q11.2),-15]. Both translocations were shown to have telomere repeat sequences at the translocation breakpoints. There was no apparent imbalance of euchromatic material in either translocation, and no associated abnormal phenotype.

An 11p;17p telomeric translocation in two families associated with recurrent miscarriages and Miller-Dieker syndrome.

Translocations occur in a proportion of couples affected by recurrent miscarriages. We describe two such families in which the underlying cause was a cryptic subtelomeric 11p;17p translocation detected only after the birth of an affected child carrying an unbalanced form of the rearrangement. Unbalanced subtelomeric rearrangements are now recognised as a significant cause of mental impairment and we believe that these rearrangements may also be an important cause of recurrent miscarriages. In these two families the translocation is most likely to have arisen from a single ancestral event because all translocation carriers shared almost identical haplotypes around the breakpoints on both chromosomes.

Subtelomeric rearrangements: results from a study of selected and unselected probands with idiopathic mental retardation and control individuals by using high-resolution G-banding and FISH.

The cause of mental retardation, present in approximately 3% of the population, is unexplained in the majority of cases. Recent reports have suggested that cryptic telomeric rearrangements resulting in segmental aneuploidy and gene-dosage imbalance might represent a significant cause of idiopathic mental retardation (IMR). Two groups of patients with unexplained developmental delay (unselected and selected) and a group of control individuals have been investigated to determine the frequency of submicroscopic telomeric rearrangements associated with IMR and the frequency within the normal population. In contrast to current thinking, our data have shown that true cryptic telomeric rearrangements are not a significant cause of IMR. No fully cryptic abnormalities were detected in our IMR groups, although a semi-cryptic unbalanced telomeric translocation was identified in one selected patient by high-resolution G-band analysis. This abnormality was confirmed and characterised by fluorescence in situ hybridisation (FISH) with telomere-specific probes. A further 13 cytogenetically detected subtle terminal rearrangements were characterised by using multi-telomere FISH. Seven of these had previously been reported as normal, three of which were shown to be interstitial deletions. These cases illustrate the importance of high-resolution analysis to exclude subtle but cytogenetically visible abnormalities prior to subtelomere FISH screening when determining the frequency of cryptic telomeric rearrangements. Unexpectedly, two cryptic telomeric abnormalities were detected among our control individuals, suggesting that submicroscopic telomeric abnormalities may be a not uncommon finding in the general population. Hence, our data have important implications when defining the significance of cryptic telomeric rearrangements detected during screening programmes.

Fluorescence In Situ Hybridization Detection of Two Telomeres on the Short Arm of a Derived Chromosome 16 in an Infant with Thrombocytopenia

We report a case of severe thrombocytopenia with an abnormal bone marrow karyotype described by G-banding analysis as t(16;21)(p?13;q11). Using fluorescence in situ hybridization (FISH) analysis with whole chromosome paints, the chromosome rearrangement was shown to be more complex, with the additional cryptic involvement of the long arm of chromosome 3. The chromosome rearrangement involved the breakpoints 3q26, 16p13.3, and 21q11; this rearrangement has not been previously described. The size of genomic material translocated from the chromosome 16 homologue was too small to be detected by chromosome paint. A 16p-specific telomeric probe was hybridized to locate the translocated 16p material. The 16p telomeric unique sequence DNA was retained on the der(16) chromosome, indicating a more distal breakpoint. This study demonstrates that telomeric translocations can occur that would be undetected by telomeric-specific FISH probes.

Silencing at Drosophila telomeres: nuclear organization and chromatin structure play critical roles.

Transgenes inserted into the telomeric regions of Drosophila melanogaster chromosomes exhibit position effect variegation (PEV), a mosaic silencing characteristic of euchromatic genes brought into juxtaposition with heterochromatin. Telomeric transgenes on the second and third chromosomes are flanked by telomeric associated sequences (TAS), while fourth chromosome telomeric transgenes are most often associated with repetitious transposable elements. Telomeric PEV on the second and third chromosomes is suppressed by mutations in Su(z)2, but not by mutations in Su(var)2-5 (encoding HP1), while the converse is true for telomeric PEV on the fourth chromosome. This genetic distinction allowed for a spatial and molecular analysis of telomeric PEV. Reciprocal translocations between the fourth chromosome telomeric region containing a transgene and a second chromosome telomeric region result in a change in nuclear location of the transgene. While the variegating phenotype of the white transgene is suppressed, sensitivity to a mutation in HP1 is retained. Corresponding changes in the chromatin structure and inducible activity of an associated hsp26 transgene are observed. The data indicate that both nuclear organization and local chromatin structure play a role in this telomeric PEV.

The impact of the new fish technologies on the cytogenetics of haematological malignancies.

The impact of the new fish technologies on the cytogenetics of haematological malignancies.

Centromere–telomere (12;8p) fusion, telomeric 12q translocation, and i(12p) trisomy 1

The concurrence of a short arm isochromosome and a translocation of the entire long arm of the same chromosome to a telomere of another chromosome, implying trisomy for 4p, 5p, 7p, 9p, 10p or 12p, has been described in 13 patients. We have now used fluorescence in situ hybrization (FISH) to better characterize one of these rearrangements in which 12q was translocated to 8pter, whereas 12p was converted into an isochromosome. An alphoid centromere-12 repeat gave a strong signal on the i( 2p) and a weak but distinct signal at the breakpoint junction of the der(8), whereas the pantelomeric probe revealed three clear hybridization sites on the der(8): one at each end and another at the breakpoint junction. These findings suggest that the prime event was a post-fertilization centric fission of chromosome 12 leading to the 12q translocation via a real centromere telomere fusion and the i(12p). Alternatively, the crucial event may have been a centromere telomere recombination. An interstitial telomere has been documented by means of FISH at the breakpoint junction of the sole derivative usually present in 20 constitutional translocations including eight with a jumping behavior. In addition, six other telomeric translocations defined by banding methods, including another case of 12q translocation/i(12p), have also been jumping ones. These telomeric translocations have been de noro events and their proneness to exhibit a jumping behavior appears to be independent of the involved chromosomes, size of the translocated segments, and concomitant abnormalities.

A new strategy for cryptic telomeric translocation screening in patients with idiopathic mental retardation.

Cryptic unbalanced chromosome rearrangements in the telomeric bands of human chromosomes constitute a significant cause of "idiopathic" mental retardation. Here, we have described a new strategy based upon comparative genomic...

Identification of an unbalanced cryptic translocation t(9;17)(q34.3;p13.3) in a child with dysmorphic features

We report a case of an unbalanced cryptic telomeric translocation 46,XY,der(17),t(9;17)(q34.3;p13.3) in a boy with dysmorphic features and developmental delay. The proband had intrauterine growth retardation, postnatal short stature, and mild microcephaly. Magnetic resonance imaging showed incomplete myelination, but no evidence of lissencephaly. Cytogenetic analysis of the proband's peripheral blood showed an abnormal 17p. Fluorescence in situ hybridisation (FISH) with a Miller-Dieker cosmid probe did not detect a deletion for that area. Further analysis with a 17p telomere specific probe identified an unbalanced telomeric translocation. The same probe was used to determine the presence of an apparent balanced translocation t(9;17)(q34.3;p13.3) in the mother of the proband. The balanced translocation was confirmed with two cosmids that map distally on 9q34.3. Two phenotypically normal half sibs, a maternal aunt, a maternal uncle, and the maternal grandmother were found to be balanced translocation carriers as well. A subtle translocation carriers as well. A subtle translocation is one mechanism that can produce an abnormal phenotype in a patient who had a normal karyotype at lower band resolution levels.

True telomeric translocation in a baby with the Prader‐Willi phenotype

We report on a baby with a nonreciprocal de novo unbalanced translocation between chromosomes 12 and 15. Her karyotype was 45,XX, -12, -15, +der(12)t(12;15)(pter-->qter::q13-->qter). The paternal origin of the 15q11-13 region was shown by DNA marker studies and, consistent with this, the baby had the Prader-Willi (PWS) phenotype. The breakpoint on 12q was distal to D12S11 (lambda MS43) which maps to 12q24.3-qter. Fluorescent in situ hybridization using the oligonucleotides (TTAGGG)7 and (AATCCC)7 showed that the 12q telomere was still present within the translocated chromosome. Thus, the translocation was within or onto the end of the telomere of 12q. This unusual translocation is further evidence of an unexplained instability of the 15q11-13 region.

Trisomy 20q. A new case and further phenotypic delineation

The present report concerns the clinical and cytogenetic findings in a liveborn girl with trisomy for the long arm of chromosome 20. She was the unbalanced product of a maternal t(18;20)(q23.2;q13.1) translocation. Our case is compared to the 3 previous reports of trisomy 20q associated with telomeric translocation. Adenosine deaminase dosage falls in the normal range and confirms the exclusion of the ADA locus from the region extending distally to 20q13.1.

On telomere replication and fusion in eukaryotes: apropos of a case of 45, X/46, X, ter rea(X;X)(p22.3;p22.3)

A Mexican 181/2-year-old girl with short stature, primary amenorrhea, and mild Turner stigmata was found to have a 45,X/46,X,ter rea(X;X)(p22.3;p22.3) karyotype in her lymphocytes. The rearranged chromosome was twice the size of a normal X, appeared to be attached head-to-head, had no detectable chromatin loss, only one primary constriction, constitutive heterochromatin at both the centromere and pseudocentromere regions, was mitotically stable, and always showed late replication. From the analysis of this and other X;X terminal rearrangements we draw four conclusions: (1) Terminal rearrangements may arise either by telomeric fusion (tel fus) without loss of genetic material or from a conventional telomeric translocation. (2) Telomeric fusions between homologous chromosomes (the commonest type) can be secondary to impaired telomeric replication. (3) Phenotypically, patients with an X;X terminal rearrangement show great variability which depends mainly on whether or not chromatin has been lost in the rejoining process and a 45,X clone. (4) Patients with an X;X telomeric fusion without mosaicism are likely to have an XXX phenotype, whereas turneroid features are expected in mixoploidies that include an X monosomic clone and in cases of translocations involving the short arms.