Narrowing the localization of the region breakpoint in most frequent Robertsonian translocations.
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ABSTRACT:
SUBMITTER: Jarmuz-Szymczak M
PROVIDER: S-EPMC4257996 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Robertsonian translocations (ROBs) have an estimated incidence rate of 1/1000 births, making this type of rearrangement the most common structural chromosomal abnormalities seen in the general population. In this study, we reports 872 cases of ROBs from 205,001 specimens karyotyped postnatally in a single accredited laboratory in China, including 583 balanced ROBs, 264 unbalanced ROBs, 9 mosaic ROBs, and 18 complex ROBs. Ninety-three percent of the balanced ROBs observed were adults with infertility, miscarriage, or offspring(s) with known chromosomal abnormalities. Significant excess of females were found to be carriers of balanced ROBs with an adjusted male/female ratio of 0.77. Ninety-eight percent of the unbalanced ROBs observed were children with variable referral reasons. Almost all of the unbalanced ROBs involved chromosome 21 except a single ROB with [46,XX,der(13;14),+13] identified in a newborn girl with multiple congenital anomalies. Multiple novel ROB karyotypes were reported in this report. This study represents the largest collections of ROBs in Chinese population.
| S-EPMC4416705 | biostudies-literature
Project description:Robertsonian translocations (ROBs) are whole arm rearrangements involving the acrocentric chromosomes 13-15 and 21-22 and carriers are at increased risk for aneuploidy and thus uniparental disomy (UPD). Chromosomes 14 and 15 are imprinted with expression of genes dependent on the parental origin of the chromosome. Correction of a trisomic or monosomic conceptus for chromosomes 14 or 15 would lead to one of the established UPD 14mat/pat or UPD 15 (Prader-Willi/Angelman) syndromes (PWS/AS). In view of this, prenatal UPD testing should be considered for balanced carriers of a ROB, fetuses with a familial or de novo balanced ROB that contains chromosome 14 or 15 or with a normal karyotype when a parent is a carrier of a balanced ROB with a 14 or 15. Individuals with congenital anomalies and an abnormal phenotype and carry a ROB involving the two imprinted chromosomes should also be UPD tested.
| S-EPMC4729106 | biostudies-literature
Project description:Robertsonian translocations are common chromosomal alterations. Chromosome variability affects human health and natural evolution. Despite the significance of such mutations, no mechanisms explaining the emergence of such translocations have yet been demonstrated. Several models have explored possible changes in interphase nuclei. Evidence for non-homologous chromosomes end joining in meiosis is scarce, and is often limited to uncovering mechanisms in damaged cells only. This study presents a primarily qualitative analysis of contacts of non-homologous chromosomes by short arms, during meiotic prophase I in the mole vole, Ellobius alaicus, a species with a variable karyotype, due to Robertsonian translocations. Immunocytochemical staining of spermatocytes demonstrated the presence of four contact types for non-homologous chromosomes in meiotic prophase I: (1) proximity, (2) touching, (3) anchoring/tethering, and (4) fusion. Our results suggest distinct mechanisms for chromosomal interactions in meiosis. Thus, we propose to change the translocation mechanism model from 'contact first' to 'contact first in meiosis'.
| S-EPMC7230836 | biostudies-literature
Project description:This study presents a novel approach that combines next-generation sequencing (NGS) and cytogenetic technologies for identifying chromosomes involved in chromosomal anomalies. This research focuses on a chromosome anomaly discovered in male Alpine Grey cattle, as well as two previously reported cases of reciprocal translocations (rcps), namely rcp(9;11) and rcp(4;7). Abnormal chromosomes from Alpine Grey cattle were microdissected from conventional preparations, and the amplified products were sequenced using NGS. The sequencing reads were then mapped to the reference genome, and the leverage effect was calculated to identify abnormal reads/Mb values. The result revealed the presence of rob(26;29), which was further confirmed through traditional cytogenetic analyses such as Giemsa staining, CBA-banding, RBA-banding, and FISH techniques. Furthermore, the feasibility of this approach on preserved metaphases was demonstrated through analysis of old slides from previously characterized cases. The study highlights the challenges involved in identifying and characterizing chromosomal aberrations in bovine species and offers a potential solution for analyzing historical anomalies when fresh blood material is unavailable. The combination of NGS and cytogenetic techniques provides a cost-effective and reliable approach for characterizing chromosomal anomalies in various species, including those identified before the availability of modern banding technologies and FISH mapping using specific molecular markers.
| S-EPMC10571785 | biostudies-literature
Project description:Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. TBP-related factor 2 (Trf2) encodes an alternative general transcription factor. A decrease of TRF2 expression disrupts the structure of the pericentromeric regions and prevents their association into chromocenter. We revealed several centric fusions in two lines of Drosophila melanogaster with weak Trf2 alleles in genetic experiments. We performed an RNAi-mediated knock-down of Trf2 in Drosophila and S2 cells and demonstrated that Trf2 upregulates expression of D1-one of the major genes responsible for chromocenter formation and nuclear integrity in Drosophila. Our data, for the first time, indicate that Trf2 may be involved in transcription program responsible for structuring of pericentromeric regions and may contribute to new karyotypes formation in particular by promoting centric fusion. Insight into the molecular mechanisms of Trf2 function and its new targets in different tissues will contribute to our understanding of its phenomenon.
| S-EPMC7700478 | biostudies-literature
Project description:BackgroundRobertsonian translocations are common structural rearrangements and confer an increased genetic reproductive risk due to the formation of trivalent structure during meiosis. Studies on trivalent structure show meiotic heterogeneity between different translocation carriers, although the factors causing heterogeneity have not been well elaborated in blastocysts. It is also not yet known whether interchromosomal effect (ICE) phenomenon occurs in comparison with suitable non-translocation control patients. Herein, we aimed to evaluate the factors that cause meiotic heterogeneity of trivalent structure and the ICE phenomenon.MethodsWe designed a retrospective study, comprising 217 Robertsonian translocation carriers and 134 patients with the risk of transmitting monogenic inherited disorders (RTMIDs) that underwent preimplantation genetic testing (PGT). Data was collected between March 2014 and December 2019. The segregation products of trivalent structure were analyzed based on the carrier's gender, age and translocation type. In addition, to analyze ICE phenomenon, aneuploidy abnormalities of non-translocation chromosomes from Robertsonian translocation carriers were compared with those from patients with RTMIDs.ResultsWe found that the percentage of male carriers with alternate segregation pattern was significantly higher [P < 0.001, odds ratio (OR) = 2.95] than that in female carriers, while the percentage of adjacent segregation pattern was lower (P < 0.001, OR = 0.33). By contrast, no difference was observed between young and older carriers when performing stratified analysis by age. Furthermore, segregation pattern was associated with the D;G chromosomes involved in Robertsonian translocation: the rate of alternate segregation pattern in Rob(13;14) carriers was significantly higher (P = 0.010, OR = 1.74) than that in Rob(14;21) carriers, whereas the rate of adjacent segregation pattern was lower (P = 0.032, OR = 0.63). Moreover, the results revealed that the trivalent structure could significantly increase the frequencies of chromosome aneuploidies 1.30 times in Robertsonian translocation carriers compared with patients with RTMIDs (P = 0.026), especially for the male and young subgroups (P = 0.030, OR = 1.35 and P = 0.012, OR = 1.40), while the mosaic aneuploidy abnormalities presented no statistical difference.ConclusionsOur study demonstrated that meiotic segregation heterogeneity of trivalent structure is associated with the carrier's gender and translocation type, and it is independent of carrier's age. ICE phenomenon exists during meiosis and then increases the frequencies of additional chromosome abnormalities.
| S-EPMC7928295 | biostudies-literature
Project description:A balanced robertsonian translocation (rob) results from fusion of 2 acrocentric chromosomes. Carriers are phenotypically normal and are often diagnosed because of recurrent miscarriages, infertility, or aneuploid offspring. Mortality and site-specific cancer risks in carriers have not been prospectively investigated. We followed 1,987 carriers diagnosed in Great Britain for deaths and cancer risk, over an average of 24.1 years. Standardized mortality and incidence ratios were calculated comparing the number of observed events against population rates. Overall mortality was higher for carriers diagnosed before age 15 years (standardized mortality ratio (SMR) = 2.00, 95% confidence interval (CI): 1.09, 3.35), similar for those diagnosed aged 15-44 years (SMR = 1.06, 95% CI: 0.86-1.28), and lower for those diagnosed aged 45-84 years (SMR = 0.81, 95% CI: 0.68, 0.95). Cancer incidence was higher for non-Hodgkin lymphoma (standardized incidence ratio (SIR) = 1.90, 95% CI: 1.01, 3.24) and childhood leukemia (SIR = 14.5, 95% CI: 1.75, 52.2), the latter particularly in rob(15;21) carriers (SIR = 447.8, 95% CI: 11.3, 2,495). Rob(13;14) carriers had a higher breast cancer risk (SIR = 1.58, 95% CI: 1.12, 2.15). Mortality risks relative to the population in diagnosed carriers depend on age at cytogenetic diagnosis, possibly reflecting age-specific cytogenetic referral reasons. Carriers might be at greater risk of childhood leukemia and non-Hodgkin lymphoma and those diagnosed with rob(13;14) of breast cancer.
| S-EPMC6395160 | biostudies-literature
Project description:Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of neuroblastoma and the two tumors belong to the group of neuroblastoma exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis.
| S-EPMC3753337 | biostudies-literature
Project description:PurposeThe purpose of this study was to apply next-generation sequencing (NGS) technology to identify chromosomally normal embryos for transfer in preimplantation genetic diagnosis (PGD) cycles for translocations.MethodsA total of 21 translocation couples with a history of infertility and repeated miscarriage presented at our PGD clinic for 24-chromosome embryo testing using copy number variation sequencing (CNV-Seq).ResultsTesting of 98 embryo samples identified 68 aneuploid (69.4 %) and 30 (30.6 %) euploid embryos. Among the aneuploid embryos, the most common abnormalities were segmental translocation imbalances, followed by whole autosomal trisomies and monosomies, segmental imbalances of non-translocation chromosomes, and mosaicism. In all unbalanced embryos resulting from reciprocal translocations, CNV-Seq precisely identified both segmental imbalances, extending from the predicted breakpoints to the chromosome termini. From the 21 PGD cycles, eight patients had all abnormal embryos and 13 patients had at least one normal/balanced and euploid embryo available for transfer. In nine intrauterine transfer cycles, seven healthy babies have been born. In four of the seven children tested at 18 weeks gestation, the karyotypes matched with the original PGD results.ConclusionIn clinical PGD translocation cycles, CNV-Seq displayed the hallmarks of a comprehensive diagnostic technology for high-resolution 24-chromosome testing of embryos, capable of identifying true euploid embryos for transfer.
| S-EPMC4930785 | biostudies-literature
Project description:PurposeTo provide more genetic information about meiotic segregation behavior and the possibility of interchromosomal effects (ICE) in spermatozoa from carriers of Robertsonian (Rob) translocations.Materials and methodsMeiotic segregation behavior in spermatozoa from six carriers of Rob translocations, four t(13;14), one t(14;22) and one t(13;21), was investigated by dual fluorescence in-situ hybridization (FISH). Aneuploidy for chromosomes 18, X and Y was studied by triple FISH.ResultsThe rate of normal/balanced spermatozoa resulting from alternate segregation ranged from 78.14 to 86.88%. The frequency of unbalanced spermatozoa resulting from adjacent segregation varied between 11.70 and 19.53%. The higher frequencies of aneuploidy for sex chromosome were observed in three Rob translocation carriers. In addition, the increased rates of diploid were found in two t(13;14) carriers.ConclusionsAlternate segregation is dominant in the different types of Rob translocations. Some carriers may be at an increased risk for ICE.
| S-EPMC3454947 | biostudies-literature