Showing papers on "Ring chromosome published in 2016"

Chromosome therapy: Potential strategies for the correction of severe chromosome aberrations.

Abstract: Large chromosomal aberrations occur commonly during development, resulting in complex and multisystem diseases. In spite of this high frequency, there are currently no means for correcting these disorders due to their complexity and involvement of multiple genes. Recently, several new approaches have been devised that target whole chromosomes in vitro, which are collectively referred to as "Chromosome Therapies." These include silencing and selection for loss of the extra chromosome in trisomies, promotion of euploidy in an aneuploid culture, and forced loss and replacement of a chromosome. Here, we provide a review of Chromosome Therapy, and discuss potential directions for these methods clinically, as well as research applications and cellular models that can be made using these technologies. © 2016 Wiley Periodicals, Inc.

Position effect modifying gene expression in a patient with ring chromosome 14.

Abstract: The clinical phenotype of patients with ring chromosomes usually reflects the loss of genomic material during ring formation. However, phenotypic alterations can also be found in the presence of complete ring chromosomes, in which the breakage and rejoining in terminal regions of both chromosome arms result in no gene loss. Here, we present a patient with a ring chromosome 14 that lost nothing but the telomeres. Since he and other patients with a similar chromosome abnormality present certain abnormal characteristics, we investigated the gene expression of eight chromosome 14 genes to find out whether the configuration of the ring had changed it, possibly producing some of these clinical features. The expression of these eight genes was studied by quantitative real-time polymerase chain reaction (qPCR) in the patient and in seven controls matched for gender and age. Two of them were found to be downregulated in the patient compared to the controls, indicating that his phenotype might be related to alterations in the expression of genes located in the abnormal chromosome, even when the copy number is normal. Thus, the phenotypic alterations found in the presence of complete ring chromosomes may be related to changes in the chromatin architecture, bringing about a change of expression by position effect. These results may explain some of the characteristics presented by our patient.

Molecular characterization of a novel ring 6 chromosome using next generation sequencing

Abstract: Karyotyping is the gold standard cytogenetic method for detection of ring chromosomes. In this study we report the molecular characterization of a novel ring 6 (r6) chromosome in a six-year-old girl with severe mental retardation, congenital heart disease and craniofacial abnormalities. Cytogenetic analysis was performed by conventional karyotyping. Molecular genetic analyses were performed using high-resolution chromosome microarray analysis (CMA) and next generation sequencing (NGS). OMIM, UCSC and PubMed were used as reference databases to determine potential genotype to phenotype associations. Peripheral blood and skin fibroblast karyotyping revealed the presence of a dominant cell line, 46,XX,(r6)(p25.3;q27) and a minor cell line 45,XX,-6. Molecular karyotyping using NGS identified 6p25.3 and 6q27 subtelomeric deletions of 1.78 Mb and a 0.56 Mb, respectively. Based on the known genes located within the r6 deletion interval 6q25.3-pter, genotype to phenotype association studies found compelling evidence to suggest that hemizygous expression of disease genes FOXC1, FOXF2, IRF4 and GMDS was the main underlying cause of the patient’s phenotype. We further speculate that the severity of the patient’s symptoms may have been exacerbated by low-level instability of the r6 chromosome. This is the first report of a novel r6 chromosome characterized at the molecular level using NGS.

Breakpoints and deleted genes identification of ring chromosome 18 in a Chinese girl by whole-genome low-coverage sequencing: a case report study

Abstract: Ring chromosome 18 [r(18)] is formed by 18p- and 18q- partial deletion and generates a ring chromosome. Loss of critical genes on each arm of chromosome 18 may contribute to the specific phenotype, and the clinical spectrum varieties may heavily depend on the extent of the genomic deletion. The aim of this study is to identify the detailed breakpoints location and the deleted genes result from the r18. Here we describe a detailed diagnosis of a seven-year-old Chinese girl with a ring chromosome 18 mutation by a high-throughput whole-genome low-coverage sequencing approach without karyotyping and other cytogenetic analysis. This method revealed two fragment heterozygous deletions of 18p and 18q, and further localized the detailed breakpoint sites and fusion, as well as the deleted genes. To our knowledge, this is the first report of a ring chromosome 18 patient in China analyzed by whole-genome low-coverage sequencing approach. Detailed breakpoints location and deleted genes identification help to estimate the risk of the disease in the future. The data and analysis here demonstrated the feasibility of next-generation sequencing technologies for chromosome structure variation including ring chromosome in an efficient and cost effective way.

Long-term EEG in patients with the ring chromosome 20 epilepsy syndrome

Abstract: The recognizable electroencephalography (EEG) pattern of ring chromosome 20 epilepsy syndrome can be missing in patients with r(20) chromosomal anomaly, and may be found in patients with frontal lobe epilepsy of other origin. This study aims to search for more specific EEG signs by using long-term recordings and measuring the duration of paroxysmal anomalies. The series included 12 adult patients with r(20) anomaly, and 12 controls without any chromosomal aberration. We measured the duration of every paroxysmal burst and calculated the sum of their durations for each long-term EEG recording. We compared patients to controls using the Mann-Whitney U-test. Every patient showed long-lasting paroxysmal EEG bursts, up to 60 min; controls did not show any bursts longer than 60 s (p < 0.0001). The total duration of paroxysmal anomalies was significantly longer in patients (31-692 min) compared to controls (0-48 min) (p < 0.0001). Thus, long-term recordings enhance the contribution of EEG methods for characterizing the ring 20 chromosome epilepsy syndrome.

Down-Turner Syndrome: A Case with Double Monoclonal Chromosomal Abnormality

Abstract: Introduction. The coexistence of Down and Turner syndromes due to double chromosome aneuploidy is very rare; it is even more rare to find the presence of a double monoclonal chromosomal abnormality. Objective. To report a unique case of double monoclonal chromosomal abnormality with trisomy of chromosome 21 and an X ring chromosome in all cells studied; no previous report has been found. Case Report. Female, 28 months old, with pathological short stature from birth, with the following dysmorphic features: tilted upward palpebral fissures, short neck, brachycephaly, and low-set ears. During the neonatal period, the infant presented generalized hypotonia and lymphedema of hands and feet. Karyotype showed 47,X,r(X),+21 [30]. Conclusion. Clinical features of both Down and Turner syndromes were found, highlighting short stature that has remained below 3 z score from birth to the present, associated with delayed psychomotor development. G-banded karyotype analysis in peripheral blood is essential for a definitive diagnosis.

Ring Chromosome 9 and Chromosome 9p Deletion Syndrome in a Patient Associated with Developmental Delay: A Case Report and Review of the Literature.

Abstract: Ring chromosomes have been described for all human chromosomes and are typically associated with physical and/or mental abnormalities resulting from a deletion of the terminal ends of both chromosome arms. This report describes the presence of a ring chromosome 9 in a 2-year-old male child associated with developmental delay. The proband manifested a severe phenotype comprising facial dysmorphism, congenital heart defects, and seizures. The child also exhibited multiple cell lines with mosaic patterns of double rings, a dicentric ring and loss of the ring associated with mitotic instability and dynamic tissue-specific mosaicism. His karyotype was 46,XY,r(9)(p22q34)[89]/46,XY,dic r(9; 9)(p22q34;p22q34)[6]/45, XY,-9[4]/47,XY,r(9),+r(9)[1]. However, the karyotypes of his parents and elder brother were normal. FISH using mBAND probe and subtelomeric probes specific for p and q arms for chromosome 9 showed no deletion in any of the regions. Chromosomal microarray analysis led to the identification of a heterozygous deletion of 15.7 Mb from 9p22.3 to 9p24.3. The probable role of the deleted genes in the manifestation of the phenotype of the proband is discussed.

Ring chromosome 18 in combination with 18q12.1 (DTNA) interstitial microdeletion in a patient with multiple congenital defects.

Abstract: Ring chromosome 18 [r(18)] syndrome represents a relatively rare condition with a complex clinical picture including multiple congenital dysmorphia and varying degrees of mental retardation. The condition is cytogenetically characterized by a complete or mosaic form of ring chromosome 18, with ring formation being usually accompanied by the partial loss of both chromosomal arms. Here we observed a 20-year-old male patient who along with the features typical for r(18) carriers additionally manifested a severe congenital subaortic stenosis. To define the genetic basis of such a compound phenotype, standard cytogenetic and high-resolution molecular-cytogenetic analysis of the patient was performed. Standard chromosome analysis of cultured lymphocytes confirmed 46, XY, r(18) karyotype. Array-based comparative genomic hybridization (array-CGH) allowed to define precisely the breakpoints of 18p and 18q terminal deletions, thus identifying the hemizygosity extent, and to reveal an additional duplication adjoining the breakpoint of the 18p deletion. Apart from the terminal imbalances, we found an interstitial microdeletion of 442 kb in size (18q12.1) that encompassed DTNA gene encoding α-dystrobrevin, a member of dystrophin-associated glycoprotein complex. While limited data on the role of DTNA missense mutations in pathogenesis of human cardiac abnormalities exist, a microdeletion corresponding to whole DTNA sequence and not involving other genes has not been earlier described. A detailed molecular-cytogenetic characterization of the patient with multiple congenital abnormalities enabled to unravel a combination of genetic defects, namely, a ring chromosome 18 with terminal imbalances and DTNA whole-gene deletion. We suggest that such combination could contribute to the complex phenotype. The findings obtained allow to extend the knowledge of the role of DTNA haploinsufficiency in congenital heart malformation, though further comprehensive functional studies are required.

Expanding the ocular phenotype of 14q terminal deletions: A novel presentation of microphthalmia and coloboma in ring 14 syndrome with associated 14q32.31 deletion and review of the literature

Abstract: A variety of ocular anomalies have been described in the rare ring 14 and 14q terminal deletion syndromes, yet the character, prevalence, and extent of these anomalies are not well defined. Identification of these ocular anomalies can be central to providing diagnoses and facilitating optimal individual patient management. We report a child with a 14q32.31 terminal deletion and ring chromosome formation, presenting with severe visual impairment secondary to significant bilateral coloboma and microphthalmia. This patient is compared to previously reported patients with similar ocular findings and deletion sizes to further refine a locus for coloboma in the 14q terminal region. Those with ring formation and linear deletions are compared and the possibility of ring formation affecting the proximal 14q region is discussed. This report highlights the severity of ocular anomalies that can be associated with ring 14 and 14q terminal deletion syndromes and reveals the limited documentation of ocular examination in these two related syndromes. This suggests that many children with these genetic changes do not undergo an ophthalmology examination as part of their clinical assessment, yet it is only when this evaluation becomes routine that the true prevalence and extent of ocular involvement can be defined. This report therefore advocates for a thorough ophthalmological exam in children with ring 14 or 14q terminal deletion syndrome.

Anterior Pituitary Aplasia in an Infant with Ring Chromosome 18p Deletion.

Abstract: We present the first reported case of an infant with 18p deletion syndrome with anterior pituitary aplasia secondary to a ring chromosome. Endocrine workup soon after birth was reassuring; however, repeat testing months later confirmed central hypopituitarism. While MRI reading initially indicated no midline defects, subsequent review of the images confirmed anterior pituitary aplasia with ectopic posterior pituitary. This case demonstrates how deletion of genetic material, even if resulting in a chromosomal ring, still results in a severe syndromic phenotype. Furthermore, it demonstrates the necessity of close follow-up in the first year of life for children with 18p deletion syndrome and emphasizes the need to verify radiology impressions if there is any doubt as to the radiologic findings.

Refractory and severe status epilepticus in a patient with ring chromosome 20 syndrome.

Abstract: Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder that is characterized by the development of refractory epilepsy during childhood with gradual declines in cognitive performance and behavior. Although the prognoses of seizures and intellectual disability associated with this condition are poor, life-threatening complications have rarely been described. We herein presented a case of a 17-year-old female with [r(20)] syndrome who developed recurrent status epilepticus (SE) at 14years of age that evolved into unremitting SE in spite of vigorous antiepileptic treatments. She was administered thiopental anesthesia for 1year, and was subsequently left in severe neurological sequelae. It is important to note that patients with this syndrome not only have severe epileptic encephalopathy persisting into adulthood, but are also at risk of fatal SE.

Patchy white matter hyperintensity in ring chromosome 18 syndrome

Abstract: Ring chromosome 18 syndrome is a chromosomal abnormality in which partial deletions occur at both ends of chromosome 18, that is, distally on the short and long arms. Previously reported brain magnetic resonance imaging (MRI) abnormalities include diffuse hyperintensity in the white matter, which has been regarded as hypomyelination because the gene for myelin basic protein production is located on the long arm of chromosome 18. We report the case of a 14-year-old boy with ring chromosome 18 syndrome, whose MRI showed patchy asymmetrical T2 and fluid-attenuated inversion-recovery hyperintensities in the deep white matter as well as diffuse hypomyelination. These patchy lesions may indicate demyelination or gliosis rather than hypomyelination. This result differs from previous reports.

Ring Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case Report and Review of the Literature

Abstract: A female child born preterm with intrauterine growth retardation and presenting with facial dysmorphism with clefts, microcephaly, limb deformities, and congenital abnormalities involving cardiovascular and urinary systems is described. Chromosomal analysis showed a de novo 46,XX,r(4)(p15.3q35) karyotype. The clinical features of the patient were compared with the phenotypic characteristics of 17 previously reported cases with ring chromosome 4 and those with Wolf-Hirschhorn syndrome (4p-). Clinical features observed in this case are consistent with the consensus phenotype in ring chromosome 4. Patent ductus arteriosus and bilateral talipes equinovarus observed in this baby widen the phenotypic spectrum associated with ring chromosome 4.

A FURTHER PATIENT OF PURE 15q DELETION: CLINICAL AND MOLECULAR CYTOGENETIC FINDINGS.

Abstract: A deletion of the distal long arm of chromosome 15 is generally reported with the formation of ring chromosome 15, whereas an isolated 15q deletion is rarely described. Here we report an 11 year-old girl, from non-consanguineous parents, who was referred to the Pediatric Genetics Department with growth retardation and multiple congenital abnormalities. In her medical history, she had a cleft palate, hip dislocation and crossed renal ectopia. Dysmorphological evaluation revealed a triangular face, low-set ears, fissured cleft tongue, micrognathia, proximally placed hypoplastic thumbs, genu valgus, 2-3 toe skin syndactyly, clinodactyly and nail hypoplasia. Speech problems were also noticed. The karyotype was normal. Subtelomeric fluorescent in-situ hybridisation (FISH) analysis showed a de novo terminal deletion about 755 kb. Furthermore, the breakpoint was located within the CHSY1 gene that is responsible for Temtamy preaxial brachydactyly syndrome which shares clinical features with 15qter deletion syndrome. To the best of our knowledge, this deletion is the smallest among reported patients. It is considered that the patient presented here significant contribution to phenotype-genotype correlation in 15q deletion patients.

Ring chromosome 15 presenting as short stature, intellectual disability and café-au-lait spots

Abstract: Ring Chromosome 15 results from loss of genetic material from both ends of chromosome 15 and joining of the ends to form ring. Only 50 cases are reported in literature with none from India. We report a case of 17 years old female approached us for short stature and low intelligence. On examination we noticed childish facial features, microcephaly and cafe-au-lait spots in significant number and size. Her karyotype result was 46xx r15. CONCLUSION: Ring chromosome 15 syndromes should be considered in a case having short stature with cafe-au-lait spots. Timely recognition and hereditary tendency counselling is required.

Ectodermal Dysplasia and Anodontia associated with Ring Chromosome 18

Abstract: Ectodermal dysplasia (ED) is a heritable condition and represents a multifarious group of diseases comprising different clinical signs and symptoms. The ED occurs as a result of disturbances in the ectoderm of the evolving embryo. Agenesis of teeth or anodontia is also the result of disturbance in this process, which prevents the proliferation of tooth buds. In the present case, an 18-month-old child with history of congenital anomalies (CAs), severely delayed developmental milestones, and mental retardation presented with complete anodontia and ED. The CA included pulmonary stenosis, pulmonary valvar regurgitation, ventricular septal defect (VSD), absence of grips, absence of head-holding capacity, inability to sit, simian crease (R), visual impairment with corectopia, blepharitis, lagophthalmos with cortical visual impairment, telecanthus, hypotrichosis, hypertelorism, high philtrum, high arched palate, degenerated nails, and depressed third toes. Routine karyotyping via peripheral blood culture revealed a ring chromosome 18, which was confirmed de novo after parental karyotyping. Although a straightforward association between r(18) and anodontia is yet to be established, it is apparent that anodontia coupled with multiple CA and systemic complications was caused by chromosomal/genetic mutations in the present case, and thus, this report strongly recommends phenotypic and genotypic examination in dental management in such a complex scenario.

Chromosome Structural Alteration an Unusual Abnormality Characterizing Human Neoplasia

Abstract: Background and Aim: Ring chromosomes are rare cytogenetic abnormalities that occur in less than 10% of hematopoietic malignancies. They are rare in blood disorder. The present review has focused on the ring chromosome associated with oncology malignancies. Materials and Methods: By reviewing the web-based search for all English scientific peer review articles published, was initiated using Medline/PubMed, Mitelman database ( http://cgap.nci.nih.gov/Chromosomes/Mitelman ), and other pertinent references on websites about ring chromosomes in Oncology. The software program as End Note was used to handle the proper references for instruction to author. Karyotype descriptions were cited according to ISCN. Conclusion: Ring chromosomes are rare chromosomal aberrations, almost many times are of de novo origin, presenting a different phenotype regarding the loss of genetic material. The karyotype represents the main analysis for detection of ring chromosomes, but other molecular technics are necessary for complete characterization. The information of this review article adds to the spectrum of both morphology and genetic rearrangements in the field of oncology malignancies.

Ring Chromosome 7: A Rare Structural Abnormality in Acute Myeloid Leukemia (AML).

Abstract: Ring chromosomes, often leading to partial deletions, are found in about 2% of cases of acute myeloid leukemia (AML) and are typically associated with a poor prognosis. Herein, we present the case of a 62-year-old female who showed markedly hypercellular marrow with sheets of myeloblasts, monoblasts, and promonocytes, confirmed by flow cytometry and cases of AML with r(7) have been reported. Analysis of these cases demonstrated that r(7) was a sole abnormality in 20%, a primary abnormality in 14%, and in the context of a complex karyotype in 66%. The most common concomitant abnormality, seen in 26% of these cases, was 5q-, though a large variety of other concurrent abnormalities were reported at lower frequencies. The most common r(7) breakpoints were r(7)(p22q22) and r(7)(p11q11), occurring in 20% and 13% of the cases that specified breakpoints, respectively. This case study and analysis of previously reported cases demonstrates the diversity of cytogenetic contexts in which r(7) can occur in AML and underscores the importance of FISH in the characterization of this abnormality. Further investigation of the role of r(7) in AML and other hematological malignancies is warranted in order to properly characterize it and concomitant abnormalities to elucidate its clinical implications.

Analysis of genetics mechanism for the phenotypic diversity in a patient carrying a rare ring chromosome 9

Abstract: Objective To explore the genetics mechanism for the phenotypic variability in a patient carrying a rare ring chromosome 9. Methods The karyotype of the patient was analyzed with cytogenetics method. Presence of sex chromosome was confirmed with fluorescence in situ hybridization. The SRY gene was subjected to PCR amplification and direct sequencing. Potential deletion and duplication were detected with array-based comparative genomic hybridization(array-CGH). Results The karyotype of the patient has comprised 6 types of cell lines containing a ring chromosome 9. The SRY gene sequence was normal. By array-CGH, the patient has carried a hemizygous deletion at 9p24.3-p23(174 201-9 721 761) encompassing 30 genes from Online Mendelian Inheritance in Man. Conclusion The phenotypic variability of the 9p deletion syndrome in conjunct with ring chromosome 9 may be attributable to multiple factors including loss of chromosomal material, insufficient dosage of genes, instability of ring chromosome, and pattern of inheritance. Key words: Ring chromosome; Chromosome deletion; Fluorescence in situ hybridization; Array-based comparative genomic hybridization; Bioinformatics

Cytogenetics profile of student with syndromic mental retardation on special schools in Banjarmasin

Abstract: Objective : This descriptive study aims to describe the cytogenetic profile of students with mental retardation disorders on special school in Banjarmasin conducted since 2012-2013. Material and methods : Cytogenetic profile described based the existence of free trisomy 21, trisomy 21 with translocation, mosaic trisomy 21 and trisomy 21 partially or in the form of numeric aberration and structure of chromosomal abnormalities such as fragile X, specific deletions of chromosomal segments or the presence of a ring chromosome forms. Result : The results obtained from the study of 22 students with physical signs of mild to severe syndromic mental retardation. The results of cytogenetic examination showed most of the sample (77.78%) with free trisomy 21 (karyotype 47, XX, + 21 or 47, XX, + 21) or a classic type of Down syndrome, 1 sample with mosaic karyotype: 46, XY (1%) / 47, XY, + 21, 1 sample with structural abnormalities of chromosomes 22 (karyotype: 46, XY, ring 22) and 2 samples with normal karyotype (karyotype: 46, XY or 46, XX). Conclusion : Cytogenetic profile of students with syndromic mental retardation on special school in Banjarmasin are free trisomy 21, mosaic trisomy 21, structure aberration (ring chromosome 22), and a normal karyotype.

Method for constructing ring chromosomes of saccharomyces cerevisiae

Abstract: The invention relates to the field of synthetic biology, in particular to a method for constructing ring chromosomes of saccharomyces cerevisiae. Telomere regions of chromosomes of the saccharomyces cerevisiae are deleted, so that the chromosomes can be circularized by the aid of homologous recombination characteristics of the saccharomyces cerevisiae, and the ring chromosomes ringV_s and ringV_b can be obtained. Compared with existing results, the method has the advantages that the chromosomes of the saccharomyces cerevisiae are artificially circularized by the aid of a homologous recombination process; circularization sites can be freely selected; a novel model is provided for research on ring chromosome diseases.

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review.

Abstract: Ring chromosome 3, r(3), is an extremely rare cytogenetic abnormality with clinical heterogeneity and only 12 cases reported in the literature. Here, we report a 1-year-old girl presenting distinctive facial features, developmental delay, and congenital heart defects with r(3) and a ∼10-Mb deletion of chromosome 3pterp25.3 (61,891-9,979,408) involving 42 known genes which was detected using G-banding karyotyping and CytoScan 750K-Array. The breakpoints in r(3) were mapped at 3p25.3 and 3q29. We also analyzed the available information on the clinical features of the reported cases with r(3) and 3p deletion syndrome in order to provide more valuable information of genotype-phenotype correlations. To our knowledge, this is the largest detected fragment described in r(3) cases and the second r(3) study using whole-genome microarray.

Philadelphia chromosome duplication as a ring-shaped chromosome.

Abstract: The gain of a second copy of the Philadelphia chromosome is one of the main secondary chromosomal changes related to the clonal evolution of cells with t(9;22) in chronic myelogenous leukemia. This gain causes the acquisition of another copy of the BCR/ABL1 fusion gene. Isochromosomes of the der(22) chromosome or double minute chromosomes are well known to lead an increased copy number of BCR/ABL1 gene. There is no antecedent of Philadelphia chromosome duplication as a ring chromosome. A recent published report contains evidence that strongly suggests that the Philadelphia chromosome was duplicated as a ring chromosome, observation that was overlooked by the authors. The instability inherent to the ring chromosome increases the risk of emergence of clones containing more and more BCR/ABL1 gene copies, which would produce increased fitness for clonal selection, resulting in worsening of the patient’s prognosis.

Cytogenetic diagnostic of chromosome abnormalities involving Y chromosome

Abstract: Introduction: Determination of the Y chromosome aberrations type has a great diagnostic and prognostic meaning. Cytogenetic and molecular cytogenetic diagnostics of Y chromosome abnormalities has several features in contrast to the autosomes. Modern cytogenetics can effectively identify not only quantitative abnormalities of Y chromosome, but also various structural aberrations, including the deletions of both arms, ring chromosomes, isochromosomes and pseudoisochromosomes derived from short or long arm of Y chromosome.However, different methods of cytogenetic and molecular cytogenetic diagnostics have a different informative value. Purpose : The aim of present study was to analyze the cytogenetic and molecular cytogenetic diagnostics results for patients with changes in Y chromosome structure, and to evaluate and compare the used methods efficiency. Methods: karyotyping was done according to the standard methods. GTG, CBG, QFQ and NOR-Ag methods of differential staining were used. FISH was performed according to the manufacturer instructions for CEP, LSI and WCP DNA-probes. Results: 135 of 3729 patients were taken for further diagnosis. 90,3% of them had variation in Yq-arm length. Structural Y chromosome changes were founded in 9.7%. QFQ staining showed 100% efficiency. The deletions in Y chromosome were clearly detected by telomere DNA-probes. Marker chromosome identification was successful by consistent application of WCP probes, CBG banding and CEP probes. The structure of marker chromosome defined using LSI probes and NOR-Ag staining. Originality:our experience shows that using simple cytogenetic diagnostic tools can define great part of Y chromosome pathology, without baseless application of complex and expensive methods. Conclusion: Prudent use of the available diagnostic methods can simplify and speed up the diagnostic process

How do tumors make ends n

Abstract: W hen Barbara McClintock irradiated resulting in dramatic kar strains of Indian corn in the early 30s, from cell to cell (8). Thi she identified ring chromosomes, which she instability, termed CIN, i soon realized were a special case of chroin many solid tumors inch mosomes broken by radiation; the broken from the colon, breast, I ends sometimes fused to one another and ynx, and lung (9-12). The formed a ring (1, 2). This discovery led ical conclusion emerging McClintock to hypothesize the existence of was that the aneuploid st a special structure at the chromosome tip solid cancers does not sir that would maintain chromosome stability. expansion of a rare aberr In 1941 she described the breakage-fusionfact the underlying rate bridge cycle, a model for a repeating pattern losses/gains is elevated of chromosome behavior that is triggered by toward cancer (13). Thes< an initial breakage (3). Normally, each chrosistent with the hypothesi matid strand has one centromere, and the a cancer cell to accumu chromosome ends remain capped by the genetic alterations requir telomeres that protect the ends from stickesis during a single huma ing to one another. But sometimes, harmful become genetically unst substances or radiation damage a chromatid have a sustained increas and cause it to break. Without telomere rate relative to normal, caps, the new ends stick to each other, and types (14). the resulting fused chromosome has two It is also widely apprec centromeres as well as a duplication of some majority of cancers frequ of the genes from that chromosome. When structural altercell division occurs, the two centromeres of ations (i.e., translothis unusual chromosome may be pulled to cations, deletions, s the opposite spindle poles of the cell, formand amplifications; ing an irregular, long chromosome bridge ref. 6). New chros between the two newly forming daughter mosome painting a cells (Fig. 1 A and B). Eventually, the abtechniques have normal chromatid breaks in two or may be dramatically faciliC left behind during cell division. If the chrotated the analysis of mosome ends are broken, they are likely to such complex chrorejoin again, reforming a chromosome mosomal changes (15, 1 bridge at the next division. translocations are detec In this issue of PNAS, Gisselsson et al. (4) cally as a fusion between provide some experimental evidence that somes or between norma telomere dysfunction triggers extensive segments of a single chr chromosome fragmentation through persismolecular level, such tran tent bridge-breakage events in solid tumors rise to fusions between tv that consequentially leads to a continuous endowing the fused trans reorganization of the tumor genome. Their genic properties. Specific findings shed some light on a possible conrender a selective advant; nection between telomere function and the allow the outgrowth of origin of chromosomal instability (CIN) in carrying such an aberrati human cancers. In leukemias and lymp Over the last decades, the cytogenetic tions are characteristic c analyses of thousands of tumor karyotypes entities and seem critical have lead to the conclusion that aneuploidy ment of these neoplasms was rampant in cancers (5-7), so much so tailed molecular analysis < that some investigators questioned whether regions led to the identific any truly diploid cancers could exist. When oncogenes and in at leasl single clones derived from such aneuploid the development of rati tumors are grown in vitro and analyzed drug implementation an( cytogenetically, they virtually always display ample, acute promyele high rates of chromosome losses and gains, (APL; refs. 19 and 20) an

Artificial Chromosome Preparation in Arabidopsis

Abstract: In Arabidopsis thaliana, various attempts have been made to create artificial chromosomes as a new tool for cytological and genetic analyses. However, most of the efforts have been unsuccessful until recently. Most eukaryotic chromosomes are linear, and therefore the Arabidopsis artificial chromosomes have also been designed to be linear and to carry the telomere structure at both ends. In contrast, circular artificial chromosomes were successfully created by the Cre/LoxP system combined with Ac/Ds transposon system, on the basis of the discovery that ring minichromosomes are relatively stable and transmissible to the next generations in A. thaliana. Because ring minichromosomes ∼1 to 6 Mb in size have been generated, in this article, the protocol for inducing large chromosomal rearrangements resulting in ring chromosome formation is described. © 2016 by John Wiley & Sons, Inc.