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Sample records for chromosome instability phenotype

  1. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  2. Radiation-induced chromosomal instability

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    Ritter, S. [GSI, Biophysics, Darmstadt (Germany)

    1999-03-01

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/{mu}m) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  3. JC Virus T-Antigen in Colorectal Cancer Is Associated with p53 Expression and Chromosomal Instability, Independent of CpG Island Methylator Phenotype

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    Katsuhiko Nosho

    2009-01-01

    Full Text Available JC virus has a transforming gene encoding JC virus T-antigen (JCVT. JCVT may inactivate wild-type p53, cause chromosomal instability (CIN, and stabilize β-catenin. A link between JCVT and CpG island methylator phenotype (CIMP has been suggested. However, no large-scale study has examined the relations of JCVT with molecular alterations, clinical outcome, or prognosis in colon cancer. We detected JCVT expression (by immunohistochemistry in 271 (35% of 766 colorectal cancers. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1 and eight other loci (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, WRN by MethyLight. We examined loss of heterozygosity in 2p, 5q, 17q, and 18q. JCVT was significantly associated with p53 expression (P < .0001, p21 loss (P < .0001, CIN (≥2 chromosomal segments with LOH; P < .0001, nuclear β-catenin (P = .006, LINE-1 hypomethylation (P = .002, and inversely with CIMP-high (P = .0005 and microsatellite instability (MSI (P < .0001, but not with PIK3CA mutation. In multivariate logistic regression analysis, the associations of JCVT with p53 [adjusted odds ratio (OR, 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003, cyclin D1 (adjusted OR, 1.57; P = .02, LINE-1 hypomethylation (adjusted OR, 1.97 for a 30% decline as a unit; P = .03, BRAF mutation (adjusted OR, 2.20; P = .04, and family history of colorectal cancer (adjusted OR, 0.64; P = .04 remained statistically significant. However, JCVT was no longer significantly associated with CIMP, MSI, β-catenin, or cyclooxygenase-2 expression in multivariate analysis. JCVT was unrelated with patient survival. In conclusion, JCVT expression in colorectal cancer is independently associated with p53 expression and CIN, which may lead to uncontrolled cell proliferation.

  4. Chromosomal instability determines taxane response

    OpenAIRE

    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C.; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells....

  5. Radiation induced chromosome instability in human fibroblasts

    International Nuclear Information System (INIS)

    Evidence has been arising that some biological effects can manifest many cell divisions after irradiation. We have demonstrated that de novo chromosome instability can be detected 10- 15 mean population doubling after heavy ion irradiations. This chromosome instability is characterized by end to end fusions between specific chromosomes. The specificity of the instability may differ from one donor to another but for the same donor, the same instability should be observed after irradiation, during the senescence process and after SV40 transfection (before crisis). In irradiated primary culture fibroblasts, the expression of the delayed chromosomal instability lasts for several cell divisions without inducing cell death. Several rounds of fusions- breakage-fusions can be performed and unbalanced clones emerge (gain or loss of chromosomes with the shorter telomeres would become unstable first.. The difference in the chromosomal instability among donors could be due to a polymorphism in telomere lengths. This could induce large variation in long term response to irradiation among individuals. (author)

  6. Chromosomal instability determines taxane response.

    Science.gov (United States)

    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang; Howell, Michael; Ried, Thomas; Habermann, Jens K; Auer, Gert; Brenton, James D; Szallasi, Zoltan; Downward, Julian

    2009-05-26

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival" genes is associated with poor outcome in estrogen receptor-positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents. PMID:19458043

  7. Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome.

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    Maraschio, P; Zuffardi, O; Dalla Fior, T; Tiepolo, L

    1988-01-01

    Instability of the heterochromatic centromeric regions of chromosomes 1, 9, and 16 associated with immunodeficiency was found in a four year old girl. Similar phenotypic and chromosomal abnormalities were described in a previous patient studied by us and in four other published cases. All these patients have facial anomalies in addition to combined immunodeficiency and chromosomal instability. Stretching of the heterochromatic centromeric regions of chromosomes 1, 16, and to a lesser extent, ...

  8. Cancer chromosomal instability: therapeutic and diagnostic challenges

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    McGranahan, Nicholas; Burrell, Rebecca A.; Endesfelder, David; Novelli, Marco R; Swanton, Charles

    2012-01-01

    This review provides a much-needed translational perspective into the issue of aneuploidy and chromosomal instability, discussing the prognostic value of CIN assessment in human tumours, methods to analyze it and how it could be therapeutically targeted.

  9. Delayed chromosomal instability induced by DNA damage.

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    Marder, B A; Morgan, W. F.

    1993-01-01

    DNA damage induced by ionizing radiation can result in gene mutation, gene amplification, chromosome rearrangements, cellular transformation, and cell death. Although many of these changes may be induced directly by the radiation, there is accumulating evidence for delayed genomic instability following X-ray exposure. We have investigated this phenomenon by studying delayed chromosomal instability in a hamster-human hybrid cell line by means of fluorescence in situ hybridization. We examined ...

  10. Breast tumor copy number aberration phenotypes and genomic instability

    International Nuclear Information System (INIS)

    Genomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. Genes likely to have genomic instability phenotypes when mutated (e.g. those involved in mitosis, replication, repair, and telomeres) are rarely mutated in chromosomally unstable sporadic tumors, even though such mutations are associated with some heritable cancer prone syndromes. We applied array comparative genomic hybridization (CGH) to the analysis of breast tumors. The variation in the levels of genomic instability amongst tumors prompted us to investigate whether alterations in processes/genes involved in maintenance and/or manipulation of the genome were associated with particular types of genomic instability. We discriminated three breast tumor subtypes based on genomic DNA copy number alterations. The subtypes varied with respect to level of genomic instability. We find that shorter telomeres and altered telomere related gene expression are associated with amplification, implicating telomere attrition as a promoter of this type of aberration in breast cancer. On the other hand, the numbers of chromosomal alterations, particularly low level changes, are associated with altered expression of genes in other functional classes (mitosis, cell cycle, DNA replication and repair). Further, although loss of function instability phenotypes have been demonstrated for many of the genes in model systems, we observed enhanced expression of most genes in tumors, indicating that over expression, rather than deficiency underlies instability. Many of the genes associated with higher frequency of copy number aberrations are direct targets of E2F, supporting the hypothesis that deregulation of the Rb pathway is a major contributor to chromosomal instability in breast tumors. These observations are consistent with failure to find mutations in sporadic tumors in genes that have roles in maintenance or manipulation of the genome

  11. A computer simulation of chromosomal instability

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    Goodwin, E.; Cornforth, M.

    The transformation of a normal cell into a cancerous growth can be described as a process of mutation and selection occurring within the context of clonal expansion. Radiation, in addition to initial DNA damage, induces a persistent and still poorly understood genomic instability process that contributes to the mutational burden. It will be essential to include a quantitative description of this phenomenon in any attempt at science-based risk assessment. Monte Carlo computer simulations are a relatively simple way to model processes that are characterized by an element of randomness. A properly constructed simulation can capture the essence of a phenomenon that, as is often the case in biology, can be extraordinarily complex, and can do so even though the phenomenon itself is incompletely understood. A simple computer simulation of one manifestation of genomic instability known as chromosomal instability will be presented. The model simulates clonal expansion of a single chromosomally unstable cell into a colony. Instability is characterized by a single parameter, the rate of chromosomal rearrangement. With each new chromosome aberration, a unique subclone arises (subclones are defined as having a unique karyotype). The subclone initially has just one cell, but it can expand with cell division if the aberration is not lethal. The computer program automatically keeps track of the number of subclones within the expanding colony, and the number of cells within each subclone. Because chromosome aberrations kill some cells during colony growth, colonies arising from unstable cells tend to be smaller than those arising from stable cells. For any chosen level of instability, the computer program calculates the mean number of cells per colony averaged over many runs. These output should prove useful for investigating how such radiobiological phenomena as slow growth colonies, increased doubling time, and delayed cell death depend on chromosomal instability. Also of

  12. Cancer chromosomal instability: therapeutic and diagnostic challenges.

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    McGranahan, Nicholas; Burrell, Rebecca A; Endesfelder, David; Novelli, Marco R; Swanton, Charles

    2012-06-01

    Chromosomal instability (CIN)-which is a high rate of loss or gain of whole or parts of chromosomes-is a characteristic of most human cancers and a cause of tumour aneuploidy and intra-tumour heterogeneity. CIN is associated with poor patient outcome and drug resistance, which could be mediated by evolutionary adaptation fostered by intra-tumour heterogeneity. In this review, we discuss the clinical consequences of CIN and the challenges inherent to its measurement in tumour specimens. The relationship between CIN and prognosis supports assessment of CIN status in the clinical setting and suggests that stratifying tumours according to levels of CIN could facilitate clinical risk assessment. PMID:22595889

  13. Chromosomal instability determines taxane sensitivity - supplementary materials

    OpenAIRE

    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C.; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells....

  14. Mechanisms of ring chromosome formation, ring instability and clinical consequences

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    Guilherme Roberta S

    2011-12-01

    Full Text Available Abstract Background The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients. Methods Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification and FISH (Fluorescent in situ Hybridization. Results The ring chromosomes of patients I to XIV were determined to be, respectively: r(3(p26.1q29, r(4(p16.3q35.2, r(10(p15.3q26.2, r(10(p15.3q26.13, r(13(p13q31.1, r(13(p13q34, r(14(p13q32.33, r(15(p13q26.2, r(18(p11.32q22.2, r(18(p11.32q21.33, r(18(p11.21q23, r(22(p13q13.33, r(22(p13q13.2, and r(22(p13q13.2. These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV; a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II; a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X; fusion of two subtelomeric regions (patient VII; and telomere-telomere fusion (patient XII. Thus, the r(14 and one r(22 can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI with r(13 showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV. Conclusions We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14 and r(22.

  15. Chromosomal instability in multiple endocrine neoplasia type 1. Cytogenetic evaluation with DEB test.

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    Tomassetti, P; Cometa, G; Del Vecchio, E; Baserga, M; Faccioli, P; Bosoni, D; Paolucci, G; Barbara, L

    1995-02-01

    Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant condition with high penetrance and variable expressivity, in which tumors or hyperplasia occur in two or more endocrine organs. Some authors have investigated chromosomal instability in MEN 1 and MEN 2; the results are controversial. Chromosome analyses were performed on lymphocytes from seven patients with MEN 1, four healthy first-degree relatives (three of whom were children), six phenotypically normal volunteers, and three patients with Fanconi's anemia. To evaluate chromosomal instability we analyzed phytohemagglutinin-stimulated lymphocyte cultures with and without diepoxibutane. We observed an increase in the frequency of spontaneous chromosomal alterations in four patients. After the DEB test we found an increase in chromatid breakages, gaps, and exchange figures. These findings support the inclusion of the MEN 1 syndrome among the disorders with "chromosomal instability." PMID:7889502

  16. Chromosomal instability in patients with Fanconi anemia from Serbia

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    Ćirković Sanja

    2014-01-01

    Full Text Available Background/Aim. Fanconi anemia (FA is a rare hereditary disease in a heterogeneous group of syndromes, so-called chromosome breakage disorders. Specific hypersensitivity of its cells to chemical agents, such as diepoxybutane (DEB, was used as a part of screening among patients with clinical suspicion of FA. The aim of this study was to determine chromosomal instability in patients with FA symptoms in Serbia. Methods. A total of 70 patients with phenotypic symptoms of FA, diagnosed at the Mother and Child Health Care Institute of Serbia “Dr Vukan Čupić”, Belgrade and University Children’s Hospital, Belgrade from February 2004 to September 2011, were included in this study. Cytogenetic instability analysis was performed on untreated and DEBtreated 72 h-cultures of peripheral blood. Results. Ten patients in the group of 70 suspected of FA, showed increased DEB induced chromosome breakage and were classified into the FA group. The range of DEB induced aberrant cells percentages in the FA group was from 32% to 82%. DEB sensitivity of 58 tested patients were bellow FA values (range: 0-6% (non-FA group, with no overlapping. The remaining two patients showed borderline sensitivity (borderline FA group - FA*, comparing to the healthy controls. Conclusion. This study revealed 10 patients with FA on the basis of cytogenetic analysis of DEB induced chromosome aberrations. Our results are in consistency with those from the literature. Early and precise diagnosis of FA is very important in further treatment of these patients, considering its cancer prone and lethal effects. [Projekat Ministarstva nauke Republike Srbije, br. 173046

  17. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

    OpenAIRE

    Bakheet, Saleh A.; Attia, Sabry M.

    2011-01-01

    We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cell...

  18. Mitotic Origins of Chromosomal Instability in Colorectal Cancer

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    Dalton, W. Brian; Yang, Vincent W.

    2007-01-01

    Mitosis is a crucial part of the cell cycle. A successful mitosis requires the proper execution of many complex cellular behaviors. Thus, there are many points at which mitosis may be disrupted. In cancer cells, chronic disruption of mitosis can lead to unequal segregation of chromosomes, a phenomenon known as chromosomal instability. A majority of colorectal tumors suffer from this instability, and recent studies have begun to reveal the specific ways in which mitotic defects promote chromos...

  19. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

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    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  20. Radiation-induced chromosomal instability in human mammary epithelial cells

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    Durante, M.; Grossi, G. F.; Yang, T. C.

    1996-01-01

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  1. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

    Directory of Open Access Journals (Sweden)

    Saleh A. Bakheet

    2011-01-01

    Full Text Available We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients.

  2. Topoisomerase IIα in chromosome instability and personalized cancer therapy.

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    Chen, T; Sun, Y; Ji, P; Kopetz, S; Zhang, W

    2015-07-30

    Genome instability is a hallmark of cancer cells. Chromosome instability (CIN), which is often mutually exclusive from hypermutation genotypes, represents a distinct subtype of genome instability. Hypermutations in cancer cells are due to defects in DNA repair genes, but the cause of CIN is still elusive. However, because of the extensive chromosomal abnormalities associated with CIN, its cause is likely a defect in a network of genes that regulate mitotic checkpoints and chromosomal organization and segregation. Emerging evidence has shown that the chromosomal decatenation checkpoint, which is critical for chromatin untangling and packing during genetic material duplication, is defective in cancer cells with CIN. The decatenation checkpoint is known to be regulated by a family of enzymes called topoisomerases. Among them, the gene encoding topoisomerase IIα (TOP2A) is commonly altered at both gene copy number and gene expression level in cancer cells. Thus, abnormal alterations of TOP2A, its interacting proteins, and its modifications may have a critical role in CIN in human cancers. Clinically, a large arsenal of topoisomerase inhibitors has been used to suppress DNA replication in cancer. However, they often lead to the secondary development of leukemia because of their effect on the chromosomal decatenation checkpoint. Therefore, topoisomerase drugs must be used judiciously and administered on an individual basis. In this review, we highlight the biological function of TOP2A in chromosome segregation and the mechanisms that regulate this enzyme's expression and activity. We also review the roles of TOP2A and related proteins in human cancers, and raise a perspective for how to target TOP2A in personalized cancer therapy. PMID:25328138

  3. Down syndrome phenotypes: The consequences of chromosomal imbalance

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    Korenberg, J.R.; Chen, X.N.; Schipper, R.; Sun, Z.; Gonsky, R.; Gerwehr, S.; Graham, J.M. Jr. (Univ. of California, Los Angeles, CA (United States)); Carpenter, N.; Say, B. (H.A. Chapman Institute of Medical Genetics, Tulsa, OK (United States)); Daumer, C. (Univ. of Munich (Germany)) (and others)

    1994-05-24

    Down syndrome (DS) is a major cause of mental retardation and congenital heart disease. Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an Alzheimer-like dementia. Moreover, DS is a model for the study of human aneuploidy. Although usually caused by the presence of an extra chromosome 21, subsets of the phenotypic features of DS may be caused by the duplication of small regions of the chromosome. The physical map of chromosome 21 allows the molecular definition of the regions duplicated in these rare cases of partial trisomy. As a first step in identifying the genes responsible for individual DS features and their pathophysiology, a panel of cell lines derived from 16 such individuals has been established and the molecular break points have been determined using fluorescence in situ hybridization and Southern blot dosage analysis of 32 markers unique to human chromosome 21. Combining this information with detailed clinical evaluations of these patients, the authors have now constructed a [open quotes]phenotypic map[close quotes] that includes 25 features and assigns regions of 2-20 megabases as likely to contain the genes responsible. This study provides evidence for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation. This strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the DS phenotypic features.

  4. Hexavalent chromium induces chromosome instability in human urothelial cells.

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    Wise, Sandra S; Holmes, Amie L; Liou, Louis; Adam, Rosalyn M; Wise, John Pierce

    2016-04-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. PMID:26908176

  5. Chromosomal duplication strains of Aspergillus nidulans and their instability

    International Nuclear Information System (INIS)

    Strains of Aspergillus nidulans with chromosomal duplication were obtained after gamma irradiation followed by crossing of the translocated strains with normal strains. From 20 analysed colonies, 12 have shown translocations induced by irradiation. Segregants from four of these translocation strains crossed to normal strains have shown to be unstable although presenting normal morphology. Two segregants were genetically analysed. The first one has shown a duplication of part of linkage groups VIII and the second one presented a duplication of a segment of linkage group V. These new duplication strains in A. nidulans open new perspectives of a more detailed study of the instability phenomenon in this fungus. (Author)

  6. Chromosomal instability as a prognostic marker in cervical cancer

    International Nuclear Information System (INIS)

    Cervical cancer is the third most common cancer in women globally, and despite treatment, distant metastasis and nodal recurrence will still develop in approximately 30% of patients. The ability to predict which patients are likely to experience distant relapse would allow clinicians to better tailor treatment. Previous studies have investigated the role of chromosomal instability (CIN) in cancer, which can promote tumour initiation and growth; a hallmark of human malignancies. In this study, we sought to examine the published CIN70 gene signature in a cohort of cervical cancer patients treated at the Princess Margaret (PM) Cancer Centre and an independent cohort of The Cancer Genome Atlas (TCGA) cervical cancer patients, to determine if this CIN signature associated with patient outcome. Cervical cancer samples were collected from 79 patients, treated between 2000–2007 at the PM, prior to undergoing curative chemo-radiation. Total RNA was extracted from each patient sample and analyzed using the GeneChip Human Genome U133 Plus 2.0 array (Affymetrix). High CIN70 scores were significantly related to increased chromosomal alterations in TCGA cervical cancer patients, including a higher percentage of genome altered and a higher number of copy number alterations. In addition, this same CIN70 signature was shown to be predictive of para-aortic nodal relapse in the PM Cancer Centre cohort. These findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. For the first time, this CIN70 gene signature provided prognostic value for patients with cervical cancer

  7. Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.

    Science.gov (United States)

    Clemente-Ruiz, Marta; Murillo-Maldonado, Juan M; Benhra, Najate; Barrio, Lara; Pérez, Lidia; Quiroga, Gonzalo; Nebreda, Angel R; Milán, Marco

    2016-02-01

    Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis. PMID:26859353

  8. Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei

    International Nuclear Information System (INIS)

    Folic acid deficiency can lead to uracil incorporation into DNA, hypomethylation of DNA, inefficient DNA repair and increase chromosome malsegregation and breakage. Because ionising radiation increases demand for efficient DNA repair and also causes chromosome breaks we hypothesised that folic acid deficiency may increase sensitivity to radiation-induced chromosome breakage. We tested this hypothesis by using the cytokinesis-block micronucleus assay in 10 day WIL2-NS cell cultures at four different folic acid concentrations (0.2, 2, 20, and 200 nM) that span the 'normal' physiological range in humans. The study showed a significant dose-dependent increase in frequency of binucleated cells with micronuclei and/or nucleoplasmic bridges with decreasing folic acid concentration (P < 0.0001, P = 0.028, respectively). These biomarkers of chromosomal instability were also increased in cells irradiated (1.5 Gy γ-rays) on day 9 relative to un-irradiated controls (P < 0.05). Folic acid deficiency and γ-irradiation were shown to have a significant interactive effect on frequency of cells containing micronuclei (two-way ANOVA, interaction P 0.0039) such that the frequency of radiation-induced micronucleated cells (i.e. after subtracting base-line frequency of un-irradiated controls) increased with decreasing folic acid concentration (P-trend < 0.0001). Aneuploidy of chromosome 21, apoptosis and necrosis were increased by folic acid deficiency but not by ionising radiation. The results of this study show that folate status has an important impact on chromosomal stability and is an important modifying factor of cellular sensitivity to radiation-induced genome damage

  9. Reprogramming to pluripotency can conceal somatic cell chromosomal instability.

    Directory of Open Access Journals (Sweden)

    Masakazu Hamada

    Full Text Available The discovery that somatic cells are reprogrammable to pluripotency by ectopic expression of a small subset of transcription factors has created great potential for the development of broadly applicable stem-cell-based therapies. One of the concerns regarding the safe use of induced pluripotent stem cells (iPSCs in therapeutic applications is loss of genomic integrity, a hallmark of various human conditions and diseases, including cancer. Structural chromosome defects such as short telomeres and double-strand breaks are known to limit reprogramming of somatic cells into iPSCs, but whether defects that cause whole-chromosome instability (W-CIN preclude reprogramming is unknown. Here we demonstrate, using aneuploidy-prone mouse embryonic fibroblasts (MEFs in which chromosome missegregation is driven by BubR1 or RanBP2 insufficiency, that W-CIN is not a barrier to reprogramming. Unexpectedly, the two W-CIN defects had contrasting effects on iPSC genomic integrity, with BubR1 hypomorphic MEFs almost exclusively yielding aneuploid iPSC clones and RanBP2 hypomorphic MEFs karyotypically normal iPSC clones. Moreover, BubR1-insufficient iPSC clones were karyotypically unstable, whereas RanBP2-insufficient iPSC clones were rather stable. These findings suggest that aneuploid cells can be selected for or against during reprogramming depending on the W-CIN gene defect and present the novel concept that somatic cell W-CIN can be concealed in the pluripotent state. Thus, karyotypic analysis of somatic cells of origin in addition to iPSC lines is necessary for safe application of reprogramming technology.

  10. The TP53 dependence of radiation-induced chromosome instability in human lymphoblastoid cells

    Science.gov (United States)

    Schwartz, Jeffrey L.; Jordan, Robert; Evans, Helen H.; Lenarczyk, Marek; Liber, Howard

    2003-01-01

    The dose and TP53 dependence for the induction of chromosome instability were examined in cells of three human lymphoblastoid cell lines derived from WIL2 cells: TK6, a TP53-normal cell line, NH32, a TP53-knockout created from TK6, and WTK1, a WIL2-derived cell line that spontaneously developed a TP53 mutation. Cells of each cell line were exposed to (137)Cs gamma rays, and then surviving clones were isolated and expanded in culture for approximately 35 generations before the frequency and characteristics of the instability were analyzed. The presence of dicentric chromosomes, formed by end-to-end fusions, served as a marker of chromosomal instability. Unexposed TK6 cells had low levels of chromosomal instability (0.002 +/- 0.001 dicentrics/cell). Exposure of TK6 cells to doses as low as 5 cGy gamma rays increased chromosome instability levels nearly 10-fold to 0.019 +/- 0.008 dicentrics/cell. There was no further increase in instability levels beyond 5 cGy. In contrast to TK6 cells, unexposed cultures of WTK1 and NH32 cells had much higher levels of chromosome instability of 0.034 +/- 0.007 and 0.041 +/- 0.009, respectively, but showed little if any effect of radiation on levels of chromosome instability. The results suggest that radiation exposure alters the normal TP53-dependent cell cycle checkpoint controls that recognize alterations in telomere structure and activate apoptosis.

  11. The Relationship Between Spontaneous Telomere Loss and Chromosome Instability in a Human Tumor Cell Line

    Directory of Open Access Journals (Sweden)

    Bijan Fouladi

    2000-01-01

    Full Text Available Chromosome instability plays an important role in cancer by promoting the alterations in the genome required for tumor cell progression. The loss of telomeres that protect the ends of chromosomes and prevent chromosome fusion has been proposed as one mechanism for chromosome instability in cancer cells, however, there is little direct evidence to support this hypothesis. To investigate the relationship between spontaneous telomere loss and chromosome instability in human cancer cells, clones of the EJ-30 tumor cell line were isolated in which a herpes simplex virus thymidine kinase (HSV-tk gene was integrated immediately adjacent to a telomere. Selection for HSV-tkdeficient cells with ganciclovir demonstrated a high rate of loss of the end these "marked" chromosomes (10-4 events/cell per generation. DNA sequence and cytogenetic analysis suggests that the loss of function of the HSV-tk gene most often involves telomere loss, sister chromatid fusion, and prolonged periods of chromosome instability. In some HSV-tk-deficient cells, telomeric repeat sequences were added on to the end of the truncated HSV-tk gene at a new location, whereas in others, no telomere was detected on the end of the marked chromosome. These results suggest that spontaneous telomere loss is a mechanism for chromosome instability in human cancer cells.

  12. Radiation induced chromosomal instability in lymphocytes of cancer patients

    International Nuclear Information System (INIS)

    Full text: Cytokinesis-blocked micronucleus (CBMN) assay has been extensively used to evaluate the radiation sensitivity of human individuals. Using the CBMN assay, Scott et al (1998, 1999) demonstrated that a fraction of radiosensitive individuals in breast cancer case population was larger than in normal individual population. However, Vral et al were very skeptical about the Scott et al's findings (2002). Under the approval from the ethical committee of NIRS, peripheral blood was obtained from 46 normal healthy females, 131 breast cancer patients, 32 cervical cancer patients and 7 female head and neck cancer patients. Radiosensitivity of T-lymphocytes was assessed by using a CBMN assay. The frequencies of MN per binucleated cell in healthy donors were 0.031(±0.010) and 0.151(±0.066) for cells treated before and after X-ray-irradiation (2Gy), respectively. Spontaneous MN frequencies in cancer patients were significantly higher than healthy donors (p < 0.001). Radiation sensitivities of breast- and head and neck-cancer patients were significantly higher than normal individuals (p < 0.001). Cervical cancer patients were more resistant to irradiation than healthy donors, though the number of cases for statistical analysis was small. (p < 0.001). We are considering that the HPV infection affected the radiosensitivity of cervical cancer cases. Because it is widely believed that one key mechanism which leads to spontaneous micronucleus formation involves an imbalance of chromosomal segregation and a chromosomal instability in patients' lymphocytes might be greater than that in normal individuals' lymphocytes. Recently, Kuschel et al (2002) demonstrated that ratios in two SNPs on XRCC3 were significantly different between cancer patients and healthy females. Then, we can suppose that the radiation-related genes with low penetrance may be involved in tumorigenesis of mammary- and head and neck-cells, and also, in patients' radiation susceptibility

  13. Phenotypic consequences of a mosaic marker chromosome identified by fluorescence in situ hybridization (FISH) as being derived from chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Ray, J.H.; Zhou, X.; Pletcher, B.A. [Cornell Univ. Medical College, Manhasset, NY (United States)] [and others

    1994-09-01

    De novo marker chromosomes are detected in 1 in 2500 amniotic fluid samples and are associated with a 10-15% risk for phenotypic abnormality. FISH can be utilized as a research tool to identify the origins of marker chromosomes. The phenotypic consequences of a marker chromosome derived from the short arm of chromosome 16 are described. A 26-year-old woman underwent amniocentesis at 28 weeks gestation because of a prenatally diagnosed tetralogy of Fallot. Follow-up ultrasounds also showed ventriculomegaly and cleft lip and palate. 32 of 45 cells had the karyotype 47,XY,+mar; the remaining cells were 46,XY. The de novo marker chromosome was C-band positive and non-satellited and failed to stain with distamycin A/DAPI. At birth the ultrasound findings were confirmed and dysmorphic features and cryptorchidism were noted. Although a newborn blood sample contained only normal cells, mosaicism was confirmed in 2 skin biopsies. FISH using whole-chromosome painting and alpha-satellite DNA probes showed that the marker chromosome had originated from chromosome 16. As proximal 16q is distamycin A/DAPI positive, the marker is apparently derived from proximal 16p. At 15 months of age, this child is hypotonic, globally delayed and is gavage-fed. His physical examination is significant for microbrachycephaly, a round face, sparse scalp hair, ocular hypertelorism, exotropia, a flat, wide nasal bridge and tip, mild micrognathia, and tapered fingers with lymphedema of hands and feet. Inguinal hernias have been repaired. His features are consistent with those described for patients trisomic for most or all of the short arm of chromosome 16. Marker chromosomes derived from the short arm of chromosome 16 appear to have phenotypic consequences. As the origin of more marker chromosomes are identified using FISH, their karyotype/phenotype correlations will become more apparent, which will permit more accurate genetic counseling.

  14. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Woo, Seon Rang [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jung-Kee [Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735 (Korea, Republic of); Kim, Hae Kwon [Department of Biotechnology, Seoul Woman' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-74-2 (Korea, Republic of); Park, Gil Hong [Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2011-01-14

    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

  15. Tolerance whole of genome doubling propagates chromosomal instability and accelerates cancer genome evolution

    OpenAIRE

    Dewhurst, Sally M; McGranahan, Nicholas; Burrell, Rebecca A.; Rowan, Andrew J.; Grönroos, Eva; Endesfelder, David; Joshi, Tejal; Mouradov, Dmitri; Gibbs, Peter; Ward, Robyn L.; Hawkins, Nicholas J.; Szallasi, Zoltan; Sieber, Oliver M.; Swanton, Charles

    2014-01-01

    The contribution of whole genome doubling to chromosomal instability (CIN) and tumour evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, t...

  16. Persistent Increase in Chromosome Instability in Lung Cancer : Possible Indirect Involvement of p53 Inactivation

    OpenAIRE

    Haruki, Nobuhiro; Harano, Tomoko; Masuda, Akira; Kiyono, Tohru; TAKAHASHI, TAKAO; Tatematsu, Yoshio; Shimizu, Shigeki; Mitsudomi, Tetsuya; Konishi, Hiroyuki; Osada, Hirotaka; Fujii, Yoshitaka; Takahashi, Takashi

    2001-01-01

    Karyotype and fluorescence in situ hybridization analyses have demonstrated the frequent presence of an altered static state of the number of chromosomes (ie, aneuploidy) in lung cancer, but it has not been directly established whether aneuploidy is in fact associated with a persistent increase in the rate of chromosomal losses and gains (ie, chromosome instability, or CIN). The study presented here used a panel of 10 lung cancer cell lines to provide for the first time direct evidence that C...

  17. Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and death in mice.

    Directory of Open Access Journals (Sweden)

    Rabindra N Bhattacharjee

    Full Text Available BACKGROUND: Telomeres are essential to maintain chromosomal stability. Cells derived from mice lacking telomerase RNA component (mTERC-/- mice display elevated telomere-mediated chromosome instability. Age-dependent telomere shortening and associated chromosome instability reduce the capacity to respond to cellular stress occurring during inflammation and cancer. Inflammation is one of the important risk factors in cancer progression. Controlled innate immune responses mediated by Toll-like receptors (TLR are required for host defense against infection. Our aim was to understand the role of chromosome/genome instability in the initiation and maintenance of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: We examined the function of TLR4 in telomerase deficient mTERC-/- mice harbouring chromosome instability which did not develop any overt immunological disorder in pathogen-free condition or any form of cancers at this stage. Chromosome instability was measured in metaphase spreads prepared from wildtype (mTERC+/+, mTERC+/- and mTERC-/- mouse splenocytes. Peritoneal and/or bone marrow-derived macrophages were used to examine the responses of TLR4 by their ability to produce inflammatory mediators TNFalpha and IL6. Our results demonstrate that TLR4 is highly up-regulated in the immune cells derived from telomerase-null (mTERC-/- mice and lipopolysaccharide, a natural ligand for TLR4 stabilises NF-kappaB binding to its promoter by down-regulating ATF-3 in mTERC-/- macrophages. CONCLUSIONS/SIGNIFICANCE: Our findings implied that background chromosome instability in the cellular level stabilises the action of TLR4-induced NF-kappaB action and sensitises cells to produce excess pro-inflammatory mediators. Chromosome/genomic instability data raises optimism for controlling inflammation by non-toxic TLR antagonists among high-risk groups.

  18. Correlation of chromosomal instability, telomere length and telomere maintenance in microsatellite stable rectal cancer: a molecular subclass of rectal cancer.

    Directory of Open Access Journals (Sweden)

    Lisa A Boardman

    Full Text Available INTRODUCTION: Colorectal cancer (CRC tumor DNA is characterized by chromosomal damage termed chromosomal instability (CIN and excessively shortened telomeres. Up to 80% of CRC is microsatellite stable (MSS and is historically considered to be chromosomally unstable (CIN+. However, tumor phenotyping depicts some MSS CRC with little or no genetic changes, thus being chromosomally stable (CIN-. MSS CIN- tumors have not been assessed for telomere attrition. EXPERIMENTAL DESIGN: MSS rectal cancers from patients ≤50 years old with Stage II (B2 or higher or Stage III disease were assessed for CIN, telomere length and telomere maintenance mechanism (telomerase activation [TA]; alternative lengthening of telomeres [ALT]. Relative telomere length was measured by qPCR in somatic epithelial and cancer DNA. TA was measured with the TRAPeze assay, and tumors were evaluated for the presence of C-circles indicative of ALT. p53 mutation status was assessed in all available samples. DNA copy number changes were evaluated with Spectral Genomics aCGH. RESULTS: Tumors were classified as chromosomally stable (CIN- and chromosomally instable (CIN+ by degree of DNA copy number changes. CIN- tumors (35%; n=6 had fewer copy number changes (<17% of their clones with DNA copy number changes than CIN+ tumors (65%; n=13 which had high levels of copy number changes in 20% to 49% of clones. Telomere lengths were longer in CIN- compared to CIN+ tumors (p=0.0066 and in those in which telomerase was not activated (p=0.004. Tumors exhibiting activation of telomerase had shorter tumor telomeres (p=0.0040; and tended to be CIN+ (p=0.0949. CONCLUSIONS: MSS rectal cancer appears to represent a heterogeneous group of tumors that may be categorized both on the basis of CIN status and telomere maintenance mechanism. MSS CIN- rectal cancers appear to have longer telomeres than those of MSS CIN+ rectal cancers and to utilize ALT rather than activation of telomerase.

  19. The evolution of chromosomal instability in Chinese hamster cells: a changing picture?

    Science.gov (United States)

    Ponnaiya, B.; Limoli, C. L.; Corcoran, J.; Kaplan, M. I.; Hartmann, A.; Morgan, W. F.

    1998-01-01

    PURPOSE: To investigate the kinetics of chromosomal instability induced in clones of Chinese hamster cells following X-irradiation. MATERIALS AND METHODS: X-irradiated clones of GM10115, human-hamster hybrid cells containing a single human chromosome 4 (HC4), have been previously established. These clones were defined as unstable if they contained > or = three subpopulations of cells with unique rearrangements of HC4 as detected by FISH. Stable and unstable clones were analysed by FISH and Giemsa staining at various times post-irradiation. RESULTS: While most of the stable clones continued to show chromosomal stability of HC4 over time, one became marginally unstable at approximately 45 population doublings post-irradiation. Clones exhibiting chromosomal instability had one of several fates. Many of the unstable clones were showed similar levels of instability over time. However, one unstable clone became stable with time in culture, while another became even more unstable over time. Cytogenetic analyses of all clones after Giemsa staining indicated that in some clones the hamster chromosomes were rearranged independent of HC4, demonstrating increased frequencies of chromatid breaks and dicentric chromosomes. The majority of the unstable clones also had higher yields of chromatid gaps. CONCLUSIONS: These data demonstrate the dynamic nature of chromosomal instability as measured by two different cytogenetic assays.

  20. A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.

    OpenAIRE

    Estabrooks, L L; Lamb, A.N.; Kirkman, H N; Callanan, N P; Rao, K W

    1992-01-01

    We report two families with a satellited chromosome 4 short arm (4ps). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited nonacrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is the first report of 4ps chromosomes. Our families are remarkable in that both unaffected and affected individuals carry the 4ps chromosome. The phenotypes observed in aff...

  1. Functions of spindle check-point and its relationship to chromosome instability

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is generally believed that the equal distribution of genetic materials to two daughter cells during mitosis is the key to cell health and development. During the dynamic process, spindle checkpoint plays a very important role in chromosome movements and final sister chromatid separation. The equal and precise segregation of chromosomes contributes to the genomic stability while aberrant separations result in chromosome instability that causes pathogenesis of certain diseases such as Down's syndrome and cancers. Kinetochore and its regulatory proteins consist of the spindle checkpoint and determine the spatial and temporal orders of chromosome segregation.

  2. Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Hisakatsu Nawata

    Full Text Available A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells by using microcell-mediated chromosome transfer technique. In addition to decreased proliferation, the trisomy 8 cells lost contact inhibition and reproliferated after exhibiting senescence-like characteristics that are typical of transformed cells. Furthermore, the trisomy 8 cells exhibited chromosome instability, and the overall gene expression profile based on microarray analyses was significantly different from that of diploid human primary fibroblasts. Our data suggest that aneuploidy, even a single chromosome gain, can be introduced into normal human cells and causes, in some cases, a partial cancer phenotype due to a disruption in overall gene expression.

  3. Numerical chromosomal instability mediates susceptibility to radiation treatment

    Science.gov (United States)

    Bakhoum, Samuel F.; Kabeche, Lilian; Wood, Matthew D.; Laucius, Christopher D.; Qu, Dian; Laughney, Ashley M.; Reynolds, Gloria E.; Louie, Raymond J.; Phillips, Joanna; Chan, Denise A.; Zaki, Bassem I.; Murnane, John P.; Petritsch, Claudia; Compton, Duane A.

    2015-01-01

    The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated radiation therapy. However, the mechanism for this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads to mitotic chromosome segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell lines. These mitotic errors generate an abundance of micronuclei that predispose chromosomes to subsequent catastrophic pulverization thereby independently amplifying radiation-induced genome damage. Experimentally suppressing whole-chromosome missegregation reduces downstream chromosomal defects and significantly increases the viability of irradiated mitotic cells. Further, orthotopically transplanted human glioblastoma tumours in which chromosome missegregation rates have been reduced are rendered markedly more resistant to IR, exhibiting diminished markers of cell death in response to treatment. This work identifies a novel mitotic pathway for radiation-induced genome damage, which occurs outside of the primary nucleus and augments chromosomal breaks. This relationship between radiation treatment and whole-chromosome missegregation can be exploited to modulate therapeutic response in a clinically relevant manner. PMID:25606712

  4. Alternative Splicing of CHEK2 and Codeletion with NF2 Promote Chromosomal Instability in Meningioma

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    Hong Wei Yang

    2012-01-01

    Full Text Available Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.

  5. Cytokinesis-block micronucleus assay evolves into a 'cytome' assay of chromosomal instability, mitotic dysfunction and cell death

    International Nuclear Information System (INIS)

    The cytokinesis-block micronucleus (CBMN) assay was originally developed as an ideal system for measuring micronuclei (MNi) however it can also be used to measure nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), cell death (necrosis or apoptosis) and nuclear division rate. Current evidence suggests that (a) NPBs originate from dicentric chromosomes in which the centromeres have been pulled to the opposite poles of the cell at anaphase and are therefore indicative of DNA mis-repair, chromosome rearrangement or telomere end-fusions, (b) NPBs may break to form MNi, (c) the nuclear budding process is the mechanism by which cells remove amplified and/or excess DNA and is therefore a marker of gene amplification and/or altered gene dosage, (d) cell cycle checkpoint defects result in micronucleus formation and (e) hypomethylation of DNA, induced nutritionally or by inhibition of DNA methyl transferase can lead to micronucleus formation either via chromosome loss or chromosome breakage. The strong correlation between micronucleus formation, nuclear budding and NPBs (r = 0.75-0.77, P < 0.001) induced by either folic acid deficiency or exposure to ionising radiation is supportive of the hypothesis that folic acid deficiency and/or ionising radiation cause genomic instability and gene amplification by the initiation of breakage-fusion-bridge cycles. In its comprehensive mode, the CBMN assay measures all cells including necrotic and apoptotic cells as well as number of nuclei per cell to provide a measure of cytotoxicity and mitotic activity. The CBMN assay has in fact evolved into a 'cytome' method for measuring comprehensively chromosomal instability phenotype and altered cellular viability caused by genetic defects and/or nutrional deficiencies and/or exogenous genotoxins thus opening up an exciting future for the use of this methodology in the emerging fields of nutrigenomics and toxicogenomics and their combinations

  6. A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells

    International Nuclear Information System (INIS)

    Aneuploidy is a feature of most cancer cells that is often accompanied by an elevated rate of chromosome mis-segregation termed chromosome instability (CIN). While CIN can act as a driver of cancer genome evolution and tumor progression, recent findings point to the existence of a threshold level beyond which CIN becomes a barrier to tumor growth and therefore can be exploited therapeutically. Drugs known to increase CIN beyond the therapeutic threshold are currently few in number, and the clinical promise of targeting the CIN phenotype warrants new screening efforts. However, none of the existing methods, including the in vitro micronuclei (MNi) assay, developed to quantify CIN, is entirely satisfactory. We have developed a new assay for measuring CIN. This quantitative assay for chromosome mis-segregation is based on the use of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene. Thus, cells that inherit the HAC display green fluorescence, while cells lacking the HAC do not. This allows the measurement of HAC loss rate by routine flow cytometry. Using the HAC-based chromosome loss assay, we have analyzed several well-known anti-mitotic, spindle-targeting compounds, all of which have been reported to induce micronuclei formation and chromosome loss. For each drug, the rate of HAC loss was accurately measured by flow cytometry as a proportion of non-fluorescent cells in the cell population which was verified by FISH analysis. Based on our estimates, despite their similar cytotoxicity, the analyzed drugs affect the rates of HAC mis-segregation during mitotic divisions differently. The highest rate of HAC mis-segregation was observed for the microtubule-stabilizing drugs, taxol and peloruside A. Thus, this new and simple assay allows for a quick and efficient screen of hundreds of drugs to identify those affecting chromosome mis-segregation. It also allows ranking of compounds with the same or similar mechanism of

  7. Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells and maintains chromosomal stability over long-term culture.

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    Akira Shimamoto

    Full Text Available Werner syndrome (WS is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.

  8. Chromosomal instability selects gene copy number variants encoding core regulators of proliferation in ER+ breast cancer

    Science.gov (United States)

    Endesfelder, David; McGranahan, Nicholas; Howell, Mike; Parker, Peter J.; Downward, Julian; Swanton, Charles; Kschischo, Maik

    2014-01-01

    Chromosomal instability (CIN) is associated with poor outcome in epithelial malignancies including breast carcinomas. Evidence suggests that prognostic signatures in estrogen receptor-positive (ER+) breast cancer define tumors with CIN and high proliferative potential. Intriguingly, CIN induction in lower eukaryotic cells and human cells is context-dependent, typically resulting in a proliferation disadvantage but conferring a fitness benefit under strong selection pressures. We hypothesised that CIN permits accelerated genomic evolution through the generation of diverse DNA copy number events that may be selected during disease development. In support of this hypothesis, we found evidence for selection of gene amplification of core regulators of proliferation in CIN-associated cancer genomes. Stable DNA copy number amplifications of the core regulators TPX2 and UBE2C were associated with expression of a gene module involved in proliferation. The module genes were enriched within prognostic signature gene sets for ER+ breast cancer, providing a logical connection between CIN and prognostic signature expression. Our results provide a framework to decipher the impact of intratumor heterogeneity on key cancer phenotypes, and they suggest that CIN provides a permissive landscape for selection of copy number alterations which drive cancer proliferation. PMID:24970479

  9. Recombinant Chromosome 4 from a Familial Pericentric Inversion: Prenatal and Adulthood Wolf-Hirschhorn Phenotypes

    Directory of Open Access Journals (Sweden)

    Francesca Malvestiti

    2013-01-01

    Full Text Available Pericentric inversion of chromosome 4 can give rise to recombinant chromosomes by duplication or deletion of 4p. We report on a familial case of Wolf-Hirschhorn Syndrome characterized by GTG-banding karyotypes, FISH, and array CGH analysis, caused by a recombinant chromosome 4 with terminal 4p16.3 deletion and terminal 4q35.2 duplication. This is an aneusomy due to a recombination which occurred during the meiosis of heterozygote carrier of cryptic pericentric inversion. We also describe the adulthood and prenatal phenotypes associated with the recombinant chromosome 4.

  10. Molecular cytogenetic and phenotypic characterization of ring chromosome 13 in three unrelated patients

    Science.gov (United States)

    Abdallah-Bouhjar, Inesse B.; Mougou-Zerelli, Soumaya; Hannachi, Hanene; Gmidène, Abir; Labalme, Audrey; Soyah, Najla; Sanlaville, Damien; Saad, Ali; Elghezal, Hatem

    2013-01-01

    We report on the cytogenetic and molecular investigations of constitutional de-novo ring chromosome 13s in three unrelated patients for better understanding and delineation of the phenotypic variability characterizing this genomic rearrangement. The patient’s karyotypes were as follows: 46,XY,r(13)(p11q34) dn for patients 1 and 2 and 46,XY,r(13)(p11q14) dn for patient 3, as a result of the deletion in the telomeric regions of chromosome 13. The patients were, therefore, monosomic for the segment 13q34 → 13qter; in addition, for patient 3, the deletion was larger, encompassing the segment 13q14 → 13qter. Fluorescence in situ hybridization confirmed these rearrangement and array CGH technique showed the loss of at least 2.9 Mb on the short arm and 4.7 Mb on the long arm of the chromosome 13 in patient 2. Ring chromosome 13 (r(13)) is associated with several phenotypic features like intellectual disability, marked short stature, brain and heart defects, microcephaly and genital malformations in males, including undescended testes and hypospadias. However, the hearing loss and speech delay that were found in our three patients have rarely been reported with ring chromosome 13. Although little is known about its etiology, there is interesting evidence for a genetic cause for the ring chromosome 13. We thus performed a genotype-phenotype correlation analysis to ascertain the contribution of ring chromosome 13 to the clinical features of our three cases.

  11. Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

    DEFF Research Database (Denmark)

    Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.; Rowan, Andrew J.; Grönroos, Eva; Endesfelder, David; Joshi, Tejal; Mouradov, Dmitri; Gibbs, Peter; Ward, Robyn L.; Hawkins, Nicholas J.; Szallasi, Zoltan Imre; Sieber, Oliver M.; Swanton, Charles

    2014-01-01

    The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells ...

  12. Telomerase reverse transcriptase expression protects transformed human cells against DNA-damaging agents, and increases tolerance to chromosomal instability.

    Science.gov (United States)

    Fleisig, H B; Hukezalie, K R; Thompson, C A H; Au-Yeung, T T T; Ludlow, A T; Zhao, C R; Wong, J M Y

    2016-01-14

    Reactivation of telomerase reverse transcriptase (TERT) expression is found in more than 85% of human cancers. The remaining cancers rely on the alternative lengthening of telomeres (ALT), a recombination-based mechanism for telomere-length maintenance. Prevalence of TERT reactivation over the ALT mechanism was linked to secondary TERT function unrelated to telomere length maintenance. To characterize this non-canonical function, we created a panel of ALT cells with recombinant expression of TERT and TERT variants: TERT-positive ALT cells showed higher tolerance to genotoxic insults compared with their TERT-negative counterparts. We identified telomere synthesis-defective TERT variants that bestowed similar genotoxic stress tolerance, indicating that telomere synthesis activity is dispensable for this survival phenotype. TERT expression improved the kinetics of double-strand chromosome break repair and reduced DNA damage-related nuclear division abnormalities, a phenotype associated with ALT tumors. Despite this reduction in cytological abnormalities, surviving TERT-positive ALT cells were found to have gross chromosomal instabilities. We sorted TERT-positive cells with cytogenetic changes and followed their growth. We found that the chromosome-number changes persisted, and TERT-positive ALT cells surviving genotoxic events propagated through subsequent generations with new chromosome numbers. Our data confirm that telomerase expression protects against double-strand DNA (dsDNA)-damaging events, and show that this protective function is uncoupled from its role in telomere synthesis. TERT expression promotes oncogene-transformed cell growth by reducing the inhibitory effects of cell-intrinsic (telomere attrition) and cell-extrinsic (chemical- or metabolism-induced genotoxic stress) challenges. These data provide the impetus to develop new therapeutic interventions for telomerase-positive cancers through simultaneous targeting of multiple telomerase activities. PMID

  13. Phenotypic correlations in a patient with ring chromosome 22

    Directory of Open Access Journals (Sweden)

    Demirhan Osman

    2010-01-01

    Full Text Available Ring chromosome 22, a rare cytogenetic anomaly, has been described in over 60 cases in the medical literature. The aim of this report was to present a case carrying ring chromosome 22, and her family. It is a case report of a patient presented at Medical Faculty of Ηukurova University in Turkey. An 8-year-old girl with ring chromosome 22 and her family were evaluated cytogenetically and clinically. A chromosome analysis of the proband revealed a de novo 46,XX,r(22(p11.2;q13 karyotype. Our subject demonstrated the prominent features of this syndrome including profound mental retardation, language impairment, dysmorphic features, lack of speech, hyperactivity, and behavioral disorders. There is lack of consistency between the physical abnormalities that we observed in our subject and those observed for such patients in the literature. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region.

  14. Distinct Patterns of Structural and Numerical Chromosomal Instability Characterize Sporadic Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jane Bayani

    2008-10-01

    Full Text Available Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex genomic changes in tumors arise as a consequence of chromosomal instability (CIN, which can generate both numerical [(N-CIN] and structural chromosomal instability [(S-CIN]. In this study, molecular cytogenetic analysis was used to evaluate the relative levels of both (N-CIN and (S-CIN. Six tumors had a near-diploid chromosome number, two were near-tetraploid, and two were near-triploid. (N-CIN levels increased as a function of overall tumor genomic content, with near-diploid tumors exhibiting numerical instability indices ranging from 7.0 to 21.0 and near-tetraploid and triploid tumors exhibiting instability indices ranging from 24.9 to 54.9. In contrast, the extent of (S-CIN was generally more evident in the diploid tumors compared with the near-tetraploid tumors. To determine whether the associated chromosomal constitution and/or ploidy changes were influenced by mitotic segregation errors, centrosome analyses were performed on all 10 tumors. The near-diploid tumors, with the lowest numerical change, were observed to possess fewer cells with centrosome abnormalities (5.5% to 14.0%, whereas the near-tetraploid tumors possessed much higher levels of (N-CIN and were characterized by a trend of elevating percentages of cells with abnormal centrosomes (16.0% to 20.5%. These observations suggest that two distinct processes governing genome stability may be disrupted in ovarian cancer: those that impact on numerical segregation and ploidy of chromosomes and those that affect the fidelity of DNA repair and lead to structural aberrations.

  15. Two siblings with immunodeficiency, facial abnormalities and chromosomal instability without mutation in DNMT3B gene but liability towards malignancy; a new chromatin disorder delineation?

    Directory of Open Access Journals (Sweden)

    Neitzel Heidemarie

    2010-03-01

    Full Text Available Abstract Background ICF syndrome (standing for Immunodeficiency, Centromere instability and Facial anomalies syndrome is a very rare autosomal recessive immune disorder caused by mutations of the gene de novo DNA-methyltransferase 3B (DNMT3B. However, in the literature similar clinical cases without such mutations are reported, as well. Results We report on a family in which the unrelated spouses had two female siblings sharing similar phenotypic features resembling ICF-syndrome, i.e. congenital abnormalities, immunodeficiency, developmental delay and high level of chromosomal instability, including high frequency of centromeric/pericentromeric rearrangements and breaks, chromosomal fragments despiralization or pulverization. However, mutations in DNMT3B could not be detected. Conclusion The discovery of a new so-called 'chromatin disorder' is suggested. Clinical, molecular genetic and cytogenetic characteristics are reported and compared to other 'chromatin disorders'.

  16. Evidence of increased chromosomal instability in infertile males after exposure to mitomycin C and caffeine

    Institute of Scientific and Technical Information of China (English)

    Fotini Papachristou; Theodore Lialiaris; Stavros Touloupidis; Christos Kalaitzis; Constantinos Simopoulos; Nikolaos Sofikitis

    2006-01-01

    Aim: To evaluate the genetic instability of 11 fertile and 25 infertile men. Methods: The methodology of sister chromatid exchanges (SCEs) was applied to cultures of peripheral blood lymphocytes, and the levels of SCEss were analyzed as a quantitative index of genotoxicity, along with the values of the mitotic index (MI) and the proliferation rate index (PRI) as qualitative indices of cytotoxicity and cytostaticity, respectively. The genotoxic and antineoplastic agent, mitomycin C (MMC), and caffeine (CAF) - both well-known inhibitors of DNA repair mechanism - were used in an attempt to induce chromosomal instability in infertile men, so as to more easily detect the probable underlying damage on DNA. Results: Our experiments illustrated that infertile men, compared with fertile ones, demonstrated a statistically significant DNA instability in peripheral blood lymphocytes after being exposed simultaneously to MMC and CAF. Conclusion: The current study showed vividly that there was genetic instability in infertile men which probably contributes to the development of an impaired reproductive capacity.

  17. Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer

    DEFF Research Database (Denmark)

    Birkbak, Nicolai Juul; Eklund, Aron Charles; Li, Qiyuan;

    2011-01-01

    70 scores. These results suggest a nonmonotonic relationship between gene signature expression and HR for survival outcome, which may explain the difficulties encountered in the identification of prognostic expression signatures in ER- breast cancer. Furthermore, the data are consistent with the...... cancer cell biological fitness and its relationship with clinical outcome, we applied the CIN70 expression signature, which correlates with DNA-based measures of structural chromosomal complexity and numerical CIN in vivo, to gene expression profiles of 2,125 breast tumors from 13 published cohorts...... intolerance of excessive CIN in carcinomas and provide a plausible strategy to define distinct prognostic patient cohorts with ER- breast cancer. Inclusion of a surrogate measurement of CIN may improve cancer risk stratification and future therapeutic approaches. Cancer Res; 71(10); 3447-52. (C) 2011 AACR....

  18. Chromosome instability in human hepatocellular carcinoma depends on p53 status and aflatoxin exposure.

    Science.gov (United States)

    Pineau, Pascal; Marchio, Agnès; Battiston, Carlo; Cordina, Emilie; Russo, Alessandro; Terris, Benoît; Qin, Lun-Xiu; Turlin, Bruno; Tang, Zhao-You; Mazzaferro, Vincenzo; Dejean, Anne

    2008-05-31

    Hepatocellular carcinoma (HCC) is a heterogeneous disease triggered by various risk factors and frequently characterized by chromosome instability. This instability is considered to be caused primarily by Hepatitis B virus (HBV), although aflatoxin B1 (AFB1), a potent fungal mutagen is also suspected to influence chromosomal repair. We studied 90 HCCs from Italy, the country with the highest incidence of hepatocellular carcinoma in Europe, 81 samples from France and 52 specimens from Shanghai, in a region where intake of AFB1 via the diet is known to be high. All 223 tumours were characterized for 15 different genomic targets, including allelic loss at 13 chromosome arms and mutations of beta-catenin and p53 genes. Despite disparity in risk-factor distribution, Italian and French cases did not significantly differ for 14 of the 15 targets tested. beta-Catenin and p53 displayed moderate and similar mutation rates (18-29% of cases) in European series. By contrast, tumours from Shanghai were significantly different, with a lower mutation rate for beta-catenin (4% vs. 26%, p<0.0003) and a higher mutation rate for p53 (48% vs. 22%, p<0.0001) when compared with tumours of European origin. The Arg249Ser mutation, hallmark of exposure to AFB1, represented half of the changes in p53 in Shanghai. Furthermore, when stratified for the presence of HBV or p53 mutations, chromosome instability was always higher in Chinese than in European patients. This difference was particularly strong in p53-wildtype tumours (fractional allelic loss, 29.4% vs. 16.7%, p<0.0001). We suggest that AFB1-associated mutagenesis represents a plausible cause for the higher chromosome instability observed in Chinese HCCs, when compared with European primary liver carcinomas. PMID:18467159

  19. The pathological phenotype of colon cancer with microsatellite instability

    DEFF Research Database (Denmark)

    Andersen, Helene Schou; Bertelsen, Claus Anders; Henriksen, Rikke; Campos, André; Kristensen, Bent; Ingeholm, Peter; Gögenur, Ismail

    2016-01-01

    INTRODUCTION: Colorectal cancer is a common malignant disease, caused by different aetiologies and molecular pathways. Heterogeneous results have been published regarding the association of microsatellite instability and clinicopathological features. The aim of this study was to compare clinicopa......INTRODUCTION: Colorectal cancer is a common malignant disease, caused by different aetiologies and molecular pathways. Heterogeneous results have been published regarding the association of microsatellite instability and clinicopathological features. The aim of this study was to compare...... clinicopathological features of microsatellite unstable tumours with stable ones. METHODS: Data were collected retrospectively, but the pathological analyses were all made prospectively. The study included a total of 833 patients undergoing resection of their colon tumour at Nordsjællands Hospital - Hillerød, with...... analysis, we demonstrated that microsatellite unstable cancers were significantly associated with a lower degree of lymph node metastases (odds ratio (OR) = 0.92), distant metastases (OR = 0.33) and tumour budding (OR = 0.41). CONCLUSIONS: We found that microsatellite unstable tumours show a pathological...

  20. The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components.

    Directory of Open Access Journals (Sweden)

    Peter C Stirling

    2011-04-01

    Full Text Available Chromosome instability (CIN is observed in most solid tumors and is linked to somatic mutations in genome integrity maintenance genes. The spectrum of mutations that cause CIN is only partly known and it is not possible to predict a priori all pathways whose disruption might lead to CIN. To address this issue, we generated a catalogue of CIN genes and pathways by screening ∼ 2,000 reduction-of-function alleles for 90% of essential genes in Saccharomyces cerevisiae. Integrating this with published CIN phenotypes for other yeast genes generated a systematic CIN gene dataset comprised of 692 genes. Enriched gene ontology terms defined cellular CIN pathways that, together with sequence orthologs, created a list of human CIN candidate genes, which we cross-referenced to published somatic mutation databases revealing hundreds of mutated CIN candidate genes. Characterization of some poorly characterized CIN genes revealed short telomeres in mutants of the ASTRA/TTT components TTI1 and ASA1. High-throughput phenotypic profiling links ASA1 to TTT (Tel2-Tti1-Tti2 complex function and to TORC1 signaling via Tor1p stability, consistent with the role of TTT in PI3-kinase related kinase biogenesis. The comprehensive CIN gene list presented here in principle comprises all conserved eukaryotic genome integrity pathways. Deriving human CIN candidate genes from the list allows direct cross-referencing with tumor mutational data and thus candidate mutations potentially driving CIN in tumors. Overall, the CIN gene spectrum reveals new chromosome biology and will help us to understand CIN phenotypes in human disease.

  1. Chromosomal instability selects gene copy number variants encoding core regulators of proliferation in ER+ breast cancer

    OpenAIRE

    Endesfelder, David; Burrell, Rebecca; Kanu, Nnennaya; McGranahan, Nicholas; Howell, Mike; Parker, Peter J.; Downward, Julian; Swanton, Charles; Kschischo, Maik

    2014-01-01

    Chromosomal instability (CIN) is associated with poor outcome in epithelial malignancies including breast carcinomas. Evidence suggests that prognostic signatures in estrogen receptor-positive (ER+) breast cancer define tumors with CIN and high proliferative potential. Intriguingly, CIN induction in lower eukaryotic cells and human cells is context-dependent, typically resulting in a proliferation disadvantage but conferring a fitness benefit under strong selection pressures. We hypothesised ...

  2. Aberrant Wnt/β-catenin signaling can induce chromosomal instability in colon cancer

    OpenAIRE

    Hadjihannas, Michel V; Brückner, Martina; Jerchow, Boris; Birchmeier, Walter; Dietmaier, Wolfgang; Behrens, Jürgen

    2006-01-01

    Chromosomal instability (CIN), a hallmark of most colon tumors, may promote tumor progression by increasing the rate of genetic aberrations. CIN is thought to arise as a consequence of improper mitosis and spindle checkpoint activity, but its molecular basis remains largely elusive. The majority of colon tumors develop because of mutations in the tumor suppressor APC that lead to Wnt/β-catenin signaling activation and subsequent transcription of target genes, including conductin/AXIN2. Here w...

  3. Array-CGH characterization and genotype-phenotype analysis in a patient with a ring chromosome 6

    OpenAIRE

    Ciocca, Laura; Surace, Cecilia; Digilio, Maria Cristina; Roberti, Maria Cristina; Sirleto, Pietro; Lombardo, Antonietta; Russo, Serena; Brizi, Valerio; Grotta, Simona; Cini, Claudio; Angioni, Adriano

    2013-01-01

    Background Ring chromosome 6 is a rare constitutional abnormality that generally occurs de novo. The related phenotype may be highly variable ranging from an almost normal phenotype to severe malformations and mental retardation. These features are mainly present when genetic material at the end of the chromosome is lost. The severity of the phenotype seems to be related to the size of the deletion. About 25 cases have been described to date, but the vast majority reports only conventional cy...

  4. Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype

    OpenAIRE

    Korenberg, Julie R; Kawashima, Hiroko; Pulst, Stefan-M.; Ikeuchi, T; Ogasawara, N; Yamamoto, K.; Schonberg, Steven A.; West, Ruth; Allen, Leland; Magenis, Ellen; Ikawa, K; Taniguchi, N; Epstein, Charles J.

    1990-01-01

    Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22. We now present evidence that significantly narrows the chromosomal region responsible for several of the phenotypic features of DS. We report a molecular and cytogenetic analysis of a three-generation family containing four individuals with clinical DS as manif...

  5. Alternative Lengthening of Telomeres-An Enhanced Chromosomal Instability in Aggressive Non-MYCN Amplified and Telomere Elongated Neuroblastomas

    NARCIS (Netherlands)

    G. Lundberg; D. Sehic; J.K. Lansberg; I. Ora; A. Frigyesi; V. Castel; S. Navarro; M. Piqueras; T. Martinsson; R. Noguera; D. Gisselsson

    2011-01-01

    Telomere length alterations are known to cause genomic instability and influence clinical course in several tumor types, but have been little investigated in neuroblastoma (NB), one of the most common childhood tumors. In the present study, telomere-dependent chromosomal instability and telomere len

  6. Influence of gamma irradiation on chromosomal instability in seeds of welsh onion (Allium fistulosum L.) at storage

    International Nuclear Information System (INIS)

    The levels of chromosomal instability and germinating capacity of welsh onion (Allium fistulosum L.) seeds were studied in control and gamma-irradiated (5 and 10 Gy) groups of seeds. We compared relative chromosome destabilizing effects of the seed age at the moment of irradiation and the time period of storage after irradiation to germination. The second factor was significantly more effective than the first one. It increased the rate of chromosomal aberration and decreased the germinative capacity of seeds. (authors)

  7. Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells

    OpenAIRE

    Kim, Jung Hyun; Lee, Hee Sheung; Lee, Nicholas C.O.; Goncharov, Nikolay V.; Kumeiko, Vadim; Masumoto, Hiroshi; Earnshaw, William C.; Kouprina, Natalay; Larionov, Vladimir

    2016-01-01

    Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" a...

  8. Misregulation of Scm3p/HJURP causes chromosome instability in Saccharomyces cerevisiae and human cells.

    Directory of Open Access Journals (Sweden)

    Prashant K Mishra

    2011-09-01

    Full Text Available The kinetochore (centromeric DNA and associated proteins is a key determinant for high fidelity chromosome transmission. Evolutionarily conserved Scm3p is an essential component of centromeric chromatin and is required for assembly and function of kinetochores in humans, fission yeast, and budding yeast. Overexpression of HJURP, the mammalian homolog of budding yeast Scm3p, has been observed in lung and breast cancers and is associated with poor prognosis; however, the physiological relevance of these observations is not well understood. We overexpressed SCM3 and HJURP in Saccharomyces cerevisiae and HJURP in human cells and defined domains within Scm3p that mediate its chromosome loss phenotype. Our results showed that the overexpression of SCM3 (GALSCM3 or HJURP (GALHJURP caused chromosome loss in a wild-type yeast strain, and overexpression of HJURP led to mitotic defects in human cells. GALSCM3 resulted in reduced viability in kinetochore mutants, premature separation of sister chromatids, and reduction in Cse4p and histone H4 at centromeres. Overexpression of CSE4 or histone H4 suppressed chromosome loss and restored levels of Cse4p at centromeres in GALSCM3 strains. Using mutant alleles of scm3, we identified a domain in the N-terminus of Scm3p that mediates its interaction with CEN DNA and determined that the chromosome loss phenotype of GALSCM3 is due to centromeric association of Scm3p devoid of Cse4p/H4. Furthermore, we determined that similar to other systems the centromeric association of Scm3p is cell cycle regulated. Our results show that altered stoichiometry of Scm3p/HJURP, Cse4p, and histone H4 lead to defects in chromosome segregation. We conclude that stringent regulation of HJURP and SCM3 expression are critical for genome stability.

  9. Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas

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    Gilson S. Baia

    2008-06-01

    Full Text Available The Notch signaling cascade is deregulated in diverse cancer types. Specific Notch function in cancer is dependent on the cellular context, the particular homologs expressed, and cross-talk with other signaling pathways. We have previously shown that components of the Notch signaling pathway are deregulated in meningiomas. How-ever, the functional consequence of abnormal Notch signaling to meningiomas is unknown. Here, we report that exogenous expression of the Notch pathway effector, HES1, is associated with tetraploid cells in meningioma cell lines. Activated Notch1 and Notch2 receptors induced endogenous HES1 expression and were associated with tetraploidy in meningiomas. Tetraploid meningioma cells exhibited nuclear features of chromosomal instability and increased frequency of nuclear atypia, such as multipolar mitotic spindles and accumulation of cells with large nuclei. FACS-sorted tetraploid cells are viable but have higher rates of spontaneous apoptosis when compared with diploid cells. We have used spectral karyotyping to show that, in contrast to diploid cells, tetraploid cells develop a higher number of both numerical and structural chromosomal abnormalities. Our findings identify a novel function for the Notch signaling pathway in generating tetraploidy and contributing to chromosomal instability. We speculate that abnormal Notch signaling pathway is an initiating genetic mechanism for meningioma and potentially promotes tumor development.

  10. Genotype/phenotype correlation in women with nonmosaic X chromosome deletions and Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Zinn, A.R. [Univ. of Texas Southwestern Medical School, Dallas, TX (United States)

    1994-09-01

    Turner syndrome is a complex human developmental disorder associated with the absence of the second sex chromosome (monosomy X). Cardinal features of the Turner phenotype include high intrauterine lethality, growth retardation, gonadal failure, and the variable presence of specific somatic abnormalities such as webbed neck, lymphedema, and skeletal abnormalities. Recent observations support the hypothesis that the phenotype associated with monosomy X results from haploid dosage of genes common the X and Y chromosomes that escape X-inactivation ({open_quotes}Turner genes{close_quotes}). Apart from a locus causing short stature that maps to the pseudoautosomal region on the distal short arm, the location of X-linked Turner genes is not known. Karyotype/phenotype correlations in women with partial X deletions have been inconsistent. However, previous studies have focused on sporadic sex chromosome aberrations and may have been confounded by occult mosaicism. In addition, mapping of deletions was limited by the resolution of cytogenetic techniques. I am reexamining genotype/phenotype correlations in partial X monosomy, focusing on a subset of cases in which mosaicism is highly unlikely (e.g., unbalanced X-autosome translocations, familial X deletions), and using molecular techniques to map deletions. I have collected eight cases of nonmosaic X deletions in women with varied manifestations of Turner syndrome. Cytogenetic data suggests that genes responsible for Turner anatomic abnormalities may lie within a critical region of the very proximal portion of the short arm (Xp11). Molecular characterization of the deletions is in progress. Methods include (1) fluorescence in situ hybridization of metaphase spreads from patient-derived cell lines, using cosmid probes that map to known locations on Xp, and (2) sequence tagged site (STS) content mapping of somatic cell hybrids retaining the deleted X chromosomes derived from these cell lines.

  11. Deregulation of the Replisome Factor MCMBP Prompts Oncogenesis in Colorectal Carcinomas through Chromosomal Instability

    Directory of Open Access Journals (Sweden)

    Mauricio Quimbaya

    2014-09-01

    Full Text Available Genetic instability has emerged as an important hallmark of human neoplasia. Although most types of cancers exhibit genetic instability to some extent, in colorectal cancers genetic instability is a distinctive characteristic. Recent studies have shown that deregulation of genes involved in sister chromatid cohesion can result in chromosomal instability in colorectal cancers. Here, we show that the replisome factor minichromosome maintenance complex–binding protein (MCMBP, which is directly involved in the dynamics of the minichromosome maintenance complex and contributes to maintaining sister chromatid cohesion, is transcriptionally misregulated in different types of carcinomas. Cellular studies revealed that both MCMBP knockdown and overexpression in different breast and colorectal cell lines is associated with the emergence of a subpopulation of cells with abnormal nuclear morphology that likely arise as a consequence of aberrant cohesion events. Association analysis integrating gene expression data with clinical information revealed that enhanced MCMBP transcript levels correlate with an increased probability of relapse risk in colorectal cancers and different types of carcinomas. Moreover, a detailed study of a cohort of colorectal tumors showed that the MCMBP protein accumulates to high levels in cancer cells, whereas in normal proliferating tissue its abundance is low, indicating that MCMBP could be exploited as a novel diagnostic marker for this type of carcinoma.

  12. Tumor progression: analysis of the instability of the metastatic phenotype, sensitivity to radiation and chemotherapy

    International Nuclear Information System (INIS)

    The major complications for tumor therapy are 1) tumor spread (metastasis); 2) the mixed nature of tumors (heterogeneity); and 3) the capacity of tumors to evolve (progress). To study these tumor characteristics, the rat 13762NF mammary adenocarcinoma was cloned and studied for metastatic properties and sensitivities to therapy (chemotherapy, radiation and hyperthermia). The cell clones were heterogeneous and no correlation between metastatic potential and therapeutic sensitivities was observed. Further, these phenotypes were unstable during pasage in vitro; yet, the changes were clone dependent and reproducible using different cryoprotected cell stocks. To understand the phenotypic instability, subclones were isolated from low and high passage cell clones. The results demonstrated that 1) tumor cells are heterogeneous for multiple phenotypes; 2) tumor cells are unstable for multiple phenotypes; 3) the magnitude, direction and time of occurrence of phenotypic drift is clone dependent; 4) the sensitivity of cell clones to ionizing radiation (γ or heat) and chemotherapy agents is independent of their metastatic potential; 5) shifts in metastatic potential and sensitivity to therapy may occur simultaneously but are not linked; and 6) tumor cells independently diverge to form several subpopulations with unique phenotypic profiles

  13. Phenotypic instability of Arabidopsis alleles affecting a disease Resistance gene cluster

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    Richards Eric J

    2008-04-01

    Full Text Available Abstract Background Three mutations in Arabidopsis thaliana strain Columbia – cpr1, snc1, and bal – map to the RPP5 locus, which contains a cluster of disease Resistance genes. The similar phenotypes, gene expression patterns, and genetic interactions observed in these mutants are related to constitutive activation of pathogen defense signaling. However, these mutant alleles respond differently to various conditions. Exposure to mutagens, such as ethyl methanesulfonate (EMS and γ-irradiation, induce high frequency phenotypic instability of the bal allele. In addition, a fraction of the bal and cpr1 alleles segregated from bal × cpr1 F1 hybrids also show signs of phenotypic instability. To gain more insight into the mechanism of phenotypic instability of the bal and cpr1 mutations, we systematically compared the behavior of these unusual alleles with that of the missense gain-of-function snc1 allele in response to DNA damage or passage through F1 hybrids. Results We found that the cpr1 allele is similar to the bal allele in its unstable behavior after EMS mutagenesis. For both the bal and cpr1 mutants, destabilization of phenotypes was observed in more than 10% of EMS-treated plants in the M1 generation. In addition, exceptions to simple Mendelian inheritance were identified in the M2 generation. Like cpr1 × bal F1 hybrids, cpr1 × snc1 F1 hybrids and bal × snc1 F1 hybrids exhibited dwarf morphology. While only dwarf F2 plants were produced from bal × snc1 F1 hybrids, about 10% wild-type F2 progeny were produced from cpr1 × snc1 F1 hybrids, as well as from cpr1 × bal hybrids. Segregation analysis suggested that the cpr1 allele in cpr1 × snc1 crosses was destabilized during the late F1 generation to early F2 generation. Conclusion With exposure to EMS or different F1 hybrid contexts, phenotypic instability is induced for the bal and cpr1 alleles, but not for the snc1 allele. Our results suggest that the RPP5 locus can adopt different

  14. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  15. Centrosome amplification, chromosomal instability and cancer: mechanistic, clinical and therapeutic issues.

    Science.gov (United States)

    Cosenza, Marco Raffaele; Krämer, Alwin

    2016-01-01

    Centrosomes, the main microtubule-organizing centers in most animal cells, are of crucial importance for the assembly of a bipolar mitotic spindle and subsequent faithful segregation of chromosomes into two daughter cells. Centrosome abnormalities can be found in virtually all cancer types and have been linked to chromosomal instability (CIN) and tumorigenesis. Although our knowledge on centrosome structure, replication, and amplification has greatly increased within recent years, still only very little is known on nature, causes, and consequences of centrosome aberrations in primary tumor tissues. In this review, we summarize our current insights into the mechanistic link between centrosome aberrations, aneuploidy, CIN and tumorigenesis. Mechanisms of induction and cellular consequences of aneuploidy, tetraploidization and CIN, as well as origin and effects of supernumerary centrosomes will be discussed. In addition, animal models for both CIN and centrosome amplification will be outlined. Finally, we describe approaches to exploit centrosome amplification, aneuploidy and CIN for novel and specific anticancer treatment strategies based on the modulation of chromosome missegregation rates. PMID:26645976

  16. Chromosomal instability selects gene copy-number variants encoding core regulators of proliferation in ER+ breast cancer.

    Science.gov (United States)

    Endesfelder, David; Burrell, Rebecca A; Kanu, Nnennaya; McGranahan, Nicholas; Howell, Mike; Parker, Peter J; Downward, Julian; Swanton, Charles; Kschischo, Maik

    2014-09-01

    Chromosomal instability (CIN) is associated with poor outcome in epithelial malignancies, including breast carcinomas. Evidence suggests that prognostic signatures in estrogen receptor-positive (ER(+)) breast cancer define tumors with CIN and high proliferative potential. Intriguingly, CIN induction in lower eukaryotic cells and human cells is context dependent, typically resulting in a proliferation disadvantage but conferring a fitness benefit under strong selection pressures. We hypothesized that CIN permits accelerated genomic evolution through the generation of diverse DNA copy-number events that may be selected during disease development. In support of this hypothesis, we found evidence for selection of gene amplification of core regulators of proliferation in CIN-associated cancer genomes. Stable DNA copy-number amplifications of the core regulators TPX2 and UBE2C were associated with expression of a gene module involved in proliferation. The module genes were enriched within prognostic signature gene sets for ER(+) breast cancer, providing a logical connection between CIN and prognostic signature expression. Our results provide a framework to decipher the impact of intratumor heterogeneity on key cancer phenotypes, and they suggest that CIN provides a permissive landscape for selection of copy-number alterations that drive cancer proliferation. PMID:24970479

  17. Genetic control of chromosome instability in Aspergillus nidulans as a means for gene amplification in eukaryotic microorganisms

    International Nuclear Information System (INIS)

    A haploid strain of Aspergillus nidulans carrying I-II duplication homozygous for the leaky mutation adE20 shows improved growth on minimal medium. The duplication, though more stable than disomics, still shows instability. Several methods were used for detecting genetic control of improved stability. a) visual selection, using a duplicated strain which is very unstable due to UV sensitivity, (adE20, biAl/dp yA2; uvsB). One stable strain showed a deletion (or a lethal mutation) distal to biA on the segment at the original position (on chromosome I). This deletion reduces crossing-over frequency detween the two homologous segments. As the deletion of the non-translated segment (yellow sectors) must be preceded by crossing-over, the above reduces the frequency of yellow sectors. A deletion of the translocated segment (green sectors) results in non-viability due to the deletion, and such sectors do not appear. The net result is a stable duplication involving only 12 C.O. units carrying the gene in concern. b) Suppressors of UV sensitivity (su-uvsB) were attempted using the above uvs duplicated strain. Phenotypic revertants were easily obtained, but all were back mutations at the uvsB locus. c) Mutations for UV resistance higher than that of the wild type were not obtained, in spite of the strong selective pressure inserted. d) Recombination deficient mutations (rec), six altogether, all uvs+, did not have any effect on stability. (orig.)

  18. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

    2008-04-02

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

  19. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    International Nuclear Information System (INIS)

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

  20. Widespread Impact of Chromosomal Inversions on Gene Expression Uncovers Robustness via Phenotypic Buffering.

    Science.gov (United States)

    Naseeb, Samina; Carter, Zorana; Minnis, David; Donaldson, Ian; Zeef, Leo; Delneri, Daniela

    2016-07-01

    The nonrandom gene organization in eukaryotes plays a significant role in genome evolution and function. Chromosomal structural changes impact meiotic fitness and, in several organisms, are associated with speciation and rapid adaptation to different environments. Small sized chromosomal inversions, encompassing few genes, are pervasive in Saccharomyces "sensu stricto" species, while larger inversions are less common in yeasts compared with higher eukaryotes. To explore the effect of gene order on phenotype, reproductive isolation, and gene expression, we engineered 16 Saccharomyces cerevisiae strains carrying all possible paracentric and pericentric inversions between Ty1 elements, a natural substrate for rearrangements. We found that 4 inversions were lethal, while the other 12 did not show any fitness advantage or disadvantage in rich and minimal media. At meiosis, only a weak negative correlation with fitness was seen with the size of the inverted region. However, significantly lower fertility was seen in heterozygote invertant strains carrying recombination hotspots within the breakpoints. Altered transcription was observed throughout the genome rather than being overrepresented within the inversions. In spite of the large difference in gene expression in the inverted strains, mitotic fitness was not impaired in the majority of the 94 conditions tested, indicating that the robustness of the expression network buffers the deleterious effects of structural changes in several environments. Overall, our results support the notion that transcriptional changes may compensate for Ty-mediated rearrangements resulting in the maintenance of a constant phenotype, and suggest that large inversions in yeast are unlikely to be a selectable trait during vegetative growth. PMID:26929245

  1. X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria.

    Science.gov (United States)

    Brancaleoni, V; Balwani, M; Granata, F; Graziadei, G; Missineo, P; Fiorentino, V; Fustinoni, S; Cappellini, M D; Naik, H; Desnick, R J; Di Pierro, E

    2016-01-01

    X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromosomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP. PMID:25615817

  2. Gene Expression Signature TOPFOX Reflecting Chromosomal Instability Refines Prediction of Prognosis in Grade 2 Breast Cancer

    DEFF Research Database (Denmark)

    Szasz, A.; Li, Qiyuan; Sztupinszki, Z.; Tokes, A. M.; Szekely, B.; Szendroi, M.; Gyorffy, B.; Szallasi, Z.; Swanton, C.; Kulkal, J.

    Purpose: To assess the ability of genes selected from those reflecting chromosomal instability to identify good and poor prognostic subsets of Grade 2 breast carcinomas. Methods: We selected genes for splitting grade 2 tumours into low and high grade type groups by using public databases. Patients...... immunophenotypical characterization of tumours. 1509 samples were in silico analyzed for further validation of the selected genes. Results: Grade 1 and 3 groups were used as training set for the selected genes. The 4-gene signature was able to split grade 2 carcinomas (n = 62) into a good and a poor prognosis group...... (RFS: 83.8±4.9 months and 69.4±8.2 months, respectively, p = 0.016). Furthermore, independent of grade, the identified signature containing only TOP2A and FOXM1 (TOPFOX) was able to separate ER+ tumours in an efficient manner (p = 0.009), which is further supported by validation in a dataset containing...

  3. Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

    KAUST Repository

    Kashuba, Elena

    2015-05-12

    We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways that control cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions were activated in the immortalized cells. Here we report that, upon overexpression of S18-2 protein, primary rat skin fibroblasts underwent cell transformation. Cells passed more than 300 population doublings, and two out of three tested clones gave rise to tumors in experimental animals. Transformed cells showed anchorage-independent growth and loss of contact inhibition; they expressed epithelial markers, such as E-cadherin and β-catenin. Transformed cells showed increased telomerase activity, disturbance of the cell cycle, and chromosomal instability. Taken together, our data suggest that S18-2 is a newly identified oncoprotein that may be involved in cancerogenesis.

  4. Chromosome instability and X-ray hypersensitivity in a microcephalic and growth-retarded child

    International Nuclear Information System (INIS)

    The authors report on a microcephalic, growth-retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. They propose that their patient belongs to the expanding category of AT-related genetic disorders, probably to the Nijmegen breakage syndrome

  5. Radiation induced chromosomal instability in peripheral blood lymphocytes obtained from breast cancer patients

    International Nuclear Information System (INIS)

    If the breast cancer patients include a disproportionately large number of radiosensitive persons, some radiation-related genes may be involved in the mammary tumorigenesis. To test this hypothesis, the in vitro radiation sensitivities of peripheral blood lymphocytes obtained from 48 normal females and 131 breast cancer patients were measured with a cytokinesis-blocking micronucleus assay. Both the spontaneous- and the X-ray-induced-micronucleus frequencies in patients' blood were significantly higher than those in normal individuals. Our data demonstrate that the chromosomal instability is higher in patients' cells than in normal individuals' cells, and that the radiation-related genes with low penetrance may be involved in mammary tumorigenesis and also, in patients' radiation susceptibility. (author)

  6. Instability of Multiple Sex Chromosomes Systems in Fish: The Case of Erythrinus erythrinus (Bloch & Schneider, 1801) (Characiformes, Erythrinidae).

    Science.gov (United States)

    Bueno, Vanessa; Moresco, Rafaela Maria; Konerat, Jocicléia Thums; Moreira-Filho, Orlando; Margarido, Vladimir Pavan

    2016-02-01

    The fish species Erythrinus erythrinus belongs to the family Erythrinidae (order Characiformes, superorder Teleostei) and is considered a species complex because of the considerable differences between the karyotypes of analyzed populations. Whereas some populations present a sex chromosome system with male heterogamety, others do not show differentiated sex chromosomes. In this article, two novel karyotypes of E. erythrinus with the occurrence of male and female heterogamety are described, and a discussion of the stability of multiple sex chromosome systems is provided. A possible cause for sex chromosomes instability is that the Robertsonian rearrangements that originated the multiple systems did not prevent recombination with ancestral chromosomes, which also did not pass through a heterochromatinization process, the opposite of what usually happens with simple systems, especially of the ZZ/ZW or XX/XY type. It is suggested that multiple sex chromosome systems would not act as an effective postzygotic barrier, especially when there are hybridization zones between distinct karyomorphs that bear and that do not bear sex chromosome systems, allowing the generation of hybrids. This finding is important both for the comprehension of sex chromosomes evolution in fish and for conservation biology since the contact between populations with and without multiple sex chromosomes may compromise the regional biodiversity. PMID:26618235

  7. Detailed phenotype-genotype study in five patients with chromosome 6q16 deletion : narrowing the critical region for Prader-Willi-like phenotype

    NARCIS (Netherlands)

    Bonaglia, Maria Clara; Ciccone, Roberto; Gimelli, Giorgio; Gimelli, Stefania; Marelli, Susan; Verheij, Joke; Giorda, Roberto; Grasso, Rita; Borgatti, Renato; Pagone, Filomena; Rodriguez, Laura; Martinez-Frias, Maria-Luisa; van Ravenswaaij, Conny; Zuffardi, Orsetta

    2008-01-01

    Most patients with an interstitial deletion of 6q16 have Prader-Willi-like phenotype, featuring obesity, hypotonia, short hands and feet, and developmental delay. In all reported studies, the chromosome rearrangement was detected by karyotype analysis, which provides an overview of the entire genome

  8. Stabilization of MCRS1 by BAP1 prevents chromosome instability in renal cell carcinoma.

    Science.gov (United States)

    Peng, Jingtao; Ma, Jian; Li, Weiguo; Mo, Ren; Zhang, Pingzhao; Gao, Kun; Jin, Xiaofeng; Xiao, Jiantao; Wang, Chenji; Fan, Jie

    2015-12-01

    Characterization of the exome and genome of carcinoma (ccRCC) by next-generation sequencing identified numerous genetic alternations. BRCA1-associated protein-1 (BAP1) was identified as one of the most frequently mutated genes in ccRCC, suggesting that BAP1 is a potential key driver for ccRCC cancer initiation and progression. However, how BAP1 mutations contribute to ccRCC remains to be elucidated. BAP1 is a nuclear de-ubiquitinating enzyme and cleaves the ubiquitin chain from the substrates. Here, we identified MCRS1 as a bona fide substrate for BAP1. MCRS1 is a component of the centrosome proteins, and plays an essential role in spindle assembly. BAP1 binds to MCRS1 and stabilizes MCRS1 by de-ubiquitination. BAP1 contributes to chromosome stability partially via MCRS1. A positive correlation was identified between BAP1 and MCRS1 expression in ccRCC tissues. Both BAP1 loss and MCRS1 down-regulation in ccRCC were associated with adverse clinicopathological features. This study revealed a novel mechanism for BAP1 involved in MCRS1 stability regulation, and provided insight in understanding the relationship between BAP1 mutations and chromosome instability in ccRCC. PMID:26300492

  9. Molecular analysis of chromosome 21 in a patient with a phenotype of down syndrome and apparently normal karyotype

    Energy Technology Data Exchange (ETDEWEB)

    Ahlbom, B.E.; Wadelius, C.; Zech, L.; Anneren, G. [Uppsala Univ. (Sweden)] [and others

    1996-06-28

    Down syndrome (DS) is caused in most cases by the presence of an extra chromosome 21. It has been shown that the DS phenotype is produced by duplication of only a small part of the long arm of chromosome 21, the 21q22 region, including and distal to locus D21S55. We present molecular investigations on a woman with clinically typical DS but apparently normal chromosomes. Her parents were consanguineous and she had a sister with a DS phenotype, who died at the age of 15 days. Repeated cytogenetic investigations (G-banding and high resolution banding) on the patient and her parents showed apparently normal chromosomes. Autoradiographs of quantitative Southern blots of DNAs from the patient, her parents, trisomy 21 patients, and normal controls were analyzed after hybridization with unique DNA sequences regionally mapped on chromosome 21. Sequences D21S59, D21S1, D21S11, D21S8, D21S17, D21S55, ERG, D21S15, D21S112, and COL6A1 were all found in two copies. Fluorescent in situ hybridization with a chromosome 21-specific genomic library showed no abnormalities and only two copies of chromosome 21 were detected. Nineteen markers from the critical region studied with polymerase chain reaction amplification of di- and tetranucleotide repeats did not indicate any partial trisomy 21. From his study we conclude that the patient does not have any partial submicroscopic trisomy for any segment of chromosome 21. It seems reasonable to assume that she suffers from an autosomal recessive disorder which is phenotypically indistinguishable from DS. 23 refs., 6 figs., 3 tabs.

  10. Dynamic Bcl-xL (S49) and (S62) Phosphorylation/Dephosphorylation during Mitosis Prevents Chromosome Instability and Aneuploidy in Normal Human Diploid Fibroblasts

    Science.gov (United States)

    Baruah, Prasamit Saurav; Beauchemin, Myriam; Hébert, Josée; Bertrand, Richard

    2016-01-01

    Bcl-xL proteins undergo dynamic phosphorylation/dephosphorylation on Ser49 and Ser62 residues during mitosis. The expression of Bcl-xL(S49A), (S62A) and dual (S49/62A) phosphorylation mutants in tumor cells lead to severe mitotic defects associated with multipolar spindle, chromosome lagging and bridging, and micro-, bi- and multi-nucleated cells. Because the above observations were made in tumor cells which already display genomic instability, we now address the question: will similar effects occur in normal human diploid cells? We studied normal human diploid BJ foreskin fibroblast cells expressing Bcl-xL (wild type), (S49A), (S49D), (S62A), (S62D) and the dual-site (S49/62A) and (S49/62D) mutants. Cells expressing S49 and/or S62 phosphorylation mutants showed reduced kinetics of cell population doubling. These effects on cell population doubling kinetics correlated with early outbreak of senescence with no impact on the cell death rate. Senescent cells displayed typical senescence-associated phenotypes including high-level of senescence-associated β-galactosidase activity, interleukin-6 (IL-6) secretion, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21Waf1/Cip1 activation as well as γH2A.X-associated nuclear chromatin foci. Fluorescence in situ hybridization analysis and Giemsa-banded karyotypes revealed that the expression of Bcl-xL phosphorylation mutants in normal diploid BJ cells provoked chromosome instability and aneuploidy. These findings suggest that dynamic Bcl-xL(S49) and (S62) phosphorylation/dephosphorylation cycles are important in the maintenance of chromosome integrity during mitosis in normal cells. They could impact future strategies aiming to develop and identify compounds that could target not only the anti-apoptotic domain of Bcl-xL protein, but also its mitotic domain for cancer therapy. PMID:27398719

  11. HIV Provirus Stably Reproduces Parental Latent and Induced Transcription Phenotypes Regardless of the Chromosomal Integration Site

    Science.gov (United States)

    Hashemi, Farhad B.; Barreto, Kris; Bernhard, Wendy; Hashemi, Pargol; Lomness, Adam

    2016-01-01

    ABSTRACT Understanding the mechanisms of HIV proviral latency is essential for development of a means to eradicate infection and achieve a cure. We have previously described an in vitro latency model that reliably identifies HIV expression phenotypes of infected cells using a dual-fluorescence reporter virus. Our results have demonstrated that ∼50% of infected cells establish latency immediately upon integration of provirus, a phenomenon termed early latency, which appears to occur by mechanisms that are distinct from epigenetic silencing observed with HIV provirus that establishes productive infections. In this study, we have used a mini-dual HIV reporter virus (mdHIV) to compare the long-term stability of provirus produced as early latent or productive infections using Jurkat-Tat T cell clones. Cloned lines bearing mdHIV provirus integrated at different chromosomal locations display unique differences in responsiveness to signaling agonists and chromatin-modifying compounds, and they also produce characteristic expression patterns from the 5′ long terminal repeat (LTR) dsRed and internal EIF1α-enhanced green fluorescent protein (EIF1α-eGFP) reporters. Furthermore, reporter expression profiles of single cell sorted subcultures faithfully reproduce expression profiles identical to that of their original parental population, following prolonged growth in culture, without shifting toward expression patterns resembling that of cell subclones at the time of sorting. Comparison of population dispersion coefficient (CV) and mean fluorescence intensity (MFI) of the subcloned lines showed that both untreated and phorbol myristate acetate (PMA)-ionomycin-stimulated cultures produce expression patterns identical to those of their parental lines. These results indicate that HIV provirus expression characteristics are strongly influenced by the epigenetic landscape at the site of chromosomal integration. IMPORTANCE There is currently considerable interest in development

  12. Frequent induction of chromosomal aberrations in in vivo skin fibroblasts after allogeneic stem cell transplantation: hints to chromosomal instability after irradiation

    International Nuclear Information System (INIS)

    Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively. We studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23–65 months after SCT for G-banded chromosome analysis. Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group. High-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability

  13. Expression of chromosome instability in children with thyroid pathology born to parents suffered from Chernobyl accident factors

    International Nuclear Information System (INIS)

    Under the usage of long-term human peripheral blood lymphocytes' cultures, the association between thyroid pathology in the children born to irradiated parents and the expression of the hidden cytogenetic effect in delayed cells' generations had been determined. The interindividual variability in the observed children as regard as the response of somatic cells' chromosomes to different terms of the lymphocytes cultivation had been revealed. The possible promotion of delayed chromosome instability on the realization of thyroid pathology in children with a hidden functional failure of the endocrine system has been assumed

  14. A case report of a patient with microcephaly, facial dysmorphism, chromosomal radiosensitivity and telomere length alterations closely resembling "Nijmegen breakage syndrome" phenotype.

    Science.gov (United States)

    Berardinelli, F; di Masi, A; Salvatore, M; Banerjee, S; Myung, K; De Villartay, J P; Revy, P; Plebani, A; Soresina, A; Taruscio, D; Tanzarella, C; Antoccia, A

    2007-01-01

    Genetic heterogeneity in Nijmegen breakage syndrome (NBS) is highlighted by patients showing clinical and cellular features of NBS but with no mutations in NBS1 and normal levels of nibrin. NBS is an autosomal recessive disorder, whose clinical cellular signs include growth and developmental defects, dysmorphic facies, immunodeficiency, cancer predisposition, chromosomal instability and radiosensitivity. NBS is caused by mutations in the NBS1 gene, whose product is part of the MRE11/RAD50/NBS1 complex involved in the DNA double-strand break (DSB) response pathway. Since the identification of the NBS1 gene, patients with NBS clinical signs, particularly severe congenital microcephaly, are screened for mutations in the NBS1 gene. Further analyses include X-ray-induced chromosome aberrations, telomere analysis, kinetics of DSBs repair, levels of a panel of proteins involved in the maintenance of genetic stability, radiation-induced phosphorylation of various substrates and cell cycle analysis. We describe a patient with a NBS clinical phenotype, chromosomal sensitivity to X-rays but without mutations in the whole NBS1 or in the Cernunnos gene. Enhanced response to irradiation was mediated neither by DSBs rejoining defects nor by the NBS/AT-dependent DNA-damage response pathway. Notably, we found that primary fibroblasts from this patient displayed telomere length alterations. Cross-talk between pathways controlling response to DSBs and those involved in maintaining telomeres has been shown in the present patient. Dissecting the cellular phenotype of radiosensitive NBS-like patients represents a useful tool for the research of new genes involved in the cellular response to DSBs. PMID:17395558

  15. Ultraviolet-induced chromosomal instability in cultured fibroblasts of heterozygote carriers for xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Fibroblast cultures of seven patients with xeroderma pigmentosum (XP), 19 healthy sibs or parents of XP patients (XP-heterozygotes), and 24 healthy normal controls were studied for chromosome instability induced by ultraviolet rays (UV). We used a UV source that contained predominantly UV-A and UV-B at an intensity of 500 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). the XP homozygotes had a UV sensitivity that was clearly above that of all heterozygotes and normal controls. Heterozygotes had an increased rate of UV-induced MN (4.76 ± 1.96 vs. 1.82 ± 2.05, p less than 0.0001) and increased UV induction of SCE (13.21 ± 3.49 vs. 9.01 ± 1.25, p less than 0.001), as compared to normal controls. These data support epidemiologic findings that suggest that XP heterozygotes are particularly cancer prone. In addition, the determination of the UV sensitivity in vitro as described may be used for genetic counseling of asymptomatic relatives of XP patients

  16. Early embryonic chromosome instability results in stable mosaic pattern in human tissues.

    Directory of Open Access Journals (Sweden)

    Hasmik Mkrtchyan

    Full Text Available The discovery of copy number variations (CNV in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations.

  17. HIPK2 deficiency causes chromosomal instability by cytokinesis failure and increases tumorigenicity

    Science.gov (United States)

    Valente, Davide; Bossi, Gianluca; Moncada, Alice; Tornincasa, Mara; Indelicato, Stefania; Piscuoglio, Salvatore; Karamitopoulou, Eva Diamantis; Bartolazzi, Armando; Pierantoni, Giovanna Maria; Fusco, Alfredo; Soddu, Silvia; Rinaldo, Cinzia

    2015-01-01

    HIPK2, a cell fate decision kinase inactivated in several human cancers, is thought to exert its oncosuppressing activity through its p53-dependent and -independent apoptotic function. However, a HIPK2 role in cell proliferation has also been described. In particular, HIPK2 is required to complete cytokinesis and impaired HIPK2 expression results in cytokinesis failure and tetraploidization. Since tetraploidy may yield to aneuploidy and chromosomal instability (CIN), we asked whether unscheduled tetraploidy caused by loss of HIPK2 might contribute to tumorigenicity. Here, we show that, compared to Hipk2+/+ mouse embryo fibroblasts (MEFs), hipk2-null MEFs accumulate subtetraploid karyotypes and develop CIN. Accumulation of these defects inhibits proliferation and spontaneous immortalization of primary MEFs whereas increases tumorigenicity when MEFs are transformed by E1A and Harvey-Ras oncogenes. Upon mouse injection, E1A/Ras-transformed hipk2-null MEFs generate tumors with genetic alterations resembling those of human cancers derived by initial tetraploidization events, such as pancreatic adenocarcinoma. Thus, we evaluated HIPK2 expression in different stages of pancreatic transformation. Importantly, we found a significant correlation among reduced HIPK2 expression, high grade of malignancy, and high nuclear size, a marker of increased ploidy. Overall, these results indicate that HIPK2 acts as a caretaker gene, whose inactivation increases tumorigenicity and causes CIN by cytokinesis failure. PMID:25868975

  18. Hepatocellular telomere shortening correlates with chromosomal instability and the development of human hepatoma.

    Science.gov (United States)

    Plentz, Ruben R; Caselitz, Martin; Bleck, Joerg S; Gebel, Michael; Flemming, Peer; Kubicka, Stefan; Manns, Michael P; Rudolph, K Lenhard

    2004-07-01

    The telomere hypothesis of cancer initiation indicates that telomere shortening initiates cancer by induction of chromosomal instability. To test whether this hypothesis applies to human hepatocellular carcinoma (HCC), we analyzed the telomere length of hepatocytes in cytological smears of fine-needle biopsies of liver tumors from patients with cirrhosis (n = 39). The tumors consisted of 24 HCC and 15 regenerative nodules as diagnosed by combined histological and cytological diagnostics. In addition, we analyzed the telomere length of hepatocytes in HCC and surrounding noncancerous liver tissue within individual patients in another cohort of 10 patients with cirrhosis. Telomere length analysis of hepatocytes was correlated with tumor pathology and ploidy grade of the tumors, which was analyzed by cytophotometry. Telomeres were significantly shortened in hepatocytes of HCC compared to hepatocytes in regenerative nodules or surrounding noncancerous liver tissue. Hepatocyte telomere shortening in HCC was independent of the patient's age. There was no overlap in mean telomere lengths of individual samples when comparing HCC with regenerative nodules or noncancerous surrounding liver. Within the HCC group, telomeres were significantly shorter in hepatocytes of aneuploid tumors compared to diploid tumors. In conclusion, our data suggest that the telomere hypothesis of cancer initiation applies to human HCC and that cell type-specific telomere length analysis might indicate the risk of HCC development. PMID:15239089

  19. A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Marshall Wallace F

    2005-05-01

    Full Text Available Abstract Background The role of centrioles in mitotic spindle function remains unclear. One approach to investigate mitotic centriole function is to ask whether mutation of centriole-associated proteins can cause genomic instability. Results We addressed the role of the centriole-associated EF-hand protein centrin in genomic stability using a Chlamydomonas reinhardtii centrin mutant that forms acentriolar bipolar spindles and lacks the centrin-based rhizoplast structures that join centrioles to the nucleus. Using a genetic assay for loss of heterozygosity, we found that this centrin mutant showed increased genomic instability compared to wild-type cells, and we determined that the increase in genomic instability was due to a 100-fold increase in chromosome loss rates compared to wild type. Live cell imaging reveals an increased rate in cell death during G1 in haploid cells that is consistent with an elevated rate of chromosome loss, and analysis of cell death versus centriole copy number argues against a role for multipolar spindles in this process. Conclusion The increased chromosome loss rates observed in a centrin mutant that forms acentriolar spindles suggests a role for centrin protein, and possibly centrioles, in mitotic fidelity.

  20. A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables

    DEFF Research Database (Denmark)

    Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai Juul; Szallasi, Zoltan Imre; Kschischo, Maik; A. Graham, Trevor; Swanton, Charles

    2011-01-01

    Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours...

  1. A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables.

    OpenAIRE

    Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai Juul; Szallasi, Zoltan Imre; Kschischo, Maik; A. Graham, Trevor; Swanton, Charles

    2011-01-01

    Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to...

  2. Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Sawyer, J.R.; North, P.E.; Hassed, S.J. [Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States)] [and others

    1997-04-14

    We describe the cytogenetic evolution of multiple cell lines in the gonadal tissue of a 10-year-old girl with mosaic Ullrich-Turner syndrome (UTS) involving clonal telomeric associations (tas) of the Y chromosome. G-band analysis of all tissues showed at least 2 cell lines; 45,X and 46,X,tas(Y;21)(q12;p13). However, analysis of left gonadal tissue of this patient showed the evolution of 2 additional cell lines, one designated 45,X,tas(Y;21)(q12;p13),-22 and the other 46,X,tas(Y;21)(q12;p13),+tas(Y;14)(q12;p13),-22. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei from uncultured gonadal tissue confirmed the findings of aneuploidy in the left gonadal tissue and extended the findings of aneuploidy to the tissue of the right gonad. The chromosome findings in the gonadal tissue of this patient suggest a preneoplastic karyotype relating to several distinct tumor associations. The clonal evolution of telomeric fusions indicates chromosome instability and suggests the extra copy of the Y chromosome may have resulted from a fusion-related malsegregation. In addition, the extra Y suggests low-level amplification of a putative gonadoblastoma gene, while the loss of chromosome 22 suggests the loss of heterozygosity for genes on chromosome 22. This case demonstrates the utility of the study of gonadal tissue in 45X46,XY UTS patients, and provides evidence that clonal telomeric fusions may, in rare cases, be associated with chromosomal malsegregation and with the subsequent evolution of unstable karyotypes. 27 refs., 3 figs.

  3. A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables.

    Science.gov (United States)

    Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai J; Szallasi, Zoltan; Kschischo, Maik; Graham, Trevor A; Swanton, Charles

    2011-07-01

    Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to address whether younger age at diagnosis is associated with increased tumour genome instability. We find that CIN, assessed by the two independently derived CIN expression signatures, is significantly associated with increased tumour size, ER negative or HER2 positive disease, higher tumour grade and younger age at diagnosis in ER negative breast cancer. These data support the hypothesis that chromosomal instability may be a defining feature of breast cancer biology and clinical outcome. PMID:21709316

  4. Chromosome 17p13.2 transfer reverts transformation phenotypes and Fas-mediated apoptosis in breast epithelial cells.

    Science.gov (United States)

    Lareef, Mohamed H; Tahin, Quivo; Song, Joon; Russo, Irma H; Mihaila, Dana; Slater, Carolyn M; Balsara, Binaifer; Testa, Joseph R; Broccoli, Dominique; Grobelny, Jennifer V; Mor, Gil; Cuthbert, Andrew; Russo, Jose

    2004-04-01

    Transformation of the human breast epithelial cells (HBEC) MCF-10F with the carcinogen benz(a)pyrene (BP) into BP1-E cells resulted in the loss of the chromosome 17 p13.2 locus (D17S796 marker) and formation of colonies in agar-methocel (colony efficiency (CE)), loss of ductulogenic capacity in collagen matrix, and resistance to anti-Fas monoclonal antibody (Mab)-induced apoptosis. For testing the role of that specific region of chromosome 17 in the expression of transformation phenotypes, we transferred chromosome 17 from mouse fibroblast donors to BP1-E cells. Chromosome 11 was used as negative control. After G418 selection, nine clones each were randomly selected from BP1-E-11neo and BP1-E-17neo hybrids, respectively, and tested for the presence of the donor chromosomes by fluorescent in situ hybridization and polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analyses. Sensitivity to Fas Mab-induced apoptosis and evaluation of transformation phenotype expression were tested in MCF-10F, BP1-E, and nine BP1-E-11neo and BP1-E-17neo clones each. Six BP1-E-17neo clones exhibited a reversion of transformation phenotypes and a dose dependent sensitivity to Fas Mab-induced apoptosis, behaving similarly to MCF-10F cells. All BP1-E-11neo, and three BP1-E-17neo cell clones, like BP1-E cells, retained a high CE, loss of ductulogenic capacity, and were resistant to all Fas Mab doses tested. Genomic analysis revealed that those six BP1-E-17neo clones that were Fas-sensitive and reverted their transformed phenotypes had retained the 17p13.2 (D17S796 marker) region, whereas it was absent in all resistant clones, indicating that the expression of transformation phenotypes and the sensitivity of the cells to Fas-mediated apoptosis were under the control of genes located in this region. PMID:15057875

  5. Crossing-over between Y chromosomes: another possible source of phenotypic variability in the guppy, Poecilia reticulata Peters

    Directory of Open Access Journals (Sweden)

    I. Valentin Petrescu-Mag

    2008-09-01

    Full Text Available Genetic linkage acting through crossing-over between X and X chromosomes, X and Y chromosomes, and autosomal gene recombination are the most important sources of color pattern polymorphisms in animals. Variability in male color patterns and fin morphologies in the guppy, Poecilia reticulata, a livebearing fish is an example of extreme pattern polymorphism. We explored the possibility that crossing-over between Y chromosomes can also contribute to the high degree of pattern polymorphism in guppies because YY individuals are easily induced in the boratory. However, note that YY individuals are also produced in natural populations. Our results indicated that YY crossing-over was another important source of phenotypic variability - probably because recombination may be possible ver the entire length of Y chromosomes, and at very high frequencies due to high degrees of homology. Thus, crossing-over between Y chromosomes is yet another mechanism that can contribute to extreme pattern polymorphism in the guppy, a popular aquarium and important research model species.

  6. Duration of the hidden chromosome instability persistence in peripheral blood lymphocytes of persons occupationally exposed to ionizing radiation

    International Nuclear Information System (INIS)

    With compatible use of tests 'G2-bleomycin sensitivity assay' and two-term (48 and 100 h) cultivation of human peripheral blood lymphocytes, the voluntary cytogenetic examination of persons who have occupational contact with ionizing radiation is carried out. The results are compared with those obtained in a similar observation of the unexposed group. Principal differences between the groups in the manifestation and the dynamics of the hidden chromosome instability (HCI) in time are found. Its indicators were significantly higher in the occupational group. The possibility of the persistence of radiation-associated HCI in successive generations of human somatic cells with significant interindividual differences is established

  7. Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells.

    Science.gov (United States)

    Kim, Jung-Hyun; Lee, Hee-Sheung; Lee, Nicholas C O; Goncharov, Nikolay V; Kumeiko, Vadim; Masumoto, Hiroshi; Earnshaw, William C; Kouprina, Natalay; Larionov, Vladimir

    2016-03-22

    Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" assay). Using this system, anticancer drugs can be easily ranked on by their effect on HAC loss. However, it is problematic to covert this "loss of signal" assay into a high-throughput screen to identify drugs and mutations that increase CIN levels. To address this point, we re-designed the HAC-based assay. In this new system, the HAC carries a constitutively expressed shRNA against the EGFP transgene integrated into human genome. Thus, cells that inherit the HAC display no green fluorescence, while cells lacking the HAC do. We verified the accuracy of this "gain of signal" assay by measuring the level of CIN induced by known antimitotic drugs and added to the list of previously ranked CIN inducing compounds, two newly characterized inhibitors of the centromere-associated protein CENP-E, PF-2771 and GSK923295 that exhibit the highest effect on chromosome instability measured to date. The "gain of signal" assay was also sensitive enough to detect increase of CIN after siRNA depletion of known genes controlling mitotic progression through distinct mechanisms. Hence this assay can be utilized in future experiments to uncover novel human CIN genes, which will provide novel insight into the pathogenesis of cancer. Also described is the possible conversion of this new assay into a high-throughput screen using a fluorescence microplate reader to characterize chemical libraries and identify new conditions that modulate CIN level. PMID:26943579

  8. The Social Behavioral Phenotype in Boys and Girls with an Extra X Chromosome (Klinefelter Syndrome and Trisomy X) : A Comparison with Autism Spectrum Disorder

    NARCIS (Netherlands)

    van Rijn, Sophie; Stockmann, Lex; Borghgraef, Martine; Bruining, Hilgo; van Ravenswaaij-Arts, Conny; Govaerts, Lutgarde; Hansson, Kerstin; Swaab, Hanna

    2014-01-01

    The present study aimed to gain more insight in the social behavioral phenotype, and related autistic symptomatology, of children with an extra X chromosome in comparison to children with ASD. Participants included 60 children with an extra X chromosome (34 boys with Klinefelter syndrome and 26 girl

  9. The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription

    Directory of Open Access Journals (Sweden)

    Wael M. Abdel-Rahman

    2016-01-01

    Full Text Available All colorectal cancer cell lines except RKO displayed active β-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers; hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various β-catenin localizations as a surrogate marker for β-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1 confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors with membranous β-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.

  10. Chromosomal instability in Afrotheria: fragile sites, evolutionary breakpoints and phylogenetic inference from genome sequence assemblies

    OpenAIRE

    Ruiz-Herrera Aurora; Robinson Terence J

    2007-01-01

    Abstract Background Extant placental mammals are divided into four major clades (Laurasiatheria, Supraprimates, Xenarthra and Afrotheria). Given that Afrotheria is generally thought to root the eutherian tree in phylogenetic analysis of large nuclear gene data sets, the study of the organization of the genomes of afrotherian species provides new insights into the dynamics of mammalian chromosomal evolution. Here we test if there are chromosomal bands with a high tendency to break and reorgani...

  11. Determination of hidden chromosome instability in persons suffered from the action of factors of the Chernobyl accident by the modified 'G2 bleomycin sensitivity assay'

    International Nuclear Information System (INIS)

    With the help of the modified 'G2-bleomycin sensitivity assay' the voluntary investigation of hidden chromosome instability in 53 persons with different radiation exposures had been fulfilled. In all examined groups, the individual levels of chromosome injuries under identical bleomycin exposure varied in a wide range and didn't depend on their initial values in intact cultures. Among control donors and individuals with low radiation exposure, ∼ 33 % hypertensive persons had been identified that can be considered as a genetically caused phenomenon. In patients recovered from acute radiation, 57.9 % persons expressed the hidden chromosome instability. The data obtained allow us to assume that high doses of ionizing radiation can modify the inherited susceptibility of human chromosomes to a mutagen exposure.

  12. Primary infertility in a phenotypic male with 46XX chromosomal constitution.

    OpenAIRE

    Tan, T. T.; Khalid, B A

    1993-01-01

    The case of a 32 year old male with normal male adrenarchal hair pattern, bilateral gynaecomastia, a small phallus, hypospadias and bilateral poorly developed testes presenting with primary infertility secondary to azoospermia and a pelvic cyst is described. Repeated chromosomal analysis showed 46XX chromosomal constitution. Laparotomy revealed a simple cyst between the urinary bladder and the rectum. XX male syndrome is a rare cause of male infertility. The majority of cases is due to interc...

  13. Phenotypic differences among patients with Bardet-Biedl syndrome linked to three different chromosome loci

    Energy Technology Data Exchange (ETDEWEB)

    Carmi, R.; Elbedour, K. [Ben-Gurion Univ., Beer-Sheva (Israel); Stone, E.M.; Sheffield, V.C. [Univ. of Iowa, IA (United States)

    1995-11-06

    Bardet-Biedl syndrome (BBS) is an autosomal-recessive disorder of mental retardation, obesity, retinal dystrophy, polydactyly, and hypogenitalism. Renal and cardiac abnormalities are also frequent in this disorder. Previous clinical suggestions of heterogeneity of BBS were confirmed recently by the identification of four different chromosome loci linked to the disease. In this study we compared clinical manifestations of the syndrome in patients form 3 unrelated, extended Arab-Bedouin kindreds which were used for the linkage mapping of the BBS loci to chromosomes 3, 15, and 16. The observed differences included the limb distribution of the postaxial polydactyly and the extent and age-association of obesity. It appears that the chromosome 3 locus is associated with polydactyly of all four limbs, while polydactyly of the chromosome 15 type is mostly confined to the hands. On the other hand, the chromosome 15 type is associated with early-onset morbid obesity, while the chromosome 16 type appears to present the {open_quotes}leanest{close_quotes} form of BBS. Future cloning of the various BB genes will contribute to the understanding of the molecular basis of limb development and the identification of human obesity-related genes. 22 refs., 1 fig., 4 tabs.

  14. Polytene chromosomes of Chironomidae (Diptera as a bioassay of trace-metal-induced genome instability

    Directory of Open Access Journals (Sweden)

    Paraskeva Vladimirova Michailova

    2012-10-01

    Full Text Available Chironomids are a ubiquitous group of aquatic insects that are very sensitive to environmental stress. Due to the presence of polytene (‘giant’ salivary gland chromosomes, it is possible to define the genome response of several Chironomid species to various stress agents. The aim of this study was to assess the genotoxic changes in populations of widely distributed chironomid species from aquatic basins in Bulgaria, Italy, Russia, U.K. and Poland, which were exposed to high concentrations of trace metals. We analyzed the structural and functional alterations of polytene chromosomes of the salivary glands of larvae belonging to three different cytocomplexes of the genus Chironomus (“thummi”, “lacunarius”, “pseudothummi”, and genera Glyptotendipes and Kiefferulus. Somatic structural chromosome rearrangements (para- and pericentric heterozygous inversions, deletions, deficiencies and amplifications were used to estimate a Somatic index (S for each population. The highest S indexes were detected in Chironomus riparius populations from locations with high concentrations of trace metals in the sediment. Each species showed specific genome responses to stress agents which we discussed in the light of the specific DNA structures and cytogenetic characteristics of the species. In larvae from polluted sediments two key structures of the salivary gland chromosomes (Balbiani Rings and Nucleolar Organizer sharply reduced their activity to levels below those observed under non-polluted conditions. It is concluded that polytene chromosomes can be used as tools for evaluating the genotoxicity of the aquatic environment. Structural and functional chromosome alterations provide cost-effective early-warning signals of genotoxic concentrations of environmental pollutants.doi: 10.5324/fn.v31i0.1355.Published online: 17 October 2012.

  15. Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex changes and multiple forms of chromosomal instability in colorectal cancers

    DEFF Research Database (Denmark)

    Gaasenbeek, Michelle; Howarth, Kimberley; Rowan, Andrew J;

    2006-01-01

    Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid with multiple large-scale gains/deletions, but the processes underlying CIN are unclear and different types of CIN might exist. We investigated colorectal cancer cell lines using array-comparative genomic hybridization ...

  16. Increased chromosomal breakage in Tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: Preliminary findings and hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Gericke, G.S.; Simonic, I.; Cloete, E.; Buckle, C. [Univ. of Pretoria (South Africa)] [and others

    1995-10-09

    Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites. 32 refs., 1 tab.

  17. Sexual dimorphism in white campion: deletion on the Y chromosome results in a floral asexual phenotype

    International Nuclear Information System (INIS)

    White campion is a dioecious plant with heteromorphic X and Y sex chromosomes. In male plants, a filamentous structure replaces the pistil, while in female plants the stamens degenerate early in flower development. Asexual (asx) mutants, cumulating the two developmental defects that characterize the sexual dimorphism in this species, were produced by gamma ray irradiation of pollen and screening in the M1 generation. The mutants harbor a novel type of mutation affecting an early function in sporogenous/parietal cell differentiation within the anther. The function is called stamen-promoting function (SPF). The mutants are shown to result from interstitial deletions on the Y chromosome. We present evidence that such deletions tentatively cover the central domain on the (p)-arm of the Y chromosome (Y2 region). By comparing stamen development in wild-type female and asx mutant flowers we show that they share the same block in anther development, which results in the production of vestigial anthers. The data suggest that the SPF, a key function(s) controlling the sporogenous/parietal specialization in premeiotic anthers, is genuinely missing in females (XX constitution). We argue that this is the earliest function in the male program that is Y-linked and is likely responsible for ''male dimorphism'' (sexual dimorphism in the third floral whorl) in white campion. More generally, the reported results improve our knowledge of the structural and functional organization of the Y chromosome and favor the view that sex determination in this species results primarily from a trigger signal on the Y chromosome (Y1 region) that suppresses female development. The default state is therefore the ancestral hermaphroditic state

  18. Chromosomal instability in Afrotheria: fragile sites, evolutionary breakpoints and phylogenetic inference from genome sequence assemblies

    Directory of Open Access Journals (Sweden)

    Ruiz-Herrera Aurora

    2007-10-01

    Full Text Available Abstract Background Extant placental mammals are divided into four major clades (Laurasiatheria, Supraprimates, Xenarthra and Afrotheria. Given that Afrotheria is generally thought to root the eutherian tree in phylogenetic analysis of large nuclear gene data sets, the study of the organization of the genomes of afrotherian species provides new insights into the dynamics of mammalian chromosomal evolution. Here we test if there are chromosomal bands with a high tendency to break and reorganize in Afrotheria, and by analyzing the expression of aphidicolin-induced common fragile sites in three afrotherian species, whether these are coincidental with recognized evolutionary breakpoints. Results We described 29 fragile sites in the aardvark (OAF genome, 27 in the golden mole (CAS, and 35 in the elephant-shrew (EED genome. We show that fragile sites are conserved among afrotherian species and these are correlated with evolutionary breakpoints when compared to the human (HSA genome. Inddition, by computationally scanning the newly released opossum (Monodelphis domestica and chicken sequence assemblies for use as outgroups to Placentalia, we validate the HSA 3/21/5 chromosomal synteny as a rare genomic change that defines the monophyly of this ancient African clade of mammals. On the other hand, support for HSA 1/19p, which is also thought to underpin Afrotheria, is currently ambiguous. Conclusion We provide evidence that (i the evolutionary breakpoints that characterise human syntenies detected in the basal Afrotheria correspond at the chromosomal band level with fragile sites, (ii that HSA 3p/21 was in the amniote ancestor (i.e., common to turtles, lepidosaurs, crocodilians, birds and mammals and was subsequently disrupted in the lineage leading to marsupials. Its expansion to include HSA 5 in Afrotheria is unique and (iii that its fragmentation to HSA 3p/21 + HSA 5/21 in elephant and manatee was due to a fission within HSA 21 that is probably shared

  19. Tumor suppressors, chromosomal instability and hepatitis C virus-associated liver cancer

    OpenAIRE

    McGivern, David R.; Lemon, Stanley M.

    2009-01-01

    Hepatitis C virus is the only known RNA virus with an exclusively cytoplasmic life cycle that is associated with cancer. The mechanisms by which it causes cancer are unclear, but chronic immune-mediated inflammation and associated oxidative chromosomal DNA damage are likely to play a role. Nonetheless, compelling data suggest that the path to hepatocellular carcinoma in chronic hepatitis C shares some important features with human papillomavirus-induced carcinogenesis. Interactions of viral p...

  20. 5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH

    Directory of Open Access Journals (Sweden)

    Jaime Gosálvez

    2013-02-01

    Full Text Available We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH. A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL, 10 with high-grade SIL (HG-SIL, and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

  1. Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity.

    Science.gov (United States)

    Nakagawa, Hidetoshi; Sido, Jessica M; Reyes, Edwin E; Kiers, Valerie; Cantor, Harvey; Kim, Hye-Jung

    2016-05-31

    Expression of the transcription factor Helios by Tregs ensures stable expression of a suppressive and anergic phenotype in the face of intense inflammatory responses, whereas Helios-deficient Tregs display diminished lineage stability, reduced FoxP3 expression, and production of proinflammatory cytokines. Here we report that selective Helios deficiency within CD4 Tregs leads to enhanced antitumor immunity through induction of an unstable phenotype and conversion of intratumoral Tregs into T effector cells within the tumor microenvironment. Induction of an unstable Treg phenotype is associated with enhanced production of proinflammatory cytokines by tumor-infiltrating but not systemic Tregs and significantly delayed tumor growth. Ab-dependent engagement of Treg surface receptors that result in Helios down-regulation also promotes conversion of intratumoral but not systemic Tregs into T effector cells and leads to enhanced antitumor immunity. These findings suggest that selective instability and conversion of intratumoral CD4 Tregs through genetic or Ab-based targeting of Helios may represent an effective approach to immunotherapy. PMID:27185917

  2. The Effects of X Chromosome Loss on Neuroanatomical and Cognitive Phenotypes During Adolescence: a Multi-modal Structural MRI and Diffusion Tensor Imaging Study.

    Science.gov (United States)

    Xie, Sheng; Zhang, Zhixin; Zhao, Qiuling; Zhang, Jiaying; Zhong, Suyu; Bi, Yanchao; He, Yong; Pan, Hui; Gong, Gaolang

    2015-09-01

    The absence of all or part of one X chromosome in female humans causes Turner's syndrome (TS), providing a unique "knockout model" to investigate the role of the X chromosome in neuroanatomy and cognition. Previous studies have demonstrated TS-associated brain differences; however, it remains largely unknown 1) how the brain structures are affected by the type of X chromosome loss and 2) how X chromosome loss influences the brain-cognition relationship. Here, we addressed these by investigating gray matter morphology and white matter connectivity using a multimodal MRI dataset from 34 adolescent TS patients (13 mosaic and 21 nonmosaic) and 21 controls. Intriguingly, the 2 TS groups exhibited significant differences in surface area in the right angular gyrus and in white matter integrity of the left tapetum of corpus callosum; these data support a link between these brain phenotypes and the type of X chromosome loss in TS. We further showed that the X chromosome modulates specific brain-cognition relationships: thickness and surface area in multiple cortical regions are positively correlated with working-memory performance in controls but negatively in TS. These findings provide novel insights into the X chromosome effect on neuroanatomical and cognitive phenotypes and highlight the role of genetic factors in brain-cognition relationships. PMID:24770708

  3. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

    Science.gov (United States)

    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P.; Islas-Morris-Hernandez, A.; Borget, I.; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. Results ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24–55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7–11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. Conclusion We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged

  4. Eleven Polish patients with microcephaly, immunodeficiency, and chromosomal instability: The Nijmegan breakage syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Chrzanowska, K.H.; Krajewska-Walasek, M.; Gutkowska, A. [Memorial Hospital-Child Health Center, Warsaw (Poland)] [and others

    1995-07-03

    We report on 11 patients with 8 independent families (3 pairs of sibs) with a complex clinical pattern including microcephaly, peculiar {open_quotes}bird-like{close_quotes} face, growth retardation, and, in some cases, mild-to-moderate mental deficiency. Most of the patients have recurring respiratory tract infections. One girl has developed B-cell lymphoma. A detailed anthropometric study of 15 physical parameters, including 3 cephalic traits, was performed. It was possible to study the chromosomes of PHA-stimulated lymphocytes in all of the patients. We found structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14 in a proportion of metaphases in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were hitherto studied in this respect. Our patients fulfill the criteria of the Nijmegen breakage syndrome, which belongs to the growing category of ataxia telangiectasia-related genetic disorders. In light of the increased predisposition to malignancy in this syndrome, an accurate diagnosis is important for the patient. 27 refs., 5 figs., 4 tabs.

  5. Two Elderly Patients with Philadelphia Chromosome Positive Mixed Phenotype Acute Leukemia Who Were Successfully Treated with Dasatinib and Prednisolone.

    Science.gov (United States)

    Takata, Hiroyuki; Ikebe, Taichi; Sasaki, Hitohiro; Miyazaki, Yasuhiko; Ohtsuka, Eiichi; Saburi, Yoshio; Ogata, Masao; Shirao, Kuniaki

    2016-01-01

    Philadelphia chromosome positive (Ph+) mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia having both myeloid and lymphoid features for which no optimal treatment has yet been established. We herein describe two elderly Ph+MPAL patients who achieved molecular remission without any serious adverse events by treatment with dasatinib and prednisolone. Although dasatinib induction therapy combined with prednisolone is known to be a highly effective treatment for Ph+ acute lymphoblastic leukemia, its efficacy for Ph+MPAL has not been shown. The clinical courses of the present cases suggest that combination therapy with dasatinib and prednisolone is a safe and effective therapeutic modality in elderly Ph+MPAL patients. PMID:27150875

  6. Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size

    OpenAIRE

    Halder Ashutosh; Jain Manish; Chaudhary Isha; Varma Binuja

    2012-01-01

    Abstract We report on a pair of male monozygotic twins with 22q11.2 microdeletion, discordant phenotype and discordant deletion size. The second twin had findings suggestive of DiGeorge syndrome, while the first twin had milder anomalies without any cardiac malformation. The second twin had presented with intractable convulsion, cyanosis and cardiovascular failure in the fourth week of life and expired on the sixth week of life, whereas the first twin had some characteristic facial appearance...

  7. Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report

    Directory of Open Access Journals (Sweden)

    Rongen Michel A

    2009-07-01

    Full Text Available Abstract Background Complex chromosomal rearrangements (CCR are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic imbalances, for instance near the multiple breakpoints, to explain the abnormal phenotype in these patients. We applied several molecular techniques to elucidate the complexity of the CCRs of two adult patients with abnormal phenotypes. Results Multicolour fluorescence in situ hybridization (M-FISH showed that in patient 1 the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array analysis uncovered a deletion in chromosome region 10p13 for patient 1, harbouring 17 genes, while patient 2 showed no pathogenic gains or losses. Additional FISH analysis with locus specific BAC-probes was performed, leading to the identification of cryptic interstitial structural rearrangements in both patients. Conclusion Application of M-FISH and SNP-array analysis to apparently balanced CCRs is useful to delineate the complex chromosomal rearrangement in detail. However, it does not always identify cryptic imbalances as an explanation for the abnormal phenotype in patients with a CCR.

  8. A case-control study identifying chromosomal polymorphic variations as forms of epigenetic alterations associated with the infertility phenotype

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Athalye, Arundhati S; Madon, Prochi F;

    2009-01-01

    To study the association of chromosomal polymorphic variations with infertility and subfertility.......To study the association of chromosomal polymorphic variations with infertility and subfertility....

  9. Chromosomal Instability and Molecular Defects in Induced Pluripotent Stem Cells from Nijmegen Breakage Syndrome Patients.

    Science.gov (United States)

    Halevy, Tomer; Akov, Shira; Bohndorf, Martina; Mlody, Barbara; Adjaye, James; Benvenisty, Nissim; Goldberg, Michal

    2016-08-30

    Nijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here, we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress, and abnormal cell-cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs) show downregulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed light on the molecular mechanisms underlying this severe syndrome, and further expand our knowledge of the genomic stress cells experience during the reprogramming process. PMID:27545893

  10. Tumor environmental factors glucose deprivation and lactic acidosis induce mitotic chromosomal instability--an implication in aneuploid human tumors.

    Directory of Open Access Journals (Sweden)

    Chunyan Dai

    Full Text Available Mitotic chromosomal instability (CIN plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis--two tumor microenvironmental factors--could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy.

  11. Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells.

    Science.gov (United States)

    Congras, Annabelle; Barasc, Harmonie; Canale-Tabet, Kamila; Plisson-Petit, Florence; Delcros, Chantal; Feraud, Olivier; Oudrhiri, Noufissa; Hadadi, Eva; Griscelli, Franck; Bennaceur-Griscelli, Annelise; Turhan, Ali; Afanassieff, Marielle; Ferchaud, Stéphane; Pinton, Alain; Yerle-Bouissou, Martine; Acloque, Hervé

    2016-01-01

    The pig is an emerging animal model, complementary to rodents for basic research and for biomedical and agronomical purposes. However despite the progress made on mouse and rat models to produce genuine pluripotent cells, it remains impossible to produce porcine pluripotent cell lines with germline transmission. Reprogramming of pig somatic cells using conventional integrative strategies remains also unsatisfactory. In the present study, we compared the outcome of both integrative and non-integrative reprogramming strategies on pluripotency and chromosome stability during pig somatic cell reprogramming. The porcine cell lines produced with integrative strategies express several pluripotency genes but they do not silence the integrated exogenes and present a high genomic instability upon passaging. In contrast, pig induced pluripotent-like stem cells produced with non-integrative reprogramming system (NI-iPSLCs) exhibit a normal karyotype after more than 12 months in culture and reactivate endogenous pluripotency markers. Despite the persistent expression of exogenous OCT4 and MYC, these cells can differentiate into derivatives expressing markers of the three embryonic germ layers and we propose that these NI-iPSLCs can be used as a model to bring new insights into the molecular factors controlling and maintaining pluripotency in the pig and other non-rodent mammalians. PMID:27245508

  12. Unexpected rates of chromosomal instabilities and alterations of hormone levels in Namibian uranium miners.

    Science.gov (United States)

    Zaire, R; Notter, M; Riedel, W; Thiel, E

    1997-05-01

    A common problem in determining the health consequences of radiation exposure is factoring out other carcinogenic influences. The conditions in Namibia provide a test case for distinguishing the effects of long-term low-dose exposure to uranium from the other environmental factors because of good air quality and the lack of other industries with negative health effects. Present records indicate a much higher prevalence of cancer among male workers in the open-pit uranium mine in Namibia compared with the general population. The objective of the present study was to determine whether long-term exposure to low doses of uranium increases the risk of a biological radiation damage which would lead to malignant diseases and to derive a dose-response model for these miners. To investigate this risk, we measured uranium excretion in urine, neutrophil counts and the serum level of FSH, LH and testosterone and analyzed chromosome aberrations in whole blood cells using fluorescence in situ hybridization. A representative cohort of 75 non-smoking, HIV-negative miners was compared to a control group of 31 individuals with no occupational history in mining. A sixfold increase in uranium excretion among the miners compared to the controls was recorded (P atomic bomb or the Chernobyl accident. We conclude that the miners exposed to uranium are at an increased risk to acquire various degrees of genetic damage, and that the damage may be associated with an increased risk for malignant transformation. As expected, the chronic radiation injury of the hematopoietic system resulted in low neutrophil counts. Also, low hormone levels probably reflect damage to the gonadal endocrine system. PMID:9146703

  13. Heterozygosity of Knob-Associated Tandem Repeats and Knob Instability in Mitotic Chromosomes of Zea (Zea mays L. and Z. diploperennis Iltis Doebley)

    Institute of Scientific and Technical Information of China (English)

    Zhi-Yong XIONG; Yong LIU; Yong-Gang HE; Yun-Chun SONG; Ke-Xiu LI; Guan-Yuan HE

    2005-01-01

    Knobs are blocks of heterochromatin present on chromosomes of maize (Zea mays L.) and its relatives that have effects on the frequency of genetic recombination, as well as on chromosome behavior.Knob heterozygosity and instability in six maize inbred lines and one Z. diploperennis Iltis Doebley line were investigated using the fluorescence in situ hybridization (FISH) technique with knob-associated tandem repeats (180 bp and 350 bp (TR-1)) as probes. Signals of seven heterozygous knobs containing 180-bp repeats and of one heterozygous knob containing TR- 1 were captured in chromosomes of all materials tested according to the results of FISH, which demonstrates that the 180-bp repeat is the main contributor to knob heterozygosity compared with the TR-1 element. In addition, one target cell with two TR-1 signals on one homolog of chromosome 2L, which was different from the normal cells in the maize inbred line GB57,was observed, suggesting knob duplication and an instability phenomenon in the maize genome.

  14. Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white

    Science.gov (United States)

    Ponnaiya, B.; Cornforth, M. N.; Ullrich, R. L.

    1997-01-01

    Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.

  15. Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

    Science.gov (United States)

    Grams, Sarah E; Argiropoulos, Bob; Lines, Matthew; Chakraborty, Pranesh; Mcgowan-Jordan, Jean; Geraghty, Michael T; Tsang, Marilyn; Eswara, Marthand; Tezcan, Kamer; Adams, Kelly L; Linck, Leesa; Himes, Patricia; Kostiner, Dana; Zand, Dina J; Stalker, Heather; Driscoll, Daniel J; Huang, Taosheng; Rosenfeld, Jill A; Li, Xu; Chen, Emily

    2016-04-01

    We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication. © 2015 Wiley Periodicals, Inc. PMID:26692240

  16. Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Tatsunari Sasada

    Full Text Available The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma--caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc(+/flox, abbreviated to CPC;Apc or microsatellite (CDX2P9.5-G19Cre;Apc(flox/flox and CDX2P9.5-G22Cre;Apc(flox/flox instability, respectively--were administered chlorinated (10.0 mg/L chlorine or tap (0.7 mg/L chlorine water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apc(flox/flox and CDX2P9.5-G22Cre;Apc(flox/flox mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to

  17. Antagonizing pathways leading to differential dynamics in colon carcinogenesis in Shugoshin1 (Sgo1)-haploinsufficient chromosome instability model.

    Science.gov (United States)

    Rao, Chinthalapally V; Sanghera, Saira; Zhang, Yuting; Biddick, Laura; Reddy, Arun; Lightfoot, Stan; Dai, Wei; Yamada, Hiroshi Y

    2016-05-01

    Colon cancer is the second most lethal cancer. It is predicted to claim 50,310 lives in 2014. Chromosome Instability (CIN) is observed in 80-90% of colon cancers, and is thought to contribute to colon cancer progression and recurrence. However, there are no animal models of CIN that have been validated for studies of colon cancer development or drug testing. In this study, we sought to validate a mitotic error-induced CIN model mouse, the Shugoshin1 (Sgo1) haploinsufficient mouse, as a colon cancer study model. Wild-type and Sgo1(-/+) mice were treated with the colonic carcinogen, azoxymethane (AOM). We tracked colon tumor development 12, 24, and 36 wk after treatment to assess progression of colon tumorigenesis. Initially, more precancerous lesions, Aberrant Crypt Foci (ACF), developed in Sgo1(-/+) mice. However, the ACF did not develop straightforwardly into larger tumors. At the 36-wk endpoint, the number of gross tumors in Sgo1(-/+) mice was no different from that in wild-type controls. However, Copy Number Variation (CNV) analysis indicated that fully developed colon tumor in Sgo1(-/+) mice carried 13.75 times more CNV. Immunohistological analyses indicated that Sgo1(-/+) mice differentially expressed IL-6, Bcl2, and p16(INK4A) . We propose that formation of ACF in Sgo1(-/+) mice is facilitated by the IL6-STAT3-SOCS3 oncogenic pathway and by the Bcl2-anti-apoptotic pathway, yet further development of the ACF to tumors is inhibited by the p16(INK4A) tumor suppressor pathway. Manipulating these pathways would be beneficial for inhibiting development of colon cancer with CIN. © 2015 Wiley Periodicals, Inc. PMID:25773652

  18. Instability of chromosome number and DNA methylation variation induced by hybridization and amphidiploid formation between Raphanus sativus L. and Brassica alboglabra Bailey

    Directory of Open Access Journals (Sweden)

    Wang Yanjie

    2010-09-01

    Full Text Available Abstract Background Distant hybridization can result genome duplication and allopolyploid formation which may play a significant role in the origin and evolution of many plant species. It is unclear how the two or more divergent genomes coordinate in one nucleus with a single parental cytoplasm within allopolyploids. We used cytological and molecular methods to investigate the genetic and epigenetic instabilities associated with the process of distant hybridization and allopolyploid formation, measuring changes in chromosome number and DNA methylation across multiple generations. Results F1 plants from intergeneric hybridization between Raphanus sativus L. (2n = 18, RR and Brassica alboglabra Bailey (2n = 18, CC were obtained by hand crosses and subsequent embryo rescue. Random amplification of polymorphic DNA (RAPD markers were used to identify the F1 hybrid plants. The RAPD data indicated that the hybrids produced specific bands similar to those of parents and new bands that were not present in either parent. Chromosome number variation of somatic cells from allotetraploids in the F4 to F10 generations showed that intensive genetic changes occurred in the early generations of distant hybridization, leading to the formation of mixopolyploids with different chromosome numbers. DNA methylation variation was revealed using MSAP (methylation-sensitive amplification polymorphism, which showed that cytosine methylation patterns changed markedly in the process of hybridization and amphidiploid formation. Differences in cytosine methylation levels demonstrated an epigenetic instability of the allopolyploid of Raphanobrassica between the genetically stable and unstable generations. Conclusions Our results showed that chromosome instability occurred in the early generations of allopolyploidy and then the plants were reverted to largely euploidy in later generations. During this process, DNA methylation changed markedly. These results suggest that

  19. Quantitative trait loci influencing cholesterol and phospholipid phenotypes map to chromosomes that contain genes regulating blood pressure in the spontaneously hypertensive rat.

    OpenAIRE

    Bottger, A.; van Lith, H.A.; Kren, V.; Krenová, D; Bílá, V; Vorlícek, J; Zídek, V; Musilová, A; Zdobinská, M; J. M. Wang; van Zutphen, B F; Kurtz, T. W.; Pravenec, M.

    1996-01-01

    The frequent coincidence of hypertension and dyslipidemia suggests that related genetic factors might underlie these common risk factors for cardiovascular disease. To investigate whether quantitative trait loci (QTLs) regulating lipid levels map to chromosomes known to contain genes regulating blood pressure, we used a genome scanning approach to map QTLs influencing cholesterol and phospholipid phenotypes in a large set of recombinant inbred strains and in congenic strains derived from the ...

  20. An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.

    Directory of Open Access Journals (Sweden)

    Heike Vogel

    Full Text Available A region on mouse distal chromosome 1 (Chr. 1 that is highly enriched in quantitative trait loci (QTLs controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38, which we identified in an intercross of New Zealand Obese (NZO mice with C57BL/6J (B6. By positional cloning we recently identified a microdeletion within this locus causing the disruption of Ifi202b that protects from adiposity by suppressing expression of 11β-Hsd1. Here we show that the Nob3.38 segment also corresponds with the QTL rich region (Qrr1 on Chr. 1 and associates with increased voluntary running wheel activity, Rota-rod performance, decreased grip strength, and anxiety-related traits. The characterization of a subcongenic line carrying 14.2 Mbp of Nob3.38 with a polymorphic region of 4.4 Mbp indicates that the microdeletion and/or other polymorphisms in its proximity alter body weight, voluntary activity, and exploration. Since 27 out of 32 QTL were identified in crosses with B6, we hypothesized that the microdeletion and or adjacent SNPs are unique for B6 mice and responsible for some of the complex Qrr1-mediated effects. Indeed, a phylogenic study of 28 mouse strains revealed a NZO-like genotype for 22 and a B6-like genotype for NZW/LacJ and 4 other C57BL strains. Thus, we suggest that a Nob3.38 interval (173.0-177.4 Mbp does not only modify adiposity but also neurobehavioral traits by a haplotype segregating with C57BL strains.

  1. An Interval of the Obesity QTL Nob3.38 within a QTL Hotspot on Chromosome 1 Modulates Behavioral Phenotypes

    Science.gov (United States)

    Vogel, Heike; Montag, Dirk; Kanzleiter, Timo; Jonas, Wenke; Matzke, Daniela; Scherneck, Stephan; Chadt, Alexandra; Töle, Jonas; Kluge, Reinhart; Joost, Hans-Georg; Schürmann, Annette

    2013-01-01

    A region on mouse distal chromosome 1 (Chr. 1) that is highly enriched in quantitative trait loci (QTLs) controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38), which we identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6). By positional cloning we recently identified a microdeletion within this locus causing the disruption of Ifi202b that protects from adiposity by suppressing expression of 11β-Hsd1. Here we show that the Nob3.38 segment also corresponds with the QTL rich region (Qrr1) on Chr. 1 and associates with increased voluntary running wheel activity, Rota-rod performance, decreased grip strength, and anxiety-related traits. The characterization of a subcongenic line carrying 14.2 Mbp of Nob3.38 with a polymorphic region of 4.4 Mbp indicates that the microdeletion and/or other polymorphisms in its proximity alter body weight, voluntary activity, and exploration. Since 27 out of 32 QTL were identified in crosses with B6, we hypothesized that the microdeletion and or adjacent SNPs are unique for B6 mice and responsible for some of the complex Qrr1-mediated effects. Indeed, a phylogenic study of 28 mouse strains revealed a NZO-like genotype for 22 and a B6-like genotype for NZW/LacJ and 4 other C57BL strains. Thus, we suggest that a Nob3.38 interval (173.0–177.4 Mbp) does not only modify adiposity but also neurobehavioral traits by a haplotype segregating with C57BL strains. PMID:23308133

  2. IGFBP3 Promoter Methylation in Colorectal Cancer: Relationship with Microsatellite Instability, CpG Island Methylator Phenotype, p53

    Directory of Open Access Journals (Sweden)

    Takako Kawasaki

    2007-12-01

    Full Text Available Insulin-like growth factor binding protein 3 (IGFBP3, which is induced by wild-type p53, regulates IGF and interacts with the TGF-β pathway. IGFBP3 promoter methylation may occur in colorectal cancer with or without the CpG island methylator phenotype (CIMP, which is associated with microsatellite instability (MSI and TGFBR2 mutation. We examined the relationship between IGFBP3 methylation, p53 expression, CIMP and MSI in 902 population-based colorectal cancers. Utilizing real-time PCR (MethyLight, we quantified promoter methylation in IGFBP3 and eight other CIMP-high-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1. IGFBP3 methylation was far more frequent in non-MSI-high CIMP-high tumors (85% = 35/41 than in MSI-high CIMPhigh (49% = 44/90, P < .0001, MSI-high non-CIMP-high (17% = 6/36, P < .0001, non-MSI-high non-CIMP-high tumors (22% = 152/680, P < .0001. Among CIMPhigh tumors, the inverse relationship between MSI and IGFBP3 methylation persisted in p53-negative tumors (P < .0001, but not in p53-positive tumors. IGFBP3 methylation was associated inversely with TGFBR2 mutation in MSI-high non-CIMP-high tumors (P = .02. In conclusion, IGFBP3 methylation is inversely associated with MSI in CIMP-high colorectal cancers, this relationship is limited to p53-negative tumors. Our data suggest complex relationship between global genomic/epigenomic phenomena (such as MSI/ CIMP, single molecular events (e.g., IGFBP3 methylation, TP53 mutation, TGFBR2 mutation, the related pathways.

  3. Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers

    International Nuclear Information System (INIS)

    Purpose: To investigate a potential link between telomere length, chromosomal instability, and the advent of a second cancer (SC) in patients with Hodgkin's lymphoma (HL), who are known to be at risk for SCs. This study was premised on the finding that telomere dysfunction and DNA repair pathways were related to many pathologic conditions. Methods and Materials: Three cohorts of patients with HL were studied: 73 who were prospectively followed >5 years after diagnosis (prospective HL cohort), 28 who developed a SC (SC HL cohort), and 18 long-term survivors with no evidence of disease or complication since their initial treatment (NED HL cohort). Telomere length was analyzed by a telomeric restriction fragment assay in peripheral blood lymphocytes. Thirty healthy donors and 70 patients with a newly diagnosed solid tumor were the control population. Results: Compared with controls, patients from the prospective HL cohort, before any treatment, showed age-independent shorter telomeres (mean, 8.3 vs. 11.7 kb in healthy donors; -4 each). After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations. Moreover, the two cases of SC in the prospective HL patients had short telomeres and CCR initially. In addition, the SC HL cohort was characterized by markedly short telomeres (6.6 vs. 9.7 kb in the NED HL cohort), the presence of complex chromosome rearrangements, and increased in vitro radiation sensitivity. Conclusions: An intimate relationship between pre-treatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of SC was found in HL patients

  4. Evaluation of chromosome aberration frequency instable in individual groups residents at the municipality of Monte Alegre, Para, Brazil, exposed to radon

    International Nuclear Information System (INIS)

    The municipality of Monte Alegre is a region that presents natural radiation high due to the presence of the radionuclide uranium (238U) in its soil, which through its decay gives rise to element Rn, a gas. The radioactivity of the rocks has become a problem for the population of Monte Alegre, from the moment when the radioactive material began to be used in the construction of houses and paving of streets. Among all bio markers related to environmental exposures and its biological effects, the chromosomal aberrations are considered good bio markers as predictors of the risk of cancer. Studies suggest that the frequency of chromosomal aberrations may be related to the genetic instability individual and/or exposure to ionizing radiation. Our work aimed to evaluate the frequency of chromosomal aberrations in individuals in the region of high natural radioactivity in Monte Alegre-PA. As well as to correlate the cytogenetic analysis made in this study with the results of analysis of frequency of polymorphisms of genes of DNA repair carried out in another study that resulted in other dissertation. In accordance with the distribution of the data obtained in characterizing environmental radiological and in the calculation of dose, were chosen residents of homes with more and less exposure to radiation. The samples of peripheral blood of 85 individuals of the resident population of the region of Monte Alegre - PA were collected and examine provided two slides for individual was performed to verify the quality of the sample. Through this evaluation we decide that 33% of the material collected, or is, samples of 28 individuals were in suitable conditions for analysis of the frequency of chromosomal aberrations. After the collections lymphocytes present in the sample were cultivated in accordance with the methodology proposed for obtaining of cells in metaphase. were analyzed 6,177 metaphases of 28 individuals among which were found dicentric chromosomes 4 and 19 fragments

  5. Phenotypic Spectrum of 20 Novel Patients With Molecularly Defined Supernumerary Marker Chromosomes 15 and a Review of the Literature

    NARCIS (Netherlands)

    Kleefstra, Tjitske; de Leeuw, Nicole; Wolf, Roy; Nillesen, Willy M.; Schobers, Gaby; Mieloo, Hanneke; Willemsen, Marjolein; Perrotta, Concetta Simona; Poddighe, Pino J.; Feenstra, Ilse; Draaisma, Jos; van Ravenswaaij-Arts, Conny M. A.

    2010-01-01

    Supernumerary marker chromosomes (SMC) originating from chromosome 15 are the most common SMCs. They encompass clinically irrelevant SMC(15)s containing only heterochromatin and 15p material, and clinically relevant SMC(15)s that consist of both eu- and heterochromatic 15q material. On the basis of

  6. No significant effect of monosomy for distal 21q22. 3 on the Down syndrom phenotype in mirror' duplications of chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Pangalos, C.; Prieur, M.; Rethore, M.O.; Lejeune, J. (Institut de Progenese, Paris (France)); Theophile, D.; Sinet, P.M.; Chettouh, Z.; Delabar, J.M. (Hopital Necker Enfants Malades, Paris (France)); Marks, A. (Univ. of Toronto, Ontario (Canada)); Stamboulieh-Abazis, D. (Diagnostic Genetic Center, Athens (Greece)); Verellen, C. (Centre de Genetique Humaine, Brussels (Belgium))

    1992-12-01

    Three Down syndrome patients for whom karyotypic analysis showed a mirror' (reverse tandem) duplication of chromosome 21 were studied by phenotypic, cytogenetic, and molecular methods. On high-resolution R-banding analysis performed in two cases, the size of the fusion 21q22.3 band was apparently less than twice the size of the normal 21q22.3, suggesting a partial deletion of distal 21q. The evaluation of eight chromosome 21 single-copy sequences of the 21q22 region - namely, SOD1, D21S15, D21S42, CRYA1, PFKL, CD18, COL6A1, and S100B - by a slot blot method showed in all three cases a partial deletion of 21q22.3 and partial monosomy. The translocation breakpoints were different in each patient, and in two cases the rearranged chromosome was found to be asymmetrical. The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1-S100B, CD18-S100B, and PFKL-S100B. DNA polymorphism analysis indicated in all cases a homozygosity of the duplicated material. The duplicated region was maternal in two patients and paternal in one patient. These data suggest that the reverse tandem chromosomes did not result from a telomeric fusion between chromosomes 21 but from a translocation between sister chromatids. The phenotypes of these patients did not differ significantly from that of individuals with full trisomy 21, except in one case with large ears with an unfolded helix. The fact that monosomy of distal 21q22.3 in these patients resulted in a phenotype very similar to Down syndrome suggests that the duplication of the genes located in this part of chromosome 21 is not necessary for the pathogenesis of the Down syndrome features observed in these patients, including most of the facial and hand features, muscular hypotonia, cardiopathy of the Fallot tetralogy type, and part of the mental retardation. 54 refs., 5 figs., 3 tabs.

  7. Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background

    DEFF Research Database (Denmark)

    Krausz, C; Giachini, C; Xue, Y;

    2008-01-01

    of duplications and the Y-chromosomal haplogroup were characterised. Although the study had good power to detect factors that accounted for >or=5.5% of the variation in sperm concentration, no such factor was found. A negative effect of gr/gr deletions followed by b2/b4 duplication was found within...

  8. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

    Science.gov (United States)

    Jacquemont, Sébastien; Reymond, Alexandre; Zufferey, Flore; Harewood, Louise; Walters, Robin G.; Kutalik, Zoltán; Martinet, Danielle; Shen, Yiping; Valsesia, Armand; Beckmann, Noam D.; Thorleifsson, Gudmar; Belfiore, Marco; Bouquillon, Sonia; Campion, Dominique; De Leeuw, Nicole; De Vries, Bert B. A.; Esko, Tõnu; Fernandez, Bridget A.; Fernández-Aranda, Fernando; Fernández-Real, José Manuel; Gratacòs, Mònica; Guilmatre, Audrey; Hoyer, Juliane; Jarvelin, Marjo-Riitta; Kooy, Frank R.; Kurg, Ants; Le Caignec, Cédric; Männik, Katrin; Platt, Orah S.; Sanlaville, Damien; Van Haelst, Mieke M.; Villatoro Gomez, Sergi; Walha, Faida; Wu, Bai-Lin; Yu, Yongguo; Aboura, Azzedine; Addor, Marie-Claude; Alembik, Yves; Antonarakis, Stylianos E.; Arveiler, Benoît; Barth, Magalie; Bednarek, Nathalie; Béna, Frédérique; Bergmann, Sven; Beri, Mylène; Bernardini, Laura; Blaumeiser, Bettina; Bonneau, Dominique; Bottani, Armand; Boute, Odile; Brunner, Han G.; Cailley, Dorothée; Callier, Patrick; Chiesa, Jean; Chrast, Jacqueline; Coin, Lachlan; Coutton, Charles; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; David, Albert; De Freminville, Bénédicte; Delobel, Bruno; Delrue, Marie-Ange; Demeer, Bénédicte; Descamps, Dominique; Didelot, Gérard; Dieterich, Klaus; Disciglio, Vittoria; Doco-Fenzy, Martine; Drunat, Séverine; Duban-Bedu, Bénédicte; Dubourg, Christèle; El-Sayed Moustafa, Julia S.; Elliott, Paul; Faas, Brigitte H. W.; Faivre, Laurence; Faudet, Anne; Fellmann, Florence; Ferrarini, Alessandra; Fisher, Richard; Flori, Elisabeth; Forer, Lukas; Gaillard, Dominique; Gerard, Marion; Gieger, Christian; Gimelli, Stefania; Gimelli, Giorgio; Grabe, Hans J.; Guichet, Agnès; Guillin, Olivier; Hartikainen, Anna-Liisa; Heron, Délphine; Hippolyte, Loyse; Holder, Muriel; Homuth, Georg; Isidor, Bertrand; Jaillard, Sylvie; Jaros, Zdenek; Jiménez-Murcia, Susana; Joly Helas, Géraldine; Jonveaux, Philippe; Kaksonen, Satu; Keren, Boris; Kloss-Brandstätter, Anita; Knoers, Nine V. A. M.; Koolen, David A.; Kroisel, Peter M.; Kronenberg, Florian; Labalme, Audrey; Landais, Emilie; Lapi, Elisabetta; Layet, Valérie; Legallic, Solenn; Leheup, Bruno; Leube, Barbara; Lewis, Suzanne; Lucas, Josette; Macdermot, Kay D.; Magnusson, Pall; Marshall, Christian R.; Mathieu-Dramard, Michèle; Mccarthy, Mark I.; Meitinger, Thomas; Antonietta Mencarelli, Maria; Merla, Giuseppe; Moerman, Alexandre; Mooser, Vincent; Morice-Picard, Fanny; Mucciolo, Mafalda; Nauck, Matthias; Coumba Ndiaye, Ndeye; Nordgren, Ann; Pasquier, Laurent; Petit, Florence; Pfundt, Rolph; Plessis, Ghislaine; Rajcan-Separovic, Evica; Paolo Ramelli, Gian; Rauch, Anita; Ravazzolo, Roberto; Reis, Andre; Renieri, Alessandra; Richart, Cristobal; Ried, Janina S.; Rieubland, Claudine; Roberts, Wendy; Roetzer, Katharina M.; Rooryck, Caroline; Rossi, Massimiliano; Saemundsen, Evald; Satre, Véronique; Schurmann, Claudia; Sigurdsson, Engilbert; Stavropoulos, Dimitri J.; Stefansson, Hreinn; Tengström, Carola; Thorsteinsdóttir, Unnur; Tinahones, Francisco J.; Touraine, Renaud; Vallée, Louis; Van Binsbergen, Ellen; Van Der Aa, Nathalie; Vincent-Delorme, Catherine; Visvikis-Siest, Sophie; Vollenweider, Peter; Völzke, Henry; Vulto-Van Silfhout, Anneke T.; Waeber, Gérard; Wallgren-Pettersson, Carina; Witwicki, Robert M.; Zwolinksi, Simon; Andrieux, Joris; Estivill, Xavier; Gusella, James F.; Gustafsson, Omar; Metspalu, Andres; Scherer, Stephen W.; Stefansson, Kari; Blakemore, Alexandra I. F.; Beckmann, Jacques S.; Froguel, Philippe

    2011-01-01

    Both underweight and obesity have been associated with increased mortality1,2. Underweight, defined as body mass index (BMI) ≤ 18,5 kg/m2 in adults 3 and ≤ −2 standard deviations (SD) in children4,5, is the main sign of a series of heterogeneous clinical conditions such as failure to thrive (FTT) 6–8, feeding and eating disorder and/or anorexia nervosa9,10. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported 11, 12. We previously demonstrated that hemizygosity of a ~600 kb region on the short arm of chromosome 16 (chr16:29.5–30.1Mb), causes a highly-penetrant form of obesity often associated with hyperphagia and intellectual disabilities13. Here we show that the corresponding reciprocal duplication is associated with underweight. We identified 138 (132 novel cases) duplication carriers (108 unrelated carriers) from over 95,000 individuals clinically-referred for developmental or intellectual disabilities (DD/ID), psychiatric disorders or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight (mean Z-score −0.6; p=4.4×10−4) and BMI (mean Z-score −0.5; p=2.0×10−3). In particular, half of the boys younger than 5 years are underweight with a probable diagnosis of FTT, while adult duplication carriers have an 8.7-fold (p=5.9×10−11; CI_95=[4.5–16.6]) increased risk of being clinically underweight. We observe a significant trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive feeding behaviours and a significant reduction in head circumference (mean Z-score −0.9; p=7.8×10−6). Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus, correlating with changes in transcript levels for genes mapping within the duplication but not within flanking

  9. Chromosome instability and global gene expression patterns in proliferating human T-lymphocytes after low dose rate γ-irradiation, and genetic instability in cells from in vivo radiation-exposed persons

    International Nuclear Information System (INIS)

    Chromosomal instability (Cl), and radiation induced Cl in particular, as well as in a wider sense, genomic instability, has been of great interest lately, as it provides an explanation for the occurrence of multiple mutations during transformation of a normal cell to a malignant tumor cell. To explore this phenomenon, we developed an in vitro system to study the long term, cytogenetic effects of ionizing radiation in human T-lymphocytes. Irradiated or non-irradiated T-cells were grown for up to two months as monoclonal or bulk cell cultures in medium enriched with T-cell growth factors. Analysis of G-banded karyotypes at different time intervals demonstrated clonal aberrations in 65% of the clones derived from irradiated cells, and in only 5% of the clones from non-irradiated cells. Delayed occurrence of de novo aberrations, and a progressive development of subclones with karyotypic abnormalities of increasing complexity, was observed many cell generations after the radiation exposure. Moreover, cells exposed to γ-radiation at a low dose rate (LDR, 0.024 Gy h-1) for 5 days in G0-phase, e.g. a dose that gives the cells time to repair between subsequent hits, also demonstrated CI. Following a radiological accident in Estonia 1994, we studied the possible induction of CI in vivo. Both long term bulk cultures and single cell clones were established from one high and three low exposed persons, as well as control individuals from Estonia. Compared to our historical Swedish controls, we found CI to occur in both bulk cultures and clones, and the aberrations were more complex in the exposed individuals than in the controls, indicating that the aberrations were caused by the irradiation. However, due to the high frequency of CI in the Estonian controls, no conclusion with regard to chromosomal instability in vivo could be drawn from the study. In order to trace factors that induce and maintain the chromosomal instability, and clarify which steps are affected in the

  10. Normal telomere length and chromosomal end capping in poly(ADP-ribose) polymerase–deficient mice and primary cells despite increased chromosomal instability

    OpenAIRE

    Samper, Enrique; Goytisolo, Fermín A.; Murcia, Josiane Ménissier-de; González-Suárez, Eva; Cigudosa, Juan C.; de Murcia, Gilbert; Blasco, María A

    2001-01-01

    Poly(ADP-ribose) polymerase (PARP)-1, a detector of single-strand breaks, plays a key role in the cellular response to DNA damage. PARP-1–deficient mice are hypersensitive to genotoxic agents and display genomic instability due to a DNA repair defect in the base excision repair pathway. A previous report suggested that PARP-1–deficient mice also had a severe telomeric dysfunction consisting of telomere shortening and increased end-to-end fusions (d'Adda di Fagagna, F., M.P. Hande, W.-M. Tong,...

  11. Phenotype and 244k array-CGH characterization of chromosome 13q deletions: an update of the phenotypic map of 13q21.1-qter

    DEFF Research Database (Denmark)

    Kirchhoff, Maria; Bisgaard, Anne-Marie; Stoeva, Radka;

    2009-01-01

    breakpoints in 14 patients with partial deletions of this region. Subsequently, we linked the genotype to the patient's phenotype. Using this approach, we were able to refine the smallest deletion region linked to short stature (13q31.3: 89.5-91.6 Mb), microcephaly (13q33.3-q34), cortical development...

  12. [Effect of gametocidal chromosome 4S' on the phenotype segregation ratio in genetic analysis of common wheat lines].

    Science.gov (United States)

    Vdovichenko, Zh V; Antoniuk, M Z; Ternovskaia, T K

    2003-01-01

    Using experimental data on genetic analysis of introgressive lines for the character "hairy leaf sheath" controlled by the "cuckoo" chromosome 4S1, the algorithm for calculation of the theoretical segregation ratio in F2 was developed. Segregation distortion is caused by non-viability of the majority of gametes lacking the chromosome 4S1. The frequency of functioning gametes without the chromosome 4S1 is determined by the probability p versus the theoretically expected ratio 7 nonviable: 9 viable ones. Since segregation involves two characters, gamete viability and hairiness, the ratio 15 hairy: 1 hairless was used as a basis for search of the frequency p by maximum-likelihood method using 16 populations F2 from crossing the lines differing in the character studied. PMID:14650327

  13. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

    OpenAIRE

    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P; Islas-Morris-Hernandez, A.; Borget, I; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluoresce...

  14. GENOME-WIDE LINKAGE ANALYSIS TO IDENTIFY CHROMOSOMAL REGIONS AFFECTING PHENOTYPIC TRAITS IN THE CHICKEN. IV. SKELETAL INTEGRITY

    Science.gov (United States)

    Two unique chicken F2 populations generated from a broiler breeder male line and two genetically distinct inbred (greater than 99%) chicken lines (Leghom and Fayoumi), were used for whole genome QTL analysis. Twelve phenotypic skeletal integrity traits (6 absolute and 6 relative traits) were measure...

  15. Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion.

    Science.gov (United States)

    Verhoeven, Willem M A; Egger, Jos I M; Goffin, Luc; van Zutven, Laura J C M; Mancini, Grazia M S

    2013-06-01

    A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms. To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype. PMID:23542664

  16. Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer

    DEFF Research Database (Denmark)

    Roylance, Rebecca; Endesfelder, David; Gorman, Patricia;

    2011-01-01

    reflect tumor CIN status, efficiently delineate outcome in estrogen receptor ER-positive reast cancer in contrast to ERnegative breast cancer, suggesting that the relationship of CIN with prognosis differs in these two breast cancer subtypes. Methods: Direct assessment of CIN requires single-cell analysis...... methods, such as centromeric FISH, aimed at determining the variation around the modal number of two or more chromosomes within individual tumor nuclei. Here, we document the frequency of tumor CIN by dual centromeric FISH analysis in a retrospective primary breast cancer cohort of 246 patients with...... in multivariate analysis. In contrast, a linear relationship of increasing CIN with poorer prognosis in ER-positive breast cancer was observed, using three independent measures of CIN. Conclusions: The paradoxical relationship between extreme CIN and cancer outcome in the ER-negative cohorts may...

  17. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

    Swanton, C.; Nicke, B.; Schuett, M.;

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting...

  18. Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells

    International Nuclear Information System (INIS)

    Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state

  19. A network of clinically and functionally relevant genes is involved in the reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after transfer of human chromosome 8.

    Science.gov (United States)

    Seitz, Susanne; Frege, Renate; Jacobsen, Anja; Weimer, Jörg; Arnold, Wolfgang; von Haefen, Clarissa; Niederacher, Dieter; Schmutzler, Rita; Arnold, Norbert; Scherneck, Siegfried

    2005-01-27

    Several investigations have supposed that tumor suppressor genes might be located on human chromosome 8. We used microcell-mediated transfer of chromosome 8 into MDA-MB-231 breast cancer cells and generated independent hybrids with strongly reduced tumorigenic potential. Loss of the transferred chromosome results in reappearance of the malignant phenotype. Expression analysis identified a set of 109 genes (CT8-ps) differentially expressed in microcell hybrids as compared to the tumorigenic MDA-MB-231 and rerevertant cells. Of these, 44.9% are differentially expressed in human breast tumors. The expression pattern of CT8-ps was associated with prognostic factors such as tumor size and grading as well as loss of heterozygosity at the short arm of chromosome 8. We identified CT8-ps networks suggesting that these genes act cooperatively to cause reversion of tumorigenicity in MDA-MB-231 cells. Our findings provide a conceptual basis and experimental system to identify and evaluate genes and gene networks involved in the development and/or progression of breast cancer. PMID:15580292

  20. Fusion of nearby inverted repeats by a replication-based mechanism leads to formation of dicentric and acentric chromosomes that cause genome instability in budding yeast

    OpenAIRE

    Paek, Andrew L.; Kaochar, Salma; Jones, Hope; Elezaby, Aly; Shanks, Lisa; Weinert, Ted

    2009-01-01

    Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and are often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats in budding yeast fuse to form a dicentric chromosome intermediate, which then rearranges to form a translocation and other GCRs. We next show that fusion of nearby inverted repeats is general; we found that many nearby inverted repeats that are present in the yeast genome also fuse, as does a p...

  1. Tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity.

    Directory of Open Access Journals (Sweden)

    Yuanjie Hu

    Full Text Available Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7 copy number variation (CNV in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers.

  2. Aneuploid progeny of the American oyster, Crassostrea virginica, produced by tetraploid × diploid crosses: another example of chromosome instability in polyploid oysters.

    Science.gov (United States)

    de Sousa, Joana Teixeira; Allen, Standish K; Baker, Haley; Matt, Joseph L

    2016-05-01

    The commercial production of triploids, and the creation of tetraploid broodstock to support it, has become an important technique in aquaculture of the eastern oyster, Crassostrea virginica. Tetraploids are produced by cytogenetic manipulation of embryos and have been shown to undergo chromosome loss (to become a mosaic) with unknown consequences for breeding. Our objective was to determine the extent of aneuploidy in triploid progeny produced from both mosaic and non-mosaic tetraploids. Six families of triploids were produced using a single diploid female and crossed with three mosaic and non-mosaic tetraploid male oysters. A second set of crosses was performed with the reciprocals. Chromosome counts of the resultant embryos were tallied at 2-4 cell stage and as 6-hour(h)-old embryos. A significant level of aneuploidy was observed in 6-h-old embryos. For crosses using tetraploid males, aneuploidy ranged from 53% to 77% of observed metaphases, compared to 36% in the diploid control. For crosses using tetraploid females, 51%-71% of metaphases were aneuploidy versus 53% in the diploid control. We conclude that somatic chromosome loss may be a regular feature of early development in triploids, and perhaps polyploid oysters in general. Other aspects of chromosome loss in polyploid oysters are also discussed. PMID:27070368

  3. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K; Tsai, Y C; Spruck, C H; Miyao, N; Nichols, P W; Hermann, G G; Horn, T; Steven, K

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X chr...

  4. Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic traits in the chicken. I. Growth and average daily gain

    Science.gov (United States)

    A genome scan was used to detect chromosomal regions and QTL that control quantitative traits of economic importance in chickens. Two unique F2 crosses generated from a commercial broiler male line and 2 genetically distinct inbred lines (Leghorn and Fayoumi) were used to identify QTL affecting BW a...

  5. 用FISH技术分析一例表型异常的 染色体平衡易位%Analysis of a case of balanced chromosome translocation and phenotypic abnormality by fluorescence in situ hybridization

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective  To delineate the chromosome structural aberration in a case of chromosome translocation by fluorescence in situ hybridization(FISH) technique and precisely identify the breakpoints. Methods  The whole chromosome point 5(wcp5) and locus-specific probes derived from yeast artificial chromosomes(YACs) mapping the nearby region of breakpoints were used to delineate the translocation t(5;10) found by high resolution G-banding examination in a case with congenital abnormality. Results A balanced translocation was confirmed and the breakpoints were located in the 1.5 Mb area on chromosome 5 and within the approximately 3 Mb interval on chromosome 10. Conclusion  The phenotypic abnormality might result from the disruption of disease-associated gene(s) or microrearrangement(s) on the site of breakpoint(s).%目的应用荧光原位杂交技术对1例染色体结构异常患者进行分析,阐明结构异常性质,并精细定位断点。方法对一先天表型异常经细胞遗传学检查有t(5;10)的病例,分别选用5号染色体探针池以及用酵母人工染色体作为DNA来源制备的断点区位点特异性探针,进行荧光染色体原位杂交。结果证实患者染色体异常属平衡易位,并将5号和10号染色体的断点分别定位到1.5 Mb及约3 Mb的范围。结论患者的先天性表型异常可能由断点处染色体细微重排或致病基因断裂所致。

  6. Mre11 deficiency in Arabidopsis is associated with chromosomal instability in somatic cells and Spo11-dependent genome fragmentation during meiosis

    Czech Academy of Sciences Publication Activity Database

    Puizina, J.; Široký, Jiří; Schweizer, D.; Říha, K.

    2004-01-01

    Roč. 16, č. 8 (2004), s. 1968-1978. ISSN 1040-4651 R&D Projects: GA ČR GA522/03/0354; GA AV ČR IAA6004304 Grant ostatní: Austrian Science Foundation(AT) P16405 Institutional research plan: CEZ:AV0Z5004920 Keywords : MRE11 * Arabidopsis thaliana * chromosomes Subject RIV: BO - Biophysics Impact factor: 11.295, year: 2004

  7. Instability of chromosome number and DNA methylation variation induced by hybridization and amphidiploid formation between Raphanus sativus L. and Brassica alboglabra Bailey

    OpenAIRE

    Wang Yanjie; Wei Lihua; Chen Honggao; Li Xiangsong; Wang Bing; Guo Weiwei; Li Xuanli; Wu Jiangsheng; Long Hong

    2010-01-01

    Abstract Background Distant hybridization can result genome duplication and allopolyploid formation which may play a significant role in the origin and evolution of many plant species. It is unclear how the two or more divergent genomes coordinate in one nucleus with a single parental cytoplasm within allopolyploids. We used cytological and molecular methods to investigate the genetic and epigenetic instabilities associated with the process of distant hybridization and allopolyploid formation...

  8. An Extra X or Y Chromosome: Contrasting the Cognitive and Motor Phenotypes in Childhood in Boys with 47,XYY Syndrome or 47,XXY Klinefelter Syndrome

    Science.gov (United States)

    Ross, Judith L.; Zeger, Martha P. D.; Kushner, Harvey; Zinn, Andrew R.; Roeltgen, David P.

    2009-01-01

    Objective: The goal of this study was to contrast the cognitive phenotypes in boys with 47,XYY (XYY) karyotype and boys with 47,XXY karyotype [Klinefelter syndrome, (KS)], who share an extra copy of the X-Y pseudoautosomal region but differ in their dosage of strictly sex-linked genes. Methods: Neuropsychological evaluation of general cognitive…

  9. Cat3vl and Cat3vao cataract mutations on mouse chromosome 10: phenotypic characterization, linkage studies and analysis of candidate genes.

    Science.gov (United States)

    Löster, J; Immervoll, T; Schmitt-John, T; Graw, J

    1997-12-01

    Cat3vl and Cat3vao are two allelic, dominant cataract mutations that arose independently in the F1 generation after gamma-irradiation of male mice. The cataracts are already present at birth. Examination of the eyes with a slit lamp revealed completely vacuolated lenses in Cat3vl mutants and anteriorly located opacity in Cat3vao mutants. The appearance of the opacities does not differ between the individuals or between heterozygotes and homozygotes. Penetrance of the mutations is complete. Viability and fertility of the mutants are normal except in the case of the Cat3vl homozygotes. Cat3vao was assigned to the distal part of mouse chromosome 10, 3.2 +/- 0.9 cM away from the visible marker Steel (SlgbH). Using polymorphic markers the following locus order was found: D10Mit230-(0.2 +/- 0.1 cM)-Cat3vao-(2.5 +/- 0.6 cM)-D10Mit70. No recombinants were found between Cat3vao and the markers D10Mit4l and D10Mit95 among 921 offspring. The results exclude allelism of Cat3vao with CatLop or To2, which also map to chromosome 10. Candidate genes were tested by examination of their expression in the eye of newborn mice and by analysis of cDNA sequences. So far, negative results have been obtained for the genes encoding the proteoglycans lumican and decorin, the nuclear orphan receptor Tr2-11 and the transcription factor Elk3. Based on syntenic homology of the Cat3 region to the human chromosome 12q, the Cat3 mutants are discussed as mouse models for cornea plana congenita in man. The recovery of the Cat3 mutations demonstrates the importance of the corresponding locus for proper eye development. PMID:9439574

  10. Motion as a phenotype: the use of live-cell imaging and machine visual screening to characterize transcription-dependent chromosome dynamics

    Directory of Open Access Journals (Sweden)

    Silver Pamela A

    2006-04-01

    Full Text Available Abstract Background Gene transcriptional activity is well correlated with intra-nuclear position, especially relative to the nuclear periphery, which is a region classically associated with gene silencing. Recently however, actively transcribed genes have also been found localized to the nuclear periphery in the yeast Saccharomyces cerevisiae. When genes are activated, they become associated with the nuclear pore complex (NPC at the nuclear envelope. Furthermore, chromosomes are not static structures, but exhibit constrained diffusion in real-time, live-cell studies of particular loci. The relationship of chromosome motion with transcriptional activation and active-gene recruitment to the nuclear periphery has not yet been investigated. Results We have generated a yeast strain that enables us to observe the motion of the galactose-inducible GAL gene locus relative to the nuclear periphery in real-time under transcriptionally active and repressed conditions. Using segmented geometric particle tracking, we show that the repressed GAL locus undergoes constrained diffusive movement, and that transcriptional induction with galactose is associated with an enrichment in cells with GAL loci that are both associated with the nuclear periphery and much more constrained in their movement. Furthermore, we report that the mRNA export factor Sac3 is involved in this galactose-induced enrichment of GAL loci at the nuclear periphery. In parallel, using a novel machine visual screening technique, we find that the motion of constrained GAL loci correlates with the motion of the cognate nuclei in galactose-induced cells. Conclusion Transcriptional activation of the GAL genes is associated with their tethering and motion constraint at the nuclear periphery. We describe a model of gene recruitment to the nuclear periphery involving gene diffusion and the mRNA export factor Sac3 that can be used as a framework for further experimentation. In addition, we applied to

  11. Trisomy 21 and facial developmental instability.

    Science.gov (United States)

    Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T

    2013-05-01

    The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. PMID:23505010

  12. Genomic instability following irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hacker-Klom, U.B.; Goehde, W. [Inst. fuer Strahlenbiologie, Muenster Univ. (Germany)

    2001-07-01

    Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

  13. Genomic instability following irradiation

    International Nuclear Information System (INIS)

    Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

  14. Induction of chromosome instability and stomach cancer by altering the expression pattern of mitotic checkpoint genes in mice exposed to areca-nut

    International Nuclear Information System (INIS)

    developed cancer earlier, (b) perturbations in components of the chromosome segregation machinery could be involved in the initial process of carcinogenicity and (c) the importance of precocious anaphase as a screening marker for identification of mitotic checkpoint defects during early days

  15. Lack of segregation of a Marfan-like phenotype associating marfanoie habitus and mitral valve disease with fibrillin gene on chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    VanMaldergen, L.; Hilbert, P.; Gillerot, Y. [Institut de Morphologie Pathologique, Loverval (Belgium)] [and others

    1994-09-01

    Apart from typical Marfan syndrome (MS), several Marfan-like conditions are known. One of those is the MASS syndrome (Mitral involvement, Aortic dilatation, Skin and Skeletal abnormalities) defined by Pyeritz et al. Among these, a dominantly inherited mitral valve prolapse with marfanoid habitus have also been reported. Until now, except for a Marfan-like condition described by Boileau et al., all Marfan families are linked to fib 15. A large Belgian pedigree with 25 affected patients among 62 at risk subjects spanning four generations is described. A syndrome including marfanoid skeletal dysplasia (tall stature, dolichostenomelia, arachnodactyly, pectus carinatum joint dislocation), prolapse and/or myxomatous degeneration of the mitral valve, but without aortic dilatation of eye involvement was observed. Although the phenotype fulfills Berlin diagnostic criteria for MS, it closely resembles MASS syndrome. Preliminary linkage results show discordance aggregation insertion in the fib 15 gene, as evaluated by intragenic microsatellite fib 15. Since Dietz et al. described a similar patient with fib 15 gene, we suggest that this variant of Marfan syndrome is genetically heterogeneous and caused by mutations, some of which are allelic to classical Marfan syndrome plus a subtype, some of which are not. Linkage studies are under way to further characterize the gene involved in the present family.

  16. Correlation between chromosome deletion and phenotypes in two cases of ring chromosome 6 syndrome%二例环6号染色体综合征病例染色体缺失片段及其与临床表型的关系

    Institute of Scientific and Technical Information of China (English)

    付杰; 王松涛; 潘虹; 马京梅; 于丽; 杨慧霞

    2014-01-01

    Objective To understand the correlation between chromosome deletion and the phenotypes in cases of ring chromosome 6 syndrome.Methods Two cases of ring chromosome 6 syndrome persented to the Peking University First Hospital in 2013 were studied.Case 1 was a fetus diagnosed as having ring chromosome 6 with karyotype 46,XY,r (6) [14]/46,XY,r (6; 6) [1]/45,XY,-6[15] from a pregnant woman who received prenatal examination because of high risk found in serum screening for Down's syndrome at 21 +1 weeks of gestation.Case 2 was an eight-month-old female infant with growth retardation and congenital facial anomaly,whose karyotype was 46,XX,r (6) /47,XX,r (6) × 2/46,XX,r (6; 6) /45,XX,-6.Multiplex ligation-dependent probe amplification and array-based comparative genomic hybridization were used to detect the location of chromosome telomeric loss and its size,and the correlation between chromosome deletion and the phenotypes was analyzed by reviewing related literatures.Results Case 1 was confirmed to have short-arm terminal deletions on 6p25.3-25.2 (2.42 Mb) which mainly included DUSP22,IRF4,EXOC2,FOXC1,FOXF2 and FOXQ genes,and long-arm terminal deletions on 6q26-27 (7.84 Mb) mainly included PARK2,PACRG,LOC28596 and RPS6KA2 genes.Case 2 had short-arm terminal deletions on 6p25.3-25.1 (5.44 Mb) which included DUSP22,IRF4,EXOC2,FOXC1,FOXF2,FOXQ and SERPINB6 genes,and long-arm terminal deletions on 6q27 (0.16 Mb) which included PSMB1,TBP and PDCD2 genes.Except for the growth retardation,the common feature of "ring syndrome",in both cases,cerebellum hypoplasia was observed in case 1,and microcephaly and esotropia were observed in case 2.Conclusions The difference of phenotypes in patients with a ring chromosome 6 is closely associated with the location and size of the deletion in chromosome 6.%目的 探讨环6号染色体综合征病例染色体缺失片段和定位于其中的基因与临床表型的关系. 方法 2013年就诊于北京大学第一医院的2例环6号染色

  17. Causes of genome instability

    DEFF Research Database (Denmark)

    Langie, Sabine A S; Koppen, Gudrun; Desaulniers, Daniel;

    2015-01-01

    Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus......, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other...... chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling...

  18. Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Brandon L Pierce

    Full Text Available Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10(-8 for percentages of both monomethylarsonic acid (MMA and dimethylarsinic acid (DMA near the AS3MT gene (arsenite methyltransferase; 10q24.32, with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity and 1,794 controls, we show that one of these five variants (rs9527 is also associated with skin lesion risk (P = 0.0005. Using a subset of individuals with prospectively measured arsenic (n = 769, we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01. Expression quantitative trait locus (eQTL analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10(-12 and neighboring gene C10orf32 (P = 10(-44, which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical

  19. GENETIC ALTERRATIONS OF MICROSATELLITE MARKERS AT CHROMOSOME 17 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    GUO; Xue-jun

    2001-01-01

    [1]Froudarakis ME, Bouros D, Spandidos DA, et al. Microsatellite instability and loss of heterozygosity at chromosomes 17 in non-small cell lung cancer [J]. Chest 1998; 113:1091.[2]Fong KM, Zimmerman PV, Smith PJ. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer [J]. Cancer Res 1994; 54:2098.[3]Mountain CF. A new international staging system for lung cancer [J]. Chest 1986; 89(suppl):225.[4]Shridhar V, Siegfried J, Hunt J, et al. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas [J]. Cancer Res 1994; 54:2084.[5]Loeb LA. Microsatellite instability: Marker of a mutator phenotype in cancer [J]. Cancer Res 1994; 54:5059.[6]Sanchez CM, Monzo M, Rosell R, et al. Detection of chromosome 3p alterations in serum DNA of non-small cell lung cancer patients [J]. Ann Oncol 1989; 113.

  20. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells.

    Directory of Open Access Journals (Sweden)

    William T Silkworth

    Full Text Available Many cancer cells display a CIN (Chromosome Instability phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, a number of different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes of CIN. However, a comprehensive theory of how CIN is perpetuated is still lacking. We used CIN colorectal cancer cells as a model system to investigate the possible cellular mechanism(s underlying CIN. We found that CIN cells frequently assembled multipolar spindles in early mitosis. However, multipolar anaphase cells were very rare, and live-cell experiments showed that almost all CIN cells divided in a bipolar fashion. Moreover, fixed-cell analysis showed high frequencies of merotelically attached lagging chromosomes in bipolar anaphase CIN cells, and higher frequencies of merotelic attachments in multipolar vs. bipolar prometaphases. Finally, we found that multipolar CIN prometaphases typically possessed gamma-tubulin at all spindle poles, and that a significant fraction of bipolar metaphase/early anaphase CIN cells possessed more than one centrosome at a single spindle pole. Taken together, our data suggest a model by which merotelic kinetochore attachments can easily be established in multipolar prometaphases. Most of these multipolar prometaphase cells would then bi-polarize before anaphase onset, and the residual merotelic attachments would produce chromosome mis-segregation due to anaphase lagging chromosomes. We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells.

  1. Shoulder Instability

    Science.gov (United States)

    ... Risk Factors Is shoulder instability the same as shoulder dislocation? No. The signs of dislocation and instability might ... the same to you--weakness and pain. However, dislocation occurs when your shoulder goes completely out of place. The shoulder ligaments ...

  2. Holoprosencephaly due to numeric chromosome abnormalities.

    Science.gov (United States)

    Solomon, Benjamin D; Rosenbaum, Kenneth N; Meck, Jeanne M; Muenke, Maximilian

    2010-02-15

    Holoprosencephaly (HPE) is the most common malformation of the human forebrain. When a clinician identifies a patient with HPE, a routine chromosome analysis is often the first genetic test sent for laboratory analysis in order to assess for a structural or numerical chromosome anomaly. An abnormality of chromosome number is overall the most frequently identified etiology in a patient with HPE. These abnormalities include trisomy 13, trisomy 18, and triploidy, though several others have been reported. Such chromosome number abnormalities are almost universally fatal early in gestation or in infancy. Clinical features of specific chromosome number abnormalities may be recognized by phenotypic manifestations in addition to the HPE. PMID:20104610

  3. Chromosomal Instability Confers Intrinsic Multidrug Resistance

    DEFF Research Database (Denmark)

    Lee, Alvin J. X.; Endesfelder, David; Rowan, Andrew J.;

    2011-01-01

    . Identification of distinct therapeutic agents that target tumor karyotypic complexity has important clinical implications. To identify distinct therapeutic approaches to specifically limit the growth of CIN tumors, we focused on a panel of colorectal cancer (CRC) cell lines, previously classified as either...... progression-free or disease-free survival relative to patients with CIN- disease. Our results suggest that stratifying tumor responses according to CIN status should be considered within the context of clinical trials to minimize the confounding effects of tumor CIN status on drug sensitivity. Cancer Res; 71...

  4. Shoulder instability

    International Nuclear Information System (INIS)

    In the shoulder, the advantages of range of motion are traded for the disadvantages of vulnerability to injury and the development of instability. Shoulder instability and the lesion it produces represent one of the main causes of shoulder discomfort and pain. Shoulder instability is defined as a symptomatic abnormal motion of the humeral head relative to the glenoid during active shoulder motion. Glenohumeral instabilities are classified according to their causative factors as the pathogenesis of instability plays an important role with respect to treatment options: instabilities are classified in traumatic and atraumatic instabilities as part of a multidirectional instability syndrome, and in microtraumatic instabilities. Plain radiographs ('trauma series') are performed to document shoulder dislocation and its successful reposition. Direct MR arthrography is the most important imaging modality for delineation the different injury patterns on the labral-ligamentous complex and bony structures. Monocontrast CT-arthrography with use of multidetector CT scanners may be an alternative imaging modality, however, regarding the younger patient age, MR imaging should be preferred in the diagnostic work-up of shoulder instabilities. (orig.)

  5. The CRO-1 gene of Saccharomyces cerevisiae controls mitotic crossing over, chromosomal stability and sporulation

    International Nuclear Information System (INIS)

    The properties of a novel temperature-sensitive recombination-defective mutant of Saccharomyces cerevisiae, cro1-1 is described. The cro1-1 mutant is the first instance of a rec mutation that reduces drastically the rates of spontaneous mitotic crossing-over events but not those of gene conversional events. The cro1-1 mutation thus provides evidence that mitotic crossing-over is dependent upon gene products that are not essential for gene conversional events. The cro1-1 mutation also results in enhanced mitotic-chromosomal instability and MATa/MATα cro1-1/cro1-1 mutants are sporulation deficient. These phenotypes indicate that the CRO1 gene modulates mitotic chromosomal integrity and is essential for normal meiosis. The cro1-1 mutant possesses Holliday junction resolvase activity, hence its recombinational defect does not involve failure to execute this putative final recombinational step. 7 refs., 1 fig., 5 tabs

  6. Hip instability.

    Science.gov (United States)

    Smith, Matthew V; Sekiya, Jon K

    2010-06-01

    Hip instability is becoming a more commonly recognized source of pain and disability in patients. Traumatic causes of hip instability are often clear. Appropriate treatment includes immediate reduction, early surgery for acetabular rim fractures greater than 25% or incarcerated fragments in the joint, and close follow-up to monitor for avascular necrosis. Late surgical intervention may be necessary for residual symptomatic hip instability. Atraumatic causes of hip instability include repetitive external rotation with axial loading, generalized ligamentous laxity, and collagen disorders like Ehlers-Danlos. Symptoms caused by atraumatic hip instability often have an insidious onset. Patients may have a wide array of hip symptoms while demonstrating only subtle findings suggestive of capsular laxity. Traction views of the affected hip can be helpful in diagnosing hip instability. Open and arthroscopic techniques can be used to treat capsular laxity. We describe an arthroscopic anterior hip capsular plication using a suture technique. PMID:20473129

  7. Quantitative Proteomic Analysis of Mitochondrial Proteins Reveals Pro-Survival Mechanisms in the Perpetuation of Radiation-Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Stefani N.; Waters, Katrina M.; Morgan, William F.; Yang, Austin; Baulch, Janet E.

    2012-07-26

    Radiation induced genomic instability is a well-studied phenomenon that is measured as mitotically heritable genetic alterations observed in the progeny of an irradiated cell. The mechanisms that perpetuate this instability are unclear, however, a role for chronic oxidative stress has consistently been demonstrated. In the chromosomally unstable LS12 cell line, oxidative stress and genomic instability were correlated with mitochondrial dysfunction. To clarify this mitochondrial dysfunction and gain insight into the mechanisms underlying radiation induced genomic instability we have evaluated the mitochondrial sub-proteome and performed quantitative mass spectrometry (MS) analysis of LS12 cells. Of 98 quantified mitochondrial proteins, 17 met criteria for fold changes and reproducibility; and 11 were statistically significant in comparison with the stable parental GM10115 cell line. Previous observations implicated defects in the electron transport chain (ETC) in the LS12 cell mitochondrial dysfunction. Proteomic analysis supports these observations, demonstrating significantly reduced levels of mitochondrial cytochrome c, the intermediary between complexes III and IV of the ETC. Results also suggest that LS12 cells compensate for ETC dysfunction and oxidative stress through increased levels of tricarboxylic acid cycle enzymes and up-regulation of proteins that protect against oxidative stress and apoptosis. More than one cellular defect is likely to contribute to the genomic instability phenotype. These data suggest that LS12 cells have adapted mechanisms that allow survival under sub-optimal conditions of oxidative stress and compromised mitochondrial function to perpetuate genomic instability.

  8. Evaluation of chromosome aberration frequency instable in individual groups residents at the municipality of Monte Alegre, Para, Brazil, exposed to radon; Avaliacao da frequencia de aberracoes cromossomicas instaveis em grupos de individuos residentes no municipio de Monte Alegre - PA expostos diferencialmente ao radonio

    Energy Technology Data Exchange (ETDEWEB)

    Yunes, Samira Nogarol

    2010-07-01

    The municipality of Monte Alegre is a region that presents natural radiation high due to the presence of the radionuclide uranium ({sup 238}U) in its soil, which through its decay gives rise to element Rn, a gas. The radioactivity of the rocks has become a problem for the population of Monte Alegre, from the moment when the radioactive material began to be used in the construction of houses and paving of streets. Among all bio markers related to environmental exposures and its biological effects, the chromosomal aberrations are considered good bio markers as predictors of the risk of cancer. Studies suggest that the frequency of chromosomal aberrations may be related to the genetic instability individual and/or exposure to ionizing radiation. Our work aimed to evaluate the frequency of chromosomal aberrations in individuals in the region of high natural radioactivity in Monte Alegre-PA. As well as to correlate the cytogenetic analysis made in this study with the results of analysis of frequency of polymorphisms of genes of DNA repair carried out in another study that resulted in other dissertation. In accordance with the distribution of the data obtained in characterizing environmental radiological and in the calculation of dose, were chosen residents of homes with more and less exposure to radiation. The samples of peripheral blood of 85 individuals of the resident population of the region of Monte Alegre - PA were collected and examine provided two slides for individual was performed to verify the quality of the sample. Through this evaluation we decide that 33% of the material collected, or is, samples of 28 individuals were in suitable conditions for analysis of the frequency of chromosomal aberrations. After the collections lymphocytes present in the sample were cultivated in accordance with the methodology proposed for obtaining of cells in metaphase. were analyzed 6,177 metaphases of 28 individuals among which were found dicentric chromosomes 4 and 19

  9. Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21

    DEFF Research Database (Denmark)

    McGinniss, M J; Kazazian, H H; Stetten, G;

    1992-01-01

    ), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another......We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage......). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy....

  10. Chromosomal aberration

    International Nuclear Information System (INIS)

    Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G1 phase. (author)

  11. Genomic regulatory landscapes and chromosomal rearrangements

    DEFF Research Database (Denmark)

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

    determine the complex spatio-temporal expression of the associated trans-dev gene. Rare chromosomal breakpoints that disrupt the integrity of these regulatory landscapes may be used as a tool, not only to make genotype-phenotype associations, but also to link the associated phenotype with the position and...... of CNEs in a zebrafish assay supported the hypothesis that the disruption of the putative regulatory landscapes was responsible for the phenotypes due to long-range position effects....

  12. Genetic instability in urinary bladder cancer: An evolving hallmark

    Directory of Open Access Journals (Sweden)

    N Wadhwa

    2013-01-01

    Full Text Available Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA mismatch repair (MMR system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.

  13. Chromosome evolution in Neotropical butterflies.

    Science.gov (United States)

    Saura, Anssi; Von Schoultz, Barbara; Saura, Anja O; Brown, Keith S

    2013-06-01

    We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results in the context of chromosome numbers of over 1400 Neotropical butterfly species and subspecies derived from about 3000 populations published here and in earlier papers of a series. The overall results show that many Neotropical groups are characterized by karyotype instability with several derived modal numbers or none at all, while almost all taxa of Lepidoptera studied from the other parts of the world have one of n = 29-31 as modal numbers. Possibly chromosome number changes become fixed in the course of speciation driven by biotic interactions. Population subdivision and structuring facilitate karyotype change. Factors that stabilize chromosome numbers include hybridization among species sharing the same number, migration, sexual selection and possibly the distribution of chromosomes within the nucleus. PMID:23865963

  14. Baroclinic instabilities

    OpenAIRE

    Joly, Laurent; Chassaing, Patrick; Chapin, Vincent; Reinaud, Jean; Micallef, J; Suarez, Juan; Bretonnet, L

    2003-01-01

    1. Introduction - Illustrative examples from experiments and simulations 2. The baroclinic torque in high Froude number flows, its organization, scale and order of magnitude 3. Stability of the inhomogeneous mixing-layer 4. Transition of the inhomogeneous mixing-layer and the 2D secondary baroclinic instability 5. The strain field of 2D light jets 6. Transition to three-dimensionality in light jets and the question of side-jets 7. Baroclinic instability of heavy vortices and...

  15. Carpal instability

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, R.; Froehner, S.; Coblenz, G.; Christopoulos, G. [Institut fuer Diagnostische und Interventionelle Radiologie, Herz- und Gefaessklinik GmbH, Bad Neustadt an der Saale (Germany)

    2006-10-15

    This review addresses the pathoanatomical basics as well as the clinical and radiological presentation of instability patterns of the wrist. Carpal instability mostly follows an injury; however, other diseases, like CPPD arthropathy, can be associated. Instability occurs either if the carpus is unable to sustain physiologic loads (''dyskinetics'') or suffers from abnormal motion of its bones during movement (''dyskinematics''). In the classification of carpal instability, dissociative subcategories (located within proximal carpal row) are differentiated from non-dissociative subcategories (present between the carpal rows) and combined patterns. It is essential to note that the unstable wrist initially does not cause relevant signs in standard radiograms, therefore being ''occult'' for the radiologic assessment. This paper emphasizes the high utility of kinematographic studies, contrast-enhanced magnetic resonance imaging (MRI) and MR arthrography for detecting these predynamic and dynamic instability stages. Later in the natural history of carpal instability, static malalignment of the wrist and osteoarthritis will develop, both being associated with significant morbidity and disability. To prevent individual and socio-economic implications, the handsurgeon or orthopedist, as well as the radiologist, is challenged for early and precise diagnosis. (orig.)

  16. Adults with Chromosome 18 Abnormalities.

    Science.gov (United States)

    Soileau, Bridgette; Hasi, Minire; Sebold, Courtney; Hill, Annice; O'Donnell, Louise; Hale, Daniel E; Cody, Jannine D

    2015-08-01

    The identification of an underlying chromosome abnormality frequently marks the endpoint of a diagnostic odyssey. However, families are frequently left with more questions than answers as they consider their child's future. In the case of rare chromosome conditions, a lack of longitudinal data often makes it difficult to provide anticipatory guidance to these families. The objective of this study is to describe the lifespan, educational attainment, living situation, and behavioral phenotype of adults with chromosome 18 abnormalities. The Chromosome 18 Clinical Research Center has enrolled 483 individuals with one of the following conditions: 18q-, 18p-, Tetrasomy 18p, and Ring 18. As a part of the ongoing longitudinal study, we collect data on living arrangements, educational level attained, and employment status as well as data on executive functioning and behavioral skills on an annual basis. Within our cohort, 28 of the 483 participants have died, the majority of whom have deletions encompassing the TCF4 gene or who have unbalanced rearrangement involving other chromosomes. Data regarding the cause of and age at death are presented. We also report on the living situation, educational attainment, and behavioral phenotype of the 151 participants over the age of 18. In general, educational level is higher for people with all these conditions than implied by the early literature, including some that received post-high school education. In addition, some individuals are able to live independently, though at this point they represent a minority of patients. Data on executive function and behavioral phenotype are also presented. Taken together, these data provide insight into the long-term outcome for individuals with a chromosome 18 condition. This information is critical in counseling families on the range of potential outcomes for their child. PMID:25403900

  17. Role of Ku80-dependent end-joining in delayed genomic instability in mammalian cells surviving ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Keiji, E-mail: kzsuzuki@nagasaki-u.ac.jp [Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Kodama, Seiji [Research Institute for Advanced Science and Technology, Osaka Prefecture University, 1-2 Gakuen-machi, Sakai 599-8570 (Japan); Watanabe, Masami [Kyoto University Research Reactor Institute, Kumatori-cho Sennan-gun, Osaka 590-0494 (Japan)

    2010-01-05

    Ionizing radiation induces delayed destabilization of the genome in the progenies of surviving cells. This phenomenon, which is called radiation-induced genomic instability, is manifested by delayed induction of radiation effects, such as cell death, chromosome aberration, and mutation in the progeny of cells surviving radiation exposure. Previously, there was a report showing that delayed cell death was absent in Ku80-deficient Chinese hamster ovary (CHO) cells, however, the mechanism of their defect has not been determined. We found that delayed induction of DNA double strand breaks and chromosomal breaks were intact in Ku80-deficient cells surviving X-irradiation, whereas there was no sign for the production of chromosome bridges between divided daughter cells. Moreover, delayed induction of dicentric chromosomes was significantly compromised in those cells compared to the wild-type CHO cells. Reintroduction of the human Ku86 gene complimented the defective DNA repair and recovered delayed induction of dicentric chromosomes and delayed cell death, indicating that defective Ku80-dependent dicentric induction was the cause of the absence of delayed cell death. Since DNA-PKcs-defective cells showed delayed phenotypes, Ku80-dependent illegitimate rejoining is involved in delayed impairment of the integrity of the genome in radiation-survived cells.

  18. Making chromosome abnormalities treatable conditions.

    Science.gov (United States)

    Cody, Jannine DeMars; Hale, Daniel Esten

    2015-09-01

    Individuals affected by the classic chromosome deletion syndromes which were first identified at the beginning of the genetic age, are now positioned to benefit from genomic advances. This issue highlights five of these conditions (4p-, 5p-, 11q-, 18p-, and 18q-). It focuses on the increased in understanding of the molecular underpinnings and envisions how these can be transformed into effective treatments. While it is scientifically exciting to see the phenotypic manifestations of hemizygosity being increasingly understood at the molecular and cellular level, it is even more amazing to consider that we are now on the road to making chromosome abnormalities treatable conditions. PMID:26351122

  19. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes. PMID:26111960

  20. GENETIC INSTABILITY IN CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    赵旻; 伍欣星; 邱小萍; 李晖; 戴天力; 谭云

    2002-01-01

    Objective: The role of human papillomavirus (HPV) in the development of cervical carcinoma has been clearly established but other factors could be involved in cervical tumorigenesis such as loss of heterozygosity (LOH) and microsatellite instability (MI). The aim of the present study was to investigate the genetic instability in cervical carcinoma tissues and provide evidence for discoveringnew tumor suppressor genes and screening diagnostic molecular marker of cervical carcinoma. Methods: Fifty primary cervical carcinoma samples from high-incidence area were analyzed by PCR for HPV16 infection, LOH and microsatellite instability. Results: HPV16 was detected in 88% of the cases. Sixty-six percent of total cases showed LOH with no more than 3 different loci per case. The highest frequency of the allelic loss was found in D18S474 (18q21, 40.5%). MI was detected in 4 cases (8%) only. Conclusion: Different percentages of LOH on specific chromosomal regions were found and MI was very infrequent in cervical carcinoma. The putative suppressor gene(s) could be located on specific chromosome regions such as 18q, and genetic instability could be involved in cervical tumorigenesis.

  1. Shoulder instability

    International Nuclear Information System (INIS)

    Shoulder instability is a common clinical feature leading to recurrent pain and limitated range of motion within the glenohumeral joint. Instability can be due a single traumatic event, general joint laxity or repeated episodes of microtrauma. Differentiation between traumatic and atraumatic forms of shoulder instability requires careful history and a systemic clinical examination. Shoulder laxity has to be differentiated from true instability followed by the clinical assessment of direction and degree of glenohumeral translation. Conventional radiography and CT are used for the diagnosis of bony lesions. MR imaging and MR arthrography help in the detection of soft tissue affection, especially of the glenoid labrum and the capsuloligamentous complex. The most common lesion involving the labrum is the anterior labral tear, associated with capsuloperiostal stripping (Bankart lesion). A number of variants of the Bankart lesion have been described, such as ALPSA, SLAP or HAGL lesions. The purpose of this review is to highlight different forms of shoulder instability and its associated radiological findings with a focus on MR imaging. (orig.)

  2. Role of oxidative DNA damage in genome instability and cancer

    International Nuclear Information System (INIS)

    Inactivation of mismatch repair (MMR) is associated with a dramatic genomic instability that is observed experimentally as a mutator phenotype and micro satellite instability (MSI). It has been implicit that the massive genetic instability in MMR defective cells simply reflects the accumulation of spontaneous DNA polymerase errors during DNA replication. We recently identified oxidation damage, a common threat to DNA integrity to which purines are very susceptible, as an important cofactor in this genetic instability

  3. Beam Instabilities

    CERN Document Server

    Rumolo, G

    2014-01-01

    When a beam propagates in an accelerator, it interacts with both the external fields and the self-generated electromagnetic fields. If the latter are strong enough, the interplay between them and a perturbation in the beam distribution function can lead to an enhancement of the initial perturbation, resulting in what we call a beam instability. This unstable motion can be controlled with a feedback system, if available, or it grows, causing beam degradation and loss. Beam instabilities in particle accelerators have been studied and analysed in detail since the late 1950s. The subject owes its relevance to the fact that the onset of instabilities usually determines the performance of an accelerator. Understanding and suppressing the underlying sources and mechanisms is therefore the key to overcoming intensity limitations, thereby pushing forward the performance reach of a machine.

  4. Genetic and Epigenetic Changes in Chromosomally Stable and Unstable Progeny of Irradiated Cells

    Energy Technology Data Exchange (ETDEWEB)

    Baulch, Janet E.; Aypar, Umut; Waters, Katrina M.; Yang, Austin; Morgan, William F.

    2014-09-24

    Radiation induced genomic instability is a well-studied phenomenon, the underlying mechanisms of which are poorly understood. Persistent oxidative stress, mitochondrial dysfunction, elevated cytokine levels and epigenetic changes are among the mechanisms invoked in the perpetuation of the phenotype. To determine whether epigenetic aberrations affect genomic instability we measured DNA methylation, mRNA and microRNA (miR) levels in well characterized chromosomally stable and unstable clonally expanded single cell survivors of irradiation. While no changes in DNA methylation were observed for the gene promoters evaluated, increased LINE-1 methylation was observed for two unstable clones (LS12, CS9) and decreased Alu element methylation was observed for the other two unstable clones (115, Fe5.0-8). These relationships also manifested for mRNA and miR expression. mRNA identified for the LS12 and CS9 clones were most similar to each other (261 mRNA), while the 115 and Fe5.0-8 clones were more similar to each other, and surprisingly also similar to the two stable clones, 114 and 118 (286 mRNA among these four clones). Pathway analysis showed enrichment for pathways involved in mitochondrial function and cellular redox, themes routinely invoked in genomic instability. The commonalities between the two subgroups of clones were also observed for miR. The number of miR for which anti-correlated mRNA were identified suggests that these miR exert functional effects in each clone. The results of this study demonstrate significant genetic and epigenetic changes in unstable cells, but similar changes almost equally common in chromosomally stable cells. Possible conclusions might be that the chromosomally stable clones have some other form of instability, or that some of the observed changes represent a sort of radiation signature for and that other changes are related to genomic instability. Irrespective, these findings again suggest that a spectrum of changes both drive genomic

  5. Chromosome number evolution in skippers (Lepidoptera, Hesperiidae).

    Science.gov (United States)

    Lukhtanov, Vladimir A

    2014-01-01

    Lepidoptera (butterflies and moths), as many other groups of animals and plants, simultaneously represent preservation of ancestral karyotype in the majority of families with a high degree of chromosome number instability in numerous independently evolved phylogenetic lineages. However, the pattern and trends of karyotype evolution in some Lepidoptera families are poorly studied. Here I provide a survey of chromosome numbers in skippers (family Hesperiidae) based on intensive search and analysis of published data. I demonstrate that the majority of skippers preserve the haploid chromosome number n=31 that seems to be an ancestral number for the Hesperiidae and the order Lepidoptera at whole. However, in the tribe Baorini the derived number n=16 is the most typical state which can be used as a (syn)apomorphic character in further phylogenetic investigations. Several groups of skippers display extreme chromosome number variations on within-species (e.g. the representatives of the genus Carcharodus Hübner, [1819]) and between-species (e.g. the genus Agathymus Freeman, 1959) levels. Thus, these groups can be used as model systems for future analysis of the phenomenon of chromosome instability. Interspecific chromosomal differences are also shown to be useful for discovering and describing new cryptic species of Hesperiidae representing in such a way a powerful tool in biodiversity research. Generally, the skipper butterflies promise to be an exciting group that will significantly contribute to the growing knowledge of patterns and processes of chromosome evolution. PMID:25610542

  6. Chromosome number evolution in skippers (Lepidoptera, Hesperiidae

    Directory of Open Access Journals (Sweden)

    Vladimir Lukhtanov

    2014-11-01

    Full Text Available Lepidoptera (butterflies and moths, as many other groups of animals and plants, simultaneously represent preservation of ancestral karyotype in the majority of families with a high degree of chromosome number instability in numerous independently evolved phylogenetic lineages. However, the pattern and trends of karyotype evolution in some Lepidoptera families are poorly studied. Here I provide a survey of chromosome numbers in skippers (family Hesperiidae based on intensive search and analysis of published data. I demonstrate that the majority of skippers preserve the haploid chromosome number n=31 that seems to be an ancestral number for the Hesperiidae and the order Lepidoptera at whole. However, in the tribe Baorini the derived number n=16 is the most typical state which can be used as a (synapomorphic character in further phylogenetic investigations. Several groups of skippers display extreme chromosome number variations on within-species (e.g. the representatives of the genus Carcharodus Hübner, [1819] and between-species (e.g. the genus Agathymus Freeman, 1959 levels. Thus, these groups can be used as model systems for future analysis of the phenomenon of chromosome instability. Interspecific chromosomal differences are also shown to be useful for discovering and describing new cryptic species of Hesperiidae representing in such a way a powerful tool in biodiversity research. Generally, the skipper butterflies promise to be an exciting group that will significantly contribute to the growing knowledge of patterns and processes of chromosome evolution.

  7. A dominant negative mutant of TLK1 causes chromosome missegregation and aneuploidy in normal breast epithelial cells

    Directory of Open Access Journals (Sweden)

    Williams Briana

    2003-10-01

    Full Text Available Abstract Background In Arabidopsis thaliana, the gene Tousled encodes a protein kinase of unknown function, but mutations in the gene lead to flowering and leaf morphology defects. We have recently cloned a mammalian Tousled-Like Kinase (TLK1B and found that it phosphorylates specifically histone H3, in vitro and in vivo. We now report the effects that overexpression of a kinase-dead mutant of TLK1B mediates in a normal diploid cell line. Results Expression of a kinase-dead mutant resulted in reduction of phosphorylated histone H3, which could have consequences in mitotic segregation of chromosomes. When analyzed by FACS and microscopy, these cells displayed high chromosome number instability and aneuploidy. This phenomenon was accompanied by less condensed chromosomes at mitosis; failure of a number of chromosomes to align properly on the metaphase plate; failure of some chromosomes to attach to microtubules; and the occasional presentation of two bipolar spindles. We also used a different method (siRNA to reduce the level of endogenous TLK1, but in this case, the main result was a strong block of cell cycle progression suggesting that TLK1 may also play a role in progression from G1. This block in S phase progression could also offer a different explanation of some of the later mitotic defects. Conclusions TLK1 has a function important for proper chromosome segregation and maintenance of diploid cells at mitosis in mammalian cells that could be mediated by reduced phosphorylation of histone H3 and condensation of chromosomes, although other explanations to the phenotype are possible.

  8. Chromosome Microarray.

    Science.gov (United States)

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104

  9. Genome organization, instabilities, stem cells, and cancer

    Directory of Open Access Journals (Sweden)

    Senthil Kumar Pazhanisamy

    2009-01-01

    Full Text Available It is now widely recognized that advances in exploring genome organization provide remarkable insights on the induction and progression of chromosome abnormalities. Much of what we know about how mutations evolve and consequently transform into genome instabilities has been characterized in the spatial organization context of chromatin. Nevertheless, many underlying concepts of impact of the chromatin organization on perpetuation of multiple mutations and on propagation of chromosomal aberrations remain to be investigated in detail. Genesis of genome instabilities from accumulation of multiple mutations that drive tumorigenesis is increasingly becoming a focal theme in cancer studies. This review focuses on structural alterations evolve to raise a variety of genome instabilities that are manifested at the nucleotide, gene or sub-chromosomal, and whole chromosome level of genome. Here we explore an underlying connection between genome instability and cancer in the light of genome architecture. This review is limited to studies directed towards spatial organizational aspects of origin and propagation of aberrations into genetically unstable tumors.

  10. Persistent genetic instability induced by synergistic interaction between x-irradiation and 6-thioguanine

    International Nuclear Information System (INIS)

    Clonal karyotypic analysis was performed using G-banding on four groups of clones derived from TK6 human lymphoblasts: 25 HPRT- total gene deletion mutants induced by exposure to 2 Gy of x-rays; 8 spontaneous HPRT- total gene deletion mutants; 25 clones irradiated with 2 Gy, not selected with 6-thioguanine. Ten to twenty metaphases were examined for each clone. Extensive karyotypic heterogeneity was observed among x-ray induced HPRT - mutants involving translocations, deletions, duplications and aneuploidy; recovery of chromosomal aberrations and karyotypic heterogeneity was greater than the additive effects of clones treated with x-irradiation or 6-thioguanine alone. This synergistic interaction between x-irradiation and 6-thioguanine was observed despite a 7 day phenotypic expression interval between exposure to the two agents. Thus, x-irradiated TK6 cells appear to be persistently hypersensitive to the induction of genetic instability. Several mutants appeared to exhibit evidence of clonal evolution since aberrant chromosomes observed in one metaphase, were found to be further modified in other metaphases. In order to determine if genetic instability, identified by clonal karyotypic heterogeneity, affected specific locus mutation rates, we utilized the heterozygous thymidine kinase (tk) locus as a genetic marker. Four x-ray induced HPRT- mutants with extensive karyotypic heterogeneity, exhibited mutation rates at tk ranging from 5 to 8 fold higher than the parental TK6 cells. Further analysis, using fractionated low dose radiation exposure, is currently in progress

  11. Phenotypic plasticity in Drosophila pigmentation caused by temperature sensitivity of a chromatin regulator network.

    Directory of Open Access Journals (Sweden)

    Jean-Michel Gibert

    2007-02-01

    Full Text Available Phenotypic plasticity is the ability of a genotype to produce contrasting phenotypes in different environments. Although many examples have been described, the responsible mechanisms are poorly understood. In particular, it is not clear how phenotypic plasticity is related to buffering, the maintenance of a constant phenotype against genetic or environmental variation. We investigate here the genetic basis of a particularly well described plastic phenotype: the abdominal pigmentation in female Drosophila melanogaster. Cold temperature induces a dark pigmentation, in particular in posterior segments, while higher temperature has the opposite effect. We show that the homeotic gene Abdominal-B (Abd-B has a major role in the plasticity of pigmentation in the abdomen. Abd-B plays opposite roles on melanin production through the regulation of several pigmentation enzymes. This makes the control of pigmentation very unstable in the posterior abdomen, and we show that the relative spatio-temporal expression of limiting pigmentation enzymes in this region of the body is thermosensitive. Temperature acts on melanin production by modulating a chromatin regulator network, interacting genetically with the transcription factor bric-à-brac (bab, a target of Abd-B and Hsp83, encoding the chaperone Hsp90. Genetic disruption of this chromatin regulator network increases the effect of temperature and the instability of the pigmentation pattern in the posterior abdomen. Colocalizations on polytene chromosomes suggest that BAB and these chromatin regulators cooperate in the regulation of many targets, including several pigmentation enzymes. We show that they are also involved in sex comb development in males and that genetic destabilization of this network is also strongly modulated by temperature for this phenotype. Thus, we propose that phenotypic plasticity of pigmentation is a side effect reflecting a global impact of temperature on epigenetic mechanisms

  12. Effect of the Major Repeat Sequence on Chromosome Loss in Candida albicans

    OpenAIRE

    Lephart, Paul R.; Chibana, Hiroji; Magee, Paul T.

    2005-01-01

    The major repeat sequence (MRS) is found at least once on all but one chromosome in Candida albicans, but as yet it has no known relation to the phenotype. The MRS affects karyotypic variation by serving as a hot spot for chromosome translocation and by expanding and contracting internal repeats, thereby changing chromosome length. Thus, MRSs on different chromosomes and those on chromosome homologues can differ in size. We proposed that the MRS's unique repeat structure and, more specificall...

  13. Adaptation through chromosomal inversions in Anopheles

    Directory of Open Access Journals (Sweden)

    Diego eAyala

    2014-05-01

    Full Text Available Chromosomal inversions have been repeatedly involved in local adaptation in a large number of animals and plants. The ecological and behavioral plasticity of Anopheles species - human malaria vectors - is mirrored by high amounts of polymorphic inversions. The adaptive significance of chromosomal inversions has been consistently attested by strong and significant correlations between their frequencies and a number of phenotypic traits. Here, we provide an extensive literature review of the different adaptive traits associated with chromosomal inversions in the genus Anopheles. Traits having important consequences for the success of present and future vector control measures, such as insecticide resistance and behavioral changes, are discussed.

  14. Exceptional Complex Chromosomal Rearrangements in Three Generations

    Directory of Open Access Journals (Sweden)

    Hannie Kartapradja

    2015-01-01

    Full Text Available We report an exceptional complex chromosomal rearrangement (CCR found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband’s mother, which was confirmed using the whole chromosome painting (WCP FISH. High resolution whole genome microarray analysis of DNA from the proband’s mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother’s and grandmother’s CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations.

  15. Chromosome damage evolution after low and high LET irradiation

    Science.gov (United States)

    Andreev, Sergey; Eidelman, Yuri

    Ionizing radiation induces DNA and chromatin lesions which are converted to chromosome lesions detected in the first post-irradiation mitosis by classic cytogenetic techniques as chromosomal aberrations (CAs). These techniques allow to monitor also delayed aberrations observed after many cell generations post-irradiation - the manifestation of chromosomal instability phenotype (CIN). The problem discussed is how to predict time evolution from initial to delayed DNA/chromosome damage. To address this question, in the present work a mechanistic model of CIN is elaborated which integrates pathways of (*) DNA damage induction and its conversion to chromosome lesions (aberrations), (**) lesion transmission and generation through cell cycles. Delayed aberrations in subsequent cycles are formed in the model owing to two pathways, DNA damage generation de novo as well as CA transmission from previous cycles. DNA damage generation rate is assumed to consist of bystander and non-bystander components. Bystander signals impact all cells roughly equally, whereas non-bystander DSB generation rate differs for the descendants of unirradiated and irradiated cells. Monte Carlo simulation of processes underlying CIN allows to predict the time evolution of initial radiation-induced damage - kinetics curve for delayed unstable aberrations (dicentrics) together with dose response and RBE as a function of time after high vs low LET irradiation. The experimental data for radiation-induced CIN in TK6 lymphoblastoid cells and human lymphocytes irradiated with low (gamma) and high (Fe, C) LET radiation are analyzed on the basis of the proposed model. One of the conclusions is that without bystander signaling, just taking into account the initial DNA damage and non-bystander DSB generation, it is impossible to describe the available experimental data for high-LET-induced CIN. The exact contribution of bystander effects for high vs low LET remains unknown, but the relative contribution may be

  16. X-chromosome workshop.

    Science.gov (United States)

    Paterson, A D

    1998-01-01

    Researchers presented results of ongoing research to the X-chromosome workshop of the Fifth World Congress on Psychiatric Genetics, covering a wide range of disorders: X-linked infantile spasms; a complex phenotype associated with deletions of Xp11; male homosexuality; degree of handedness; bipolar affective disorder; schizophrenia; childhood onset psychosis; and autism. This report summarizes the presentations, as well as reviewing previous studies. The focus of this report is on linkage findings for schizophrenia and bipolar disorder from a number of groups. For schizophrenia, low positive lod scores were obtained for markers DXS991 and DXS993 from two studies, although the sharing of alleles was greatest from brother-brother pairs in one study, and sister-sister in the other. Data from the Irish schizophrenia study was also submitted, with no strong evidence for linkage on the X chromosome. For bipolar disease, following the report of a Finnish family linked to Xq24-q27, the Columbia group reported some positive results for this region from 57 families, however, another group found no evidence for linkage to this region. Of interest, is the clustering of low positive linkage results that point to regions for possible further study. PMID:9686435

  17. Chromosome segregation errors: a double-edged sword

    NARCIS (Netherlands)

    Janssen, A.

    2012-01-01

    Unequal separation of the mother cells’ DNA over its two daughter cells upon cell division is a prevalent phenotype found in cancer cells. This imbalanced nuclear division manifests itself as chromosome segregation errors in the final phases of Mitosis. Chromosome unstable (CIN) cancer cells continu

  18. Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy

    OpenAIRE

    Kohlhase, J; Schubert, L.; Liebers, M; Rauch, A; Becker, K.; Mohammed, S; Newbury-Ecob, R.; REARDON, W.

    2003-01-01

    We have recently shown that Okihiro syndrome results from mutation in the putative zinc finger transcription factor gene SALL4 on chromosome 20q13.13-13.2. There is considerable overlap of clinical features of Okihiro syndrome with other conditions, most notably Holt-Oram syndrome, a condition in part resulting from mutation of the TBX5 locus, as well as acro-renal-ocular syndrome. We analysed further families/patients with the clinical diagnosis of Holt-Oram syndrome and acro-renal-ocular sy...

  19. Genome instability and aging.

    Science.gov (United States)

    Vijg, Jan; Suh, Yousin

    2013-01-01

    Genome instability has long been implicated as the main causal factor in aging. Somatic cells are continuously exposed to various sources of DNA damage, from reactive oxygen species to UV radiation to environmental mutagens. To cope with the tens of thousands of chemical lesions introduced into the genome of a typical cell each day, a complex network of genome maintenance systems acts to remove damage and restore the correct base pair sequence. Occasionally, however, repair is erroneous, and such errors, as well as the occasional failure to correctly replicate the genome during cell division, are the basis for mutations and epimutations. There is now ample evidence that mutations accumulate in various organs and tissues of higher animals, including humans, mice, and flies. What is not known, however, is whether the frequency of these random changes is sufficient to cause the phenotypic effects generally associated with aging. The exception is cancer, an age-related disease caused by the accumulation of mutations and epimutations. Here, we first review current concepts regarding the relationship between DNA damage, repair, and mutation, as well as the data regarding genome alterations as a function of age. We then describe a model for how randomly induced DNA sequence and epigenomic variants in the somatic genomes of animals can result in functional decline and disease in old age. Finally, we discuss the genetics of genome instability in relation to longevity to address the importance of alterations in the somatic genome as a causal factor in aging and to underscore the opportunities provided by genetic approaches to develop interventions that attenuate genome instability, reduce disease risk, and increase life span. PMID:23398157

  20. Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana

    OpenAIRE

    Ji, X.

    2014-01-01

    Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. I studied numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. The large genomic changes are important for gene balance control, gene expression and regulation, and may affect the plant’s phenotype. Moreover, chromosome changes, in particular polyploidy, inversions and translocations play a signif...

  1. Genetic instability and strain degeneration in Streptomyces rimosus.

    OpenAIRE

    Gravius, B; Bezmalinović, T; Hranueli, D.; Cullum, J

    1993-01-01

    During a strain selection program to improve oxytetracycline production in Streptomyces rimosus R6, isolates that showed extreme morphological instability appeared. Propagation via spores gave much higher instability than did propagation via mycelial fragments. Five phenotypic traits were affected: sporulation, pigmentation, colony morphology, oxytetracycline production, and oxytetracycline resistance. The variants were classified on the basis of oxytetracycline resistance into three classes....

  2. Using Mouse Models to Explore Genotype-Phenotype Relationship in Down Syndrome

    Science.gov (United States)

    Salehi, Ahmad; Faizi, Mehrdad; Belichenko, Pavel V.; Mobley, William C.

    2007-01-01

    Down Syndrome (DS) caused by trisomy 21 is characterized by a variety of phenotypes and involves multiple organs. Sequencing of human chromosome 21 (HSA21) and subsequently of its orthologues on mouse chromosome 16 have created an unprecedented opportunity to explore the complex relationship between various DS phenotypes and the extra copy of…

  3. Mitotic chromosome structure

    International Nuclear Information System (INIS)

    Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.

  4. Analysis of a valuable chromosome rearrangement induced by ionizing radiations in a cultivated chili pepper line (Capsicum baccatum var. Pendulum - solanaceae)

    International Nuclear Information System (INIS)

    Capsicum (chili peppers) is an important genus including five crop species consumed by man as spice and food. Most contributions about induced mutagenesis in Capsicum refer to gene mutations while induced changes at chromosome level are scarce. We started a program to achieve chromosome rearrangements by ionizing radiations in C. baccatum variety pendulum cultivar 'cayenne', which has a karyotype with 2n=2x=24, 11 metacentrics + 1 subtelocentric pairs, 4 pairs (1, 3, 10, 12) carrying nucleolar organizing regions (NORs) and associated satellites in short arm. Seeds were treated with different acute doses of X-rays developing M1-4 generations. A rearranged chromosome carrying NORs in both arms was found in M2 seedlings from the only surviving M1 plant after a 300 Gy treatment. The structural change was analyzed by: 1) Feulgen's staining to observe chromosome number, size and shape; 2) silver impregnation to detect active NORs; 3) fluorescent chromosome banding to reveal type and position of constitutive heterochromatic regions [triple staining with chromomycin/distamycin/4-6-diamidino-2-phenylindole (CMA/DA/DAPI)]; 4) fluorescent in situ hybridization with 18S- 25S rDNA repeated sequence as probe. A reciprocal translocation between two NOR-bearing chromosomes in the M1 plant has occurred, which gave viable progeny carrying the chromosomal interchange without any deviating phenotype after four generations, nor in heterozygous neither in homozygous condition. The lack of chromosome instability suggests a small reciprocal interchange between a member of pair 1 and of 3, both carrying active NORs in shorts arms. The results of this rearrangement were two chromosomes with little change in size, one of them easily recognized by the presence of NORs and associated CMA+/DAPI- heterochromatin in both arms. As the translocation here reported produced a conspicuous rearranged marker chromosome, the obtained plant line is considered very valuable for studies on chromosome

  5. Evolutionary interaction between W/Y chromosome and transposable elements.

    Science.gov (United States)

    Śliwińska, Ewa B; Martyka, Rafał; Tryjanowski, Piotr

    2016-06-01

    The W/Y chromosome is unique among chromosomes as it does not recombine in its mature form. The main side effect of cessation of recombination is evolutionary instability and degeneration of the W/Y chromosome, or frequent W/Y chromosome turnovers. Another important feature of W/Y chromosome degeneration is transposable element (TEs) accumulation. Transposon accumulation has been confirmed for all W/Y chromosomes that have been sequenced so far. Models of W/Y chromosome instability include the assemblage of deleterious mutations in protein coding genes, but do not include the influence of transposable elements that are accumulated gradually in the non-recombining genome. The multiple roles of genomic TEs, and the interactions between retrotransposons and genome defense proteins are currently being studied intensively. Small RNAs originating from retrotransposon transcripts appear to be, in some cases, the only mediators of W/Y chromosome function. Based on the review of the most recent publications, we present knowledge on W/Y evolution in relation to retrotransposable element accumulation. PMID:27000053

  6. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J;

    1983-01-01

    A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were...... unbalanced chromosome abnormality in group A (women with elevated risk) is significantly higher than in group B + C (women without elevated risk) (relative risk 2.4). Women with a known familial translocation and women 40 years or more have a relative risk of 5.7 of having an unbalanced chromosome......The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...

  7. Model selection emphasises the importance of non-chromosomal information in genetic studies.

    Directory of Open Access Journals (Sweden)

    Reda Rawi

    Full Text Available Ever since the case of the missing heritability was highlighted some years ago, scientists have been investigating various possible explanations for the issue. However, none of these explanations include non-chromosomal genetic information. Here we describe explicitly how chromosomal and non-chromosomal modifiers collectively influence the heritability of a trait, in this case, the growth rate of yeast. Our results show that the non-chromosomal contribution can be large, adding another dimension to the estimation of heritability. We also discovered, combining the strength of LASSO with model selection, that the interaction of chromosomal and non-chromosomal information is essential in describing phenotypes.

  8. Molecular Mechanisms of Radiation-Induced Genomic Instability in Human Cells

    Energy Technology Data Exchange (ETDEWEB)

    Howard L. Liber; Jeffrey L. Schwartz

    2005-10-31

    There are many different model systems that have been used to study chromosome instability. What is clear from all these studies is that conclusions concerning chromosome instability depend greatly on the model system and instability endpoint that is studied. The model system for our studies was the human B-lymphoblastoid cell line TK6. TK6 was isolated from a spontaneously immortalized lymphoblast culture. Thus there was no outside genetic manipulation used to immortalize them. TK6 is a relatively stable p53-normal immortal cell line (37). It shows low gene and chromosome mutation frequencies (19;28;31). Our general approach to studying instability in TK6 cells has been to isolate individual clones and analyze gene and chromosome mutation frequencies in each. This approach maximizes the possibility of detecting low frequency events that might be selected against in mass cultures.

  9. B-cell acute lymphoblastic leukemia with t(4;11(q21;q23 in a young woman: evolution into mixed phenotype acute leukemia with additional chromosomal aberrations in the course of therapy

    Directory of Open Access Journals (Sweden)

    Giovanni Carulli

    2012-09-01

    Full Text Available About 5% of adult B-cell acute lymphoblastic leukemias (B-ALL are characterized by t(4;11(q21;q23, which confers peculiar features to this B-ALL subtype, including a very immature immunophenotype and poor prognosis. We describe the case of a 21-year-old female who presented with B-ALL carrying the t(4;11(q21;q23 and blasts positive for CD19, TdT, CD79a, CD38, HLA-DR. Before completing the Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone therapy regimen, the B-cell leukemic clone still was detected, but an additional leukemic clone appeared, with morphology and immunophenotype (CD13, CD33, CD64, CD38, CD56, CD15, CD4dim compatible with derivation from the myeloid/monocytic lineage. Karyotype showed the co-existence of three cell lines, with persistence of t(4;11(q21;q23 and appearance of +8,+12,+13 and two der(4. The patient died because of disseminated intravas- cular coagulation. Our report describes a rare, possible evolution of such a subtype of B-ALL, with transformation into mixed phenotype acute leukemia in the course of therapy. This finding suggests a blast cell derivation from a common lymphoid/monocytic precursor leading to a final bilineal acute leukemia.

  10. Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age

    OpenAIRE

    Živković, Lada; Spremo-Potparević, Biljana; Plećaš-Solarović, Bosiljka; Djelić, Ninoslav; Ocić, Gordana; Smiljković, Predrag; Siedlak, Sandra L.; Smith, Mark A.; Bajić, Vladan

    2010-01-01

    Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X ch...

  11. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  12. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in si

  13. Understanding the basis for Down syndrome phenotypes.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Down syndrome is a collection of features that are caused by trisomy for human Chromosome 21. While elevated transcript levels of the more than 350 genes on the chromosome are primarily responsible, it is likely that multiple genetic mechanisms underlie the numerous ways in which development and function diverge in individuals with trisomy 21 compared to euploid individuals. We consider genotype-phenotype interactions with the goal of producing working concepts that will be useful for approaches to ameliorate the effects of trisomy.

  14. Mathematical Modeling of Carcinogenesis Based on Chromosome Aberration Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-bo Li

    2009-01-01

    Objective: The progression of human cancer is characterized by the accumulation of genetic instability. An increasing number of experimental genetic molecular techniques have been used to detect chromosome aberrations. Previous studies on chromosome abnormalities often focused on identifying the frequent loci of chromosome alterations, but rarely addressed the issue of interrelationship of chromosomal abnormalities. In the last few years, several mathematical models have been employed to construct models of carcinogenesis, in an attempt to identify the time order and cause-and-effect relationship of chromosome aberrations. The principles and applications of these models are reviewed and compared in this paper. Mathematical modeling of carcinogenesis can contribute to our understanding of the molecular genetics of tumor development, and identification of cancer related genes, thus leading to improved clinical practice of cancer.

  15. Genomic heterogeneity and instability in colorectal cancer: spectral karyotyping, glutathione transferase-Ml and ras.

    Science.gov (United States)

    Bartos, Jeremy D; Stoler, Daniel L; Matsui, Sei-ichi; Swede, Helen; Willmott, Lyndsay J; Sait, Sheila N; Petrelli, Nicholas J; Anderson, Garth R

    2004-12-21

    Genomic instability in cancer is frequently described as being either chromosomal instability or microsatellite instability, although when events within chromosomes are monitored, extensive intrachromosomal instability is also found. Spectral karyotyping was used to visualize how extensively genomic instability gives rise to intratumor genomic heterogeneity in sporadic colorectal carcinomas. Two factors were then examined which might relate to intrachromosomal instability in colorectal cancers: the presence of the glutathione transferase-Ml gene to detoxify potential carcinogens, and the presence of activated ras which has been associated with chromosomal instability when first expressed. Intrachromosomal genomic instability was previously determined by inter-(simple sequence repeat) PCR (inter-SSR PCR) and by fractional allelic loss rate for 348 markers. GSTM1 status was determined for each of 49 tumors through use of specific PCR, and 28 of the tumors showed the GSTM1 null genotype. A significant association was found between GSTMl-null status and elevated inter-(simple sequence repeat) PCR instability. In contrast, no association was found with fractional allelic loss rate. The first exons of the K-ras and H-ras oncogenes were sequenced in 72 colorectal cancers; 19 of the tumors had a mutation in codon 12 of the K-ras gene (24.5%), but no H-ras mutations were found. A weak correlation (p=0.10) was observed between mutant K-ras and inter-(simple sequence repeat) PCR genomic instability, and no association existed with fractional allelic loss rate. PMID:15542115

  16. Variabilidade fenotípica na síndrome do cromossomo supernumerário der(22t(11;22 (síndrome de Emanuel Phenotypical variability in supernumerary chromosome der(22t(11;22 syndrome (Emanuel syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano M. Rosa

    2010-09-01

    Full Text Available OBJETIVO: Relatar dois pacientes com a síndrome de Emanuel (SE ou cromossomo supernumerário der(22t(11;22, secundária a translocações balanceadas familiares, apresentando fenótipos distintos. DESCRIÇÃO DE CASO: O primeiro paciente é uma menina branca de cinco anos de idade, apresentando hipotonia, atraso no desenvolvimento neuropsicomotor, movimentos estereotipados, microcefalia, ptose palpebral, orelhas proeminentes, fossetas e apêndices pré-auriculares, e imperfuração anal. As avaliações adicionais identificaram hipoplasia cerebral e estenose da válvula pulmonar. Possuía história também de laringotraqueomalácia e fenda palatina. O segundo paciente é um menino branco de seis meses de idade com hipotonia, movimentos coreoatetóticos, déficit de crescimento, microcefalia, microssomia hemifacial, fenda palatina, microtia, apêndices pré-auriculares e polegares proximalmente implantados. A ecocardiografia demonstrou estenose da válvula pulmonar, comunicação interatrial e interventricular, persistência do canal arterial e da veia cava superior esquerda. A radiografia de tórax identificou uma costela cervical. O cariótipo por bandas GTG mostrou a presença, em ambos os pacientes, de um cromossomo adicional der(22t(11;22, secundário a uma translocação balanceada materna no primeiro caso e paterna no segundo caso. COMENTÁRIOS: Apesar de a primeira paciente apresentar achados frequentes da SE, o caso adicional representa a segunda descrição da literatura com um fenótipo de espectro óculo-aurículo-vertebral (EOAV. Assim, ambos salientam a variabilidade clínica observada na SE e a importância da avaliação cariotípica em indivíduos com fenótipo de EOAV.OBEJECTIVE: To report two patients with Emanuel syndrome (ES or supernumerary chromosome der(22t(11;22, secondary to familial balanced translocations, presenting distinct phenotypes. CASES DESCRIPTION: The first patient was a five-year-old white girl presenting

  17. Chromosome polymorphism in a population of ceratitis capitata

    International Nuclear Information System (INIS)

    A morphological chromosomal polymorphism along with the observation of B chromosomes in a natural population of Ceratitis capitata is reported. A variability affecting the centromere size of chromosome 3 is described. The observed B chromosome is minute, heterochromatic and telocentric. The B chromosome was found in the male and female germ cells and it exhibited, in the males, intra-individual numerical variation with OB and IB cells, which suggested a mitotic instability. It was also found, in both sexes, in somatic cells (cerebral ganglia tissue). Only males transmitted the B chromosomes to the progeny. The high rate of transmission suggested a differential utilization of the sperm carrying the B chromosomes or a preferential segregation into secondary spermatocytes. Previously reported linkage relationship between a pupal esterase gene (Est-1) and a pupa colour mutant (nig) has been extended to a line carrying a Y-chromosome (Y,B) shorter than the one previously studied (Y,A). Furthermore, an elaborate crossing scheme has been devised in order to estimate the recombination distances between these two genes and a third one affecting pupal length (lp-1). It is concluded that all three genes are in the same linkage group but Est-1 is far from the other two. In turn, nig and lp-1 are separated by 14.9 map units. It is confirmed that genetic recombination does not regularly occur at high frequency in the male and this frequency is not increased by the varying length of the Y-chromosome. Refs, figs, tabs

  18. Amifostine Protection Against Mitomycin-induced Chromosomal Breakage in Fanconi Anaemia Lymphocytes

    OpenAIRE

    Lopes, Miriam T. P.; Salas, Carlos E.; Fernanda S. G. Kehdy; Camelo, Ricardo M.

    2008-01-01

    Fanconi anaemia (FA) is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF) on basal and mitomycin C (MMC)-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronucle...

  19. DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation.

    OpenAIRE

    Deniz Simsek; Erika Brunet; Sunnie Yan-Wai Wong; Sachin Katyal; Yankun Gao; McKinnon, Peter J.; Jacqueline Lou; Lei Zhang; James Li; Rebar, Edward J; Gregory, Philip D.; Michael C. Holmes; Maria Jasin

    2011-01-01

    International audience Nonhomologous end-joining (NHEJ) is the primary DNA repair pathway thought to underlie chromosomal translocations and other genomic rearrangements in somatic cells. The canonical NHEJ pathway, including DNA ligase IV (Lig4), suppresses genomic instability and chromosomal translocations, leading to the notion that a poorly defined, alternative NHEJ (alt-NHEJ) pathway generates these rearrangements. Here, we investigate the DNA ligase requirement of chromosomal translo...

  20. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    OpenAIRE

    Payne CM; Crowley-Skillicorn C; Bernstein C; Holubec H; Bernstein H

    2011-01-01

    Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated w...

  1. Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells

    OpenAIRE

    Oumar Samassekou; Huiyu Li; Josée Hébert; Aimé Ntwari; Haixia Wang; Catherine Grenier Cliché; Eric Bouchard; Shiang Huang; Ju Yan

    2011-01-01

    Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found th...

  2. Novel Insights into Chromosome Evolution in Birds, Archosaurs, and Reptiles.

    Science.gov (United States)

    Farré, Marta; Narayan, Jitendra; Slavov, Gancho T; Damas, Joana; Auvil, Loretta; Li, Cai; Jarvis, Erich D; Burt, David W; Griffin, Darren K; Larkin, Denis M

    2016-01-01

    Homologous synteny blocks (HSBs) and evolutionary breakpoint regions (EBRs) in mammalian chromosomes are enriched for distinct DNA features, contributing to distinct phenotypes. To reveal HSB and EBR roles in avian evolution, we performed a sequence-based comparison of 21 avian and 5 outgroup species using recently sequenced genomes across the avian family tree and a newly-developed algorithm. We identified EBRs and HSBs in ancestral bird, archosaurian (bird, crocodile, and dinosaur), and reptile chromosomes. Genes involved in the regulation of gene expression and biosynthetic processes were preferably located in HSBs, including for example, avian-specific HSBs enriched for genes involved in limb development. Within birds, some lineage-specific EBRs rearranged genes were related to distinct phenotypes, such as forebrain development in parrots. Our findings provide novel evolutionary insights into genome evolution in birds, particularly on how chromosome rearrangements likely contributed to the formation of novel phenotypes. PMID:27401172

  3. Genomic instability of micronucleated cells revealed by single-cell comparative genomic hybridization.

    NARCIS (Netherlands)

    Imle, A.; Polzer, B.; Alexander, S.; Klein, C.A.; Friedl, P.H.A.

    2009-01-01

    Nuclear variation in size and shape and genomic instability are hallmarks of dedifferentiated cancer cells. Although micronuclei are a typical long-term consequence of DNA damage, their contribution to chromosomal instability and clonal diversity in cancer disease is unclear. We isolated cancer cell

  4. Systematics of shoulder instability

    International Nuclear Information System (INIS)

    Shoulder instability is defined as a symptomatic abnormal motion of the humeral head relative to the glenoid during active shoulder motion. Glenohumeral instabilities are classified according to the causative factors as the pathogenesis of instability plays an important role with respect to treatment options. Instabilities are classified into traumatic and atraumatic instabilities as part of a multidirectional instability syndrome and into microtraumatic instabilities. For diagnostics plain radiographs (''trauma series'') are performed to document shoulder dislocation and its successful repositioning. Direct magnetic resonance (MR) arthrography is the most important imaging modality for delineation of the different injury patterns of the labral-ligamentous complex and bony structures. Monocontrast computed tomography (CT) arthrography with the use of multidetector CT scanners represents an alternative imaging modality; however, MR imaging should be preferred in the work-up of shoulder instabilities due to the mostly younger age of patients. (orig.)

  5. De Novo Pericentric Inversion of Chromosome 9 in Congenital Anomaly

    OpenAIRE

    Jeong, Seon-Yong; Kim, Bo-Young; Yu, Jae Eun

    2010-01-01

    Purpose The pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal variations and has been found in both normal populations and patients with various abnormal phenotypes and diseases. The aim of this study was to re-evaluate the clinical impact of inv(9)(p11q13). Materials and Methods We studied the karyotypes of 431 neonates with congenital anomalies at the Pediatric Clinic in Ajou University Hospital between 2004 and 2008 and retrospectively reviewed...

  6. Step-wise and punctuated genome evolution drive phenotype changes of tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Stepanenko, Aleksei, E-mail: a.a.stepanenko@gmail.com [Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680 (Ukraine); Andreieva, Svitlana; Korets, Kateryna; Mykytenko, Dmytro [Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680 (Ukraine); Huleyuk, Nataliya [Institute of Hereditary Pathology, National Academy of Medical Sciences of Ukraine, Lviv 79008 (Ukraine); Vassetzky, Yegor [CNRS UMR8126, Université Paris-Sud 11, Institut de Cancérologie Gustave Roussy, Villejuif 94805 (France); Kavsan, Vadym [Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680 (Ukraine)

    2015-01-15

    Highlights: • There are the step-wise continuous and punctuated phases of cancer genome evolution. • The system stresses during the different phases may lead to very different responses. • Stable transfection of an empty vector can result in genome and phenotype changes. • Functions of a (trans)gene can be opposite/versatile in cells with different genomes. • Contextually, temozolomide can both promote and suppress tumor cell aggressiveness. - Abstract: The pattern of genome evolution can be divided into two phases: the step-wise continuous phase (step-wise clonal evolution, stable dominant clonal chromosome aberrations (CCAs), and low frequency of non-CCAs, NCCAs) and punctuated phase (marked by elevated NCCAs and transitional CCAs). Depending on the phase, system stresses (the diverse CIN promoting factors) may lead to the very different phenotype responses. To address the contribution of chromosome instability (CIN) to phenotype changes of tumor cells, we characterized CCAs/NCCAs of HeLa and HEK293 cells, and their derivatives after genotoxic stresses (a stable plasmid transfection, ectopic expression of cancer-associated CHI3L1 gene or treatment with temozolomide) by conventional cytogenetics, copy number alterations (CNAs) by array comparative genome hybridization, and phenotype changes by cell viability and soft agar assays. Transfection of either the empty vector pcDNA3.1 or pcDNA3.1-CHI3L1 into 293 cells initiated the punctuated genome changes. In contrast, HeLa-CHI3L1 cells demonstrated the step-wise genome changes. Increased CIN correlated with lower viability of 293-pcDNA3.1 cells but higher colony formation efficiency (CFE). Artificial CHI3L1 production in 293-CHI3L1 cells increased viability and further contributed to CFE. The opposite growth characteristics of 293-CHI3L1 and HeLa-CHI3L1 cells were revealed. The effect and function of a (trans)gene can be opposite and versatile in cells with different genetic network, which is defined by

  7. Step-wise and punctuated genome evolution drive phenotype changes of tumor cells

    International Nuclear Information System (INIS)

    Highlights: • There are the step-wise continuous and punctuated phases of cancer genome evolution. • The system stresses during the different phases may lead to very different responses. • Stable transfection of an empty vector can result in genome and phenotype changes. • Functions of a (trans)gene can be opposite/versatile in cells with different genomes. • Contextually, temozolomide can both promote and suppress tumor cell aggressiveness. - Abstract: The pattern of genome evolution can be divided into two phases: the step-wise continuous phase (step-wise clonal evolution, stable dominant clonal chromosome aberrations (CCAs), and low frequency of non-CCAs, NCCAs) and punctuated phase (marked by elevated NCCAs and transitional CCAs). Depending on the phase, system stresses (the diverse CIN promoting factors) may lead to the very different phenotype responses. To address the contribution of chromosome instability (CIN) to phenotype changes of tumor cells, we characterized CCAs/NCCAs of HeLa and HEK293 cells, and their derivatives after genotoxic stresses (a stable plasmid transfection, ectopic expression of cancer-associated CHI3L1 gene or treatment with temozolomide) by conventional cytogenetics, copy number alterations (CNAs) by array comparative genome hybridization, and phenotype changes by cell viability and soft agar assays. Transfection of either the empty vector pcDNA3.1 or pcDNA3.1-CHI3L1 into 293 cells initiated the punctuated genome changes. In contrast, HeLa-CHI3L1 cells demonstrated the step-wise genome changes. Increased CIN correlated with lower viability of 293-pcDNA3.1 cells but higher colony formation efficiency (CFE). Artificial CHI3L1 production in 293-CHI3L1 cells increased viability and further contributed to CFE. The opposite growth characteristics of 293-CHI3L1 and HeLa-CHI3L1 cells were revealed. The effect and function of a (trans)gene can be opposite and versatile in cells with different genetic network, which is defined by

  8. Trisomy 21 and Facial Developmental Instability

    OpenAIRE

    Starbuck, John M; Cole, Theodore M; Reeves, Roger H.; Richtsmeier, Joan T.

    2013-01-01

    The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the “amplified developmental instability” hypothesis argue that trisomy 21...

  9. Evaluating shoulder instability treatment

    OpenAIRE

    Linde, J. A.

    2016-01-01

    Shoulder instability common occurs. When treated nonoperatively, the resulting societal costs based on health care utilization and productivity losses are significant. Shoulder function can be evaluated using patient reported outcome measurements (PROMs). For shoulder instability, these include the Western Ontario Shoulder Instability index (WOSI) and the Oxford Shoulder Instability Score (OSIS). When translated and validated for the dutch population, both have good measurment properties. Sco...

  10. Earnings instability and tenure

    OpenAIRE

    Cappellari, Lorenzo; Leonardi, Marco

    2007-01-01

    We study the effect of tenure on earnings instability in Italy using two alternative estimation strategies. First we use a descriptive measure of earnings instability and fixed effects regressions. Second, we develop a formal model of earnings dynamics distinguishing permanent from transitory earnings, and exploit variation of tenure and instability over time and across birth cohorts in estimation. We use the two approaches also to evaluate earnings instability associated with temporary contr...

  11. Chimpanzee chromosome 12 is homologous to human chromosome 2q

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Most of the 46 human chromosomes find their counterparts in the 48 chimpanzee chromosomes except for chromosome 2 which has been hypothesized to have been derived from a centric fusion of two chimpanzee acrocentric chromosomes. These two chromosomes correspond to the human chromosomes 2p and 2g. This conclusion is based primarily on chromosome banding techniques, and the somatic cell hybridization technique has also been used. (HLW)

  12. Haploinsufficiency and the sex chromosomes from yeasts to humans

    Directory of Open Access Journals (Sweden)

    Oliver Stephen G

    2011-02-01

    Full Text Available Abstract Background Haploinsufficient (HI genes are those for which a reduction in copy number in a diploid from two to one results in significantly reduced fitness. Haploinsufficiency is increasingly implicated in human disease, and so predicting this phenotype could provide insights into the genetic mechanisms behind many human diseases, including some cancers. Results In the present work we show that orthologues of Saccharomyces cerevisiae HI genes are preferentially retained across the kingdom Fungi, and that the HI genes of S. cerevisiae can be used to predict haploinsufficiency in humans. Our HI gene predictions confirm known associations between haploinsufficiency and genetic disease, and predict several further disorders in which the phenotype may be relevant. Haploinsufficiency is also clearly relevant to the gene-dosage imbalances inherent in eukaryotic sex-determination systems. In S. cerevisiae, HI genes are over-represented on chromosome III, the chromosome that determines yeast's mating type. This may be a device to select against the loss of one copy of chromosome III from a diploid. We found that orthologues of S. cerevisiae HI genes are also over-represented on the mating-type chromosomes of other yeasts and filamentous fungi. In animals with heterogametic sex determination, accumulation of HI genes on the sex chromosomes would compromise fitness in both sexes, given X chromosome inactivation in females. We found that orthologues of S. cerevisiae HI genes are significantly under-represented on the X chromosomes of mammals and of Caenorhabditis elegans. There is no X inactivation in Drosophila melanogaster (increased expression of X in the male is used instead and, in this species, we found no depletion of orthologues to yeast HI genes on the sex chromosomes. Conclusion A special relationship between HI genes and the sex/mating-type chromosome extends from S. cerevisiae to Homo sapiens, with the microbe being a useful model for

  13. Dysregulation of FOXG1 by ring chromosome 14

    DEFF Research Database (Denmark)

    Alosi, Daniela; Klitten, Laura Line; Bak, Mads; Hjalgrim, Helle; Møller, Rikke Steensbjerre; Tommerup, Niels

    2015-01-01

    In this study we performed molecular characterization of a patient with an extra ring chromosome derived from chromosome 14, with severe intellectual disability, epilepsy, cerebral paresis, tetraplegia, osteoporosis and severe thoraco-lumbal scoliosis. Array CGH analysis did not show any genomic...... an interstitial excision where the phenotype is compatible with dysregulation of FOXG1. In turn, the phenotypic overlap between the present case, the FOXG1 syndrome and the r(14) syndrome supports that dysregulation of FOXG1 may contribute to the classical r(14)-syndrome, likely mediated by dynamic...

  14. Lewis phenotype, secretor status, and coeliac disease.

    OpenAIRE

    Dickey, W; Wylie, J D; Collins, J S; Porter, K G; Watson, R G; McLoughlin, J C

    1994-01-01

    Patients who cannot secrete ABO and Lewis blood group antigens into body fluids, an ability controlled by a single gene on chromosome 19, are known to be at increased risk of certain autoimmune diseases associated with human leucocyte antigen (HLA) markers. This study investigated the possibility of an association with coeliac disease using red cell Lewis (Le) blood group phenotype to infer secretor status. Among 73 patients with coeliac disease who had Le a or b antigen, 48% were non-secreto...

  15. Phenotypic impact of genomic structural variation

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Symmons, Orsolya; Spitz, François;

    2013-01-01

    Genomic structural variants have long been implicated in phenotypic diversity and human disease, but dissecting the mechanisms by which they exert their functional impact has proven elusive. Recently however, developments in high-throughput DNA sequencing and chromosomal engineering technology have...... delineating disease-causing elements that are affected by structural variants, and we discuss future directions for research on the functional consequences of structural variants....

  16. Karyotyping analysis of 396 newborns with congenital malformations and chromosomal abnormalities and the associated phenotypes%新生儿先天畸形396例染色体异常核型及其表型临床特征分析

    Institute of Scientific and Technical Information of China (English)

    王红英; 李海波; 何亚香; 杨乃超; 邵雪君; 薛永权

    2014-01-01

    目的 研究新生儿畸形的主要染色体核型及其临床表型.方法 对2006年1月至2012年5月在苏州大学附属儿童医院就诊的396例先天畸形新生儿按常规方法制备外周血淋巴细胞染色体,G显带并进行核型分析;对各型核型异常患儿的临床表型进行统计分析.结果 1.新生儿396例中检出外周血染色体异常核型159例,异常率为40.2%,其中国内外首次报道3例.2.异常核型中以21-三体(唐氏综合征)最为常见,共130例,占81.8%,其中119例为标准型,10例合并涉及D组或G组的罗伯逊易位,1例伴有性染色体异常.3.其他常见异常核型依次为del(5) (p12-14)4例、18-三体4例、45,XO 4例、inv(9) (p11q12-21)4例、X-三体1例、Rob(13;14)1例、8-三体1例、del(18) (q22)1例等.4.染色体病的临床表型有特殊面容147例(92.5%)、先天性心脏病97例(61.0%)、低出生体质量72例(45.3%)、先天性肛门闭锁13例(8.1%)、多发性畸形11例(6.8%)、肠畸形10例(6.2%)、外生殖器异常9例(5.7%)、猫叫样哭声4例(2.5%)、四肢水肿4例(2.5%)、指趾异常6例(3.6%)、先天性脑发育不良6例(3.6%)、颈蹼5例(3.1%)和唇腭裂3例(1.8%)等.结论 染色体核型异常是导致新生儿先天性疾病的重要因素;特殊面容、先天性心脏病、低出生体质量、多发性畸形是新生儿染色体病的主要临床体征.%Objective To reveal the chromosome abnormalities and their relationship with the clinical phenotype of neonates with congenital malformation.Methods Karyotype analysis of peripheral blood lymphocytes was performed on 396 newborns with congenital malformation,who were recruited at the Children's Hospital Affiliated to Soochow University from Jan.2006 to May 2012,chromosome karyotypes were prepared with neonatal peripheral lymphocytes by conventional G-banding technique.Results 1.Of 396 newborns,159 (40.2%) cases were detected to have chromosomal abnormalities

  17. Comparative analysis of cytogenetic manifestations of human genome instability

    International Nuclear Information System (INIS)

    The comparative analysis of cytogenetic manifestations of human genome instability was carried out. The studied parameters are the micronuclei rate (MNR), the level of single and double chromosome fragment and the level of premature chromatid division (PCD). PCD and chromosome fragments were chosen as anomalies that possibly result in MN formation. We analysed the MNR in buccal epithelium (BE) and peripheral blood lymphocytes (PBL), the level of single and double chromosome fragment as well as level PCD - in PBL only. Average MNR in BE was higher than in PBL. The studied parameters are independent ones and have to be considered altogether for more comprehensive evaluation of the level and peculiarities of manifestation of human genome instability

  18. Chromosomes as Vehicle in Organization and Transmission of Characters

    International Nuclear Information System (INIS)

    One of the fundamental aspects of genomes is the organization of the genes in packages known as chromosomes. All organisms from the simplest to the most complex possess chromosomes as part of their genome and they are characterized by a particular morphology and number characteristic of each species. Chromosome mutations induce changes that can originate in mitotic o meiotic errors in an individual, and these can become fixed in the population during evolution. This results either if the particular changes represent a selective advantage, or they may result in severe effects on the phenotype and fertility of its carriers that may be manifested as a genetic syndrome. In this essay I demonstrate how, using conventional and recent cytogenetic and molecular techniques we have begun understanding the function of chromosome arrangements in the differentiation of species and how particular defects or individual changes in the morphology or number of chromosomes can result in serious dysfunctions that are recognized as genetic syndromes.

  19. Research for genetic instability of human genome

    International Nuclear Information System (INIS)

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author)

  20. Centrosomal clustering contributes to chromosomal instability and cancer.

    Science.gov (United States)

    Milunović-Jevtić, A; Mooney, P; Sulerud, T; Bisht, J; Gatlin, J C

    2016-08-01

    Cells assemble mitotic spindles during each round of division to insure accurate segregation of their duplicated genome. In animal cells, stereotypical spindles have two poles, each containing one centrosome, from which microtubules are nucleated. By contrast, many cancer cells often contain more than two centrosomes and form transient multipolar spindle structures with more than two poles. In order to divide and produce viable progeny, the multipolar spindle intermediate must be reshaped into a pseudo-bipolar structure via a process called centrosomal clustering. Pseudo-bipolar spindles appear to function normally during mitosis, but they occasionally give rise to aneuploid and transformed daughter cells. Agents that inhibit centrosomal clustering might therefore work as a potential cancer therapy, specifically targeting mitosis in supernumerary centrosome-containing cells. PMID:27046071

  1. Small chromosomes among Danish Candida glabrata isolates originated through different mechanisms

    DEFF Research Database (Denmark)

    Ahmad, Khadija Mohamed; Ishchuk, Olena P.; Hellborg, Linda;

    2013-01-01

    participate in their origin: (i) through a segmental duplication which covered the centromeric region, or (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of small chromosomes carrying duplicated genes...... chromosomes, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, these C. glabrata strains had independent origin and the analyzed small chromosomes were structurally not related to each other (i.e. they contained different sets of genes). We suggest that at least two mechanisms could...... exhibited mitotic instability, while the second type, which contained the corresponding genes in only one copy in the genome, was mitotically stable. Apparently, in patients C. glabrata chromosomes are frequently reshuffled resulting in new genetic configurations, including appearance of small chromosomes...

  2. Shoulder instability; Schulterinstabilitaeten

    Energy Technology Data Exchange (ETDEWEB)

    Kreitner, Karl-Friedrich [Mainiz Univ. (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie

    2014-06-15

    In the shoulder, the advantages of range of motion are traded for the disadvantages of vulnerability to injury and the development of instability. Shoulder instability and the lesion it produces represent one of the main causes of shoulder discomfort and pain. Shoulder instability is defined as a symptomatic abnormal motion of the humeral head relative to the glenoid during active shoulder motion. Glenohumeral instabilities are classified according to their causative factors as the pathogenesis of instability plays an important role with respect to treatment options: instabilities are classified in traumatic and atraumatic instabilities as part of a multidirectional instability syndrome, and in microtraumatic instabilities. Plain radiographs ('trauma series') are performed to document shoulder dislocation and its successful reposition. Direct MR arthrography is the most important imaging modality for delineation the different injury patterns on the labral-ligamentous complex and bony structures. Monocontrast CT-arthrography with use of multidetector CT scanners may be an alternative imaging modality, however, regarding the younger patient age, MR imaging should be preferred in the diagnostic work-up of shoulder instabilities. (orig.)

  3. Symbiotic Sympatric Speciation: Compliance with Interaction-driven Phenotype Differentiation from a Single Genotype

    OpenAIRE

    Kaneko, Kunihiko

    2002-01-01

    A mechanism of sympatric speciation is presented based on the interaction-induced developmental plasticity of phenotypes. First, phenotypes of individuals with identical genotypes split into a few groups, according to instability in the developmental dynamics that are triggered with the competitive interaction among individuals. Then, through mutational change of genes, the phenotypic differences are fixed to genes, until the groups are completely separated in genes as well as phenotypes. It ...

  4. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    Genomic instability, induced by various metabolic, genetic, and environmental factors, is the driving force of tumorigenesis. Radiation exposure from different types of radiation sources induces different types of DNA damages, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo experiments. The cell survival rates and frequency of chromosome aberrations depend on the genetic background and radiation sources. To further understand genomic instability induced by charged particles, we exposed human lymphocytes ex vivo, human fibroblast cells, human mammary epithelial cells, and bone marrow cells isolated from CBA/CaH and C57BL/6 mice to high energy protons and Fe ions, and collected chromosomes at different generations after exposure. Chromosome aberrations were analyzed with fluorescent in situ hybridization with whole chromosome specific probes.

  5. How chromosome mis-segregation leads to cancer: lessons from BubR1 mouse models.

    Science.gov (United States)

    Lee, Hyunsook

    2014-10-31

    Alteration in chromosome numbers and structures instigate and foster massive genetic instability. As Boveri has seen a hundred years ago (Boveri, 1914; 2008), aneuploidy is hallmark of many cancers. However, whether aneuploidy is the cause or the result of cancer is still at debate. The molecular mechanism behind aneuploidy includes the chromo-some mis-segregation in mitosis by the compromise of spindle assembly checkpoint (SAC). SAC is an elaborate network of proteins, which monitor that all chromosomes are bipolarly attached with the spindles. Therefore, the weakening of the SAC is the major reason for chromosome number instability, while complete compromise of SAC results in detrimental death, exemplified in natural abortion in embryonic stage. Here, I will review on the recent progress on the understanding of chromosome mis-segregation and cancer, based on the comparison of different mouse models of BubR1, the core component of SAC. PMID:25256220

  6. Presencia de micronúcleos en células epiteliales de encías, como marcador de inestabilidad cromosomal: Revisión sistemática Presence of micronuclei in oral epithelium cells, as marker of chromosomal instability: Systematic review

    Directory of Open Access Journals (Sweden)

    A. Díaz Caballero

    2013-04-01

    environment, medical procedures such as radiation and chemical agents, nutrients deficiency like folic acid, habits as alcoholism, smoking, drug addiction, stress, lifestyle and genetic factors such as changes in metabolism and/or DNA repair. Objetive. To guide a critical analysis of the micronucleus test as a measure of genetic instability, its applicability from dentistry and its relationship with cancer development. Materials and methods. The most relevant papers were identifies through a systematic search on electronic databases such as Ovid, Ebsco Host, Science Direct and PubMed. Results. A total of 282872 articles were obtained of wich were selected wich fulfilled the criteria inclusion and were subsequently analyzed and discussed taking into account title, author, journal, year, volume, month and page. Conclusion. The results of this analysis of the literature review support the hypothesis that frequency of micronucleus is related to cancer development based on the fact that a substantial proportion of genetic instability of cancer cells is due to specific structural defects in chromosome segregation.

  7. A role for the fission yeast Rqh1 helicase in chromosome segregation

    DEFF Research Database (Denmark)

    Win, Thein Z; Mankouri, Hocine W; Hickson, Ian D;

    2005-01-01

    DNA repeat by deletion of reb1+ partially suppresses rqh1delta phenotypes. These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication. The chromosome segregation defects seen...

  8. Effects of Sex Chromosome Aneuploidies on Brain Development: Evidence from Neuroimaging Studies

    Science.gov (United States)

    Lenroot, Rhoshel K.; Lee, Nancy Raitano; Giedd, Jay N.

    2009-01-01

    Variation in the number of sex chromosomes is a relatively common genetic condition, affecting as many as 1/400 individuals. The sex chromosome aneuploidies (SCAs) are associated with characteristic behavioral and cognitive phenotypes, although the degree to which specific individuals are affected can fall within a wide range. Understanding the…

  9. Prenatal detection and characterization of supernumerary marker chromosomes by array-CGH

    Science.gov (United States)

    Small supernumerary marker chromosomes (sSMC) occur in about 0.043% of newborns and in 0.076% of prenatal diagnoses. The phenotypes associated with sSMC vary substantially depending on size, gene content, and chromosome origin, which cannot easily be determined by karyotype or FISH analysis. There...

  10. Statistical models for trisomic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Lamb, N.E.; Sherman, S.L.; Feingold, E. [Emory Univ., Atlanta, GA (United States)

    1996-01-01

    Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on the trisomic chromosome. As with all aneuploid syndromes, however, a considerable degree of variation exists within each phenotype so that any given trait is present only among a subset of the trisomic population. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for such traits. The mapping strategy does not depend on the simple model but works in theory under any model that predicts that affected individuals have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by investigating what kinds of models give an expected increase in disomic homozygosity. We describe a number of basic statistical models for trisomic phenotypes. Some of these are logical extensions of standard models for disomic phenotypes, and some are more specific to trisomy. Where possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait. Finally, we determine the sample sizes required to identify the increased disomic homozygosity under each model. Most of the models we explore yield detectable increases in disomic homozygosity for some reasonable range of parameter values, usually corresponding to smaller trait frequencies. It therefore appears that our mapping method should be effective for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known. 21 refs., 8 figs., 1 tab.

  11. Catastrophic chromosomal restructuring during genome elimination in plants.

    Science.gov (United States)

    Tan, Ek Han; Henry, Isabelle M; Ravi, Maruthachalam; Bradnam, Keith R; Mandakova, Terezie; Marimuthu, Mohan Pa; Korf, Ian; Lysak, Martin A; Comai, Luca; Chan, Simon Wl

    2015-01-01

    Genome instability is associated with mitotic errors and cancer. This phenomenon can lead to deleterious rearrangements, but also genetic novelty, and many questions regarding its genesis, fate and evolutionary role remain unanswered. Here, we describe extreme chromosomal restructuring during genome elimination, a process resulting from hybridization of Arabidopsis plants expressing different centromere histones H3. Shattered chromosomes are formed from the genome of the haploid inducer, consistent with genomic catastrophes affecting a single, laggard chromosome compartmentalized within a micronucleus. Analysis of breakpoint junctions implicates breaks followed by repair through non-homologous end joining (NHEJ) or stalled fork repair. Furthermore, mutation of required NHEJ factor DNA Ligase 4 results in enhanced haploid recovery. Lastly, heritability and stability of a rearranged chromosome suggest a potential for enduring genomic novelty. These findings provide a tractable, natural system towards investigating the causes and mechanisms of complex genomic rearrangements similar to those associated with several human disorders. PMID:25977984

  12. Joint instability and osteoarthritis.

    Science.gov (United States)

    Blalock, Darryl; Miller, Andrew; Tilley, Michael; Wang, Jinxi

    2015-01-01

    Joint instability creates a clinical and economic burden in the health care system. Injuries and disorders that directly damage the joint structure or lead to joint instability are highly associated with osteoarthritis (OA). Thus, understanding the physiology of joint stability and the mechanisms of joint instability-induced OA is of clinical significance. The first section of this review discusses the structure and function of major joint tissues, including periarticular muscles, which play a significant role in joint stability. Because the knee, ankle, and shoulder joints demonstrate a high incidence of ligament injury and joint instability, the second section summarizes the mechanisms of ligament injury-associated joint instability of these joints. The final section highlights the recent advances in the understanding of the mechanical and biological mechanisms of joint instability-induced OA. These advances may lead to new opportunities for clinical intervention in the prevention and early treatment of OA. PMID:25741184

  13. Modelling Financial Instability

    OpenAIRE

    Franklin Allen

    2005-01-01

    Financial instability can have large adverse effects on an economy. One major cause of instability is asset price bubbles. This paper starts by considering how such bubbles can arise due to the expansion of money and credit. The ways in which subsequent financial instability occurs are then discussed. Banking crises can arise due to panics or as a result of the business cycle. Contagion and financial fragility can cause small disturbances to have large effects. Finally, policy issues are touc...

  14. Dynamics of explosive instability

    International Nuclear Information System (INIS)

    It was shown that in general case explosive instability dynamics should be described as four wave interaction. The main difference from three wave interaction is that this dynamics may not contain explosive instability. Besides it may by irregular. If the characteristics of one of the wave is closed to one of the interacting wave and they are connected linearly then explosive instability may be suppressed.

  15. Plant sex chromosome evolution.

    Science.gov (United States)

    Charlesworth, Deborah

    2013-01-01

    It is now well established that plants have an important place in studies of sex chromosome evolution because of the repeated independent evolution of separate sexes and sex chromosomes. There has been considerable recent progress in studying plant sex chromosomes. In this review, I focus on how these recent studies have helped clarify or answer several important questions about sex chromosome evolution, and I shall also try to clarify some common misconceptions. I also outline future work that will be needed to make further progress, including testing some important ideas by genetic, molecular, and developmental approaches. Systems with different ages can clearly help show the time course of events during changes from an ancestral co-sexual state (hermaphroditism or monoecy), and I will also explain how different questions can be studied in lineages whose dioecy or sex chromosomes evolved at different times in the past. PMID:23125359

  16. Nitric Oxide: Genomic Instability And Synthetic Lethality

    Directory of Open Access Journals (Sweden)

    Vasily A. Yakovlev

    2015-08-01

    Loss or inhibition of Poly(ADP-ribose polymerase 1 (PARP1 activity results in accumulation of DNA single-strand breaks, which are subsequently converted to DSB by the transcription machinery. In BRCA-positive cells, DSB are repaired by HRR, but they cannot be properly repaired in BRCA1-deficient cells, leading to genomic instability, chromosomal rearrangements, and cell death. Our data demonstrated that combination of NO-donors with PARP inhibitors significantly sensitized the BRCA1-positive cancer cells to DNA-damaging agents.

  17. Derivative chromosome 11 in a child resulting from a complex rearrangement involving chromosomes 3, 6 and 11 in father: Significance of parental karyotyping

    Directory of Open Access Journals (Sweden)

    Prabhat Ranjan

    2013-01-01

    Full Text Available The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have additional material from chromosome 6p arising from complex chromosomal rearrangement in the father. Karyotyping is the basic, cost-effective preliminary investigation in a child with mental subnormality or congenital anomalies.

  18. Vibrio chromosomes share common history

    OpenAIRE

    Gevers Dirk; Chang Sarah; Chang LeeAnn; Kirkup Benjamin C; Polz Martin F

    2010-01-01

    Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II) were identified from 19 sequenced Vibrionales genomes ...

  19. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.; Rasmussen, Lene Juel

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA of...... the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  20. Infantile spasms associated with proximal duplication of chromosome 15q.

    Science.gov (United States)

    Bingham, P M; Spinner, N B; Sovinsky, L; Zackai, E H; Chance, P F

    1996-09-01

    We describe a case of infantile spasms associated with a chromosome abnormality (supernumerary inverted duplication of chromosome 15 [47,XX,+inv dup(15)]). The patient was nondysmorphic and presented with mild hypotonia and delay in acquisition of gross motor milestones before the diagnosis of seizures at age 7 months. Additional features included unilateral sensorineural deafness and torticollis. Molecular cytogenetic studies confirmed that the patient has a large inv dup(15). Inv dup(15) chromosomes are variable with respect to the size and genetic composition of the chromosome and in their phenotypic effects. Patients with small inv dup(15s) may have no phenotypic abnormalities, whereas patients with large inv dup(15s) may have multiple abnormalities. ACTH therapy resulted in prompt remission of seizures and resolution of EEG abnormalities. This is the second report of a patient with IS and a supernumerary inv dup(15). Several genes code for neurotransmitter receptor subunits located in the duplicated region of chromosome 15, and abnormal dosage of these genes may be involved in the genesis of seizure activity in carriers of the inv dup(15). Chromosome analysis may lead to a specific diagnosis in infants with unexplained infantile spasms. PMID:8888053

  1. DNA damage response during mitosis induces whole chromosome mis-segregation

    Science.gov (United States)

    Bakhoum, Samuel F.; Kabeche, Lilian; Murnane, John P.; Zaki, Bassem I.; Compton, Duane A.

    2014-01-01

    Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here we show that activation of the DNA damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and Plk1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or Chk2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, DDR during mitosis inappropriately stabilizes k-MTs creating a link between s-CIN and w-CIN. PMID:25107667

  2. Instability in evolutionary games.

    Directory of Open Access Journals (Sweden)

    Zimo Yang

    Full Text Available BACKGROUND: Phenomena of instability are widely observed in many dissimilar systems, with punctuated equilibrium in biological evolution and economic crises being noticeable examples. Recent studies suggested that such instabilities, quantified by the abrupt changes of the composition of individuals, could result within the framework of a collection of individuals interacting through the prisoner's dilemma and incorporating three mechanisms: (i imitation and mutation, (ii preferred selection on successful individuals, and (iii networking effects. METHODOLOGY/PRINCIPAL FINDINGS: We study the importance of each mechanism using simplified models. The models are studied numerically and analytically via rate equations and mean-field approximation. It is shown that imitation and mutation alone can lead to the instability on the number of cooperators, and preferred selection modifies the instability in an asymmetric way. The co-evolution of network topology and game dynamics is not necessary to the occurrence of instability and the network topology is found to have almost no impact on instability if new links are added in a global manner. The results are valid in both the contexts of the snowdrift game and prisoner's dilemma. CONCLUSIONS/SIGNIFICANCE: The imitation and mutation mechanism, which gives a heterogeneous rate of change in the system's composition, is the dominating reason of the instability on the number of cooperators. The effects of payoffs and network topology are relatively insignificant. Our work refines the understanding on the driving forces of system instability.

  3. Sequential cloning of chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  4. Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells12

    OpenAIRE

    Samassekou, Oumar; Li, Huiyu; Hébert, Josée; Ntwari, Aimé; Wang, Haixia; Cliché, Catherine Grenier; Bouchard, Eric; Huang, Shiang; Yan, Ju

    2011-01-01

    Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found th...

  5. A new chromosome was born: comparative chromosome painting in Boechera.

    Science.gov (United States)

    Koch, Marcus A

    2015-09-01

    Comparative chromosome painting is a powerful tool to study the evolution of chromosomes and genomes. Analyzing karyotype evolution in cruciferous plants highlights the origin of aberrant chromosomes in apomictic Boechera and further establishes the cruciferous plants as important model system for our understanding of plant chromosome and genome evolution. PMID:26228436

  6. Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

    International Nuclear Information System (INIS)

    Environmental 222radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3He2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

  7. Chimpanzee chromosome 13 is homologous to human chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Similarities between human and chimpanzee chromosomes are shown by chromosome banding techniques and somatic cell hybridization techniques. Cell hybrids were obtained from the chimpanzee lymphocyte LE-7, and the Chinese hamster mutant cell, Gal-2. Experiments showed that the ACPL, MDHs, and Gal-Act genes could be assigned to chimpanzee chromosome 13, and since these genes have been assigned to human chromosme 2p, it is suggested that chimpanzee chromosome 13 is homologous to human chromosome 2p. (HLW)

  8. Chromosome condensation and segmentation

    International Nuclear Information System (INIS)

    Some aspects of chromosome condensation in mammalians -humans especially- were studied by means of cytogenetic techniques of chromosome banding. Two further approaches were adopted: a study of normal condensation as early as prophase, and an analysis of chromosome segmentation induced by physical (temperature and γ-rays) or chemical agents (base analogues, antibiotics, ...) in order to show out the factors liable to affect condensation. Here 'segmentation' means an abnormal chromosome condensation appearing systematically and being reproducible. The study of normal condensation was made possible by the development of a technique based on cell synchronization by thymidine and giving prophasic and prometaphasic cells. Besides, the possibility of inducing R-banding segmentations on these cells by BrdU (5-bromodeoxyuridine) allowed a much finer analysis of karyotypes. Another technique was developed using 5-ACR (5-azacytidine), it allowed to induce a segmentation similar to the one obtained using BrdU and identify heterochromatic areas rich in G-C bases pairs

  9. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  10. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    Science.gov (United States)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  11. Chromosome numbers in Bromeliaceae

    OpenAIRE

    2000-01-01

    The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. u...

  12. Role of the Number of Microtubules in Chromosome Segregation during Cell Division

    CERN Document Server

    Bertalan, Zsolt; La Porta, Caterina A M; Zapperi, Stefano

    2015-01-01

    Faithful segregation of genetic material during cell division requires alignment of chromosomes between two spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated so that coherent chromosome motion emerges from a large collection of random and deterministic processes. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation during mitosis. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compa...

  13. Is delayed genomic instability specifically induced by high-LET particles?

    Science.gov (United States)

    Testard, Isabelle; Sabatier, Laure

    1998-12-01

    Ionizing radiation can induce a large variety of damages in the DNA. The processing or repair of this damage occurs in the first minutes up to several hours after irradiation. Afterwhile the remaining lesions are fixed in an irreparable state. However, in recent years, data have accumulated to suggest that genomic instability can manifest in the progeny of irradiated cells leading to accumulation of damage through cell generations. Different biological endpoints were described: delayed cell death, delayed mutations, de novo chromosomal instability. The question regarding the ability of sparsely ionizing X-or γ-rays to induce such phenomenon is still unclear for normal cells. In most of the reports, high linear energy transfer (LET) particles are able to induce genomic instability but not low-LET particles. The mechanisms underlying this phenomenon are still unknown. In human fibroblasts irradiated by heavy ions in a large range of LETs, we showed that the chromosomal instability is characterized by telomeric associations (TAS) involving specific chromosomes. The same instability is observed during the senescence process and during the first passages after viral transfection. The specific chromosomal instability that we observed after irradiation would not be a direct consequence of irradiation but would be a natural phenomenon occurring after many cell divisions. The effect of the irradiation would lie on the bypass of the senescence process that would permit cells with end to end fusions to survive and be transmitted through cell generations, accumulating chromosome rearrangements and chromosome imbalances. Research on molecular mechanisms of chromosomal instability is focused on the role of telomeres in end to end fusions. Such observations could contribute to understand why chromosomal instability is not a dose dependant phenomenon. Why high-LET particles would be so potent in inducing delayed instability? The answer might lie in the study of primary effects of

  14. Turner Syndrome with Pseudodicentric Y Chromosome Mosaicism

    OpenAIRE

    Hsieh, Yao-Yuan; Lin, Wu-Chou; Chang, Chi-Chen; Tsai, Fuu-Jen; Yu, Ming-Tsung; Tsai, Horng-Der; Tsai, Chang-Hai

    2002-01-01

    The objective was to compare the impact of gonadal cell line upon the phenotype of a Turner syndrome patient with mosaic karyotypes. A 10-year-old female presented with typical Turner syndrome. Chromosomal analysis of lymphocytes revealed 45,X (16%)/46,X,pseudodicentric Y (p ter→q12::q12→p ter) (84%). Karyotype of the gonads revealed 45,X (85%)/46,X,pseudodicentric Y (p ter→q12::q12→p ter) (15%). Discrepancy of the individual cell lines between the lymphocytes and the tissue might exist. The ...

  15. Micromechanics of human mitotic chromosomes

    International Nuclear Information System (INIS)

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed

  16. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  17. Chromosome Structural Alteration an Unusual Abnormality Characterizing Human Neoplasia

    Directory of Open Access Journals (Sweden)

    Abolfazl Movafagh

    2016-04-01

    Full Text Available 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.

  18. Paternal uniparental isodisomy for human chromosome 20 and absence of external ears

    Energy Technology Data Exchange (ETDEWEB)

    Spinner, N.B.; Rand, E.; McDonald-McGinn, D.M. [Childrens Hospital of Philadelphia, PA (United States)] [and others

    1994-09-01

    Uniparental disomy can cause disease if the involved chromosomal region contains imprinted genes. Uniparental disomy for portions of human chromosomes 6, 7, 9, 11, 14 and 15 have been associated with abnormal phenotypes. We studied a patient with multiple abnormalities including an absent left ear with a small right ear remnant, microcephaly, congenital heart disease and Hirschprung`s disease. Cytogenetics revealed a 45,XY,-20,-20,+ter rea(20;20)(p13;p13) in 10/10 cells from bone marrow and 20/20 cells from peripheral blood. Analysis of a skin culture revealed a second cell line with trisomy 20 resulting from an apparently normal chromosome 20 in addition to the terminally rearranged chromosome, in 8/100 cells studied. The unusual phenotype of our patient was not consistent with previously reported cases of deletions of 20p or mosaic trisomy 20. We hypothesized that the patient`s phenotype could either result from deletion of both copies of a gene near the p arm terminus of chromosome 20 or from uniparental disomy of chromosome 20. There were no alterations or rearrangements of PTP-alpha (which maps to distal 20p) by Southern or Northern blot analysis. A chromosome 20 sub-telomeric probe was found to be present on the rearranged 20 by FISH suggesting that subtelomeric sequences have not been lost as a consequece of this rearrangement. To determine the parental origin of the 2 chromosome 20`s in the terminal rearrangement, we studied the genotypes of the proband and his parents in lymphoblastoid cell lines at 8 polymorphic loci. Genotypes at D20S115, D20S186, and D20S119 indicated that there was paternal isodisomy. Other loci were uninformative. This is the first example of uniparental disomy for chromosome 20. Further studies are warranted to correlate phenotype with uniparental inheritance of this chromosome.

  19. Partial 1q Duplications and Associated Phenotype

    Science.gov (United States)

    Morris, Marcos L.M.; Baroneza, José E.; Teixeira, Patricia; Medina, Cristina T.N.; Cordoba, Mara S.; Versiani, Beatriz R.; Roese, Liege L.; Freitas, Erika L.; Fonseca, Ana C.S.; dos Santos, Maria C.G.; Pic-Taylor, Aline; Rosenberg, Carla; Oliveira, Silviene F.; Ferrari, Iris; Mazzeu, Juliana F.

    2016-01-01

    Duplications of the long arm of chromosome 1 are rare. Distal duplications are the most common and have been reported as either pure trisomy or unbalanced translocations. The paucity of cases with pure distal 1q duplications has made it difficult to delineate a partial distal trisomy 1q syndrome. Here, we report 2 patients with overlapping 1q duplications detected by G-banding. Array CGH and FISH were performed to characterize the duplicated segments, exclude the involvement of other chromosomes and determine the orientation of the duplication. Patient 1 presents with a mild phenotype and carries a 22.5-Mb 1q41q43 duplication. Patient 2 presents with a pure 1q42.13qter inverted duplication of 21.5 Mb, one of the smallest distal 1q duplications ever described and one of the few cases characterized by array CGH, thus contributing to a better characterization of distal 1q duplication syndrome. PMID:27022331

  20. The Collisionless Magnetothermal Instability

    CERN Document Server

    Islam, Tanim

    2013-01-01

    It is likely that nearly all central galactic massive and supermassive black holes are nonradiative: their accretion luminosities are orders of magnitude below what can be explained by efficient black hole accretion within their ambient environments. These objects, of which Sagittarius A* is the best-known example, are also dilute (mildly collisional to highly collisionless) and optically thin. In order for accretion to occur, magnetohydrodynamic instabilities must develop that not only transport angular momentum, but also gravitational energy generated through matter infall, outwards. A class of new magnetohydrodynamical fluid instabilities -- the magnetoviscous-thermal instability (MVTI) (Islam12) -- was found to transport angular momentum and energy along magnetic field lines through large (fluid) viscosities and thermal conductivities. This paper describes the collisionless and mildly collisional analogue to the MVTI, the collisional magnetothermal instability (CMTI), that similarly transports energy and ...

  1. Chronic Ankle Instability

    Science.gov (United States)

    ... ankle surgeon will ask you about any previous ankle injuries and instability. Then s/he will examine your ankle ... Weak ankles may be a result of previous ankle injuries, but in some cases they are a congenital ( ...

  2. Characterization of a rare short arm heteromorphism of chromosome 22 in a girl with down-syndrome like facies

    Directory of Open Access Journals (Sweden)

    Abdelhafid Natiq

    2014-01-01

    Full Text Available Chromosomal heteromorphisms are described as interindividual variation of chromosomes without phenotypic consequence. Chromosomal polymorphisms detected include most regions of heterochromatin of chromosomes 1, 9, 16 and Y and the short arms of all acrocentric chromosomes. Here, we report a girl with Down-syndrome such as facies and tremendously enlarged short arm of a chromosome 22. Fluorescence in situ hybridization (FISH with a probe specific for all acrocentric short arms revealed that the enlargement p arms of the chromosome 22 in question contained exclusively heterochromatic material derived from an acrocentric short arm. Parental studies identified a maternal origin of this heteromorphism. Cryptic trisomy 21 of the Down-syndrome critical region was excluded by a corresponding FISH-probe. Here, we report, to the best of our knowledge, largest ever seen chromosome 22 short arm, being ~×1.5 larger than the normal long arm.

  3. X Chromosomal effects on social cognitive processing and emotion regulation : A study with Klinefelter men (47,XXY)

    NARCIS (Netherlands)

    van Rijn, S; Swaab, H; Aleman, A; Kahn, RS

    2006-01-01

    Studying Klinefelter syndrome (47,XXY), a genetically defined disorder characterized by the presence of an additional X chromosome, can reveal insights into genotype-phenotype associations. Increased vulnerability to psychiatric disorders characterized by difficulties in social interactions, such as

  4. The Curse of Instability

    OpenAIRE

    Kuehn, Christian

    2015-01-01

    High-dimensional computational challenges are frequently explained via the curse of dimensionality, i.e., increasing the number of dimensions leads to exponentially growing computational complexity. In this commentary, we argue that thinking on a different level helps to understand, why we face the curse of dimensionality. We introduce as a guiding principle the curse of instability, which triggers the classical curse of dimensionality. Furthermore, we claim that the curse of instability is a...

  5. Rotor internal friction instability

    Science.gov (United States)

    Bently, D. E.; Muszynska, A.

    1985-01-01

    Two aspects of internal friction affecting stability of rotating machines are discussed. The first role of internal friction consists of decreasing the level of effective damping during rotor subsynchronous and backward precessional vibrations caused by some other instability mechanisms. The second role of internal frication consists of creating rotor instability, i.e., causing self-excited subsynchronous vibrations. Experimental test results document both of these aspects.

  6. Streaming gravity mode instability

    International Nuclear Information System (INIS)

    In this paper, we study the stability of a current sheet with a sheared flow in a gravitational field which is perpendicular to the magnetic field and plasma flow. This mixing mode caused by a combined role of the sheared flow and gravity is named the streaming gravity mode instability. The conditions of this mode instability are discussed for an ideal four-layer model in the incompressible limit. (author). 5 refs

  7. Methylator phenotype in colorectal cancer: A prognostic factor or not?

    Science.gov (United States)

    Gallois, C; Laurent-Puig, P; Taieb, J

    2016-03-01

    Colorectal cancer (CRC) is due to different types of genetic alterations that are translated into different phenotypes. Among them, CpG island methylator phenotype (CIMP+) is the most recently involved in carcinogenesis of some CRC. The malignant transformation in this case is mainly due to the transcriptional inactivation of tumor suppressor genes. CIMP+ are reported to be more frequently found in the elderly and in women. The tumors are more frequently located in the proximal part of the colon, BRAF mutated and are associated with microsatellite instability (MSI) phenotype. All sporadic MSI CRC belong to the methylator phenotype, however some non MSI CRC may also harbor a methylator phenotype. The prognostic value of CIMP is not well known. Most studies show a worse prognosis in CIMP+ CRC, and adjuvant treatments seem to be more efficient. We review here the current knowledge on prognostic and predictive values in CIMP+ CRC. PMID:26702883

  8. Mouse acute myeloid leukemia and abnormality in chromosome II

    International Nuclear Information System (INIS)

    This review described abnormality in chromosome II that is characteristic in the radiation-induced leukemia in the title (AML) in mice. The disease is reportedly increased in A-bomb survivors. AML occurs in mice of RFM, CBA and other strains 1-1.5 years after whole body irradiation. The incidence increases dependently on dose, however, it decreases over around the dose of 3 Gy of X- and γ-ray. The incidence (20-25%) is higher in males. Abnormality seen in chromosome II is classified in types I-IV and II-IV types involve terminal deletion, interstitial deletion and translocation. The deleted region common on the chromosome (marker chromosome) is about 1 cM long, which corresponds to human 11p11-12 region frequently deleted in AML patients. The AML marker chromosome is suggested to be yielded by genomic instability induced by radiation. It is also suggested that there are fragile sites in the chromosome II. Future investigations are conceivably to be concentrated for identification of the AML causing gene. (K.H.)

  9. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres

    OpenAIRE

    Espejel, Silvia; Franco, Sonia; Rodríguez-Perales, Sandra; Bouffler, Simon D; Cigudosa, Juan C.; Blasco, María A.

    2002-01-01

    Here we analyze the functional interaction between Ku86 and telomerase at the mammalian telomere by studying mice deficient for both proteins. We show that absence of Ku86 prevents the end-to-end chromosomal fusions that result from critical telomere shortening in telomerase-deficient mice. In addition, Ku86 deficiency rescues the male early germ cell apoptosis triggered by short telomeres in these mice. Together, these findings define a role for Ku86 in mediating chromosomal instability and ...

  10. A deficiency in chromatin repair, genetic instability, and predisposition to cancer

    International Nuclear Information System (INIS)

    This review traces steps leading to malignant neoplastic transformation of rodent and human cells in culture and in vivo. Emphasis is placed on an abnormal response characterized by persistent chromatid damage following irradiation of cells in culture with X-rays or fluorescent light during G2 phase of the cell cycle. Evidence is presented that deficient or unbalanced DNA repair during G2 accounts for the abnormal response. This G2 repair deficiency can be inherited or acquired by normal tissue cells during the process of or following attainment of infinite lifespan. It appears as an early, possibly initiating step in neoplastic transformation. It characterizes all human tumor cells examined irrespective of histopathology or tissue of origin. It has a genetic basis. In an animal model, the BALB/c mouse, this phenotype is associated with genes on chromosomes 1 and 4. It characterizes skin fibroblasts and blood lymphocytes from individuals with genetic or familial conditions predisposing to cancer and can be used to identify clinically normal family members carrying a gene(s) for any one of the three cancer-prone genetic disorders studied to date. Furthermore, it can provide the basis of a test for carriers of genes predisposing to a high risk of cancer. We conclude that the G2 repair deficiency, whether inherited or acquired, is a prerequisite for cancer development and that it accounts for the genetic instability of the cancer cell. 167 refs

  11. Colon Cancer-associated DNA Polymerase β Variant Induces Genomic Instability and Cellular Transformation*

    Science.gov (United States)

    Nemec, Antonia A.; Donigan, Katherine A.; Murphy, Drew L.; Jaeger, Joachim; Sweasy, Joann B.

    2012-01-01

    Rapidly advancing technology has resulted in the generation of the genomic sequences of several human tumors. We have identified several mutations of the DNA polymerase β (pol β) gene in human colorectal cancer. We have demonstrated that the expression of the pol β G231D variant increased chromosomal aberrations and induced cellular transformation. The transformed phenotype persisted in the cells even once the expression of G231D was extinguished, suggesting that it resulted as a consequence of genomic instability. Biochemical analysis revealed that its catalytic rate was 140-fold slower than WT pol β, and this was a result of the decreased binding affinity of nucleotides by G231D. Residue 231 of pol β lies in close proximity to the template strand of the DNA. Molecular modeling demonstrated that the change from a small and nonpolar glycine to a negatively charged aspartate resulted in a repulsion between the template and residue 231 leading to the distortion of the dNTP binding pocket. In addition, expression of G231D was insufficient to rescue pol β-deficient cells treated with chemotherapeutic agents suggesting that these agents may be effectively used to treat tumors harboring this mutation. More importantly, this suggests that the G231D variant has impaired base excision repair. Together, these data indicate that the G231D variant plays a role in driving cancer. PMID:22573322

  12. Effects of calorie restriction on chromosomal stability in rhesus monkeys (Macaca mulatta)

    OpenAIRE

    Moore, Charleen M.; Dunn, Betty G.; McMahan, C. Alex; Lane, Mark A.; Roth, George S.; Ingram, Donald K.; Mattison, Julie A.

    2006-01-01

    The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the mos...

  13. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

    Full Text Available The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. utriculosa. The chromosome number of all species was determined for the first time, except for Billbergia chlorosticta and Cryptanthus bahianus. Our data supports the hypothesis of a basic number of x = 25 for the Bromeliaceae family and decreasing aneuploidy in the genus Cryptanthus.

  14. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

    Dinoflagellates are a very large and diverse group of eukaryotic algae that play a major role in aquatic food webs of both fresh water and marine habitats. Moreover, the toxic members of this group pose a health threat in the form of red tides. Finally, dinoflagellates are of great evolutionary importance,because of their taxonomic position, and their unusual chromosome structure and composition. While the cytoplasm of dinoflagellates is typically eukaryotic, the nucleus is unique when compared to the nucleus of other eukaryotes. More specifically, while the chromosomes of all other eukaryotes contain histones,dinoflagellate chromosomes lack histones completely. There are no known exceptions to this observation: all dinoflagellates lack histones, and all other eukaryotes contain histones. Nevertheless, dinoflagellates remain a relatively unstudied group of eukaryotes.

  15. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    OpenAIRE

    Aaraby Yoheswaran Nielsen; Morten Frier Gjerstorff

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the ...

  16. Derivative chromosome 11 in a child resulting from a complex rearrangement involving chromosomes 3, 6 and 11 in father: Significance of parental karyotyping

    OpenAIRE

    Prabhat Ranjan; Kundanbala Desai; Shailaja Gada Saxena

    2013-01-01

    The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have ...

  17. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

    Full Text Available Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+ translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5 were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2 from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

  18. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15.

    OpenAIRE

    Boehm, T.; Baer, R; Lavenir, I; Forster, A; Waters, J J; Nacheva, E; Rabbitts, T H

    1988-01-01

    A chromosomal translocation t(11;14) (p15;q11) is described in a human acute T-cell leukaemia of immature phenotype (CD3-, CD4-, CD8-). The translocation occurs at a T-cell receptor joining J delta segment, 12 kb upstream of the constant C delta gene and 98 kb upstream of the C alpha gene at chromosome band 14q11. Nucleotide sequencing shows that both J delta and C delta are very conserved between mouse and man. The region of chromosome 11 involved in the translocation is transcriptionally ac...

  19. The elevation of radiation load on ecosystems and genome instability of organisms

    International Nuclear Information System (INIS)

    prophylaxis of human disorders. Thus, it was found that the action of low-dose ionizing radiation on living organisms might induce an adaptive repair response in them aimed at decreasing the genetic consequences of the exposure. However, the potentialities of defense and repair systems of an organism are limited, so an increase in genome lesions may cause inheritable mutations, cancer and other pathologies, and death. DNA lesions caused by ionizing radiation in small and sublethal doses can essentially be repaired, whereas unrepaired lesions and errors of repair, replication, and recombination systems lead to formation of mutational changes in DNA sequences. These changes may be transmitted to daughter cells and induce genome instability in the progeny. Induced genome instability in survived somatic cells is characterized by persistence of a high level of acquired variability in many generations of these cells. Genome instability manifests itself as an increased frequency of karyotypic anomalies, chromosome and gene mutations, clonal heterogeneity, and malignant transformation in the progeny of cells exposed to DNA-damaging agents. Besides, cells with genome instability show increased amplification of genes and changes in their expression, as well as disturbances in their differentiation, delays in reproductive death and other phenotypic characters of abnormal development. Whereas some progress has been made towards knowledge of genome instability in the somatic cells of mammals, the radiation-induced genome instability in germ cells transmitted to individuals of the next generation is still not clearly understood. At the same time, evidence has been obtained which suggests that the transmission of genome instability to the somatic cells of the progeny from the germ cells of gamma - radiation-exposed parents is possible. This conclusion is based on the data on mutation frequency in the progeny of parents exposed to DNA-damaging agents. For instance, a significant increase in

  20. Instability of the Heliopause

    International Nuclear Information System (INIS)

    The heliopause (HP) separates the tenuous hot heliosheath plasma from the relatively dense cool magnetized plasma of the local interstellar medium (LISM). Fluid acceleration in the HP region can therefore drive Rayleigh-Taylor-like and Kelvin-Helmholtz- like instabilities. Charge exchange coupling of plasma ions and primary interstellar neutral atoms provides an effective gravity, suggesting the possibility of Rayleigh Taylor-like (RT-like) instabilities. Shear flow due to the velocity difference between the heliosheath and the interstellar flows drives Kelvin Helmholtz-like (KH-like) modes on the heliopause. Magnetic fields damp the classical KH instability. However, we show that energetic neutral atoms (ENAs) destabilize KH-modes,even in the presence of interplanetary and interstellar magnetic fields. We consider a model that includes a number of effects that are important in the heliosphere such as resonant change exchange between the primary neutrals and the solar wind plasma, ENAs from the inner heliosheath, plasma flows along the heliopause and magnetic fields in the inner and outer heliosheath. We find that the nose region is unstable to RT-like modes for HP parameters, while the shoulder region is unstable to a new instability that has the characteristics of a mixed RT-KH-like mode. These instabilities are not stabilized by typical values of the magnetic fields in the inner and outer heliosheath close to the nose and shoulder regions. Whereas ENAs have a stabilizing influence on the RT instability in the vicinity of the nose region (due to counter streaming), they have a destabilizing influence on the KH instability in the vicinity of the flanks. We find that even in the presence of interplanetary and interstellar magnetic fields, ENAs can drive a new form of KH-like instability on the flanks. An analysis of the collisional and anomalous magnetic field diffusion time scales shows that ideal MHD is an appropriate model at the HP. The interstellar magnetic

  1. Plasma physics and instabilities

    International Nuclear Information System (INIS)

    These lectures procide an introduction to the theory of plasmas and their instabilities. Starting from the Bogoliubov, Born, Green, Kirkwood, and Yvon (BBGKY) hierarchy of kinetic equations, the additional concept of self-consistent fields leads to the fundamental Vlasov equation and hence to the warm two-fluid model and the one-fluid MHD, or cold, model. The properties of small-amplitude waves in magnetized (and unmagnetized) plasmas, and the instabilities to which they give rise, are described in some detail, and a complete chapter is devoted to Landau damping. The linear theory of plasma instabilities is illustrated by the current-driven electrostatic kind, with descriptions of the Penrose criterion and the energy principle of ideal MHD. There is a brief account of the application of feedback control. The non-linear theory is represented by three examples: quasi-linear velocity-space instabilities, three-wave instabilities, and the stability of an arbitrarily largeamplitude wave in a plasma. (orig.)

  2. Mackenzie's Demon with instabilities

    International Nuclear Information System (INIS)

    MacKenzie's Maxwell Demon, consisting of positively biased thin wires, heats plasma electrons without significantly affecting the plasma potential. Experiments were performed on the Maxwell Demon in a multi-dipole confined filament discharge. It is shown that given adequate bias, the Demon reduces a bi-Maxwellian electron distribution function to a single Maxwellian electron distribution function. It is shown that a small planar electrode can perform identical heating as the Demon, provided that the electrode has the area of approximately three times the Demon's conductive surface area. The instability that limits the Demon's operation is investigated. Time-resolved measurements of changes in global electron temperature, plasma density and plasma potential within a cycle of the instability are considered. It is found that the Demon's instability is a repeating pulsed anode spot. Density measurements indicate that the frequency of the instability is dependent on plasma production and loss rates. The neutral pressure dependence of the anode spot instability is measured and modeled for the first time. (paper)

  3. Maternal uniparental disomy for human chromosome 14, due to loss of a chromosome 14 from somatic cells with t(13; 14) trisomy 14

    Energy Technology Data Exchange (ETDEWEB)

    Antonarakis, S.E.; Blouin, J.L.; Maher, J.; Avramopoulos, D.; Thomas, G.; Talbot, C.C. Jr. (Johns Hopkins Univ., Baltimore (United States))

    1993-06-01

    Uniparental disomy (UPD) for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans. The authors recently studied a 9-year-old female with a de novo Robertsonian translocation t(13;14), short stature, mild developmental delay, scoliosis, hyperextensible joints, hydrocephalus that resolved spontaneously during the first year of life, and hyperchloesterolemia. To determine the parental origin of chromosomes 13 and 14 in the proband, they have studied the genotypes of DNA polymorphic markers due to (GT)n repeats in the patient and her parents' blood DNA. The genotypes of markers D14S43, D14S45, D14S49, and D14S54 indicated maternal UPD for chromosome 14. There was isodisomy for proximal markers and heterodisomy for distal markers, suggesting a recombination event on maternal chromosomes 14. In addition, DNA analysis first revealed -- and subsequent cytogenetic analysis confirmed -- that there was mosaic trisomy 14 in 5% of blood lymphocytes. There was normal (biparental) inheritance for chromosome 13, and there was no evidence of false paternity in genotypes of 11 highly polymorphic markers on human chromosome 21. Two cases of maternal UPD for chromosome 14 have previously been reported, one with a familial rob t(13;14) and the other with a t(14;14). There are several similarities among these patients, and a [open quotes]maternal UPD chromosome 14 syndrome[close quotes] is emerging; however, the contribution of the mosaic trisomy 14 to the phenotype cannot be evaluated. The study of de novo Robertsonian translocations of the type reported here should reveal both the extent of UPD in these events and the contribution of particular chromosomes involved in certain phenotypes. 33 refs., 3 figs., 1 tab.

  4. Detailed analysis of X chromosome inactivation in a 49,XXXXX pentasomy

    Science.gov (United States)

    Moraes, Lucia M; Cardoso, Leila CA; Moura, Vera LS; Moreira, Miguel AM; Menezes, Albert N; Llerena, Juan C; Seuánez, Héctor N

    2009-01-01

    Background Pentasomy X (49,XXXXX) has been associated with a severe clinical condition, presumably resulting from failure or disruption of X chromosome inactivation. Here we report that some human X chromosomes from a patient with 49,XXXXX pentasomy were functionally active following isolation in inter-specific (human-rodent) cell hybrids. A comparison with cytogenetic and molecular findings provided evidence that more than one active X chromosome was likely to be present in the cells of this patient, accounting for her abnormal phenotype. Results 5-bromodeoxyuridine (BrdU)-pulsed cultures showed different patterns among late replicating X chromosomes suggesting that their replication was asynchronic and likely to result in irregular inactivation. Genotyping of the proband and her mother identified four maternal and one paternal X chromosomes in the proband. It also identified the paternal X chromosome haplotype (P), indicating that origin of this X pentasomy resulted from two maternal, meiotic non-disjunctions. Analysis of the HUMANDREC region of the androgen receptor (AR) gene in the patient's mother showed a skewed inactivation pattern, while a similar analysis in the proband showed an active paternal X chromosome and preferentially inactivated X chromosomes carrying the 173 AR allele. Analyses of 33 cell hybrid cell lines selected in medium containing hypoxanthine, aminopterin and thymidine (HAT) allowed for the identification of three maternal X haplotypes (M1, M2 and MR) and showed that X chromosomes with the M1, M2 and P haplotypes were functionally active. In 27 cell hybrids in which more than one X haplotype were detected, analysis of X inactivation patterns provided evidence of preferential inactivation. Conclusion Our findings indicated that 12% of X chromosomes with the M1 haplotype, 43.5% of X chromosomes with the M2 haplotype, and 100% of the paternal X chromosome (with the P haplotype) were likely to be functionally active in the proband's cells, a

  5. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B; Vogel, F; Noer, H; Mikkelsen, M

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation with...

  6. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  7. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  8. Chromosomes, cancer and radiosensitivity

    International Nuclear Information System (INIS)

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available

  9. Chromosome Morphology in Kniphofia.

    Directory of Open Access Journals (Sweden)

    J. M. J de Wet

    1960-12-01

    Full Text Available A number of species and varieties of the genus  Kniphofia (Liliaceae were studied cytologically. The somatic chromosome number is  2n = 12 in all the species. This is also true in  Notosceptrum natalense Baker.

  10. Neutrino beam plasma instability

    Indian Academy of Sciences (India)

    Vishnu M Bannur

    2001-10-01

    We derive relativistic fluid set of equations for neutrinos and electrons from relativistic Vlasov equations with Fermi weak interaction force. Using these fluid equations, we obtain a dispersion relation describing neutrino beam plasma instability, which is little different from normal dispersion relation of streaming instability. It contains new, nonelectromagnetic, neutrino-plasma (or electroweak) stable and unstable modes also. The growth of the instability is weak for the highly relativistic neutrino flux, but becomes stronger for weakly relativistic neutrino flux in the case of parameters appropriate to the early universe and supernova explosions. However, this mode is dominant only for the beam velocity greater than 0.25 and in the other limit electroweak unstable mode takes over.

  11. Instabilities in astrophysical jets

    International Nuclear Information System (INIS)

    Instabilities in astrophysical jets are studied in the nonlinear regime by performing 2D numerical classical gasdynamical calculations. The instabilities which arise from unsteadiness in output from the central engine feeding the jets, and those which arise from a beam in a turbulent surrounding are studied. An extra power output an order of magnitude higher than is normally delivered by the engine over a time equal to (nozzle length)/(sound velocity at centre) causes a nonlinear Kelvin-Helmholtz instability in the jet walls. Constrictions move outwards, but the jet structure is left untouched. A beam in turbulent surroundings produces internal shocks over distances of a few beam widths. If viscosity is present the throughput of material is hampered on time scales of a few beam radius sound travel times. The implications are discussed. (Auth.)

  12. Nonlinear mirror instability

    CERN Document Server

    Rincon, F; Cowley, S C

    2014-01-01

    Slow dynamical changes in magnetic-field strength and invariance of the particles' magnetic moments generate ubiquitous pressure anisotropies in weakly collisional, magnetized astrophysical plasmas. This renders them unstable to fast, small-scale mirror and firehose instabilities, which are capable of exerting feedback on the macroscale dynamics of the system. By way of a new asymptotic theory of the early nonlinear evolution of the mirror instability in a plasma subject to slow shearing or compression, we show that the instability does not saturate quasilinearly at a steady, low-amplitude level. Instead, the trapping of particles in small-scale mirrors leads to nonlinear secular growth of magnetic perturbations, $\\delta B/B \\propto t^{2/3}$. Our theory explains recent collisionless simulation results, provides a prediction of the mirror evolution in weakly collisional plasmas and establishes a foundation for a theory of nonlinear mirror dynamics with trapping, valid up to $\\delta B/B =O(1)$.

  13. Organization of the bacterial chromosome.

    OpenAIRE

    Krawiec, S.; Riley, M

    1990-01-01

    Recent progress in studies on the bacterial chromosome is summarized. Although the greatest amount of information comes from studies on Escherichia coli, reports on studies of many other bacteria are also included. A compilation of the sizes of chromosomal DNAs as determined by pulsed-field electrophoresis is given, as well as a discussion of factors that affect gene dosage, including redundancy of chromosomes on the one hand and inactivation of chromosomes on the other hand. The distinction ...

  14. Photomultiplier time instability

    International Nuclear Information System (INIS)

    A short-time and slow instability of anode photocurrent in photoelectron multiplier is investigated. The analysis of sorption and desorption processes stimulated by electron excitation allowed to propose an adsorption-desorption mechanism of devices instability. Transient response and drift of photomultiplier anode photocurrent are measured as well as the curves of spent variations of spectral sensitivity of photocathode and individual amplifier cascades of the multiplying system depending on anode current. The results of calculating the proposed model are in good agreement with the experimental data

  15. Ringed accretion disks: instabilities

    CERN Document Server

    Pugliese, D

    2016-01-01

    We analyze the possibility that several instability points may be formed, due to the Paczy\\'nski mechanism of violation of mechanical equilibrium, in the orbiting matter around a supermassive Kerr black hole. We consider recently proposed model of ringed accretion disk, made up by several tori (rings) which can be corotating or counterrotating relative to the Kerr attractor due to the history of the accretion process. Each torus is governed by the general relativistic hydrodynamic Boyer condition of equilibrium configurations of rotating perfect fluids. We prove that the number of the instability points is generally limited and depends on the dimensionless spin of the rotating attractor.

  16. Longitudinal microwave instability

    International Nuclear Information System (INIS)

    A derivation of the relationship between growth rate and impedance is given. The only other instability considered here is the resonance effect produced by excessive tune shift due to space charge. We assume, without discussion, the (Δν)/sub max/ = .25; that is, this resonance growth is avoided (stability) by limiting the ring charge. On the other hand, the longitudinal microwave instability is assumed to be present (cannot be stabilized). Thus, the latter involves a limiting impedance to keep the growth rate low enough. The maximum allowed impedance for a maximum allowed growth rate is listed

  17. Ringed Accretion Disks: Instabilities

    Science.gov (United States)

    Pugliese, D.; Stuchlík, Z.

    2016-04-01

    We analyze the possibility that several instability points may be formed, due to the Paczyński mechanism of violation of mechanical equilibrium, in the orbiting matter around a supermassive Kerr black hole. We consider a recently proposed model of a ringed accretion disk, made up by several tori (rings) that can be corotating or counter-rotating relative to the Kerr attractor due to the history of the accretion process. Each torus is governed by the general relativistic hydrodynamic Boyer condition of equilibrium configurations of rotating perfect fluids. We prove that the number of the instability points is generally limited and depends on the dimensionless spin of the rotating attractor.

  18. The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

    Science.gov (United States)

    MacKinnon, Ruth N.; Campbell, Lynda J.

    2011-01-01

    Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy. PMID:22567363

  19. Fluidelastic instability in tube arrays

    International Nuclear Information System (INIS)

    When an array of tubes is subjected to crossflow, the tubes can experience dynamic instability, generally called fluidelastic instability. Instability initiates when the crossflow velocity exceeds a threshold value above which energy input from the flow exceeds that dissipated by system damping. Catastrophic failures of reactor and process plant equipment have been attributed to fluidelastic instability. As a result, extensive research studies have been conducted in the last 15 years with the objective of understanding the instability mechanisms and developing general design guidelines to avoid instability. Argonne National Laboratory has a continuing research program in this area which includes both mathematical model development and experimentation. This paper describes recent developments and accomplishments

  20. Mini-chromosomes among danish Candida glabrata isolates originated through two different mechanisms

    DEFF Research Database (Denmark)

    Ahmad, K. M.; Ishchuk, O.; Hellborg, L.;

    2012-01-01

    ) through a segmental duplication which covered the centromeric region, and (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of mini-chromosomes carrying duplicated genes exhibited mitotic instability......We analyzed 201 strains of the pathogenic yeast Candida glabrata from patients, mainly suffering from systemic infection, at Danish hospitals during 1985 – 1999. Our analysis showed that these strains were closely related but exhibited large karyotype polymorphism. Nine strains contained mini-chromosomes......, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, C. glabrata strains had independent origin and the analyzed mini-chromosomes were struc- turally not related to each other (i.e., they contained different sets o genes). We inferred two mechanisms involved in their origin: (i...

  1. B chromosomes in the species Prochilodus argenteus (Characiformes, Prochilodontidae: morphologicalidentity and dispersion

    Directory of Open Access Journals (Sweden)

    Manolo Penitente

    2015-03-01

    Full Text Available B chromosomes have attracted the attention of Neotropical fish cytogeneticists in recent years, both for their remarkable occurrence in this group and also because of the interest in studies of the genetic structure and role played in the genome of these organisms. The aim of this study was to report the first occurrence of supernumerary chromosomes in Prochilodus argenteus (Agassiz, 1829, this being the fifth carrier species among thirteen within the genus Prochilodus (Agassiz, 1829. The extra elements identified in this species are small sized heterochromatic chromosomes characterized by a low mitotic instability index, being very similar to other supernumerary chromosomes described in the species of the genus Prochilodus. Morphology, structure and dispersion of the supernumerary genomic elements which occur in species of this genus are discussed aiming to better understand aspects involved the origin of supernumerary chromosomes and the differentiation process and relationships among species of this family.

  2. B chromosomes in the species Prochilodus argenteus (Characiformes, Prochilodontidae): morphologicalidentity and dispersion

    Science.gov (United States)

    Penitente, Manolo; Foresti, Fausto; Porto-Foresti, Fábio

    2015-01-01

    Abstract B chromosomes have attracted the attention of Neotropical fish cytogeneticists in recent years, both for their remarkable occurrence in this group and also because of the interest in studies of the genetic structure and role played in the genome of these organisms. The aim of this study was to report the first occurrence of supernumerary chromosomes in Prochilodus argenteus (Agassiz, 1829), this being the fifth carrier species among thirteen within the genus Prochilodus (Agassiz, 1829). The extra elements identified in this species are small sized heterochromatic chromosomes characterized by a low mitotic instability index, being very similar to other supernumerary chromosomes described in the species of the genus Prochilodus. Morphology, structure and dispersion of the supernumerary genomic elements which occur in species of this genus are discussed aiming to better understand aspects involved the origin of supernumerary chromosomes and the differentiation process and relationships among species of this family. PMID:25893076

  3. B chromosomes in the species Prochilodusargenteus (Characiformes, Prochilodontidae): morphologicalidentity and dispersion.

    Science.gov (United States)

    Penitente, Manolo; Foresti, Fausto; Porto-Foresti, Fábio

    2015-01-01

    B chromosomes have attracted the attention of Neotropical fish cytogeneticists in recent years, both for their remarkable occurrence in this group and also because of the interest in studies of the genetic structure and role played in the genome of these organisms. The aim of this study was to report the first occurrence of supernumerary chromosomes in Prochilodusargenteus (Agassiz, 1829), this being the fifth carrier species among thirteen within the genus Prochilodus (Agassiz, 1829). The extra elements identified in this species are small sized heterochromatic chromosomes characterized by a low mitotic instability index, being very similar to other supernumerary chromosomes described in the species of the genus Prochilodus. Morphology, structure and dispersion of the supernumerary genomic elements which occur in species of this genus are discussed aiming to better understand aspects involved the origin of supernumerary chromosomes and the differentiation process and relationships among species of this family. PMID:25893076

  4. Variation in chromosome number in the seedling progeny of a somaclone of Paspalum dilatatum

    Institute of Scientific and Technical Information of China (English)

    ZHUJM; LJDAVIES; 等

    1994-01-01

    The somaclone,C39,derived by tissue culture from the obligate apomict Paspalum dilatatum cv Raki(2n=50),had 50 chromosomes and a karyotype apparently identical to Raki.SC2 seedlings of C39 showed a high degree of phenotypic variation which was often associated with increased chromosome numbers,but some of the variant seedlings were karyotypically indistinguishable from Raki or C39.Plants with increased chromosome numbers exhibited a high degree of intraplant chromosome variation(aneusomaty).In one of the SC2 seedlings,the chromosome number of root tip cells varied from 58 to 82 and in several other seedlings the range was more than 10.The results suggested that the ability to form seed apomictically was much reduced in C39 and that this plant showed some capacity for sexual reproduction and the resulting seedlings,with a chromosome number of about 70,were genetically unstable.Of 11 SC2 seedlings examined cytologically,6 did not produce any viable seed.Seedlings grown from seed of the remaining 5 plants showed that aneusomaty persisted in the SC3 generation.SC3 seedlings which were phenotypically similar to their maternal parent showed a similar range of chromosome numbers to that parent.Some of the SC3 seedlings exhibited an even wider range of chromosome numbers(e.g.56-136),and these plants were all dwarfs.

  5. The chromosome passenger complex is required for fidelity of chromosome transmission and cytokinesis in meiosis of mouse oocytes.

    Science.gov (United States)

    Sharif, Bedra; Na, Jie; Lykke-Hartmann, Karin; McLaughlin, Stephen H; Laue, Ernest; Glover, David M; Zernicka-Goetz, Magdalena

    2010-12-15

    The existence of two forms of the chromosome passenger complex (CPC) in the mammalian oocyte has meant that its role in female meiosis has remained unclear. Here we use loss- and gain-of function approaches to assess the meiotic functions of one of the shared components of these complexes, INCENP, and of the variable kinase subunits, Aurora B or Aurora C. We show that either the depletion of INCENP or the combined inhibition of Aurora kinases B and C activates the anaphase-promoting complex or cyclosome (APC/C) before chromosomes have properly congressed in meiosis I and also prevents cytokinesis and hence extrusion of the first polar body. Overexpression of Aurora C also advances APC/C activation and results in cytokinesis failure in a high proportion of oocytes, indicative of a dominant effect on CPC function. Together, this points to roles for the meiotic CPC in functions similar to the mitotic roles of the complex: correcting chromosome attachment to microtubules, facilitating the spindle-assembly checkpoint (SAC) function and enabling cytokinesis. Surprisingly, overexpression of Aurora B leads to a failure of APC/C activation, stabilization of securin and consequently a failure of chiasmate chromosomes to resolve - a dominant phenotype that is completely suppressed by depletion of INCENP. Taken together with the differential distribution of Aurora proteins B and C on chiasmate chromosomes, this points to differential functions of the two forms of CPC in regulating the separation of homologous chromosomes in meiosis I. PMID:21123620

  6. Complementation of a DNA repair defect in xeroderma pigmentosum cells by transfer of human chromosome 9

    International Nuclear Information System (INIS)

    Complementation of the repair defect in xeroderma pigmentosum cells of complementation group A was achieved by the transfer of human chromosome 9. A set of mouse-human hybrid cell lines, each containing a single Ecogpt-marked human chromosome, was used as a source of donor chromosomes. Chromosome transfer to XPTG-1 cells, a hypoxanthine/guanine phosphoribosyltransferase-deficient mutant of simian virus 40-transformed complementation group A cells, was achieved by microcell fusion and selection for Ecogpt. Chromosome-transfer clones of XPTG-1 cells, each containing a different human donor chromosome, were analyzed for complementation of sensitivity to UV irradiation. Among all the clones, increased levels of resistance to UV was observed only in clones containing chromosome 9. Since our recipient cell line XPTG-1 is hypoxanthine/guanine phosphoribosyltransferase deficient, cultivation of Ecogpt+ clones in medium containing 6-thioguanine permits selection of cells for loss of the marker and, by inference, transferred chromosome 9. Clones isolated for growth in 6-thioguanine, which have lost the Ecogpt-marked chromosome, exhibited a UV-sensitive phenotype, confirming the presence of the repair gene(s) for complementation group A on chromosome 9

  7. Demarcation of informative chromosomes in tropical sweet corn inbred lines using microsatellite DNA markers

    Directory of Open Access Journals (Sweden)

    Pedram Kashiani

    2012-01-01

    Full Text Available A study of genetic variation among 10 pairs of chromosomes extracted from 13 tropical sweet corn inbred lines, using 99 microsatellite markers, revealed a wide range of genetic diversity. Allelic richness and the number of effective alleles per chromosome ranged from 2.78 to 4.33 and 1.96 to 3.47, respectively, with respective mean values of 3.62 and 2.73. According to the Shannon's information index (I and Nei's gene diversity coefficient (Nei, Chromosome 10 was the most informative chromosome (I = 1.311 and Nei = 0.703, while Chromosome 2 possessed the least (I = 0.762 and Nei = 0.456. Based on linkage disequilibrium (LD measurements for loci less than 50 cM apart on the same chromosome, all loci on Chromosomes 1, 6 and 7 were in equilibrium. Even so, there was a high proportion of genetic variation in Chromosomes 4, 5, 8, 9 and 10, thereby revealing their appropriateness for use in the genetic diversity investigations among tropical sweet corn lines. Chromosome 4, with the highest number of loci in linkage disequilibrium, was considered the best for marker-phenotype association and QTL mapping, followed by Chromosomes 5, 8, 9 and 10.

  8. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    DNA damages induced by space radiation, consisting of protons and high-LET charged particles, can be complex in nature, which are often left unrepaired and cause chromosomal aberrations. Increased level of genomic instability is attributed to tumorigenesis and increased cancer risks. To investigate genomic instability induced by charged particles, human lymphocytes ex vivo, human fibroblasts, and human mammary epithelial cells, as well as mouse bone marrow stem cells isolated from CBA/CaH and C57BL/6 strains were exposed to high energy protons and Fe ions. Metaphase chromosome spreads at different cell divisions after radiation exposure were collected and, chromosome aberrations were analyzed with fluorescence in situ hybridization with whole chromosome-specific probes for human cells. With proton irradiation, levels of chromosome aberrations decreased by about 50% in both lymphocytes and epithelial cells after multiple cell divisions, compared to initial chromosome aberrations at 48 hours post irradiation in both cell types. With Fe ion irradiation, however, the frequency of chromosome aberrations in lymphocytes after multiple cell divisions was significantly lower than that in epithelial cells at comparable cell divisions, while their initial chromosome aberrations were at similar levels. Similar to the human cells, after Fe ion irradiation, the frequency of late chromosome aberrations was similar to that of the early damages for radio-sensitive CBA cells, but different for radio-resistant C57 cells. Our results suggest that relative biological effectiveness (RBE) values are dependent not only on radiation sources, but also on cell types and cell divisions.

  9. The role of the type of pollination in the manifestation of the radiation-induced instability of a genome of plants

    International Nuclear Information System (INIS)

    The radiation-induced genome instability of plants of tobacco Nicotiana tabacum L. and onion Allium cepa L. is investigated. The increase of the amount of chromosomal aberrations in the plants of M1 and M2 is revealed. The level of chromosomal aberrations depends on the dose of irradiation and the method of plants pollination

  10. Induction of Genomic Instability In Vivo by Low Doses of 137Cs gamma rays

    International Nuclear Information System (INIS)

    The overall goal of this project is to determine if low doses (below or equal to the level traditionally requiring human radiation protection, i.e. less than or equal to 10 cGy) of low LET radiation can induce genomic instability. The magnitude of genomic instability was measured as delayed chromosome instability in bone marrow cells of exposed mice with different levels of endogenous DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, i.e. high (C57BL/6J mice), intermediate (BALB/cJ mice), and extremely low (Scid mice). In addition, at early time points (1 and 4 hrs) following irradiation, levels of activation of nuclear factor-kappa B (NF-κB), a transcription factor known to be involved in regulating the expression of genes responsible for cell protection following stimuli, were measured in these cells. Bone marrow cells were collected at different times following irradiation, i.e. 1 hr, 4 hrs, 1 month, and 6 months. A total of five mice per dose per strain were sacrificed at each time point for sample collection. As a result, a total of 80 mice from each strain were used. The frequency and the type of metaphase chromosome aberrations in bone marrow cells collected from exposed mice at different times following irradiation were used as markers for radiation-induced genomic instability. A three-color fluorescence in situ hybridization (FISH) protocol for mouse chromosomes 1, 2, and 3 was used for the analysis of delayed stable chromosomal aberrations in metaphase cells. All other visible chromatid-type aberrations and gross structural abnormalities involving non-painted chromosomes were also evaluated on the same metaphase cells used for scoring the stable chromosomal aberrations of painted chromosomes. Levels of nuclear factor-kappa B (NF-κB) activation were also determined in cells at 1 and 4 hrs following irradiation (indicative of early responses)

  11. [Chromosomal organization of the genomes of small-chromosome plants].

    Science.gov (United States)

    Muravenko, O V; Zelenin, A V

    2009-11-01

    An effective approach to study the chromosome organization in genomes of plants with small chromosomes and/or with low-informative C-banding patterns was developed in the course of investigation of the karyotypes of cotton plant, camomile, flax, and pea. To increase the resolving power of chromosome analysis, methods were worked out for revealing early replication patterns on chromosomes and for artificial impairment of mitotic chromosome condensation with the use of a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the patterns of C-banding of small chromosomes on preparations obtained with the use of 9-AMA, it is necessary to choose a length interval that must not exceed three average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA increases the resolution of differential C- and OR-banding and the precision of physical chromosome mapping by the FISH method. Of particular importance in studying small chromosomes is optimization of the computer-aided methods used to obtain and process chromosome images. The complex approach developed for analysis of the chromosome organization in plant genomes was used to study the karyotypes of 24 species of the genus Linum L. It permitted their chromosomes to be identified for the first time, and, in addition, B chromosomes were discovered and studied in the karyotypes of the species of the section Syllinum. By similarity of the karyotypes, the studied flax species were distributed in eight groups in agreement with the clusterization of these species according to the results of RAPD analysis performed in parallel. Systematic positions and phylogenetic relationships of the studied flax species were verified. Out results can serve as an important argument in favour of the proposal to develop a special program for sequencing the genome of cultivated flax (L. usitatissimum L.), which is a major representative of small-chromosome species. PMID:20058798

  12. Cancer morphology, carcinogenesis and genetic instability: a background.

    Science.gov (United States)

    Bignold, Leon P; Coghlan, B L D; Jersmann, H P A

    2006-01-01

    Morphological abnormalities of both the nuclei and the cell bodies of tumour cells were described by Müller in the late 1830s. Abnormalities of mitoses and chromosomes in tumour cells were described in the late 1880s. Von Hansemann, in the 1890s, suggested that tumour cells develop from normal cells because of a tendency to mal-distribution and other changes of chromosomes occurring during mitosis. In the first decades of the 20th century, Mendelian genetics and "gene mapping" of chromosomes were established, and the dominant or recessive bases of the familial predispositions to certain tumour types were recognised. In the same period, the carcinogenic effects of ionising radiations, of certain chemicals and of particular viruses were described. A well-developed "somatic gene-mutational theory" of tumours was postulated by Bauer in 1928. In support of this, in the next three decades, many environmental agents were found to cause mitotic and chromosomal abnormalities in normal cells as well as mutations in germ-line cells of experimental animals. Nevertheless, mitotic, chromosomal, and other mutational theories were not popular explanations of tumour pathogenesis in the first half of the 20th century. Only in the 1960s did somatic mutational mechanisms come to dominate theories of tumour formation, especially as a result of the discoveries of the reactivity of carcinogens with DNA, and that the mutation responsible for xeroderma pigmentosum causes loss of function of a gene involved in the repair of DNA after damage by ultraviolet light (Cleaver in 1968). To explain the complexity of tumourous phenomena, "multi-hit" models gained popularity over "single-hit" models of somatic mutation, and "epigenetic" mechanisms of gene regulation began to be studied in tumour cells. More recently, the documentation of much larger-than-expected numbers of genomic events in tumour cells (by Stoler and co-workers, in 1999) has raised the issue of somatic genetic instability in

  13. A deletion map of the WAGR region on chromosome 11.

    OpenAIRE

    Gessler, M; Thomas, G H; Couillin, P; Junien, C; McGillivray, B C; Hayden, M; Jaschek, G.; Bruns, G. A.

    1989-01-01

    The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual ...

  14. Tracking Code for Microwave Instability

    Energy Technology Data Exchange (ETDEWEB)

    Heifets, S.; /SLAC

    2006-09-21

    To study microwave instability the tracking code is developed. For bench marking, results are compared with Oide-Yokoya results [1] for broad-band Q = 1 impedance. Results hint to two possible mechanisms determining the threshold of instability.

  15. Microsatellite Instability Assay — EDRN Public Portal

    Science.gov (United States)

    Microsatellite analysis (MSA) is a promising new technique for the surveillance of bladder cancer. The technology, which permits the separation by electrophoresis of polymerase chain reaction (PCR)-amplified sequences from non-malignant and malignant sources, has been applied to the diagnosis of solid tumors arising in colon, lung, oropharynx, kidney and bladder. MSA can detect genetic changes indicative of carcinoma from urothelial cells obtained in voided urine specimens. The genetic profile of DNA purified from urine is compared to that of DNA purified from peripheral lymphocytes that are considered normal. Once the DNA from uroepithelial cells has been obtained, PCR is performed with specific oligonucleotide primers for each chromosomal locus. The PCR products are then examined for evidence of microsatellite instability (MSI) and loss of heterozygosity (LOH), which are genetic characteristics of epithelial tumors. Preliminary work shows that MSA detects 95% of cancers.

  16. Two complementary recombinant chromosomes 5 in a healthy woman.

    Science.gov (United States)

    Bartsch, O; Ergun, M A; Balci, S; Kan, D; Eggermann, T; Kotzot, D

    2006-01-01

    We report a healthy woman with two abortions who is a carrier for a rare heterozygous double recombinant of an inv(5) chromosome, karyotype 46,XX,rec(5)dup(5p) inv(5)(p13q22),rec(5)dup(5q)inv(5)(p13q22). Her father had a 46,XY,inv(5)(p13q22) karyotype; his consanguineous wife had died. Molecular investigation of 11 highly polymorphic markers spanning chromosome 5 revealed biparental inheritance for two markers (D5S406, D5S681) on 5p15.3 and 5q13.1, and an allele constellation not compatible with paternal heterodisomy for marker D5S623 on 5q11.2. Eight markers were not informative. Three mechanisms of formation are proposed: First, fertilization of a normal oocyte by a sperm carrying the two recombinant chromosomes 5, followed by postzygotic recombination between the normal maternal homologue and the rec(5)dup(5p), and by loss of the mitotically recombined maternal homologue, leading to segmental paternal heterodisomy 5q13-->qter (trisomic rescue). Second, postzygotic recombination in a 46,XX,inv(5)(p13q22) zygote resulting in the 46,XX,rec(5)dup(5p)inv(5)(p13q22),rec(5) dup(5q)inv(5)(p13q22) karyotype, followed by absence of the original cell line in lymphocytes. Third and most likely, both parents were inv(5) carriers and complementary recombinations in maternal and paternal meiosis resulted in a zygote with two recombinant chromosomes 5. Our patient refused any further studies but later reported the birth of a phenotypically normal child. This is the first report known to us of complementation by two non-homologous recombinant chromosomes in a phenotypically normal woman, and the first example of a child born to a carrier of complementary recombinant chromosomes. PMID:16825772

  17. Phenotypic and genetic heterogeneity in a genome-wide linkage study of asthma families

    Directory of Open Access Journals (Sweden)

    Schuster Antje

    2005-01-01

    Full Text Available Abstract Background Asthma is a complex genetic disease with more than 20 genome-wide scans conducted so far. Regions on almost every chromosome have been linked to asthma and several genes have been associated. However, most of these associations are weak and are still awaiting replication. Methods In this study, we conducted a second-stage genome-wide scan with 408 microsatellite markers on 201 asthma-affected sib pair families and defined clinical subgroups to identify phenotype-genotype relations. Results The lowest P value for asthma in the total sample was 0.003 on chromosome 11, while several of the clinical subsets reached lower significance levels than in the overall sample. Suggestive evidence for linkage (p = 0.0007 was found for total IgE on chromosomes 1, 7 and again on chromosome 11, as well as for HDM asthma on chromosome 12. Weaker linkage signals could be found on chromosomes 4 and 5 for early onset and HDM, and, newly described, on chromosome 2 for severe asthma and on chromosome 9 for hay fever. Conclusions This phenotypic dissection underlines the importance of detailed clinical characterisations and the extreme genetic heterogeneity of asthma.

  18. Shock instability in dissipative gases

    OpenAIRE

    Radulescu, Matei I.; Sirmas, Nick

    2011-01-01

    Previous experiments have revealed that shock waves in thermally relaxing gases, such as ionizing, dissociating and vibrationally excited gases, can become unstable. To date, the mechanism controlling this instability has not been resolved. Previous accounts of the D'yakov-Kontorovich instability, and Bethe-Zel'dovich-Thompson behaviour could not predict the experimentally observed instability. To address the mechanism controlling the instability, we study the propagation of shock waves in a ...

  19. Chromosomal abnormalities and hormonal disorders of primary amenorrhea patients in Egypt

    OpenAIRE

    Faeza El-Dahtory

    2012-01-01

    Background: Primary amenorrhea is defined as the absence of menstruation and secondary sexual characteristics in phenotypic women aged 14 years or older. Hormonal disorders are main causes of primary amenorrhea. Common hormonal cause of primary amenorrhea includes pituitary dysfunction and absent ovarian function. The aim of this study was to estimate the incidence and types of chromosomal abnormalities in patients with primary amenorrhea in Egypt. Materials and Methods: Chromosomal analys...

  20. Chromosomal Alterations during Lymphatic and Liver Metastasis Formation of Colorectal Cancer1

    OpenAIRE

    Knösel, Thomas; Schlüns, Karsten; Stein, Ulrike; Schwabe, Holger; Schlag, Peter Michael; Dietel, Manfred; Petersen, Iver

    2004-01-01

    Comparative genomic hybridization (CGH) was used to screen colorectal carcinomas for chromosomal aberrations that are associated with metastatic phenotype. In total, 63 tumor specimens from 40 patients were investigated, comprising 30 primary tumors, 22 systemic metastases (12 liver, 6 brain, and 4 abdominal wall metastases) and 11 lymph node tumors. Using statistical analysis and histograms to evaluate the chromosomal imbalances, overrepresentations were detected most frequently at 20q11.2–2...

  1. Conservation of chromosomal arrangement among three strains of the genetically unstable archaeon Halobacterium salinarium.

    OpenAIRE

    Hackett, N R; Bobovnikova, Y; Heyrovska, N

    1994-01-01

    Phenotypic variants of Halobacterium salinarium NRC-1 arise at a frequency of 10(-2). These result from transpositions of halobacterial insertion sequences and rearrangements mediated by halobacterial insertion sequences. We have tested the hypothesis that such mutations are confined to only a portion of the genome by comparing the chromosomal restriction map of H. salinarium NRC-1 and that of the derivative S9, which was made in 1969. The two chromosomes were mapped by using two-dimensional ...

  2. Linked genetic variants on chromosome 10 control ear morphology and body mass among dog breeds

    OpenAIRE

    Webster, Matthew T.; Kamgari, Nona; Perloski, Michele; Höppner, Marc P.; Axelsson, Erik; Hedhammar, Ake; Pielberg, Gerli; Lindblad-Toh, Kerstin

    2015-01-01

    Background The domestic dog is a rich resource for mapping the genetic components of phenotypic variation due to its unique population history involving strong artificial selection. Genome-wide association studies have revealed a number of chromosomal regions where genetic variation associates with morphological characters that typify dog breeds. A region on chromosome 10 is among those with the highest levels of genetic differentiation between dog breeds and is associated with body mass and ...

  3. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

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

    Science.gov (United States)

    Paththinige, C S; Sirisena, N D; Kariyawasam, U G I U; Saman Kumara, L P C; Dissanayake, V H W

    2016-01-01

    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. PMID:27610251

  5. Nonlinear evolution of MHD instabilities

    International Nuclear Information System (INIS)

    A 3-D nonlinear MHD computer code was used to study the time evolution of internal instabilities. Velocity vortex cells are observed to persist into the nonlinear evolution. Pressure and density profiles convect around these cells for a weak localized instability, or convect into the wall for a strong instability. (U.S.)

  6. Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH)

    NARCIS (Netherlands)

    Maas, N. M. C.; Van Buggenhout, G.; Hannes, F.; Thienpont, B.; Sanlaville, D.; Kok, K.; Midro, A.; Andrieux, J.; Anderlid, B-M; Schoumans, J.; Hordijk, R.; Devriendt, K.; Fryns, J-P; Vermeesch, J. R.

    2008-01-01

    Background: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these fe

  7. Analysis of Genotype-Phenotype Correlations in Human Holoprosencephaly

    OpenAIRE

    Solomon, Benjamin D.; Mercier, Sandra; Vélez, Jorge I.; Pineda-Alvarez, Daniel E.; Wyllie, Adrian; Zhou, Nan; Dubourg, Christèle; David, Veronique; Odent, Sylvie; Roessler, Erich; Muenke, Maximilian

    2010-01-01

    Since the discovery of the first gene causing holoprosencephaly (HPE), over 500 patients with mutations in genes associated with non-chromosomal, non-syndromic HPE have been described, with detailed descriptions available in over 300. Comprehensive clinical analysis of these individuals allows examination for the presence of genotype-phenotype correlations. These correlations allow a degree of differentiation between patients with mutations in different HPE-associated genes and for the applic...

  8. Possible role of imprinting in the Turner phenotype.

    OpenAIRE

    Chu, C E; Donaldson, M D; Kelnar, C J; Smail, P. J.; Greene, S A; Paterson, W.F.; Connor, J M

    1994-01-01

    We have attempted to investigate the role of imprinting in the phenotype of Turner's syndrome. Sixty-three patients were investigated for parental origin of the retained normal X chromosome; 43 were found to retain the maternal X (XM) and 20 the paternal (XP). The relationship between a child's pretreatment height centile and parental height centiles was examined in 36 patients. No significant correlation was found between child and parental height centiles for XP or child and paternal height...

  9. HA novel approach to investigate tissue-specific trinucleotide repeat instability

    Directory of Open Access Journals (Sweden)

    Boily Marie-Josee

    2010-03-01

    Full Text Available Abstract Background In Huntington's disease (HD, an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. Results Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. Conclusion Our study clearly demonstrates that multiple tissue factors reflect the level of

  10. Genetic instability in Gynecological Cancer

    Institute of Scientific and Technical Information of China (English)

    ZHAO Qing-hua; ZHOU Hong-lin

    2003-01-01

    Defects of mismatch repair (MMR) genes also have beenidentified in many kinds of tumors. Loss of MMR functionhas been linked to genetic instability especially microsatelliteinstability that results in high mutation rate. In this review, wediscussed the microsatellite instability observed in thegynecological tumors. We also discussed defects in the DNAmismatch repair in these tumors and their correlation to themicrosatellite instability, as well as the gene mutations due tothe microsatellite instability in these tumors. From thesediscussion, we tried to understand the mechanism ofcarcinogenesis in gynecological tumors from the aspect ofgenetic instability due to mismatch repair defects.

  11. Cosmic ray driven instability

    International Nuclear Information System (INIS)

    The interaction between energetic charged particles and thermal plasma, which forms the basis of diffusive shock acceleration, leads also to interesting dynamical phenomena. For a compressional mode propagating in a system with homoeneous energetic particle pressure it is well known that friction with the energetic particles leads to damping. The linear theory of this effect has been analyzed in detail by Ptuskin. Not so obvious is that a non-uniform energetic particle pressure can in addition amplify compressional disturbances. If the pressure gradient is sufficiently steep this growth can dominate the frictional damping and lead to an instability. It is important to not that this effect results from the collective nature of the interaction between the energetic particles and the gas and is not connected with the Parker instability, nor with the resonant amplification of Alfven waves

  12. Whistler modulational instability.

    Science.gov (United States)

    Brinca, A. L.

    1973-01-01

    Derivation of the modulational instability characteristics of whistlers in cold and hot plasmas. The cold-plasma analysis considers both ion motion and relativistic effects; the unstable band, with a growth rate proportional to (B/B sub zero)squared, is contiguous to Omega sub e/4 and, depending on the plasma density, lies above or below that frequency (Omega sub e is the electron cyclotron frequency of the static magnetic field; B and B sub zero are the whistler and static magnetic fields). In hot plasmas, stability occurs between Omega sub e/4 and Omega prime (less than Omega sub e), with Omega prime depending mainly on the mean energy and anisotropy of the energetic electron population; the complementary unstable band has a growth rate proportional to (B/B sub zero) to the 1/2 power. The relevance of the instability to whistlers in the magnetosphere is discussed.

  13. Phenotypic heterogeneity of monogenic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Barbara Borroni

    2015-09-01

    Full Text Available Frontotemporal dementia (FTD is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e. the behavioral variant of FTD (bvFTD, the agrammatic variant of Primary Progressive Aphasia (avPPA and the semantic variant of PPA (svPPA. Some patients have an associated movement disorder, either parkinsonism, as in Progressive Supranuclear Palsy (PSP and Corticobasal Syndrome (CBS, or motor neuron disease (FTD-MND. A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal dominant inheritance. Genetic studies have identified several genes associated to monogenic FTD: microtubule-associated protein tau (MAPT, progranulin (GRN, TAR DNA-binding protein 43 (TARBDP, valosin-containing protein (VCP, charged multivesicular body protein 2B (CHMP2B, fused in sarcoma (FUS and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72 (C9orf72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease.

  14. The bar instability revisited

    OpenAIRE

    Chiodi, Filippo; Andreotti, Bruno; Claudin, Philippe

    2012-01-01

    The river bar instability is revisited, using a hydrodynamical model based on Reynolds averaged Navier-Stokes equations. The results are contrasted with the standard analysis based on shallow water Saint-Venant equations. We first show that the stability of both transverse modes (ripples) and of small wavelength inclined modes (bars) predicted by the Saint-Venant approach are artefacts of this hydrodynamical approximation. When using a more reliable hydrodynamical model, the dispersion relati...

  15. The Instability of Markets

    OpenAIRE

    Hogg, Tad; Huberman, Bernardo A.; Youssefmir, Michael

    1995-01-01

    Recent developments in the global liberalization of equity and currency markets, coupled to advances in trading technologies, are making markets increasingly interdependent. This increased fluidity raises questions about the stability of the international financial system. In this paper, we show that as couplings between stable markets grow, the likelihood of instabilities is increased, leading to a loss of general equilibrium as the system becomes increasingly large and diverse.

  16. The instability of markets

    CERN Document Server

    Huberman, B A; Huberman, Bernardo A; Youssefmir, Michael

    1995-01-01

    Recent developments in the global liberalization of equity and currency markets, coupled to advances in trading technologies, are making markets increasingly interdependent. This increased fluidity raises questions about the stability of the international financial system. In this paper, we show that as couplings between stable markets grow, the likelihood of instabilities is increased, leading to a loss of general equilibrium as the system becomes increasingly large and diverse.

  17. Non-conventional fishbone instabilities

    International Nuclear Information System (INIS)

    New instabilities of the fishbone type are predicted. The first is a trapped-particle-induced m = n = 1 instability with a mode structure that has nothing in common with the conventional rigid kink displacement. This instability takes place when the magnetic field is weak, so that the precession frequency of the energetic ions is not small as compared to the frequency of the corresponding Alfven continuum at r=0 and the magnetic shear is small inside the q = 1 radius (the case relevant to spherical tori). The second predicted instability is an Energertic Particle Mode fishbone instability driven by circulating particles, and the third is a double-kink-mode instability driven by the circulating energetic ions. In particular, the latter can have two frequencies simultaneously: we refer to it as 'doublet' fishbones. This instability can occur when the radial profile of the energetic ions has an off-axis maximum inside the region of the mode localization. (author)

  18. Partial trisomy 11q involving chromosome 1 detected by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, M.; Bereziouk, O.; McCorquodale, D.J. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    Partial trisomy 11q was detected in an infant delivered 3-4 weeks prematurely. The phenotype included slanted palpebral fissures, high arched palate, developmental delay, microcephaly, and cardiac defects, all of which occur in the majority of cases with this syndrome. Other features included a column-shaped skull, preauricular pit, single palmar crease, short, broad great toes, flat occiput, unilateral kidney agenesis, and strabismus. Chromosomes obtained from peripheral blood cells revealed the presence of extra material on the long arm of chromosome 1. The G-banding pattern of this extra material indicated that it might be derived from chromosome 1 or 11. Chromosomal {open_quotes}paints{close_quotes} showed that it was not chromosome 1 material, but was chromosome 11 material extending from band q21 to qter. Partial trisomy 11q arising from translocation of the 11q material to chromosome 2, 3, 4, 5, 6, 9, 10, 13, 17, 21, 22, and X has been reported previously, whereas translocation to chromosome 1 has not. The chromosome to which the 11q material is translocated does not alter the most frequent features of the partial trisomy 11q syndrome, but may influence other less common features.

  19. Characterization of genomic instability in Saccharomyces cerevisiae and engaging teaching strategies described in two curricula

    Science.gov (United States)

    Keller, Alexandra P.

    Cancer arises through an accumulation of mutations in the genome. In cancer cells, mutations are frequently caused by DNA rearrangements, which include chromosomal breakages, deletions, insertions, and translocations. Such events contribute to genomic instability, a known hallmark of cancer. To study cycles of chromosomal instability, we are using baker's yeast as a model organism. In yeast, a ChrVII system was previously developed (Admire et al., 2006), in which a disomic yeast strain was used to identify regions of instability on ChrVII. Using this system, a fragile site on the left arm of ChrVII (Admire et al., 2006) was identified and characterized. This study led to insight into mechanisms involved in chromosomal rearrangements and mutations that arise from them as well as to an understanding of mechanisms involved in genomic instability. To further our understanding of genomic instability, I devised a strategy to study instability on a different chromosome (ChrV) (Figure 3), so that we could determine whether lessons learned from the ChrVII system are applicable to other chromosomes, and/or whether other mechanisms of instability could be identified. A suitable strain was generated and analyzed, and our findings suggest that frequencies of instability on the right arm of ChrV are similar to those found in ChrVII. The results from the work in ChrV described in this paper support the idea that the instability found on ChrVII is not an isolated occurrence. My research was supported by an NSF GK-12 grant. The aim of this grant is to improve science education in middle schools, and as part of my participation in this program, I studied and practiced effective science communication methodologies. In attempts to explain my research to middle school students, I collaborated with others to develop methods for explaining genetics and the most important techniques I used in my research. While developing these methods, I learned more about what motivates people to learn

  20. Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1) or high grade of dysplasia are at 'high risk' of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI) is associated with high tumor stage and grade, and possibly with the risk of progression. To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with 'high-risk' non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical) resections and full prospective clinical follow-up (> 5 years). We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes) in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays). Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a 'high-risk' tumor). However, about 25% of the 'high-risk' tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Chromosomal instability (CI) was associated with 'high risk' tumors

  1. Uniparental isodisomy of chromosome 14 in two cases: An abnormal child and a normal adult

    Energy Technology Data Exchange (ETDEWEB)

    Papenhausen, P.R.; Mueller, O.T.; Sutcliffe, M.; Diamond, T.M.; Kousseff, B.G. [Univ. of South Florida College of Medicine, Tampa, FL (United States); Johnson, V.P. [Univ. of South Dakota, Sioux Falls, SD (United States)

    1995-11-20

    Uniparental disomy (UPD) of a number of different chromosomes has been found in association with abnormal phenotypes. A growing body of evidence for an imprinting effect involving chromosome 14 has been accumulating. We report on a case of paternal UPD of chromosome 14 studied in late gestation due to polyhydramnios and a ventral wall hernia. A prenatal karyotype documented a balanced Robertsonian 14:14 translocation. The baby was born prematurely with hairy forehead, retrognathia, mild puckering of the lips and finger contractures. Hypotonia has persisted since birth and at age one year, a tracheostomy for laryngomalacia and gastrostomy for feeding remain necessary. Absence of maternal VNTR polymorphisms and homozygosity of paternal polymorphisms using chromosome 14 specific probes at D14S22 and D14S13 loci indicated paternal uniparental isodisomy (pUPID). Parental chromosomes were normal. We also report on a case of maternal LTPD in a normal patient with a balanced Robertsonian 14:14 translocation and a history of multiple miscarriages. Five previous reports of chromosome 14 UPD suggest that an adverse developmental effect may be more severe whenever the UPD is paternal in origin. This is the second reported patient with paternal UPD and the fifth reported with maternal UPD, and only few phenotypic similarities are apparent. Examination of these chromosome 14 UPD cases of maternal and paternal origin suggests that there are syndromic imprinting effects. 30 refs., 3 figs.

  2. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  3. Exclusion of candidate genes for coat colour phenotypes of the American mink (Neovison vison)

    DEFF Research Database (Denmark)

    Anistoroaei, Razvan Marian; Markakis, M. N.; Vissenberg, K.;

    2012-01-01

    In a previous project, we screened the American mink Bacterial Artificial Chromosome library, CHORI-231, for genes potentially involved in various coat colour phenotypes in the American mink. Subsequently, we 454 sequenced the inserts containing these genes and developed microsatellite markers fo...... of similar phenotypes in other mammals, including horses, pigs, cows, dogs, cats, mice and humans, they do not appear to be responsible for comparable phenotypes found in American mink....

  4. Molecular fundamentals of chromosomal mutagenesis

    International Nuclear Information System (INIS)

    Precise quantitative correlation between the yield of chromosome structure damages and the yield of DNA damages is shown when comparing data on molecular and cytogenetic investigations carried out in cultural Mammalia cells. As the chromosome structure damage is to be connected with the damage of its carcass structure, then it is natural that DNA damage in loop regions is not to affect considerably the structure, while DNA damage lying on the loop base and connected with the chromosome carcass is to play a determining role in chromosomal mutagenesis. This DNA constitutes 1-2% from the total quantity of nuclear DNA. If one accepts that damages of these regions of DNA are ''hot'' points of chromosomal mutagenesis, then it becomes clear why 1-2% of preparation damages in a cell are realized in chromosome structural damages

  5. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli;

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...... impedance spectroscopy was selected as the sensing method on a microfabricated chip with array of 12 electrode sets. Two independent chips (Chip1 and Chip2) were used for targeting the chromosomal fragments involved in the translocation. Each chip was differentially functionalized with DNA probes matching...

  6. Shoulder instability; Schultergelenkinstabilitaet

    Energy Technology Data Exchange (ETDEWEB)

    Sailer, J.; Imhof, H. [Abteilung Osteoradiologie, Univ.-Klinik fuer Radiodiagnostik Wien (Austria)

    2004-06-01

    Shoulder instability is a common clinical feature leading to recurrent pain and limitated range of motion within the glenohumeral joint. Instability can be due a single traumatic event, general joint laxity or repeated episodes of microtrauma. Differentiation between traumatic and atraumatic forms of shoulder instability requires careful history and a systemic clinical examination. Shoulder laxity has to be differentiated from true instability followed by the clinical assessment of direction and degree of glenohumeral translation. Conventional radiography and CT are used for the diagnosis of bony lesions. MR imaging and MR arthrography help in the detection of soft tissue affection, especially of the glenoid labrum and the capsuloligamentous complex. The most common lesion involving the labrum is the anterior labral tear, associated with capsuloperiostal stripping (Bankart lesion). A number of variants of the Bankart lesion have been described, such as ALPSA, SLAP or HAGL lesions. The purpose of this review is to highlight different forms of shoulder instability and its associated radiological findings with a focus on MR imaging. (orig.) [German] Die Schultergelenkinstabilitaet ist haeufig fuer wiederholt auftretende Schmerzen sowie eine eingeschraenkte Beweglichkeit im Glenohumeralgelenk verantwortlich. Sie kann als Folge eines vorangegangenen Traumas, einer generellen Hyperlaxitaet oder infolge wiederholter Mikrotraumen entstehen. Die Differenzierung zwischen traumatischer und atraumatischer Form der Gelenkinstabilitaet erfordert eine sorgfaeltige Anamnese und eine genaue klinische Untersuchung. Die Gelelenklaxitaet als Differenzialdiagnose muss von der echten Instabilitaet unterschieden werden, die Instabilitaet wird dann im Rahmen des klinischen Status nach Grad und Richtung der glenohumeralen Translation unterteilt. Zur Diagnose knoecherner Laesionen werden das konventionelle Roentgen sowie die CT herangezogen. MRT sowie MR-Arthrographie dienen zur Detektion

  7. A Whole Genome Linkage Scan Identifies Multiple Chromosomal Regions Influencing Adiposity-Related Traits among Samoans

    OpenAIRE

    Dai, F.; Sun, G.; Åberg, K.; Keighley, E.D.; Indugula, S.R.; Roberts, S. T.; Smelser, D.; Viali, S.; Jin, L.; Deka, R.; Weeks, D.E.; McGarvey, S T

    2008-01-01

    We conducted a genome-wide scan in 46 pedigrees, with 671 phenotyped adults, from the independent nation of Samoa to map quantitative trait loci (QTLs) for adiposity-related phenotypes, including body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (%BFAT), and fasting serum leptin and adiponectin. A set of 378 autosomal and 14 X chromosomal microsatellite markers were genotyped in 572 of the adults. Significant genetic correlations (0.82–0.96) were detected between pairs...

  8. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  9. Reference-assisted chromosome assembly

    OpenAIRE

    Kim, Jaebum; Larkin, Denis M; Cai, Qingle; Asan,; Zhang, Yongfen; Ge, Ri-Li; Auvil, Loretta; Capitanu, Boris; Zhang, Guojie; Lewin, Harris A.; Ma, Jian

    2013-01-01

    One of the most difficult problems in modern genomics is the assembly of full-length chromosomes using next generation sequencing (NGS) data. To address this problem, we developed “reference-assisted chromosome assembly” (RACA), an algorithm to reliably order and orient sequence scaffolds generated by NGS and assemblers into longer chromosomal fragments using comparative genome information and paired-end reads. Evaluation of results using simulated and real genome assemblies indicates that ou...

  10. Alternative Lengthening of Telomeres: Recurrent Cytogenetic Aberrations and Chromosome Stability under Extreme Telomere Dysfunction

    Directory of Open Access Journals (Sweden)

    Despoina Sakellariou

    2013-11-01

    Full Text Available Human tumors using the alternative lengthening of telomeres (ALT exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines.We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted.We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth.

  11. Intra- and interindividual variability in lymphocyte chromosomal aberrations: implications for cancer risk assessment.

    Science.gov (United States)

    Peters, Susan; Portengen, Lützen; Bonassi, Stefano; Sram, Radim; Vermeulen, Roel

    2011-08-15

    Chromosomal aberration frequency in peripheral lymphocytes of healthy individuals has been found to be predictive of future cancer risk. The variability of chromosomal aberrations over time, which is largely unknown, should be clarified to interpret the strength of this association and to determine its use in cancer prediction. Intra- and interindividual variability in chromosomal aberration frequency was therefore determined. From a pooled database comprising 11 national cohorts (1965-2002), the authors included 9,433 blood samples from 3,550 subjects with at least one repeated chromosomal aberration measurement. The generalized concordance correlation coefficient of 0.19 was low, indicating high intraindividual variability compared with interindividual variability, resulting in a high likelihood of misclassification. The relation between chromosomal aberration frequency and future cancer risk has probably been underestimated in previous studies. A single chromosomal aberration measurement seems not to be representative of the whole lifespan level of chromosome instability and greatly limits the use of chromosomal aberration frequency-as measured with Giemsa staining-for individual risk assessment. PMID:21652601

  12. Alternative lengthening of telomeres: recurrent cytogenetic aberrations and chromosome stability under extreme telomere dysfunction.

    Science.gov (United States)

    Sakellariou, Despoina; Chiourea, Maria; Raftopoulou, Christina; Gagos, Sarantis

    2013-11-01

    Human tumors using the alternative lengthening of telomeres (ALT) exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN) in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines. We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted. We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs) were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth. PMID:24339742

  13. Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma.

    Science.gov (United States)

    Plentz, Ruben R; Schlegelberger, Brigitte; Flemming, Peer; Gebel, Michael; Kreipe, Hans; Manns, Michael P; Rudolph, K Lenhard; Wilkens, Ludwig

    2005-09-01

    Chromosomal instability (CIN) leads to an increase in aneuploidy and chromosomal aberrations in human hepatocellular carcinoma (HCC). Telomere shortening appears as one mechanism fostering the development of CIN. Whether telomere shortening correlates to specific genetic changes that characterize a certain type of cancer has yet to be established. In our recent study, we combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosome 8-one of the hallmark chromosomal alterations in hepatocellular carcinoma (HCC). We investigated 15 cytological fine-needle biopsies of aneuploid HCC and 5 touch prints of cadaver livers without cancer. Hepatocyte-specific TFI and the measurement of centromere-specific probe for chromosome 8 were both performed by quantitative fluorescence in situ hybridization (qFISH) or FISH. Combined analysis of both methods (coFISH) allowed measurement of telomere length and chromosome 8 copy number on a single cell level. We observed that telomere shortening correlates significantly with increasing copy number of chromosome 8 in HCC on the cellular level. Above the level of 5 copies of chromosome 8 per nucleus, no further shortening of telomeres was found, indicating that telomeres had reached a critically short length at this stage of aneuploidy. In conclusion, our study gives direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC. PMID:16116624

  14. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  15. Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells.

    Science.gov (United States)

    Yamano, Noriko; Takahashi, Mai; Ali Haghparast, Seyed Mohammad; Onitsuka, Masayoshi; Kumamoto, Toshitaka; Frank, Jana; Omasa, Takeshi

    2016-08-01

    Chromosomal instability is a characteristic of Chinese hamster ovary (CHO) cells. Cultures of these cells gradually develop heterogeneity even if established from a single cell clone. We isolated cells containing different numbers of chromosomes from a CHO-DG44-based human granulocyte-macrophage colony stimulating factor (hGM-CSF)-producing cell line and found that high chromosome number cells showed higher hGM-CSF productivity. Therefore, we focused on the relationship between chromosome aneuploidy of CHO cells and high recombinant protein-producing cell lines. Distribution and stability of chromosomes were examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes were isolated from the original CHO-DG44 cell line to investigate the effect of aneuploid cells on recombinant protein production. Both cell lines were stably transfected with a vector that expresses immunoglobulin G3 (IgG3), and specific antibody production rates were compared. Cells containing more than 30 chromosomes had higher specific antibody production rates than those with normal chromosome number. Single cell analysis of enhanced green fluorescent protein (Egfp)-gene transfected cells revealed that increased GFP expression was relative to the number of gene integration sites rather than the difference in chromosome numbers or vector locations. Our results suggest that CHO cells with high numbers of chromosomes contain more sites for vector integration, a characteristic that could be advantageous in biopharmaceutical production. PMID:26850366

  16. Chromosome analysis and sorting

    Czech Academy of Sciences Publication Activity Database

    Doležel, Jaroslav; Kubaláková, Marie; Suchánková, Pavla; Kovářová, Pavlína; Bartoš, Jan; Šimková, Hana

    Weinheim : Wiley-VCH, 2007 - (Doležel, J.; Greilhuber, J.; Suda, J.), s. 373-403 ISBN 978-3-527-31487-4 R&D Projects: GA ČR GA521/04/0607; GA ČR GP521/05/P257; GA ČR GD521/05/H013; GA MŠk(CZ) LC06004 Grant ostatní: Mendelova zemědělská a lesnická univerzita v Brně / Agronomická fakulta(CZ) ME 844 Institutional research plan: CEZ:AV0Z5038910 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : Plant flow cytometry * chromosome sorting * flow cytogenetics Subject RIV: EB - Genetics ; Molecular Biology http://books. google .com/books?id=3cwakORieqUC&pg=PA373&lpg=PA373&dq=Chromosome+analysis+and+sorting&source=web&ots=8IyvJlBQyq&sig=_NlXyQQgBCwpj1pTC9YITvvVZqU

  17. Mutations in the WTX - gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers

    OpenAIRE

    Scheel Silvio K; Porzner Marc; Pfeiffer Sabine; Ormanns Steffen; Kirchner Thomas; Jung Andreas

    2010-01-01

    Abstract Background Genetically, colorectal cancers (CRCs) can be subdivided into tumors with chromosomal instability (CIN) or microsatellite instability (MSI). In both types of CRCs genes that are involved in the degradation of β-CATENIN are frequently mutated. Whereas in CIN CRCs APC (Adenomatous Polyposis Coli) is affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations in various genes, like the APC-, AXIN2- or CTNNBI (β-CATENIN) gene itself. Recently in Wilms tumo...

  18. Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, due to ZBTB24 mutations, presenting with large cerebral cyst

    OpenAIRE

    Cerbone, Manuela; Wang, Jun; van der Maarel, Silvère M.; D’Amico, Alessandra; d’Agostino, Antonio; Romano, Alfonso; Brunetti-Pierri, Nicola

    2012-01-01

    The Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome is an autosomal recessive disease presenting with immunodeficiency secondary to hypo- or agammaglobulinemia, developmental delay, and facial anomalies. Centromeric instability is the cytogenetic hallmark of the disorder which results from targeted chromosomal rearrangements related to a genomic methylation defect. We describe a patient carrying a homozygous mutation of the ZBTB24 gene, which has been recently shown...

  19. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  20. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  1. Non-conventional Fishbone Instabilities

    International Nuclear Information System (INIS)

    New instabilities of fishbone type are predicted. First, a trapped-particle-induced m = n = 1 instability with the mode structure having nothing to do with the conventional rigid kink displacement. This instability takes place when the magnetic field is weak, so that the precession frequency of the energetic ions is not small as compared to the frequency of the corresponding Alfven continuum at r = 0 and the magnetic shear is small inside the q = 1 radius [the case relevant to spherical tori]. Second, an Energetic Particle Mode fishbone instability driven by circulating particles. Third, a double-kink-mode instability driven by the circulating energetic ions. In particular, the latter can have two frequencies simultaneously: we refer to it as ''doublet'' fishbones. This instability can occur when the radial profile of the energetic ions has an off-axis maximum inside the region of the mode localization

  2. Hypersensitivity to ionizing radiation, in vitro, in a new chromosomal breakage disorder, the Nijmegen Breakage Syndrome

    International Nuclear Information System (INIS)

    The Nijmegen Breakage Syndrome (NBS) is a new chromosomal instability disorder different from ataxia telangiectasia (AT) and other chromosome-breakage syndromes. Cells from an NBS patient appeared hypersensitive to X-irradiation. X-rays induced significantly more chromosomal damage in NBS lymphocytes and fibroblasts than in normal cells. The difference was most pronounced after irradiation in G2. Further, NBS fibroblasts were more readily by X-rays than normal fibroblasts. In addition, the DNA synthesis in NBS cells was more resistant to X-rays and bleomycin than that in normal cells. The reaction of NBS cells to X-rays and bleomycin was similar to that of cells from patients with ataxia telangiectasia. Our results indicate that NBS and AT, which also have similar chromosomal characteristics, must be closely related. (orig.)

  3. Modulational instability of nematic phase

    Indian Academy of Sciences (India)

    T Mithun; K Porsezian

    2014-02-01

    We numerically observe the effect of homogeneous magnetic field on the modulationally stable case of polar phase in = 2 spinor Bose–Einstein condensates (BECs). Also we investigate the modulational instability of uniaxial and biaxial (BN) states of polar phase. Our observations show that the magnetic field triggers the modulational instability and demonstrate that irrespective of the magnetic field effect the uniaxial and biaxial nematic phases show modulational instability.

  4. Summary of longitudinal instabilities workshop

    International Nuclear Information System (INIS)

    A five-day ISABELLE workshop on longitudinal instabilities was held at BNL, August 9--13, 1976. Heavy emphasis was put on single bunched beam instabilities in the microwave region extending above the cut-off frequency of the ISABELLE vacuum chamber. A discussion is given of the mechanism governing the instability, and calculations as well as measurements of the longitudinal coupling impedances in the ISABELLE rings are described

  5. Instability in Shocked Granular Gases

    OpenAIRE

    Sirmas, Nick; Falle, Sam; Radulescu, Matei

    2013-01-01

    Shocks in granular media, such as vertically oscillated beds, have been shown to develop instabilities. Similar jet formation has been observed in explosively dispersed granular media. Our previous work addressed this instability by performing discrete-particle simulations of inelastic media undergoing shock compression. By allowing finite dissipation within the shock wave, instability manifests itself as distinctive high density non-uniformities and convective rolls within the shock structur...

  6. Divergence of gene regulation through chromosomal rearrangements

    Directory of Open Access Journals (Sweden)

    Messing Joachim

    2010-11-01

    Full Text Available Abstract Background The molecular mechanisms that modify genome structures to give birth and death to alleles are still not well understood. To investigate the causative chromosomal rearrangements, we took advantage of the allelic diversity of the duplicated p1 and p2 genes in maize. Both genes encode a transcription factor involved in maysin synthesis, which confers resistance to corn earworm. However, p1 also controls accumulation of reddish pigments in floral tissues and has therefore acquired a new function after gene duplication. p1 alleles vary in their tissue-specific expression, which is indicated in their allele designation: the first suffix refers to red or white pericarp pigmentation and the second to red or white glume pigmentation. Results Comparing chromosomal regions comprising p1-ww[4Co63], P1-rw1077 and P1-rr4B2 alleles with that of the reference genome, P1-wr[B73], enabled us to reconstruct additive events of transposition, chromosome breaks and repairs, and recombination that resulted in phenotypic variation and chimeric regulatory signals. The p1-ww[4Co63] null allele is probably derived from P1-wr[B73] by unequal crossover between large flanking sequences. A transposon insertion in a P1-wr-like allele and NHEJ (non-homologous end-joining could have resulted in the formation of the P1-rw1077 allele. A second NHEJ event, followed by unequal crossover, probably led to the duplication of an enhancer region, creating the P1-rr4B2 allele. Moreover, a rather dynamic picture emerged in the use of polyadenylation signals by different p1 alleles. Interestingly, p1 alleles can be placed on both sides of a large retrotransposon cluster through recombination, while functional p2 alleles have only been found proximal to the cluster. Conclusions Allelic diversity of the p locus exemplifies how gene duplications promote phenotypic variability through composite regulatory signals. Transposition events increase the level of genomic complexity

  7. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  8. Causes of oncogenic chromosomal translocation

    OpenAIRE

    Aplan, Peter D.

    2005-01-01

    Non-random chromosomal translocations are frequently associated with a variety of cancers, especially hematologic malignancies and childhood sarcomas In addition to their diagnostic utility, chromosomal translocations are increasingly being used in the clinic to guide therapeutic decisions. However, the mechanisms which cause these translocations remain poorly understood. Illegit...

  9. Genetics Home Reference: ring chromosome 20 syndrome

    Science.gov (United States)

    ... 3 links) Encyclopedia: Chromosome Encyclopedia: Epilepsy Health Topic: Epilepsy Genetic and Rare Diseases Information Center (1 link) Ring chromosome 20 Additional NIH Resources (2 links) National Human Genome Research Institute: Chromosome Abnormalities National Institute of ...

  10. Genetics Home Reference: ring chromosome 14 syndrome

    Science.gov (United States)

    ... Encyclopedia: Chromosome Health Topic: Developmental Disabilities Health Topic: Epilepsy Genetic and Rare Diseases Information Center (1 link) Ring chromosome 14 Additional NIH Resources (2 links) National Human Genome Research Institute: Chromosome Abnormalities National Institute of ...

  11. Bacterial chromosome organization and segregation.

    Science.gov (United States)

    Badrinarayanan, Anjana; Le, Tung B K; Laub, Michael T

    2015-01-01

    If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation. PMID:26566111

  12. Genomic Instability Induced by Low Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, Helen H.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  13. Instability of enclosed horizons

    CERN Document Server

    Kay, Bernard S

    2013-01-01

    We study the classical massless scalar wave equation on the region of 1+1-dimensional Minkowski space between the two branches of the hyperbola $x^2-t^2=1$ with vanishing boundary conditions on it. We point out that there are initially finite-energy initially, say, right-going waves for which the stress-energy tensor becomes singular on the null-line $t+x=0$. We also construct the quantum theory of this system and show that, while there is a regular Hartle-Hawking-Israel-like state, there are coherent states built on this for which there is a similar singularity in the expectation value of the renormalized stress-energy tensor. We conjecture that in 1+3-dimensional situations with 'enclosed horizons' such as a (maximally extended) Schwarzschild black hole in equilibrium in a stationary box or the (maximally extended) Schwarzschild-AdS spacetime, there will be a similar singularity at the horizon and that would signal an instability when matter perturbations and/or gravity are switched on. Such an instability ...

  14. Libration driven multipolar instabilities

    CERN Document Server

    Cébron, David; Herreman, Wietze

    2014-01-01

    We consider rotating flows in non-axisymmetric enclosures that are driven by libration, i.e. by a small periodic modulation of the rotation rate. Thanks to its simplicity, this model is relevant to various contexts, from industrial containers (with small oscillations of the rotation rate) to fluid layers of terrestial planets (with length-of-day variations). Assuming a multipolar $n$-fold boundary deformation, we first obtain the two-dimensional basic flow. We then perform a short-wavelength local stability analysis of the basic flow, showing that an instability may occur in three dimensions. We christen it the Libration Driven Multipolar Instability (LDMI). The growth rates of the LDMI are computed by a Floquet analysis in a systematic way, and compared to analytical expressions obtained by perturbation methods. We then focus on the simplest geometry allowing the LDMI, a librating deformed cylinder. To take into account viscous and confinement effects, we perform a global stability analysis, which shows that...

  15. ADN et chromosomes

    OpenAIRE

    Hayes, Hélène

    2000-01-01

    Chaque chromosome contient une seule molécule d’ADN. L’ADN déroulé d’un noyau de cellule humaine mesurerait environ 1,8 m : chaque molécule d’ADN est enroulée et compactée en plusieurs étapes, grâce à l’association de différentes protéines, et loge dans le noyau de 6 µm de diamètre. Le degré de condensation de l’ADN est variable selon les régions chromosomiques et les régions les moins condensées sont les plus riches en gènes. L’ADN est composé d’une variété de séquences codantes ou non et ré...

  16. X-Chromosome dosage compensation.

    Science.gov (United States)

    Meyer, Barbara J

    2005-01-01

    In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the

  17. Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Li Jun; van der Does, H. C.; Borkovich, Katherine A.; Coleman, Jeffrey J.; Daboussi, Marie-Jose; Di Pietro, Antonio; Dufresne, Marie; Freitag, Michael; Grabherr, Manfred; Henrissat, Bernard; Houterman, Petra M.; Kang, Seogchan; Shim, Won-Bo; Wolochuk, Charles; Xie, Xiaohui; Xu, Jin Rong; Antoniw, John; Baker, Scott E.; Bluhm, Burton H.; Breakspear, Andrew; Brown, Daren W.; Butchko, Robert A.; Chapman, Sinead; Coulson, Richard; Coutinho, Pedro M.; Danchin, Etienne G.; Diener, Andrew; Gale, Liane R.; Gardiner, Donald; Goff, Steven; Hammond-Kossack, Kim; Hilburn, Karen; Hua-Van, Aurelie; Jonkers, Wilfried; Kazan, Kemal; Kodira, Chinnappa D.; Koehrsen, Michael; Kumar, Lokesh; Lee, Yong Hwan; Li, Liande; Manners, John M.; Miranda-Saavedra, Diego; Mukherjee, Mala; Park, Gyungsoon; Park, Jongsun; Park, Sook Young; Proctor, Robert H.; Regev, Aviv; Ruiz-Roldan, M. C.; Sain, Divya; Sakthikumar, Sharadha; Sykes, Sean; Schwartz, David C.; Turgeon, Barbara G.; Wapinski, Ilan; Yoder, Olen; Young, Sarah; Zeng, Qiandong; Zhou, Shiguo; Galagan, James; Cuomo, Christina A.; Kistler, H. Corby; Rep, Martijn

    2010-03-18

    Fusarium species are among the most important phytopathogenic and toxigenic fungi, having significant impact on crop production and animal health. Distinctively, members of the F. oxysporum species complex exhibit wide host range but discontinuously distributed host specificity, reflecting remarkable genetic adaptability. To understand the molecular underpinnings of diverse phenotypic traits and their evolution in Fusarium, we compared the genomes of three economically important and phylogenetically related, yet phenotypically diverse plant-pathogenic species, F. graminearum, F. verticillioides and F. oxysporum f. sp. lycopersici. Our analysis revealed greatly expanded lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes, accounting for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity. Experimentally, we demonstrate for the first time the transfer of two LS chromosomes between strains of F. oxysporum, resulting in the conversion of a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in the F. oxysporum species complex, putting the evolution of fungal pathogenicity into a new perspective.

  18. EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study

    Directory of Open Access Journals (Sweden)

    Phillips Evelyn

    2010-03-01

    Full Text Available Abstract Background Evidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This study's aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence. Methods Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital. Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR. Results Sixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal-occipital location. Conclusion These results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may

  19. Impact of Chromosome 4p- Syndrome on Communication and Expressive Language Skills: A Preliminary Investigation

    Science.gov (United States)

    Marshall, Althea T.

    2010-01-01

    Purpose: The purpose of this investigation was to examine the impact of Chromosome 4p- syndrome on the communication and expressive language phenotype of a large cross-cultural population of children, adolescents, and adults. Method: A large-scale survey study was conducted and a descriptive research design was used to analyze quantitative and…

  20. Morphological, cellular and molecular evidences of chromosome random elimination in vivo upon haploid induction in maize

    Directory of Open Access Journals (Sweden)

    Fazhan Qiu

    2014-08-01

    DATA: The link refers to the raw data from: Morphological, cellular and molecular evidences of chromosome random elimination in vivo upon haploid induction in maize. Current Plant Biology. Raw data for phenotype, maker sequence and cytology could be directly downloaded by the link: http://dx.doi.org/10.5061/dryad.bt963

  1. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

  2. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  3. Microsatellite Instability in Young Women with Endometrioid type Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    MR Abbaszadegan

    2009-09-01

    Full Text Available "nBackground: This study was designed to determine the frequency of Microsatellite Instability (MSI in young Iranian pa­tients with endometrial carcinoma and to evaluate its association with histopathologic and clinical features of disease."nMethods: Microsatellite status was analyzed in 23 patients with endometrioid type endometrial cancer who were less than 55 years. Clinicopathologic characteristics such as age, International Federation of Gynecology and Obstetric (FIGO grad­ing and staging of tumor, family history of Hereditary Non-polyposis Colorectal Cancer (HNPCC, oral conception (OC consump­tion, number of pregnancies, fertility, menstrual cycles and underlying disease were considered. Chi-square and Fisher exact tests were used to find the significant relationships."nResults: MSI analysis showed 8 patients (34.8% were MSS (Microsatellite Stable, 15 patients (62.5% were MSI positive. Among cases with MSI phenotype, 4 cases (17.4% had low instability (MSI-L and 11 cases (47.8% had high instability (MSI-H. Three cases with MSI-H had family history of HNPCC related cancers. Five cases (21.7% had infertility in which 4 of them (80% had MSI phenotype. There was no statistically significant relationship between MSI phenotype and tumor grade and stage."nConclusion: Few studies reported high frequency of MSI among young patients. Some studies mentioned similar results in endo­metrioid type of tumor. This study showed even higher frequency (65% when MSI analyzed in young endometrioid type endometrial patients. Most cases with infertility had MSI-H phenotype. It may suggest that beside women with family his­tory of HNPCC, EC screening using MSI would be beneficial in infertile women too.  

  4. Contributions of microtubule dynamic instability and rotational diffusion to kinetochore capture

    CERN Document Server

    Blackwell, Robert; Edelmaier, Christopher; Gergely, Zachary R; Flynn, Patrick J; Montes, Salvador; Crapo, Ammon; Doostan, Alireza; McIntosh, J Richard; Glaser, Matthew A; Betterton, Meredith D

    2016-01-01

    Microtubule dynamic instability allows search and capture of kinetochores during spindle formation, an important process for accurate chromosome segregation during cell division. Recent work has found that microtubule rotational diffusion about minus-end attachment points contributes to kinetochore capture in fission yeast, but the relative contributions of dynamic instability and rotational diffusion are not well understood. We have developed a biophysical model of kinetochore capture in small fission-yeast nuclei using hybrid Brownian dynamics/kinetic Monte Carlo simulation techniques. With this model, we have studied the importance of dynamic instability and microtubule rotational diffusion for kinetochore capture, both to the lateral surface of a microtubule and at or near its end. Over a range of biologically relevant parameters, microtubule rotational diffusion decreased capture time, but made a relatively small contribution compared to dynamic instability. At most, rotational diffusion reduced capture ...

  5. Genomic instability caused by hepatitis B virus: into the hepatoma inferno.

    Science.gov (United States)

    Hsieh, Yi-Hsuan; Hsu, Jye-Lin; Su, Ih-Jen; Huang, Wenya

    2011-01-01

    Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide, especially in Asia. HBV induces HCC through multiple oncogenic pathways. Hepatitis-induced hepatocyte inflammation and regeneration stimulates cell proliferation. The interplay between the viral and host factors activates oncogenic signaling pathways and triggers cell transformation. In this review, we summarize previous studies, which reported that HBV induces host genomic instability and that HBV-induced genomic instability is a significant factor that accelerates carcinogenesis. The various types of genomic changes in HBV-induced HCC--chromosomal instability, telomere attrition, and gene-level mutations--are reviewed. In addition, the two viral factors, HBx and the pre-S2 mutant large surface antigen, are discussed for their roles in promoting genomic instability as their main features as viral oncoproteins. PMID:21622197

  6. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  7. Mitotic chromosome condensation in vertebrates

    International Nuclear Information System (INIS)

    Work from several laboratories over the past 10–15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292–301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories—a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307–316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119–1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579–589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different

  8. Widespread over-expression of the X chromosome in sterile F₁hybrid mice.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Good

    2010-09-01

    Full Text Available The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F₁ males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F₁ hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility.

  9. Phenotypic Switching in Fungi

    OpenAIRE

    Jain, Neena; Hasan, Fahmi; Fries, Bettina C.

    2008-01-01

    Over the past three decades new fungal diseases have emerged that now constitute a major threat, especially for patients with chronic diseases and/or underlying immune defi ciencies. Despite the epidemiologic data, the emergence of stable drug-resistant or hyper-virulent fungal strains in human disease has not been demonstrated as seen in emerging viral and bacterial infections. Fungi are eukaryotic microbes that capitalize on a sophisticated built-in ability to generate phenotypic variabilit...

  10. Fluorescence in situ hybridisation in chromosome aberration detection in subjects occupationally exposed to ionising radiation

    International Nuclear Information System (INIS)

    For more than two decades, chromosomal aberration analysis has been used to detect structural chromosomal aberrations as sensitive biodosimeters of occupational exposure to ionising radiation. Its use is also recommended by the World Health Organisation. Changes in chromosome structure detected by that method are considered to be early biomarkers of a possible malignant disease. Aberrations detected by the method are unstable and can be found in the lymphocytes of irradiated personnel only within a limited time after exposure. To detect stable chromosomal aberrations, which persist after exposure, multicolour fluorescent in situ hybridisation has to be used. Using DNA probes labelled with different fluorochromes, it dyes each pair of chromosomes with different colour. Due to the dynamic of unstable aberration formation, chromosomal aberration analysis is more suitable in genome damage assessment of recent exposures. On the other hand, fluorescence in situ hybridisation gives the information on chromosome instability caused by long-term occupational exposure to ionising radiation. Considering the high costs of fluorescence in situ hybridisation and the uncertainty of the result, it should be used in biodosimetry only when it is absolutely necessary.(author)

  11. Chromosome arm-specific long telomeres: a new clonal event in primary chronic myelogenous leukemia cells.

    Science.gov (United States)

    Samassekou, Oumar; Li, Huiyu; Hébert, Josée; Ntwari, Aimé; Wang, Haixia; Cliché, Catherine Grenier; Bouchard, Eric; Huang, Shiang; Yan, Ju

    2011-06-01

    Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found that telomeres at some specific chromosome arms remain well maintained or even lengthened in a high frequency (27/32) of leukemia cases. In particular, 10 chromosome arms, 4q, 5p, 7q, 11p, 13p, 13q, 14p, 15p, 18p, and Xp, with long telomeres were consistently identified in different samples, and six of them (4q, 5p, 13p, 13q, 14p, and Xp) with relatively long telomeres were also observed in normal samples, but they appeared in lower occurrence rate and shorter RTL than in CML samples. Our results strongly indicate the presence of a special leukemia cell population, or a clone, originated from a common progenitor that is characterized with chromosome arm-specific long telomeres. We suggest that relatively long telomeres located at key chromosomes could be preferentially maintained or further elongated during the early stage of malignant transformation. PMID:21677878

  12. Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Oumar Samassekou

    2011-06-01

    Full Text Available Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML and 32 normal samples. We found that telomeres at some specific chromosome arms remain well maintained or even lengthened in a high frequency (27/32 of leukemia cases. In particular, 10 chromosome arms, 4q, 5p, 7q, 11p, 13p, 13q, 14p, 15p, 18p, and Xp, with long telomeres were consistently identified in different samples, and six of them (4q, 5p, 13p, 13q, 14p, and Xp with relatively long telomeres were also observed in normal samples, but they appeared in lower occurrence rate and shorter RTL than in CML samples. Our results strongly indicate the presence of a special leukemia cell population, or a clone, originated from a common progenitor that is characterized with chromosome arm-specific long telomeres. We suggest that relatively long telomeres located at key chromosomes could be preferentially maintained or further elongated during the early stage of malignant transformation.

  13. The microcell mediated transfer of human chromosome 8 into highly metastatic rat liver cancer cell line C5F

    Institute of Scientific and Technical Information of China (English)

    Hu Liu; Sheng-Long Ye; Jiong Yang; Zhao-You Tang; Yin-Kun Liu; Lun-Xiu Qin; Shuang-Jian Qiu; Rui-Xia Sun

    2003-01-01

    AIM: Our previous research on the surgical samples of primary liver cancer with CGH showed that the loss of human chromosome 8p had correlation with the metastatic phenotype of liver cancer. In order to seek the functional evidence that there could be a metastatsis suppressor gene (s) for liver cancer on human chromosome 8, we tried to transfer normal human chromosome 8 into rat liver cancer cell line C5F, which had high metastatic potential to lung.METHODS: Human chromosome 8 randomly marked with neo gene was introduced into C5F cell line by MMCT and positive microcell hybrids were screened by double selections of G418 and HAT. Single cell isolation cloning was applied to clone microcell hybrids. Finally, STS-PCR and WCP-FISH were used to confirm the introduction.RESULTS: Microcell hybrids resistant to HAT and G418 were obtained and 15 clones were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that human chromosome 8 had been successfully introduced into rat liver cancer cell line C5F. STS-PCR detected a random loss in the chromosome introduced and WCP-FISH found a consistent recombination of the introduced human chromosome with the rat chromosome.CONCLUSION: The successful introduction of human chromosome 8 into highly metastatic rat liver cancer cell line builds the basis for seeking functional evidence of a metastasis suppressor gene for liver cancer harboring on human chromosome 8 and its subsequent cloning.

  14. Effects on Genome Constitution and Novel Cell Wall Formation Caused by the Addition of 5RS Rye Chromosome to Common Wheat

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun Cheng; Minoru Murata; Sodmergen; Xiao-Mei Li; Hai Nian; Jian-Min Wan

    2008-01-01

    The cytological instability of common wheat-rye addition lines was investigated in the present study. The chromosome numbers of almost all addition lines were considerably stable, but those of CS + 5R were very variable. The rye chromosome added in this line was found to be much shorter than expected. Fluorescent in situ hybridization with 5S rDNA and the centromere-specific probes clearly revealed that the short rye chromosome contains only a short arm of chromosome 5R (5RS). In this line, chromosome numbers of both 5RS and common wheat were changeable. The chromosome numbers ranged from 2n = 36 to 2n = 44 in the cells carrying two 5RS, and ranged from 2n = 31 to 2n = 44 in one 5RS cells. In addition to the chromosome instability, the multicells wrapped in a sac-like structure were frequently observed in the root meristematic tissues of CS + 5RS after the enzyme treatment for chromosome preparation. Genomic in situ hybridization with rye DNA as a probe showed that all cells in sacs investigated were at the interphase stage and contained one or two 5RS chromosomes. An electron microscopic analysis revealed that the cells of CS + 5RS, particularly in sacs, have abnormal (irregular and curved) cell walls. These results indicate that 5RS has (a) specific factor(s) influencing the cell wall development as well as the genome stability.

  15. Cohabitation and Children's Family Instability

    Science.gov (United States)

    Kelly Raley, R.; Wildsmith, Elizabeth

    2004-01-01

    This study estimates how much children's family instability is missed when we do not count transitions into and out of cohabitation, and examines early life course trajectories of children to see whether children who experience maternal cohabitation face more family instability than children who do not. Using data from the 1995 National Survey of…

  16. Cinerama sickness and postural instability

    NARCIS (Netherlands)

    Bos, J.E.; Ledegang, W.D.; Lubeck, A.J.A.; Stins, J.F.

    2013-01-01

    Motion sickness symptoms and increased postural instability induced by motion pictures have been reported in a laboratory, but not in a real cinema. We, therefore, carried out an observational study recording sickness severity and postural instability in 19 subjects before, immediately and 45 min af

  17. Instability of liquid crystal elastomers

    Science.gov (United States)

    An, Ning; Li, Meie; Zhou, Jinxiong

    2016-01-01

    Nematic liquid crystal elastomers (LCEs) contract in the director direction but expand in other directions, perpendicular to the director, when heated. If the expansion of an LCE is constrained, compressive stress builds up in the LCE, and it wrinkles or buckles to release the stored elastic energy. Although the instability of soft materials is ubiquitous, the mechanism and programmable modulation of LCE instability has not yet been fully explored. We describe a finite element method (FEM) scheme to model the inhomogeneous deformation and instability of LCEs. A constrained LCE beam working as a valve for microfluidic flow, and a piece of LCE laminated with a nanoscale poly(styrene) (PS) film are analyzed in detail. The former uses the buckling of the LCE beam to occlude the microfluidic channel, while the latter utilizes wrinkling or buckling to measure the mechanical properties of hard film or to realize self-folding. Through rigorous instability analysis, we predict the critical conditions for the onset of instability, the wavelength and amplitude evolution of instability, and the instability patterns. The FEM results are found to correlate well with analytical results and reported experiments. These efforts shed light on the understanding and exploitation of the instabilities of LCEs.

  18. Genome instability in Alzheimer disease

    DEFF Research Database (Denmark)

    Hou, Yujun; Song, Hyundong; Croteau, Deborah L;

    2016-01-01

    to the development of noninvasive treatment strategies. Further investigations into the molecular mechanisms connecting DNA damage to AD pathology may help to develop novel treatment strategies for this debilitating disease. Here we provide an overview of the role of genome instability and DNA repair deficiency...... in AD pathology and discuss research strategies that include genome instability as a component....

  19. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

    Science.gov (United States)

    Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

    2013-01-01

    The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat. PMID:23884766

  20. The bar instability revisited

    CERN Document Server

    Chiodi, Filippo; Claudin, Philippe

    2012-01-01

    The river bar instability is revisited, using a hydrodynamical model based on Reynolds averaged Navier-Stokes equations. The results are contrasted with the standard analysis based on shallow water Saint-Venant equations. We first show that the stability of both transverse modes (ripples) and of small wavelength inclined modes (bars) predicted by the Saint-Venant approach are artefacts of this hydrodynamical approximation. When using a more reliable hydrodynamical model, the dispersion relation does not present any maximum of the growth rate when the sediment transport is assumed to be locally saturated. The analysis therefore reveals the fundamental importance of the relaxation of sediment transport towards equilibrium as it it is responsible for the stabilisation of small wavelength modes. This dynamical mechanism is characterised by the saturation number, defined as the ratio of the saturation length to the water depth Lsat/H. This dimensionless number controls the transition from ripples (transverse patte...

  1. Plateau Rayleigh instability simulation.

    Science.gov (United States)

    Mead-Hunter, Ryan; King, Andrew J C; Mullins, Benjamin J

    2012-05-01

    The well-known phenomena of Plateau-Rayleigh instability has been simulated using computational fluid dynamics (CFD). The breakup of a liquid film into an array of droplets on a cylindrical element was simulated using a volume-of-fluid (VOF) solver and compared to experimental observations and existing theory. It is demonstrated that the VOF method can correctly predict the breakup of thins films into an array of either axisymmetric droplets or clam-shell droplets, depending on the surface energy. The existence of unrealistically large films is precluded. Droplet spacing was found to show reasonable agreement with theory. Droplet motion and displacement under fluid flow was also examined and compared to that in previous studies. It was found that the presence of air flow around the droplet does not influence the stable film thickness; however, it reduces the time required for droplet formation. Novel relationships for droplet displacement were derived from the results. PMID:22512475

  2. Instability and Information

    CERN Document Server

    Patzelt, Felix

    2015-01-01

    Many complex systems exhibit extreme events far more often than expected for a normal distribution. This work examines how self-similar bursts of activity across several orders of magnitude can emerge from first principles in systems that adapt to information. Surprising connections are found between two apparently unrelated research topics: hand-eye coordination in balancing tasks and speculative trading in financial markets. Seemingly paradoxically, locally minimising fluctuations can increase a dynamical system's sensitivity to unpredictable perturbations and thereby facilitate global catastrophes. This general principle is studied in several domain-specific models and in behavioural experiments. It explains many findings in both fields and resolves an apparent antinomy: the coexistence of stabilising control or market efficiency and perpetual instabilities resembling critical phenomena in physical systems.

  3. From instabilities to multifragmentation

    International Nuclear Information System (INIS)

    The main purpose of this article is to show that, in many physical situations, the spinodal decomposition of unstable systems can be correctly described by stochastic mean-field approaches. Such theories predict that the occurrence of spinodal instability leading the multifragmentation of an expended nuclear system, can be signed through the observation of time scales for the fragment formation of the order of 100 fm/c and of typical fragment size around A=20. We will finally discuss the fact that these fragments are formed at finite temperature and so can subsequently decay in flight. Finally, we will give some hints about possible experimental signals of such first order phase transitions. (authors). 12 refs., 5 figs

  4. Structural and Material Instability

    DEFF Research Database (Denmark)

    Cifuentes, Gustavo Cifuentes

    This work is a small contribution to the general problem of structural and material instability. In this work, the main subject is the analysis of cracking and failure of structural elements made from quasi-brittle materials like concrete. The analysis is made using the finite element method. Three...... program based on the finite element method for the analysis of cracks in structural elements is presented; in this program the interface and elements with embedded discontinuities are implemented....... use of interface elements) is used successfully to model cases where the path of the discontinuity is known in advance, as is the case of the analysis of pull-out of fibers embedded in a concrete matrix. This method is applied to the case of non-straight fibers and fibers with forces that have...

  5. Chromosomal Islands of Streptococcus pyogenes and related streptococci: Molecular Switches for Survival and Virulence

    Directory of Open Access Journals (Sweden)

    Scott Van Nguyen

    2014-08-01

    Full Text Available Streptococcus pyogenes is a significant pathogen of humans, annually causing over 700,000,000 infections and 500,000 deaths. Virulence in S. pyogenes is closely linked to mobile genetic elements like phages and chromosomal islands (CI. S. pyogenes phage-like chromosomal islands (SpyCI confer a complex mutator phenotype on their host. SpyCI integrate into the 5’ end of DNA mismatch repair (MMR gene mutL, which also disrupts downstream operon genes lmrP, ruvA, and tag. During early logarithmic growth, SpyCI excise from the bacterial chromosome and replicate as episomes, relieving the mutator phenotype. As growth slows and the cells enter stationary phase, SpyCI reintegrate into the chromosome, again silencing the MMR operon. This system creates a unique growth-dependent and reversible mutator phenotype. Additional CI using the identical attachment site in mutL have been identified in related species, including Streptococcus dysgalactiae subsp. equisimilis, Streptococcus anginosus, Streptococcus intermedius, Streptococcus parauberis, and Streptococcus canis. These CI have small genomes, which range from 13-20 kB, conserved integrase and DNA replication genes, and no identifiable genes encoding capsid proteins. SpyCI may employ a helper phage for packaging and dissemination in a fashion similar to the Staphylococcus aureus pathogenicity islands (SaPI. Outside of the core replication and integration genes, SpyCI and related CI show considerable diversity with the presence of many indels that may contribute to the host cell phenotype or fitness. SpyCI are a subset of a larger family of streptococcal CI who potentially regulate the expression of other host genes. The biological and phylogenetic analysis of streptococcal chromosomal islands provides important clues as to how these chromosomal islands help S. pyogenes and other streptococcal species persist in human populations in spite of antibiotic therapy and immune challenges.

  6. Chromosomal islands of Streptococcus pyogenes and related streptococci: molecular switches for survival and virulence.

    Science.gov (United States)

    Nguyen, Scott V; McShan, William M

    2014-01-01

    Streptococcus pyogenes is a significant pathogen of humans, annually causing over 700,000,000 infections and 500,000 deaths. Virulence in S. pyogenes is closely linked to mobile genetic elements like phages and chromosomal islands (CI). S. pyogenes phage-like chromosomal islands (SpyCI) confer a complex mutator phenotype on their host. SpyCI integrate into the 5' end of DNA mismatch repair (MMR) gene mutL, which also disrupts downstream operon genes lmrP, ruvA, and tag. During early logarithmic growth, SpyCI excise from the bacterial chromosome and replicate as episomes, relieving the mutator phenotype. As growth slows and the cells enter stationary phase, SpyCI reintegrate into the chromosome, again silencing the MMR operon. This system creates a unique growth-dependent and reversible mutator phenotype. Additional CI using the identical attachment site in mutL have been identified in related species, including Streptococcus dysgalactiae subsp. equisimilis, Streptococcus anginosus, Streptococcus intermedius, Streptococcus parauberis, and Streptococcus canis. These CI have small genomes, which range from 13 to 20 kB, conserved integrase and DNA replication genes, and no identifiable genes encoding capsid proteins. SpyCI may employ a helper phage for packaging and dissemination in a fashion similar to the Staphylococcus aureus pathogenicity islands (SaPI). Outside of the core replication and integration genes, SpyCI and related CI show considerable diversity with the presence of many indels that may contribute to the host cell phenotype or fitness. SpyCI are a subset of a larger family of streptococcal CI who potentially regulate the expression of other host genes. The biological and phylogenetic analysis of streptococcal chromosomal islands provides important clues as to how these chromosomal islands help S. pyogenes and other streptococcal species persist in human populations in spite of antibiotic therapy and immune challenges. PMID:25161960

  7. Rejoining of prematurely condensed chromosomes in radiosensitive xrs-5 cells

    International Nuclear Information System (INIS)

    Xrs-5 cells, a radiosensitive, DNA double strand break repair deficient mutant of CHO cells have been studied with the premature chromosome condensation (PCC) technique. This mutant displayed a higher number of initial chromosome breaks with x-ray treatment as well as partial deficiency in the rejoining of interphase chromosome breaks with the standard PCC protocol. Moreover, hypertonic treatment during the incubation period which allowed for PCC did not change the yield of PCC breaks in x-irradiated xrs-5 cells. Notably the number of PCC breaks after treatment with hypertonic media is similar in CHO and xrs-5 cells. Recently, a gene product responsible for the xrs phenotype was identified as a Ku-like DNA end binding protein. The present paper summarizes completed information regarding the induction and repair of the α- and β-forms of PCC breaks in xrs-5 cells and demonstrates that this gene product predominantly affects the fast form (β-form) of interphase chromosome breaks

  8. Internal rotor friction instability

    Science.gov (United States)

    Walton, J.; Artiles, A.; Lund, J.; Dill, J.; Zorzi, E.

    1990-01-01

    The analytical developments and experimental investigations performed in assessing the effect of internal friction on rotor systems dynamic performance are documented. Analytical component models for axial splines, Curvic splines, and interference fit joints commonly found in modern high speed turbomachinery were developed. Rotor systems operating above a bending critical speed were shown to exhibit unstable subsynchronous vibrations at the first natural frequency. The effect of speed, bearing stiffness, joint stiffness, external damping, torque, and coefficient of friction, was evaluated. Testing included material coefficient of friction evaluations, component joint quantity and form of damping determinations, and rotordynamic stability assessments. Under conditions similar to those in the SSME turbopumps, material interfaces experienced a coefficient of friction of approx. 0.2 for lubricated and 0.8 for unlubricated conditions. The damping observed in the component joints displayed nearly linear behavior with increasing amplitude. Thus, the measured damping, as a function of amplitude, is not represented by either linear or Coulomb friction damper models. Rotordynamic testing of an axial spline joint under 5000 in.-lb of static torque, demonstrated the presence of an extremely severe instability when the rotor was operated above its first flexible natural frequency. The presence of this instability was predicted by nonlinear rotordynamic time-transient analysis using the nonlinear component model developed under this program. Corresponding rotordynamic testing of a shaft with an interference fit joint demonstrated the presence of subsynchronous vibrations at the first natural frequency. While subsynchronous vibrations were observed, they were bounded and significantly lower in amplitude than the synchronous vibrations.

  9. Combustion Instabilities Modeled

    Science.gov (United States)

    Paxson, Daniel E.

    1999-01-01

    NASA Lewis Research Center's Advanced Controls and Dynamics Technology Branch is investigating active control strategies to mitigate or eliminate the combustion instabilities prevalent in lean-burning, low-emission combustors. These instabilities result from coupling between the heat-release mechanisms of the burning process and the acoustic flow field of the combustor. Control design and implementation require a simulation capability that is both fast and accurate. It must capture the essential physics of the system, yet be as simple as possible. A quasi-one-dimensional, computational fluid dynamics (CFD) based simulation has been developed which may meet these requirements. The Euler equations of mass, momentum, and energy have been used, along with a single reactive species transport equation to simulate coupled thermoacoustic oscillations. A very simple numerical integration scheme was chosen to reduce computing time. Robust boundary condition procedures were incorporated to simulate various flow conditions (e.g., valves, open ends, and choked inflow) as well as to accommodate flow reversals that may arise during large flow-field oscillations. The accompanying figure shows a sample simulation result. A combustor with an open inlet, a choked outlet, and a large constriction approximately two thirds of the way down the length is shown. The middle plot shows normalized, time-averaged distributions of the relevant flow quantities, and the bottom plot illustrates the acoustic mode shape of the resulting thermoacoustic oscillation. For this simulation, the limit cycle peak-to-peak pressure fluctuations were 13 percent of the mean. The simulation used 100 numerical cells. The total normalized simulation time was 50 units (approximately 15 oscillations), which took 26 sec on a Sun Ultra2.

  10. Dynamical Instability and Soliton Concept

    International Nuclear Information System (INIS)

    The problem of dynamical instability and clustering (stable fragments formation) in a breakup of excited nuclear systems are considered from the points of view of the soliton concept. It is noted that the volume (spinodal) instability can be associated with nonlinear terms, and the surface (Rayleigh-Taylor type) instability, with the dispersion terms in the evolution equations. The spinodal instability and the Rayleigh-Taylor instability may compensate each other and lead to stable quasi-soliton type objects. The simple analytical model is presented to illustrate this physical picture. The time evolution of an initially compressed cold nuclear system is analysed in the framework of the inverse mean-field method. It is demonstrated that the nonlinearity and dispersion terms of the evolution equations can lead to clusterization in the final channel. 8 p

  11. Nonlinear evolution of MHD instabilities

    International Nuclear Information System (INIS)

    The problems of nonlinear theory of MHD instability, some analytical solutions of one-dimensional dynamic and two-dimensional kinematic problems and the problems of helical MHD instability in a plasma cylinder and axially-symmetric MHD instability in a Z-pinch are considered. The initial configuration is assumed to be equilibrium but unstable and its motion is initiated by a small initial disturbance. Instability evolution at a nonlinear stage is investigated by means of computer numerical integrating of the total system of MHD equations of motion. Limiting by two-dimensional motions class allows using the visual apparatus of freezed in functions satisfying in ideal gasodynamics the equation deltaPSIsub(i)/deltat+vector Vgrad PSIsub(i)=0. The investigation of evolution of axially symmetric MHD-instability in Z-pinch systems allows to construct on uncontradictory scheme of physical processes occuring in them from the initial discharge state to cylindrical equilibrium state

  12. Gravitational Instabilities in Circumstellar Disks

    CERN Document Server

    Kratter, Kaitlin M

    2016-01-01

    [Abridged] Star and planet formation are the complex outcomes of gravitational collapse and angular momentum transport mediated by protostellar and protoplanetary disks. In this review we focus on the role of gravitational instability in this process. We begin with a brief overview of the observational evidence for massive disks that might be subject to gravitational instability, and then highlight the diverse ways in which the instability manifests itself in protostellar and protoplanetary disks: the generation of spiral arms, small scale turbulence-like density fluctuations, and fragmentation of the disk itself. We present the analytic theory that describes the linear growth phase of the instability, supplemented with a survey of numerical simulations that aim to capture the non-linear evolution. We emphasize the role of thermodynamics and large scale infall in controlling the outcome of the instability. Despite apparent controversies in the literature, we show a remarkable level of agreement between analyt...

  13. Equilibrium Electro-osmotic Instability

    CERN Document Server

    Rubinstein, Isaak

    2014-01-01

    Since its prediction fifteen years ago, electro-osmotic instability has been attributed to non-equilibrium electro-osmosis related to the extended space charge which develops at the limiting current in the course of concentration polarization at a charge-selective interface. This attribution had a double basis. Firstly, it has been recognized that equilibrium electro-osmosis cannot yield instability for a perfectly charge-selective solid. Secondly, it has been shown that non-equilibrium electro-osmosis can. First theoretical studies in which electro-osmotic instability was predicted and analyzed employed the assumption of perfect charge-selectivity for the sake of simplicity and so did the subsequent numerical studies of various time-dependent and nonlinear features of electro-osmotic instability. In this letter, we show that relaxing the assumption of perfect charge-selectivity (tantamount to fixing the electrochemical potential in the solid) allows for equilibrium electro-osmotic instability. Moreover, we s...

  14. Beam instability Workshop - plenary sessions

    International Nuclear Information System (INIS)

    The purpose of this workshop was to provide a review of the mechanisms of limiting beam instabilities, their cures, including feedback, and beam measurement for synchrotron radiation light sources. 12 plenary sessions took place whose titles are: 1) challenging brilliance and lifetime issues with increasing currents; 2) limiting instabilities in multibunch; 3) experience from high currents in B factories; 4) longitudinal dynamics in high intensity/bunch; 5) Transverse instabilities for high intensity/bunch; 6) working group introduction from ESRF experience; 7) impedance modelling: simulations, minimization; 8) report on the broadband impedance measurements and modelling workshop; 9) feedback systems for synchrotron light sources; 10) beam instabilities diagnostics; 11) harmonic cavities: the pros and cons; and 12) experimental study of fast beam-ion instabilities at PLS. This document gathers the 12 articles that were presented during these sessions

  15. Instability in Shocked Granular Gases

    CERN Document Server

    Sirmas, Nick; Radulescu, Matei

    2013-01-01

    Shocks in granular media, such as vertically oscillated beds, have been shown to develop instabilities. Similar jet formation has been observed in explosively dispersed granular media. Our previous work addressed this instability by performing discrete-particle simulations of inelastic media undergoing shock compression. By allowing finite dissipation within the shock wave, instability manifests itself as distinctive high density non-uniformities and convective rolls within the shock structure. In the present study we have extended this work to investigate this instability at the continuum level. We modeled the Euler equations for granular gases with a modified cooling rate to include an impact velocity threshold necessary for inelastic collisions. Our results showed a fair agreement between the continuum and discrete-particle models. Discrepancies, such as higher frequency instabilities in our continuum results may be attributed to the absence of higher order effects.

  16. Instability in shocked granular gases

    International Nuclear Information System (INIS)

    Shocks in granular media, such as vertically oscillated beds, have been shown to develop instabilities. Similar jet formation has been observed in explosively dispersed granular media. Our previous work addressed this instability by performing discrete-particle simulations of inelastic media undergoing shock compression. By allowing finite dissipation within the shock wave, instability manifests itself as distinctive high density non-uniformities and convective rolls within the shock structure. In the present study we have extended this work to investigate this instability at the continuum level. We modeled the Euler equations for granular gases with a modified cooling rate to include an impact velocity threshold necessary for inelastic collisions. Our results showed a fair agreement between the continuum and discrete-particle models. Discrepancies, such as higher frequency instabilities in our continuum results may be attributed to the absence of higher order effects.

  17. Chromosome conservation in squamate reptiles revealed by comparative chromosome painting

    Czech Academy of Sciences Publication Activity Database

    Giovannotti, M.; Pokorná, Martina; Kratochvíl, L.; Caputo, V.; Olmo, E.; Ferguson-Smith, M. A.; Rens, W.

    Manchester : ICCS, 2011. 78-78. [Intarnational Chromosome Conference /18./. 29.08.2011-02.09.2011, Manchester] Institutional research plan: CEZ:AV0Z50450515 Keywords : squamate reptiles Subject RIV: EG - Zoology

  18. Numerous transitions of sex chromosomes in Diptera.

    Directory of Open Access Journals (Sweden)

    Beatriz Vicoso

    2015-04-01

    Full Text Available Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot, but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes. Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa.

  19. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.

    NARCIS (Netherlands)

    Bon, B.W.M. van; Koolen, D.A.; Brueton, L.; McMullan, D.; Lichtenbelt, K.D.; Ades, L.C.; Peters, G.; Gibson, K.; Moloney, S.; Novara, F.; Pramparo, T.; Bernardina, B. Dalla; Zoccante, L.; Balottin, U.; Piazza, F.; Pecile, V.; Gasparini, P.; Guerci, V.; Kets, M.; Pfundt, R.; Brouwer, A.P.M. de; Veltman, J.A.; Leeuw, N. de; Wilson, M.; Antony, J.; Reitano, S.; Luciano, D.; Fichera, M.; Romano, C.; Brunner, H.G.; Zuffardi, O.; Vries, L.B.A. de

    2010-01-01

    Six submicroscopic deletions comprising chromosome band 2q23.1 in patients with severe mental retardation (MR), short stature, microcephaly and epilepsy have been reported, suggesting that haploinsufficiency of one or more genes in the 2q23.1 region might be responsible for the common phenotypic fea

  20. Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

    OpenAIRE

    Pruszewicz, Antoni; Wiskirska-Woźnica, Bożena; Wojnowski, Waldemar; Czerniejewska, Hanna; Jackowska, Joanna; Jarmuż, Małgorzata; Szyfter, Krzysztof; Leszczyńska, Małgorzata

    2014-01-01

    Patient: Female, 6 Final Diagnosis: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: — Medication: — Clinical Procedure: — Specialty: Otolaryngology Objective: Congenital defects Background: Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or...

  1. Nunukan Chicken: Genetic Characteristics, Phenotype and Utilization

    Directory of Open Access Journals (Sweden)

    Tike Sartika

    2006-12-01

    Full Text Available Nunukan chicken is a local chicken from East Kalimantan which spreads out in Tarakan and Nunukan Islands . The chicken has a specific buff color and Columbian type feather and also has very late feathering (VLF trait . The Nunukan cocks and hens have no wing and tail primary feather; the tail feathers are short and fragile . The VLF trait is known to have association with a K gene on the Z chromosome. The chicken is efficient in protein metabolism . Sulfur amino acids (cystine and methionine that needed for feather growth, could be utilized for meat and egg production . The egg production of Nunukan chicken was better than the Kampung chicken . The average of hen day, hen house and peak production of Nunukan chicken was 45 . 39.1 and 62%, respectively, while the Kampung chicken was 35 .9, 30 .9 and 48%, respectively . Based on genetic analysis, the external genotype characteristic of the Nunukan chicken is ii ce ss Idld pp. It means that the phenotype appearance of the Nunukan chicken was columbian and gold feathering type, yellow and white shank color and single comb type. This phenotype is similar to Merawang Chicken . The genetic introgression of the Nunukan chicken is affected by the Rhode Island Red with the genetic introgression value of 0.964 .

  2. Instabilities of advection-dominated accretion flows

    CERN Document Server

    Chen, X

    1996-01-01

    Accretion disk instabilities are briefly reviewed. Some details are given to the short-wavelength thermal instabilities and the convective instabilities. Time-dependent calculations of two-dimensional advection-dominated accretion flows are presented.

  3. Instabilities of Advection-Dominated Accretion Flows

    OpenAIRE

    Chen, Xingming

    1996-01-01

    Accretion disk instabilities are briefly reviewed. Some details are given to the short-wavelength thermal instabilities and the convective instabilities. Time-dependent calculations of two-dimensional advection-dominated accretion flows are presented.

  4. Familial transmission of a deletion of chromosome 21 derived from a translocation between chromosome 21 and an inverted chromosome 22.

    Science.gov (United States)

    Aviv, H; Lieber, C; Yenamandra, A; Desposito, F

    1997-06-27

    Chromosome analysis of a newborn boy with Down syndrome resulted in the identification of a family with an unusual derivative chromosome 22. The child has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization (FISH) studies show that the derivative chromosome is chromosome 22 with evidence of both paracentric and pericentric inversions, joined to the long arm of chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy 21 extending from 21q21.2 to 21q terminus in the patient. The child's mother, brother, maternal aunt, and maternal grandmother are all carriers of the derivative chromosome. All have 45 chromosomes, with one normal chromosome 21, one normal chromosome 22, and the derivative chromosome 22. The rearrangement results in the absence of the short arm, the centromere, and the proximal long arm of chromosome 21 (del 21pter-21q21.2) in carriers. Carriers of the derivative chromosome in this family have normal physical appearance, mild learning disabilities and poor social adjustment. PMID:9182781

  5. Meiosis and chromosome painting of sex chromosome systems in Ceboidea.

    Science.gov (United States)

    Mudry, M D; Rahn, I M; Solari, A J

    2001-06-01

    The identity of the chromosomes involved in the multiple sex system of Alouatta caraya (Aca) and the possible distribution of this system among other Ceboidea were investigated by chromosome painting of mitotic cells from five species and by analysis of meiosis at pachytene in two species. The identity of the autosome #7 (X2) involved in the multiple system of Aca and its breakage points were demonstrated by both meiosis and chromosome painting. These features are identical to those described by Consigliere et al. [1996] in Alouatta seniculus sara (Assa) and Alouatta seniculus arctoidea (Asar). This multiple system was absent in the other four Ceboidea species studied here. However, data from the literature strongly suggest the presence of this multiple in other members of this genus. The presence of this multiple system among several species and subspecies that show high levels of chromosome rearrangements may suggest a special selective value of this multiple. The meiotic features of the sex systems of Aca and Cebus apella paraguayanus (Cap) are strikingly different at pachytene, as the latter system is similar to the sex pair of man and other primates. The relatively large genetic distances between species presently showing this multiple system suggest that its origin is not recent. Other members of the same genus should be investigated at meiosis and by chromosome painting in order to know the extent and distribution of this complex sex-chromosome system. PMID:11376445

  6. Mitotic instability of Pichia pinus diploid cells 2. Segregation induced by gamma-irradiation

    International Nuclear Information System (INIS)

    Two types of genetic damages resulted from gamma rays in diploid cells of yeasts Pichia pinus MH4: nonlethal damages resulting in increasing frequency of mitotic crossing-over and lethal damages leading to cell death or arising unstable clones have been described. Survaving irradiated cells with lethal damages (which nature is not established) originate ''grown'' colonies which instability is manifested in the increased frequency of segregation of lethal sections and aneuploid segregants; in such colonies segregants without one, two or three nonhomologous chromosomes are often found. It is concluded that losses of separate chromosomes are not those primary damages which result in radiation inactivation of cells

  7. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    OpenAIRE

    Geísa Pinheiro Paes; José Marcelo Soriano Viana; Fabyano Fonseca e Silva; Gabriel Borges Mundim

    2016-01-01

    Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kerne...

  8. The Comorbidity of Autism with the Genomic Disorders of Chromosome 15q11.2-q13

    OpenAIRE

    Hogart, Amber; Wu, David; LaSalle, Janine M.; Schanen, N. Carolyn

    2008-01-01

    A cluster of low copy repeats on the proximal long arm of chromosome 15 mediate various forms of stereotyped deletions and duplication events that cause a group of neurodevelopmental disorders that are associated with autism or autism spectrum disorders (ASD). The region is subject to genomic imprinting and the behavioral phenotypes associated with the chromosome 15q11.2-q13 disorders show a parent-of-origin specific effect that suggests that increased copy number of maternally derived allele...

  9. Mosaic Ring Chromosome 14 and Monosomy 14 Presenting with Growth Retardation, Epilepsy, and Blepharophimosis.

    Directory of Open Access Journals (Sweden)

    Jia-Woei Hou

    2004-05-01

    Full Text Available Ring chromosomes are rare chromosomal anomalies and usually not stable in nature.Patients carrying ring chromosome have various phenotypes depending on the degree ofstructural rearrangement. A 1-year-old boy, presenting with hypotonia, blepharophimosis,ptosis, a bulbous nose, mild psychomotor retardation, and epilepsy, was found to havemosaicism of chromosome ring 14 and monosomy 14. His karyotype is described as hithertounreported mos 46, XY, r(14(p11.2q32.31 or q32.2[84]/45, XY,-14[10]/46, XY, dicr(14[6]. His seizures responded well to phenobarbital. He has marked growth retardationbut less serious delays in mental and motor development than those with ring 14 describedin the literature.

  10. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

    Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

  11. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability.

    Science.gov (United States)

    Nielsen, Aaraby Yoheswaran; Gjerstorff, Morten Frier

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies. PMID:27275820

  12. Methods for chromosome-specific staining

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel

    1995-01-01

    Methods and compositions for chromosome-specific staining are provided. Compositions comprise heterogenous mixtures of labeled nucleic acid fragments having substantially complementary base sequences to unique sequence regions of the chromosomal DNA for which their associated staining reagent is specific. Methods include methods for making the chromosome-specific staining compositions of the invention, and methods for applying the staining compositions to chromosomes.

  13. Chromosome Architecture and Genome Organization

    OpenAIRE

    Giorgio Bernardi

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few...

  14. Chromosome evolution in Neotropical butterflies

    OpenAIRE

    Saura, Anssi; Von Schoultz, Barbara; Saura, Anja O.; Brown, Keith S., Jr.

    2013-01-01

    We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results i...

  15. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is currently defined as a common preventable and treatable disease that is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious...... particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association with...

  16. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  17. Chromosome Architecture and Genome Organization

    Science.gov (United States)

    Bernardi, Giorgio

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm “beads-on-a-string” structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the “mitotic memory” of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. PMID:26619076

  18. Fragile site X chromosomes in mentally retarded boys.

    OpenAIRE

    Moon, H. R.; Moon, S. Y.

    1993-01-01

    The fragile X syndrome is a common X-linked mental retardation and autism, affecting females as well as males. The fragile site X chromosomes were studied in a series of 153 mentally retarded boys of unknown etiology to determine the frequency of fragile X syndrome, and to assess the feasibility of making a clinical diagnosis of the fragile X syndrome in young boys before cytogenetic results were known. The 10 boys (6.4%) were positive for fra (X) (q27). The phenotype of fra (X) (q27) positiv...

  19. Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11

    Directory of Open Access Journals (Sweden)

    Bader Scott

    2005-07-01

    Full Text Available Abstract Background Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained through microcell mediated chromosome transfer, indicated by differentiation of neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11. Interestingly, some of these microcell hybrid clones were shown to harbour deletions in the transferred chromosome 11. We decided to further exploit this model system as a means to identify candidate tumour suppressor or differentiation genes located on chromosome 11. Results In a first step, we performed high-resolution arrayCGH DNA copy-number analysis in order to evaluate the chromosome 11 status in the hybrids. Several deletions in both parental and transferred chromosomes in the investigated microcell hybrids were observed. Subsequent correlation of these deletion events with the observed morphological changes lead to the delineation of three putative regions on chromosome 11: 11q25, 11p13->11p15.1 and 11p15.3, that may harbour the responsible differentiation gene. Conclusion Using an available model system, we were able to put forward some candidate regions that may be involved in neuroblastoma. Additional studies will be required to clarify the putative role of the genes located in these chromosomal segments in the observed differentiation phenotype specifically or in neuroblastoma pathogenesis in general.

  20. Characterization of the chromosomal inversion associated with the Koa mutation in the mouse revealed the cause of skeletal abnormalities

    Directory of Open Access Journals (Sweden)

    Suzuki Hiroetsu

    2009-09-01

    Full Text Available Abstract Background Koala (Koa is a dominant mutation in mice causing bushy muzzle and pinna, and is associated with a chromosomal inversion on the distal half of chromosome 15. To identify the gene responsible for the Koa phenotypes, we investigated phenotypes of Koa homozygous mice and determined the breakpoints of the inversion with a genetic method using recombination between two different chromosomal inversions. Results Skeletal preparation of Koa homozygotes showed marked deformity of the ribs and a wider skull with extended zygomatic arches, in addition to a general reduction in the lengths of long bones. They also had open eyelids at birth caused by a defect in the extension of eyelid anlagen during the embryonic stages. The proximal and distal breakpoints of the Koa inversion were determined to be 0.8-Mb distal to the Trsps1 gene and to 0.1-Mb distal to the Hoxc4 gene, respectively, as previously reported. The phenotypes of mice with the recombinant inverted chromosomes revealed the localization of the gene responsible the Koa phenotype in the vicinity of the proximal recombinant breakpoint. Expression of the Trsps1 gene in this region was significantly reduced in the Koa homozygous and heterozygous embryos. Conclusion While no gene was disrupted by the chromosomal inversion, an association between the Koa phenotype and the proximal recombinant breakpoint, phenotypic similarities with Trps1-deficient mice or human patients with TRSP1 mutations, and the reduced expression of the Trsps1 gene in Koa mice, indicated that the phenotypes of the Koa mice are caused by the altered expression of the Trps1 gene.

  1. Marker enzyme phenotype ratios in agamospermous sugarbeet progenies as a demonstration of multidimensional encoding of inherited information in plants

    OpenAIRE

    Levites, Evgenii V.

    2007-01-01

    It has been demonstrated that the observed ratio of phenotypes of marker enzymes in some sugarbeet plants produced by mitotic agamospermy can be explained by different degrees of endoreduplication of chromosomes carrying different alleles of the enzyme loci. In these plants, different patterns of variability of the enzymes controlled by the linked loci suggest different degrees of endoreduplication of different chromosomal regions. A concept of multidimensional encoding of inherited informati...

  2. Evolution of Sex Chromosomes in Insects

    OpenAIRE

    Kaiser, Vera B; Bachtrog, Doris

    2010-01-01

    Sex chromosomes have many unusual features relative to autosomes. Y (or W) chromosomes lack genetic recombination, are male- (female-) limited, and show an abundance of genetically inert heterochromatic DNA but contain few functional genes. X (or Z) chromosomes also show sex-biased transmission (i.e., X chromosomes show female-biased and Z-chromosomes show male-biased inheritance) and are hemizygous in the heterogametic sex. Their unusual ploidy level and pattern of inheritance imply that sex...

  3. Chromosome territories, X;Y translocation and Premature Ovarian Failure: is there a relationship?

    Directory of Open Access Journals (Sweden)

    Betri Enrico

    2009-09-01

    Full Text Available Abstract Background Premature ovarian failure (POF is a secondary hypergonadotrophic amenorrhea occurring before the age of 40 and affecting 1-3% of females. Chromosome anomalies account for 6-8% of POF cases, but only few cases are associated with translocations involving X and Y chromosomes. This study shows the cytogenetic and molecular analysis of a POF patient came to our attention as she developed a left ovary choriocarcinoma at the age of 10 and at 14 years of age she presented secondary amenorrhea with elevated levels of gonadotropins. Results Breakpoint position on X and Y chromosomes was investigated using Fluorescent In Situ Hybridisation (FISH with a panel of specific BAC probes, microsatellite analysis and evaluation of copy number changes and loss of heterozigosity by Affymetrix® GeneChip platform (Santa Clara, CA, USA. Patient's karyotype resulted 46, X, der(Yt(X;Y(q13.1;q11.223. X inactivation study was assessed by RBA banding and showed preferential inactivation of derivative chromosome. The reciprocal spatial disposition of sexual chromosome territories was investigated using whole chromosome painting and centromeres probes: patient's results didn't show a significant difference in comparison to normal controls. Conclusion The peculiar clinical case come to our attention highlighted the complexity of POF aetiology and of the translocation event, even if our results seem to exclude any effect on nuclear organisation. POF phenotype could be partially explained by skewed X chromosome inactivation that influences gene expression.

  4. Genetic architecture of sexual dimorphism in a subdioecious plant with a proto-sex chromosome.

    Science.gov (United States)

    Spigler, Rachel B; Lewers, Kim S; Ashman, Tia-Lynn

    2011-04-01

    The rise of sexual dimorphism is thought to coincide with the evolution of sex chromosomes. Yet because sex chromosomes in many species are ancient, we lack empirical evidence of the earliest stages of this transition. We use QTL analysis to examine the genetic architecture of sexual dimorphism in subdioecious octoploid Fragaria virginiana. We demonstrate that the region housing the male-function locus controls the majority of quantitative variation in proportion fruit set, confirming the existence of a proto-sex chromosome, and houses major QTL for eight additional sexually dimorphic traits, consistent with theory and data from animals and plants with more advanced sex chromosomes. We also detected autosomal QTL, demonstrating contributions to phenotypic variation in sexually dimorphic traits outside the sex-determining region. Moreover, for proportion seed set we found significant epistatic interactions between autosomal QTL and the male-function locus, indicating sex-limited QTL. We identified linked QTL reflecting trade-offs between male and female traits expected from theory and positive integration of male traits. These findings indicate the potential for the evolution of greater sexual dimorphism. Involvement of linkage groups homeologous to the proto-sex chromosome in these correlations reflects the polyploid origin of F. virginiana and raises the possibility that chromosomes in this homeologous group were predisposed to become the sex chromosome. PMID:21062281

  5. Nonlinear ideal magnetohydrodynamics instabilities

    International Nuclear Information System (INIS)

    Explosive phenomena such as internal disruptions in toroidal discharges and solar flares are difficult to explain in terms of linear instabilities. A plasma approaching a linear stability limit can, however, become nonlinearly and explosively unstable, with noninfinitesimal perturbations even before the marginal state is reached. For such investigations, a nonlinear extension of the usual MHD (magnetohydrodynamic) energy principle is helpful. (This was obtained by Merkel and Schlueter, Sitzungsberichted. Bayer. Akad. Wiss., Munich, 1976, No. 7, for Cartesian coordinate systems.) A coordinate system independent Eulerian formulation for the Lagrangian allowing for equilibria with flow and with built-in conservation laws for mass, magnetic flux, and entropy is developed in this paper which is similar to Newcomb's Lagrangian method of 1962 [Nucl. Fusion, Suppl., Pt. II, 452 (1962)]. For static equilibria nonlinear stability is completely determined by the potential energy. For a potential energy which contains second- and nth order or some more general contributions only, it is shown in full generality that linearly unstable and marginally stable systems are explosively unstable even for infinitesimal perturbations; linearly absolutely stable systems require finite initial perturbations. For equilibria with Abelian symmetries symmetry breaking initial perturbations are needed, which should be observed in numerical simulations. Nonlinear stability is proved for two simple examples, m=0 perturbations of a Bennet Z-pinch and z-independent perturbations of a θ pinch. The algebra for treating these cases reduces considerably if symmetries are taken into account from the outset, as suggested by M. N. Rosenbluth (private communication, 1992)

  6. Chromosomal Behavior during Meiosis in the Progeny of Triticum timopheevii × Hexaploid Wild Oat.

    Directory of Open Access Journals (Sweden)

    Hongzhou An

    Full Text Available The meiotic behavior of pollen mother cells (PMCs of the F2 and F3 progeny from Triticum timopheevii × hexaploid wild oat was investigated by cytological analysis and sequential C-banding-genomic in situ hybridization (GISH in the present study. A cytological analysis showed that the chromosome numbers of the F2 and F3 progeny ranged from 28 to 41. A large number of univalents, lagging chromosomes, chromosome bridges and micronuclei were found at the metaphase I, anaphase I, anaphase II and tetrad stages in the F2 and F3 progeny. The averages of univalents were 3.50 and 2.73 per cell, and those of lagging chromosomes were 3.37 and 1.87 in the F2 and F3 progeny, respectively. The PMC meiotic indices of the F2 and F3 progeny were 12.22 and 20.34, respectively, indicating considerable genetic instability. A sequential C-banding-GISH analysis revealed that some chromosomes and fragments from the hexaploid wild oat were detected at metaphase I and anaphase I in the progeny, showing that the progeny were of true intergeneric hybrid origin. The alien chromosomes 6A, 7A, 3C and 2D were lost during transmission from F2 to F3. In addition, partial T. timopheevii chromosomes appeared in the form of univalents or lagging chromosomes, which might result from large genome differences between the parents, and the wild oat chromosome introgression interfered with the wheat homologues' normally pairing.

  7. Chromosomal Behavior during Meiosis in the Progeny of Triticum timopheevii × Hexaploid Wild Oat.

    Science.gov (United States)

    An, Hongzhou; Hu, Mei; Li, Pengfei; Geng, Guangdong; Zhang, Qingqin; Zhang, Suqin

    2015-01-01

    The meiotic behavior of pollen mother cells (PMCs) of the F2 and F3 progeny from Triticum timopheevii × hexaploid wild oat was investigated by cytological analysis and sequential C-banding-genomic in situ hybridization (GISH) in the present study. A cytological analysis showed that the chromosome numbers of the F2 and F3 progeny ranged from 28 to 41. A large number of univalents, lagging chromosomes, chromosome bridges and micronuclei were found at the metaphase I, anaphase I, anaphase II and tetrad stages in the F2 and F3 progeny. The averages of univalents were 3.50 and 2.73 per cell, and those of lagging chromosomes were 3.37 and 1.87 in the F2 and F3 progeny, respectively. The PMC meiotic indices of the F2 and F3 progeny were 12.22 and 20.34, respectively, indicating considerable genetic instability. A sequential C-banding-GISH analysis revealed that some chromosomes and fragments from the hexaploid wild oat were detected at metaphase I and anaphase I in the progeny, showing that the progeny were of true intergeneric hybrid origin. The alien chromosomes 6A, 7A, 3C and 2D were lost during transmission from F2 to F3. In addition, partial T. timopheevii chromosomes appeared in the form of univalents or lagging chromosomes, which might result from large genome differences between the parents, and the wild oat chromosome introgression interfered with the wheat homologues' normally pairing. PMID:25950431

  8. Diagnosis of a constitutional five-chromosome rearrangement by fluorescent in situ hybridization (FISH)

    Energy Technology Data Exchange (ETDEWEB)

    Tsien, F.; Shapira, E. [Tulane Univ. School of Medicine, New Orleans, LA (United States); Carvalho, T. [Hospital Sarah Kubitschek, Brasilia (Brazil)] [and others

    1994-09-01

    Complex chromosomal rearrangements are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Such karyotypes are often acquired during cancer multi-step development and in chromosome instability syndromes. However, extremely rare constitutional forms have been reported, most of which are incompatible with life. We present a 2-year-old female with de novo complex rearrangement consisting of five chromosomes and nine breakpoints. Clinical evaluation at two years of age revealed a weight of 5 kg, length of 66 cm, and had circumference of 38 cm, all below the 5th percentile, microcephaly, trigonocephaly, epicanthal folds, inguinal hernia, left clubfoot, hypertonicity, and developmental delay. The neurological examination revealed chorea-acanthocytosis and psychomotor delay. Cultured lymphocytes and fibroblasts revealed a karyotype consisting of five derivative chromosomes. The metaphases were further analyzed by FISH using chromosome-specific libraries and telomeric probes in order to delineate the composition of the rearranged chromosomes; FISH results demonstrated a karyotype of: 46,XX,1pter{r_arrow}1q25::1q42.1{r_arrow}1qter, 2pter{r_arrow}q32.3::1q32.3{r_arrow}2q41::2q37.3{r_arrow}2qter, 7qter{r_arrow}7q21.2::6q22.3{r_arrow}6qter::1q31{r_arrow}1q32.3::6p23{r_arrow}6q22.3, 7pter{r_arrow}7q21.1::6p23{r_arrow}6pter, 2q33{r_arrow}2q37, 1::9p21{r_arrow}9qter. This analysis demonstrates the usefulness of FISH in characterizing complex chromosome rearrangements otherwise difficult to correctly interpret using classical cytogenetics alone.

  9. Down's/Turner's mosaicism. Double aneuploidy as a rare cause of missed prenatal diagnosis of chromosomal abnormality.

    OpenAIRE

    MacFaul, R; Turner, T.; Mason, M. K.

    1981-01-01

    Two babies with Down's/Turner's mosaic karyotype are reported. In each, because of advanced maternal age, chromosomal analysis had been carried out on the fluid obtained by amniocentesis in early pregnancy. Only the 46,X+ 21 cell line grew in the specimens and the extra 21 chromosome was wrongly identified as a Y chromosome, so that the fetus was thought to have a normal male karyotype, 46,XY. At birth both babies were phenotypically female with features predominantly of Down's syndrome and t...

  10. A Turner syndrome neurocognitive phenotype maps to Xp22.3

    Directory of Open Access Journals (Sweden)

    Elder Frederick F

    2007-05-01

    Full Text Available Abstract Background Turner syndrome (TS is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47 of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. Methods Subjects were recruited from North American genetics and endocrinology clinics. Phenotype assessment included measures of stature, ovarian function, and detailed neurocognitive testing. The neurocognitive phenotype was measured as a quantitative trait, the Turner Syndrome Cognitive Summary (TSCS score, derived from discriminant function analysis. Genetic analysis included karyotyping, X inactivation studies, fluorescent in situ hybridization, microsatellite marker genotyping, and array comparative genomic hybridization. Results We report statistical evidence that deletion of Xp22.3, an interval containing 31 annotated genes, is sufficient to cause the neurocognitive phenotype described by the TSCS score. Two other cardinal TS features, ovarian failure and short stature, as well as X chromosome inactivation pattern and subject's age, were unrelated to the TSCS score. Conclusion Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases (Mb of the X chromosome, is responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb Xp-Yp pseudoautosomal region (PAR1. Haploinsufficiency of the short stature gene SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are

  11. Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers.

    Science.gov (United States)

    Marzec, Paulina; Armenise, Claudia; Pérot, Gaëlle; Roumelioti, Fani-Marlen; Basyuk, Eugenia; Gagos, Sarantis; Chibon, Frédéric; Déjardin, Jérôme

    2015-02-26

    The breakage-fusion-bridge cycle is a classical mechanism of telomere-driven genome instability in which dysfunctional telomeres are fused to other chromosomal extremities, creating dicentric chromosomes that eventually break at mitosis. Here, we uncover a distinct pathway of telomere-driven genome instability, specifically occurring in cells that maintain telomeres with the alternative lengthening of telomeres mechanism. We show that, in these cells, telomeric DNA is added to multiple discrete sites throughout the genome, corresponding to regions regulated by NR2C/F transcription factors. These proteins drive local telomere DNA addition by recruiting telomeric chromatin. This mechanism, which we name targeted telomere insertion (TTI), generates potential common fragile sites that destabilize the genome. We propose that TTI driven by NR2C/F proteins contributes to the formation of complex karyotypes in ALT tumors. PMID:25723166

  12. Short Inverted Repeats Are Hotspots for Genetic Instability: Relevance to Cancer Genomes

    Directory of Open Access Journals (Sweden)

    Steve Lu

    2015-03-01

    Full Text Available Analyses of chromosomal aberrations in human genetic disorders have revealed that inverted repeat sequences (IRs often co-localize with endogenous chromosomal instability and breakage hotspots. Approximately 80% of all IRs in the human genome are short (<100 bp, yet the mutagenic potential of such short cruciform-forming sequences has not been characterized. Here, we find that short IRs are enriched at translocation breakpoints in human cancer and stimulate the formation of DNA double-strand breaks (DSBs and deletions in mammalian and yeast cells. We provide evidence for replication-related mechanisms of IR-induced genetic instability and a novel XPF cleavage-based mechanism independent of DNA replication. These discoveries implicate short IRs as endogenous sources of DNA breakage involved in disease etiology and suggest that these repeats represent a feature of genome plasticity that may contribute to the evolution of the human genome by providing a means for diversity within the population.

  13. Platypus chain reaction: directional and ordered meiotic pairing of the multiple sex chromosome chain in Ornithorhynchus anatinus.

    Science.gov (United States)

    Daish, Tasman; Casey, Aaron; Grützner, Frank

    2009-01-01

    Monotremes are phylogenetically and phenotypically unique animals with an unusually complex sex chromosome system that is composed of ten chromosomes in platypus and nine in echidna. These chromosomes are alternately linked (X1Y1, X2Y2, ...) at meiosis via pseudoautosomal regions and segregate to form spermatozoa containing either X or Y chromosomes. The physical and epigenetic mechanisms involved in pairing and assembly of the complex sex chromosome chain in early meiotic prophase I are completely unknown. We have analysed the pairing dynamics of specific sex chromosome pseudoautosomal regions in platypus spermatocytes during prophase of meiosis I. Our data show a highly coordinated pairing process that begins at the terminal Y5 chromosome and completes with the union of sex chromosomes X1Y1. The consistency of this ordered assembly of the chain is remarkable and raises questions about the mechanisms and factors that regulate the differential pairing of sex chromosomes and how this relates to potential meiotic silencing mechanisms and alternate segregation. PMID:19874721

  14. WELLBORE INSTABILITY: CAUSES AND CONSEQUENCES

    Directory of Open Access Journals (Sweden)

    Borivoje Pašić

    2007-12-01

    Full Text Available Wellbore instability is one of the main problems that engineers meet during drilling. The causes of wellbore instability are often classified into either mechanical (for example, failure of the rock around the hole because of high stresses, low rock strength, or inappropriate drilling practice or chemical effects which arise from damaging interaction between the rock, generally shale, and the drilling fluid. Often, field instances of instability are a result of a combination of both chemical and mechanical. This problem might cause serious complication in well and in some case can lead to expensive operational problems. The increasing demand for wellbore stability analyses during the planning stage of a field arise from economic considerations and the increasing use of deviated, extended reach and horizontal wells. This paper presents causes, indicators and diagnosing of wellbore instability as well as the wellbore stresses model.

  15. Size effects on cavitation instabilities

    DEFF Research Database (Denmark)

    Niordson, Christian Frithiof; Tvergaard, Viggo

    2006-01-01

    growth is here analyzed for such cases. A finite strain generalization of a higher order strain gradient plasticity theory is applied for a power-law hardening material, and the numerical analyses are carried out for an axisymmetric unit cell containing a spherical void. In the range of high stress......In metal-ceramic systems the constraint on plastic flow leads to so high stress triaxialities that cavitation instabilities may occur. If the void radius is on the order of magnitude of a characteristic length for the metal, the rate of void growth is reduced, and the possibility of unstable cavity...... triaxiality, where cavitation instabilities are predicted by conventional plasticity theory, such instabilities are also found for the nonlocal theory, but the effects of gradient hardening delay the onset of the instability. Furthermore, in some cases the cavitation stress reaches a maximum and then decays...

  16. Summary of longitudinal instabilities workshop

    Energy Technology Data Exchange (ETDEWEB)

    Chasman, R.

    1976-01-01

    A five-day ISABELLE workshop on longitudinal instabilities was held at Brookhaven, August 9-13, 1976. About a dozen outside accelerator experts, both from Europe and the U.S.A., joined the local staff for discussions of longitudinal instabilities in ISABELLE. An agenda of talks was scheduled for the first day of the workshop. Later during the week, a presentation was given on the subject ''A more rigorous treatment of Landau damping in longitudinal beam instabilities''. A few progress meetings were held in which disagreements regarding calculations of coupling impedances were clarified. A summary session was held on the last day. Heavy emphasis was put on single bunched beam instabilities in the microwave region extending above the cut-off frequency of the ISABELLE vacuum chamber.

  17. Intrinsic Instability of Coronal Streamers

    CERN Document Server

    Chen, Y; Song, H Q; Shi, Q Q; Feng, S W; Xia, L D; 10.1088/0004-637X/691/2/1936

    2009-01-01

    Plasma blobs are observed to be weak density enhancements as radially stretched structures emerging from the cusps of quiescent coronal streamers. In this paper, it is suggested that the formation of blobs is a consequence of an intrinsic instability of coronal streamers occurring at a very localized region around the cusp. The evolutionary process of the instability, as revealed in our calculations, can be described as follows: (1) through the localized cusp region where the field is too weak to sustain the confinement, plasmas expand and stretch the closed field lines radially outward as a result of the freezing-in effect of plasma-magnetic field coupling; the expansion brings a strong velocity gradient into the slow wind regime providing the free energy necessary for the onset of a subsequent magnetohydrodynamic instability; (2) the instability manifests itself mainly as mixed streaming sausage-kink modes, the former results in pinches of elongated magnetic loops to provoke reconnections at one or many loc...

  18. Baryon Instability in SUSY Models

    OpenAIRE

    Nath, Pran; Arnowitt, R.

    1996-01-01

    Comment: 14 pages, latex, 1 fig, to be published in proceedings of the International Workshop on " Future Prospects of Baryon Instability Search in p-Decay and n-nbar Oscillation Experiments", Oak Ridge, Tennessee, March 28-30,1996

  19. Thermal instability of gold nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Karim, Shafqat [Fachbereich Chemie, Marburg University (Germany); Toimil-Molares, Maria E.; Cornelius, Thomas; Neumann, Reinhard [Gesellschaft fuer Schwerionenforschung (GSI), Darmstadt (Germany); Balogh, Adam; Ensinger, Wolfgang [Institute of Materials Science, Darmstadt University of Technology (Germany)

    2007-07-01

    The technological implementation of nanostructures in future nano- and opto-electronic devices requires the capability to withstand elevated temperatures often encountered during routine operation. However, due to their reduced size and high surface to volume ratio, nanowires are expected to display structural and morphological instabilities. The Rayleigh instability concept, introduced to describe the instability of liquid jets, is applied to the fragmentation of metal nanowires during heating. Gold nanowires are electrochemically deposited in etched ion track membranes. After dissolving the template, the wires are put on a substrate and heated to temperatures between 300 and 600 C. The wires decay driven by Rayleigh instability, and the process depends on annealing temperature, wire diameter, and crystallinity. Wires of diameter 20 nm already fragment at 300 C being far below the bulk melting temperature of 1064 C.

  20. Endocrine abnormalities in ring chromosome 11: a case report and review of the literature

    OpenAIRE

    Lange, Renata; Von Linsingen, Caoê; Mata, Fernanda; Moraes, Aline Barbosa; Arruda, Mariana; Vieira Neto, Leonardo

    2015-01-01

    Summary Ring chromosomes (RCs) are uncommon cytogenetic findings, and RC11 has only been described in 19 cases in the literature. Endocrine abnormalities associated with RC11 were reported for two of these cases. The clinical features of RC11 can result from an alteration in the structure of the genetic material, ring instability, mosaicism, and various extents of genetic material loss. We herein describe a case of RC11 with clinical features of 11q-syndrome and endocrine abnormalities that h...