WorldWideScience

Sample records for chromosome final progress

  1. Fourth international workshop on human chromosome 5. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, J.D.

    1996-12-31

    The Fourth International Workshop on Human Chromosome 5 was held in Manchester, UK on November 9--10, 1996 and was hosted by the University of Manchester. The major goals of the workshop were: (1) to collate the various genetic, cytogenetic and physical maps of human chromosome 5; (2) to integrate these maps and identify/correct discrepancies between them wherever possible; (3) to catalogue the sequence-ready contigs of the chromosome; (4) to co-ordinate the various sequencing efforts to avoid future duplication; (5) to establish the first (to the author`s knowledge) web site for the human chromosome 5 community which contains the above information in a readily accessible form.

  2. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

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    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  3. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Josef Michl

    2011-10-31

    In this project we have established guidelines for the design on organic chromophores suitable for producing high triplet yields via singlet fission. We have proven their utility by identifying a chromophore of a structural class that had never been examined for singlet fission before, 1,3-diphenylisobenzofuran, and demonstrating in two independent ways that a thin layer of this material produces a triplet yield of 200% within experimental error. We have also designed a second chromophore of a very different type, again of a structural class that had not been examined for singlet fission before, and found that in a thin layer it produces a 70% triplet yield. Finally, we have enhanced the theoretical understanding of the quantum mechanical nature of the singlet fission process.

  4. Final Performance Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Houldin, Joseph [Delaware Valley Industrial Resource Center, Philadelphia, PA (United States); Saboor, Veronica [Delaware Valley Industrial Resource Center, Philadelphia, PA (United States)

    2016-03-30

    about assessing a company’s technical assets, broadening our view of the business to go beyond what they make or what NAICS code they have…to better understand their capacity, capability, and expertise, and to learn more about THEIR customers. Knowing more about the markets they serve can often provide insight into their level of technical knowledge and sophistication. Finally, in the spirit of realizing the intent of the Accelerator we strove to align and integrate the work and activities supported by the five funding agencies to leverage each effort. To that end, we include in the Integrated Work Plan a graphic that illustrates that integration. What follows is our summary report of the project, aggregated from prior reports.

  5. Chromosomes Progress to Metaphase in Multiple Discrete Steps via Global Compaction/Expansion Cycles.

    Science.gov (United States)

    Liang, Zhangyi; Zickler, Denise; Prentiss, Mara; Chang, Frederick S; Witz, Guillaume; Maeshima, Kazuhiro; Kleckner, Nancy

    2015-05-21

    Mammalian mitotic chromosome morphogenesis was analyzed by 4D live-cell and snapshot deconvolution fluorescence imaging. Prophase chromosomes, whose organization was previously unknown, are revealed to comprise co-oriented sister linear loop arrays displayed along a single, peripheral, regularly kinked topoisomerase II/cohesin/condensin II axis. Thereafter, rather than smooth, progressive compaction as generally envisioned, progression to metaphase is a discontinuous process involving chromosome expansion as well as compaction. At late prophase, dependent on topoisomerase II and with concomitant cohesin release, chromosomes expand, axes split and straighten, and chromatin loops transit to a radial disposition around now-central axes. Finally, chromosomes globally compact, giving the metaphase state. These patterns are consistent with the hypothesis that the molecular events of chromosome morphogenesis are governed by accumulation and release of chromosome stress, created by chromatin compaction and expansion. Chromosome state could evolve analogously throughout the cell cycle.

  6. Isolation of cDNAs from the human X chromosome and derivation of related STSs. Final progress report, April 1992--March 1995

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, D.L.

    1995-09-01

    Over the course of this funding period, the number of genes assigned to the human X chromosome has approximately tripled from less than one hundred to nearly three hundred characterized, cloned genes assigned to it. The aims of this project were to develop methods for gene identification and to identify and characterize expressed sequences from the X chromosome. The rapidly changing environment of the human genome project provided abundant resources for gene characterization, and since methods for gene identification became rather robust over this period, these aims were de-emphasized during the project. Among the methods developed was a local one (reciprocal probing) that was developed by Drs. Cheng Chi Lee and C. Thomas Caskey, with emphasis on the human X chromosome. The development of this method offered significant expressed sequence resources for this project, particularly when coupled with the efforts to identify cosmid clones from specific X chromosome locations, as the reciprocal probing process results in paired genomic (cosmid) and cDNA materials. Attention, then has been paid to characterization of genes rather than to their identification.

  7. Progressive segregation of the Escherichia coli chromosome

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2006-01-01

    We have followed the fate of 14 different loci around the Escherichia coli chromosome in living cells at slow growth rate using a highly efficient labelling system and automated measurements. Loci are segregated as they are replicated, but with a marked delay. Most markers segregate in a smooth...

  8. IRIS Final Technical Progress Report

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    M. D. Carelli

    2003-11-03

    OAK-B135 This NERI project, originally started as the Secure Transportable Autonomous Light Water Reactor (STAR-LW) and currently known as the International Reactor Innovative and Secure (IRIS) project, had the objective of investigating a novel type of water-cooled reactor to satisfy the Generation IV goals: fuel cycle sustainability, enhanced reliability and safety, and improved economics. The research objectives over the three-year (1999-2002) program were as follows: First year: Assess various design alternatives and establish main characteristics of a point design; Second year: Perform feasibility and engineering assessment of the selected design solutions; Third year: Complete reactor design and performance evaluation, including cost assessment These objectives were fully attained and actually they served to launch IRIS as a full fledged project for eventual commercial deployment. The program did not terminate in 2002 at the end of the NERI program, and has just entered in its fifth year. This has been made possible by the IRIS project participants which have grown from the original four member, two-countries team to the current twenty members, nine countries consortium. All the consortium members work under their own funding and it is estimated that the value of their in-kind contributions over the life of the project has been of the order of $30M. Currently, approximately 100 people worldwide are involved in the project. A very important constituency of the IRIS project is the academia: 7 universities from four countries are members of the consortium and five more US universities are associated via parallel NERI programs. To date, 97 students have worked or are working on IRIS; 59 IRIS-related graduate theses have been prepared or are in preparation, and 41 of these students have already graduated with M.S. (33) or Ph.D. (8) degrees. This ''final'' report (final only as far as the NERI program is concerned) summarizes the work performed

  9. Physical mapping of human chromosome 16. Annual progress report

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    Sutherland, G.R.

    1993-08-01

    We aim to isolate cDNAs mapping to human chromosome 16 and localise such cDNAs on the high resolution physical map. In collaboration with LANL, PCR primers will be synthesised from cDNA sequences mapped to chromosome 16 and used as ESTs in the generation of mega-YAC contigs for this chromosome. Probing of high density cosmid grids will enable integration of the ESTs into cosmid contigs and location of the cosmid contigs on the YAC contig. A hn-cDNA library has been constructed from the hybrid CY18 which contains chromosome 16 as the only human chromosome. A modified screening protocol has been successfully developed and 15 hn-cDNA clones have been sequenced and localised on the hybrid map. Sequence analysis of four of these revealed that they were known cDNAs, which are now mapped to chromosome 16. Development of techniques to allow the isolation of longer cDNAs from the identified exons is in progress. This will depend on PCR amplification of cDNAs from a total human CDNA library.

  10. Mapping strategies: Chromosome 16 workshop. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    1989-12-31

    The following topics from a workshop on chromosome 16 are briefly discussed: genetic map of chromosome 16; chromosome breakpoint map of chromosome 16; integrated physical/genetic map of chromosome 16; pulsed field map of the 16p13.2--p13.3 region (3 sheets); and a report of the HGM10 chromosome 16 committee.

  11. Molecular mapping of chromosomes 17 and X. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1991-01-15

    Progress toward the construction of high density genetic maps of chromosomes 17 and X has been made by isolating and characterizing a relatively large set of polymorphic probes for each chromosome and using these probes to construct genetic maps. We have mapped the same polymorphic probes against a series of chromosome breakpoints on X and 17. The probes could be assigned to over 30 physical intervals on the X chromosome and 7 intervals on 17. In many cases, this process resulted in improved characterization of the relative locations of the breakpoints with respect to each other and the definition of new physical intervals. The strategy for isolation of the polymorphic clones utilized chromosome specific libraries of 1--15 kb segments from each of the two chromosomes. From these libraries, clones were screened for those detecting restriction fragment length polymorphisms. The markers were further characterized, the chromosomal assignments confirmed and in most cases segments of the original probes were subcloned into plasmids to produce probes with improved signal to noise ratios for use in the genetic marker studies. The linkage studies utilize the CEPH reference families and other well-characterized families in our collection which have been used for genetic disease linkage work. Preliminary maps and maps of portions of specific regions of 17 and X are provided. We have nearly completed a map of the 1 megabase Mycoplasma arthritidis genome by applying these techniques to a lambda phage library of its genome. We have found bit mapping to be an efficient means to organize a contiguous set of overlapping@ clones from a larger genome.

  12. Molecular mapping of chromosomes 17 and X. Progress report

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    Barker, D.F.

    1989-12-31

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  13. 1995 PVUSA progress report. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale (US) photovoltaic (PV) electric generation systems and recent developments in PV module technology. This report updates the project`s progress, reviews the status and performance of the various PV installations during 1995, summarizes key accomplishments and conclusions, and serves as the final report under Pacific Gas and Electric Company`s project management.

  14. Mapping and ordered cloning of the human X chromosome. Progress report, September 1991--November 1992

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    Caskey, C.T.; Nelson, D.L.

    1992-12-01

    Progress is reported on gathering X chromosome specific libraries and integrating those with the library produced in this project. Further studies on understanding Fragile X Syndrome and other hereditary diseases related to the X chromosome are described. (DT)

  15. Chromosomes in the genesis and progression of ependymomas

    DEFF Research Database (Denmark)

    Rogatto, S R; Casartelli, C; Rainho, C A;

    1993-01-01

    chromosomes in three cases. Structural rearrangements of chromosome 2 were a finding for all cases and involved loss of material at 2q32-34. Other structural chromosome abnormalities detected involved chromosomes 4, 6, 10, 11, 12, and X. We also reviewed data on 22 cases previously reported....

  16. Final Technical Progress Report NANOSTRUCTURED MAGNETIC MATERIALS

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    Charles M. Falco

    2012-09-13

    This report describes progress made during the final phase of our DOE-funded program on Nanostructured Magnetic Materials. This period was quite productive, resulting in the submission of three papers and presentation of three talks at international conferences and three seminars at research institutions. Our DOE-funded research efforts were directed toward studies of magnetism at surfaces and interfaces in high-quality, well-characterized materials prepared by Molecular Beam Epitaxy (MBE) and sputtering. We have an exceptionally well-equipped laboratory for these studies, with: Thin film preparation equipment; Characterization equipment; Equipment to study magnetic properties of surfaces and ultra-thin magnetic films and interfaces in multi-layers and superlattices.

  17. The third international workshop of human chromosome 5. Final report

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    NONE

    1994-12-31

    The Third International Workshop on Human Chromosome 5 was held in Laguna Beach, California, March 5-8, 1994. The pace at which new mapping information has been published in the last year make almost any report outdated before publication. Much of the information in this report and the most recent data from the Human chromosome 5 Genome Center at U.C. Irvine on the physical map of chromosome 5 are accessible via a WWW server. For most loci referred to in this report that can be detected by Polymerase Chain Reaction, the sequences of the oligonucleotide primers are available and some primer sequences are provided in this report.

  18. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, July 1992--August 1993

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    Rowley, J.D.

    1993-09-01

    Progress in identification of chromosomal transformations associated with leukemogenesis is described. In particular progress in DNA cloning of chromosomal break points in human cancer patients is described.

  19. Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Ørntoft Torben

    2009-05-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion Chromosomal instability (CI was associated with "high risk

  20. Physical mapping of human chromosome 16. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1992-08-01

    Project aims for the past year have been to refine the cytogenetic based physical map of human chromosome 16. This has been achieved by extending the panel of mouse/human hybrids of chromosome 16 to over sixty hybrids and mapping approximately 250 DNA makers. The high resolution of this physical map, with an average distance between breakpoints of less than 1.6 Mb, and the availability of at least one STS in the majority of these intervals, will be the basis for constructing extensive contigs of cloned DNA.

  1. [Developing a physical map of human chromosome 22]. Progress report

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    Simon, M.I.

    1991-12-31

    We have developed bacterial F-factor based systems for cloning large fragments of human DNA in E. coli. In addition to large size, these systems are capable of maintaining human DNA with a high degree of stability. The cosmid size clones are called Fosmids and the clones containing larger inserts (100--200 kb) are called bacterial artificial chromosomes (BACs). The ultimate test of the effectiveness of cloning and mapping technology is the degree to which it can be efficiently applied to solve complex mapping problems. We, therefore, plan to use the large fragment cloning procedure as well as a variety of other approaches to generate a complete map of overlapping clones corresponding to human chromosome 22. We have thus far prepared two human chromosome 22 specific Fosmid libraries and we are in the process of constructing a chromosome 22 specific BAC library composed of fragments larger than 100 kb. We will further optimize the technology so that libraries of fragments larger than 200 kb can be readily prepared.

  2. Chromosome instability predicts progression of premalignant lesions of the larynx

    NARCIS (Netherlands)

    Bergshoeff, Verona E.; Van der Heijden, Stijn J. A.; Haesevoets, Annick; Litjens, Sophie G. H.; Bot, Fredrik J.; Voogd, Adri C.; Chenault, Michelene N.; Hopman, Anton H. N.; Schuuring, Ed; van der Wal, Jacqueline M.; Manni, Johannes J.; Ramaekers, Frans C. S.; Kremer, Bernd; Speel, Ernst-Jan M.

    2014-01-01

    The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice.Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and

  3. Chromosome

    Science.gov (United States)

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  4. Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast.

    Science.gov (United States)

    Matsuhara, Hirotada; Yamamoto, Ayumu

    2016-01-01

    Autophagy is a conserved intracellular degradation system, which contributes to development and differentiation of various organisms. Yeast cells undergo meiosis under nitrogen-starved conditions and require autophagy for meiosis initiation. However, the precise roles of autophagy in meiosis remain unclear. Here, we show that autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast. Autophagy-defective strains bearing a mutation in the autophagy core factor gene atg1, atg7, or atg14 exhibit deformed nuclear structures during meiosis. These mutant cells require an extracellular nitrogen supply for meiosis progression following their entry into meiosis and show delayed meiosis progression even with a nitrogen supply. In addition, they show frequent chromosome dissociation from the spindle together with spindle overextension, forming extra nuclei. Furthermore, Aurora kinase, which regulates chromosome segregation and spindle elongation, is significantly increased at the centromere and spindle in the mutant cells. Aurora kinase down-regulation eliminated delayed initiation of meiosis I and II, chromosome dissociation, and spindle overextension, indicating that increased Aurora kinase activity may cause these aberrances in the mutant cells. Our findings show a hitherto unrecognized relationship of autophagy with the nuclear structure, regulation of cell cycle progression, and chromosome segregation in meiosis. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  5. High rates of chromosome missegregation suppress tumor progression but do not inhibit tumor initiation

    Science.gov (United States)

    Zasadil, Lauren M.; Britigan, Eric M. C.; Ryan, Sean D.; Kaur, Charanjeet; Guckenberger, David J.; Beebe, David J.; Moser, Amy R.; Weaver, Beth A.

    2016-01-01

    Aneuploidy, an abnormal chromosome number that deviates from a multiple of the haploid, has been recognized as a common feature of cancers for >100 yr. Previously, we showed that the rate of chromosome missegregation/chromosomal instability (CIN) determines the effect of aneuploidy on tumors; whereas low rates of CIN are weakly tumor promoting, higher rates of CIN cause cell death and tumor suppression. However, whether high CIN inhibits tumor initiation or suppresses the growth and progression of already initiated tumors remained unclear. We tested this using the ApcMin/+ mouse intestinal tumor model, in which effects on tumor initiation versus progression can be discriminated. ApcMin/+ cells exhibit low CIN, and we generated high CIN by reducing expression of the kinesin-like mitotic motor protein CENP-E. CENP-E+/−;ApcMin/+ doubly heterozygous cells had higher rates of chromosome missegregation than singly heterozygous cells, resulting in increased cell death and a substantial reduction in tumor progression compared with ApcMin/+ animals. Intestinal organoid studies confirmed that high CIN does not inhibit tumor cell initiation but does inhibit subsequent cell growth. These findings support the conclusion that increasing the rate of chromosome missegregation could serve as a successful chemotherapeutic strategy. PMID:27146113

  6. Specific chromosomal imbalances in human papillomavirus-transfected cells during progression toward immortality

    Science.gov (United States)

    Solinas-Toldo, Sabina; Dürst, Matthias; Lichter, Peter

    1997-01-01

    High risk human papillomaviruses (HPVs) known to be closely associated with cervical cancer, such as HPV16 and HPV18, have the potential to immortalize human epithelial cells in culture. Four lines of HPV-transfected keratinocytes were analyzed by comparative genomic hybridization at different time points after transfection. A number of chromosomal imbalances was found to be highly characteristic for the cultures progressing toward immortality. Whereas several of these were new and previously not found as recurrent aberrations in cervical tumors, some were identical to chromosomal changes observed during cervical carcinogenesis. The data put new emphasis on the studied cell system as a relevant model for HPV-induced pathogenesis. PMID:9108068

  7. Chromosome 19 International Workshop. Final report, January 1, 1992--December 31, 1992

    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.

  8. [Research progress in lampbrush chromosomes and some suggestions for their use in genetics teaching].

    Science.gov (United States)

    Fanguo, Chen; Qingqing, Li

    2016-02-01

    Lampbrush chromosomes (LBCs) are transient giant transcripts that exist at the diplotene stage of the first meiotic division in female gametocytes of almost all animals except mammals. LBCs are named for their lampbrush-like structure, however, they received the lowest research attention in studies of three classical cytogenetic chromosomes. They have been excellent models for studying the structure, organization, transcription, and transcriptional processing of chromosomes during meiosis. Here we briefly summarized these studies and LBCs forming mechanism and also discussed their possible functions, such as providing enough transcriptional products for embryonic development by oocytes LBCs or polyploidy demonstrated by previous reports. Finally, we discussed the possibility of introducing this typical case into our genetics teaching to inspire students' interest in genetics.

  9. The physics of cancer: The role of epigenetics and chromosome conformation in cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Naimark, Oleg B.; Nikitiuk, Aleksandr S. [Institute of Continuous Media Mechanics UrB RAS, Perm, 614013 (Russian Federation); Baudement, Marie-Odile; Forné, Thierry [Institut de Génétique Moléculaire de Montpellier UMR 5535, CNRS, Université de Montpellier, 1919 route de Mende, Montpellier cedex 5, 34293 France (France); Lesne, Annick, E-mail: annick.lesne@igmm.cnrs.fr [Institut de Génétique Moléculaire de Montpellier UMR 5535, CNRS, Université de Montpellier, 1919 route de Mende, Montpellier cedex 5, 34293 France (France); Laboratoire de Physique Théorique de la Matière Condensée UMR 7600, CNRS, UPMC, Sorbonne Universités, 4 place Jussieu, Paris cedex 5, 75252 France (France)

    2016-08-02

    Cancer progression is generally described in terms of accumulated genetic alterations and ensuing changes in cell properties. However, intermediary modifications are involved in the establishment of cancer cell phenotypes, at different levels of nuclear organization: DNA damages and their structural consequences, epigenetic modifications and their impact on chromatin architecture, changes in chromosome 3D organization. We review some of these alterations with a focus on their physical aspects. The challenge is to understand the multiscale interplay between generic physical mechanisms and specific biological factors in cancer cells. We argue that such an interdisciplinary perspective offers a novel viewpoint on cancer progression, early diagnosis and possibly therapeutic targets.

  10. The physics of cancer: The role of epigenetics and chromosome conformation in cancer progression

    Science.gov (United States)

    Naimark, Oleg B.; Nikitiuk, Aleksandr S.; Baudement, Marie-Odile; Forné, Thierry; Lesne, Annick

    2016-08-01

    Cancer progression is generally described in terms of accumulated genetic alterations and ensuing changes in cell properties. However, intermediary modifications are involved in the establishment of cancer cell phenotypes, at different levels of nuclear organization: DNA damages and their structural consequences, epigenetic modifications and their impact on chromatin architecture, changes in chromosome 3D organization. We review some of these alterations with a focus on their physical aspects. The challenge is to understand the multiscale interplay between generic physical mechanisms and specific biological factors in cancer cells. We argue that such an interdisciplinary perspective offers a novel viewpoint on cancer progression, early diagnosis and possibly therapeutic targets.

  11. Chromosomal alterations in pure nonneoplastic breast lesions: implications for breast cancer progression.

    Science.gov (United States)

    Ellsworth, Rachel E; Ellsworth, Darrell L; Weyandt, Jamie D; Fantacone-Campbell, Jamie L; Deyarmin, Brenda; Hooke, Jeffrey A; Shriver, Craig D

    2010-06-01

    Columnar cell lesions (CCL) and atypical ductal hyperplasia (ADH) frequently coexist and share molecular changes with in situ and invasive components, suggesting that CCL and ADH may be precursors to breast cancer. These conclusions are largely based on studies examining CCL and/or ADH from patients diagnosed with more advanced disease. We assessed allelic imbalance (AI) in pure CCL or ADH specimens to characterize molecular changes in nonneoplastic breast lesions. DNA samples were obtained from laser-microdissected pure CCL (n = 42) or ADH (n = 31). AI was assessed at 26 chromosomal regions commonly altered in breast cancer. Data were analyzed using Fisher's exact and Student's t-tests using a cutoff of P .05. The average AI frequency was 6.2% in CCL and 6.1% in ADH; approximately 33% of nonneoplastic lesions had no detectable genetic changes. Levels of AI in CCL and ADH were significantly (P .0001) lower than observed in either low- or high-grade ductal carcinoma in situ (DCIS) lesions. Genetic changes characteristic of in situ and invasive disease, especially on chromosomes 16q and 17p, were infrequent in pure nonneoplastic lesions. Pure CCL and ADH lesions demonstrate lower levels of genetic alterations than DCIS, invasive carcinomas or CCL/ADH lesions from cancerous breasts; alterations of chromosomes 16q and 17p were not detected. Pure CCL and ADH lesions are not genetically advanced, and molecular profiles do not support these lesions as obligatory precursors to more advanced disease. Molecular differences between pure and synchronous lesions support re-evaluation of current models of disease initiation, progression, and risk.

  12. Chromosome mapping by FISH to metaphase and interphase nuclei. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Trask, B.

    1997-08-01

    The overall specific aims of this project were: (1) to determine the large-scale structure of interphase and metaphase chromosomes, in order to establish new capabilities for genome mapping by fluorescence in situ hybridization (FISH); (2) to detect chromosome abnormalities associated with genetic disease and map DNA sequences relative to them in order to facilitate the identification of new genes with disease-causing mutations; (3) to establish medium resolution physical maps of selected chromosomal regions using a combined metaphase and interphase mapping strategy and to corroborate physical and genetic maps and integrate these maps with the cytogenetic map; (4) to analyze the polymorphism and sequence evolution of subtelomeric regions of human chromosomes; (5) to establish a state-of-the-art FISH and image processing facility in the Department of Molecular Biotechnology, University of Washington, in order to map DNA sequences rapidly and accurately to benefit the Human Genome Project.

  13. International workshop on chromosome 3. Final report, April 15, 1991--April 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Gemmill, R.M.

    1992-07-01

    The Second Workshop on Human Chromosome 3 was held on April 4--5, 1991 at Denver, Colorado. There were 43 participants representing 8 nations. The workshop participants reviewed the current state of the chromosome 3 map, both physical and genetic, and prepared lists of markers and cell lines to be made commonly available. These markers and cell lines should be incorporated into the mapping efforts of diverse groups to permit the integration of data and development of consensus maps at future workshops. Region specific efforts were described for sections of the chromosome harboring genes thought to be involved in certain diseases including Von Hippel-Lindau disease, 3p-syndrome, lung cancer and renal cancer. Selected papers have been processed separately for inclusion in the Energy Science and Technology Database.

  14. Progress towards construction of a total restriction fragment map of a human chromosome.

    NARCIS (Netherlands)

    H. Vissing; F.G. Grosveld (Frank); E. Solomon; G. Moore; N. Lench; N. Shennan; R. Williamson

    1987-01-01

    textabstractWe present an approach to the construction of an overlapping restriction fragment map of a single human chromosome. A genomic cosmid library genome was constructed from a mouse-human hybrid cell line containing chromosome 17 as its only human genetic component. Cosmids containing human i

  15. Nuclear Physics Laboratory, University of Colorado, Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Kinney, E.R., ed.

    2004-05-12

    OAK-B135 The results and progress of research funded by DOE grant number DOE-FG03-95ER40913 at the University of Colorado at Boulder is described. Includes work performed at the HERMES experiment at DESY to study the quark structure of the nucleon and the hadronization process in nuclei, as well as hadronic reactions studied at LAMPF, KEK, and Fermilab.

  16. Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer

    Energy Technology Data Exchange (ETDEWEB)

    Goyette, M.C.; Fasching, C.L.; Stanbridge, E.J. (Univ. of California, Irvine (United States)); Cho, K.; Levy, D.B.; Kinzler, K.W.; Vogelstein, B. (John Hopkins Univ. School of Medicine and Hospital, Baltimore, MD (United States)); Paraskeva, C. (Univ. of Bristol, University Walk, Bristol (United Kingdom))

    1992-03-01

    Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, the authors have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 5 express the APC gene present on that chromosome as well as the endogenous mutant transcript. Expression of the putative tumor suppressor gene, DCC, was seen in the clones containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.

  17. International workshop on chromosome 6. Final report, June 1, 1992--May 31, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Trent, J.M.

    1994-02-01

    This report describes planning for and a brief description of the events concerning the First International Workshop in Human Chromosome 6 which took place June 7--9, 1992 in Ann Arbor, Michigan. The complete publication of the workshop report is slated to appear in the Journal of Cytogenetica and Cell Genetics.

  18. Report of the first international workshop on human chromosome 8 mapping. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Wood, S.; Ben Othmane, K.; Bergerheim, U.S.R. [and others

    1993-12-31

    The first international chromosome 8 workshop was held in Vancouver, Canada May 2--4, 1993. The conference was attended by 23 participants from Australia, Canada, Germany, the Netherlands, Sweden, the United Kingdom and the US. Twenty three abstracts are included from this workshop. The workshop was supported by CGAT/CTAG (Canadian Genome Analysis & Technology Program/Programme Canadien de Technologie & D`Analyse du Genome) as well as by travel funds allocated by the National Institutes of Health and the Department of Energy of the United States and by agencies within the countries of overseas participants. The goals of the workshop were to evaluate new locus assignments, review new data obtained for previously assigned loci, develop a consensus marker order for chromosome 8, assess and integrate physical mapping information, identify resources and foster collaboration.

  19. Final report. Human artificial episomal chromosome (HAEC) for building large genomic libraries

    Energy Technology Data Exchange (ETDEWEB)

    Jean-Michael H. Vos

    1999-12-09

    Collections of human DNA fragments are maintained for research purposes as clones in bacterial host cells. However for unknown reasons, some regions of the human genome appear to be unclonable or unstable in bacteria. Their team has developed a system using episomes (extrachromosomal, autonomously replication DNA) that maintains large DNA fragments in human cells. This human artificial episomal chromosomal (HAEC) system may prove useful for coverage of these especially difficult regions. In the broader biomedical community, the HAEC system also shows promise for use in functional genomics and gene therapy. Recent improvements to the HAEC system and its application to mapping, sequencing, and functionally studying human and mouse DNA are summarized. Mapping and sequencing the human genome and model organisms are only the first steps in determining the function of various genetic units critical for gene regulation, DNA replication, chromatin packaging, chromosomal stability, and chromatid segregation. Such studies will require the ability to transfer and manipulate entire functional units into mammalian cells.

  20. Replication fork progression is paused in two large chromosomal zones flanking the DNA replication origin in Escherichia coli.

    Science.gov (United States)

    Akiyama, Masahiro Tatsumi; Oshima, Taku; Chumsakul, Onuma; Ishikawa, Shu; Maki, Hisaji

    2016-08-01

    Although the speed of nascent DNA synthesis at individual replication forks is relatively uniform in bacterial cells, the dynamics of replication fork progression on the chromosome are hampered by a variety of natural impediments. Genome replication dynamics can be directly measured from an exponentially growing cell population by sequencing newly synthesized DNA strands that were specifically pulse-labeled with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). However, a short pulse labeling with BrdU is impracticable for bacteria because of poor incorporation of BrdU into the cells, and thus, the genomewide dynamics of bacterial DNA replication remain undetermined. Using a new thymidine-requiring Escherichia coli strain, eCOMB, and high-throughput sequencing, we succeeded in determining the genomewide replication profile in bacterial cells. We also found that fork progression is paused in two ~200-kb chromosomal zones that flank the replication origin in the growing cells. This origin-proximal obstruction to fork progression was overcome by an increased thymidine concentration in the culture medium and enhanced by inhibition of transcription. These indicate that DNA replication near the origin is sensitive to the impediments to fork progression, namely a scarcity of the DNA precursor deoxythymidine triphosphate and probable conflicts between replication and transcription machineries.

  1. 1993 annual final progress report: July 1992 through June 1993

    Energy Technology Data Exchange (ETDEWEB)

    Rohatgi, A.; Crotty, G.; Chen, Z.; Sana, P.; Salami, J.; Doolittle, A.; Pang, A.; Pham, T. [Georgia Inst. of Tech., Atlanta, GA (United States). School of Electrical and Computer Engineering

    1994-11-01

    This is the first annual report since the Inauguration of the University Center of Excellence for Photovoltaics Research and Development (UCEP) at Georgia Tech. The essential objective of the Center is to improve the fundamental understanding of the science and technology of advanced PV devices and materials, to provide training and enrich the educational experience of students in the field, and to increase US competitiveness by providing guidelines to industry and DOE for achieving cost-effective and high efficiency PV devices. These objectives are to be accomplished through a combination of research and education. This report summarizes the technical accomplishments, including modeling, processing, and characterization of cast multicrystalline silicon solar cells; use of modeling and PCD measurements to develop a road map for progressing toward 20% multicrystalline and 25% single crystalline cells; the development of a novel PECVD SiN/SiO{sub 2} AR coating that also provides good surface passivation; PECVD deposited SiO{sub 2} films with record low S and D{sub it} at the SiO{sub 2}/Si interface; and educational activities and accomplishments.

  2. 1993 annual final progress report: July 1992 through June 1993

    Energy Technology Data Exchange (ETDEWEB)

    Rohatgi, A.; Crotty, G.; Chen, Z.; Sana, P.; Salami, J.; Doolittle, A.; Pang, A.; Pham, T. [Georgia Inst. of Tech., Atlanta, GA (United States). School of Electrical and Computer Engineering

    1994-11-01

    This is the first annual report since the Inauguration of the University Center of Excellence for Photovoltaics Research and Development (UCEP) at Georgia Tech. The essential objective of the Center is to improve the fundamental understanding of the science and technology of advanced PV devices and materials, to provide training and enrich the educational experience of students in the field, and to increase US competitiveness by providing guidelines to industry and DOE for achieving cost-effective and high efficiency PV devices. These objectives are to be accomplished through a combination of research and education. This report summarizes the technical accomplishments, including modeling, processing, and characterization of cast multicrystalline silicon solar cells; use of modeling and PCD measurements to develop a road map for progressing toward 20% multicrystalline and 25% single crystalline cells; the development of a novel PECVD SiN/SiO{sub 2} AR coating that also provides good surface passivation; PECVD deposited SiO{sub 2} films with record low S and D{sub it} at the SiO{sub 2}/Si interface; and educational activities and accomplishments.

  3. Verification of Steelmaking Slags Iron Content Final Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    J.Y. Hwang

    2006-10-04

    The steel industry in the United States generates about 30 million tons of by-products each year, including 6 million tons of desulfurization and BOF/BOP slag. The recycling of BF (blast furnace) slag has made significant progress in past years with much of the material being utilized as construction aggregate and in cementitious applications. However, the recycling of desulfurization and BOF/BOP slags still faces many technical, economic, and environmental challenges. Previous efforts have focused on in-plant recycling of the by-products, achieving only limited success. As a result, large amounts of by-products of various qualities have been stockpiled at steel mills or disposed into landfills. After more than 50 years of stockpiling and landfilling, available mill site space has diminished and environmental constraints have increased. The prospect of conventionally landfilling of the material is a high cost option, a waste of true national resources, and an eternal material liability issue. The research effort has demonstrated that major inroads have been made in establishing the viability of recycling and reuse of the steelmaking slags. The research identified key components in the slags, developed technologies to separate the iron units and produce marketable products from the separation processes. Three products are generated from the technology developed in this research, including a high grade iron product containing about 90%Fe, a medium grade iron product containing about 60% Fe, and a low grade iron product containing less than 10% Fe. The high grade iron product contains primarily metallic iron and can be marketed as a replacement of pig iron or DRI (Direct Reduced Iron) for steel mills. The medium grade iron product contains both iron oxide and metallic iron and can be utilized as a substitute for the iron ore in the blast furnace. The low grade iron product is rich in calcium, magnesium and iron oxides and silicates. It has a sufficient lime value and

  4. Verification of Steelmaking Slags Iron Content Final Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    J.Y. Hwang

    2006-10-04

    The steel industry in the United States generates about 30 million tons of by-products each year, including 6 million tons of desulfurization and BOF/BOP slag. The recycling of BF (blast furnace) slag has made significant progress in past years with much of the material being utilized as construction aggregate and in cementitious applications. However, the recycling of desulfurization and BOF/BOP slags still faces many technical, economic, and environmental challenges. Previous efforts have focused on in-plant recycling of the by-products, achieving only limited success. As a result, large amounts of by-products of various qualities have been stockpiled at steel mills or disposed into landfills. After more than 50 years of stockpiling and landfilling, available mill site space has diminished and environmental constraints have increased. The prospect of conventionally landfilling of the material is a high cost option, a waste of true national resources, and an eternal material liability issue. The research effort has demonstrated that major inroads have been made in establishing the viability of recycling and reuse of the steelmaking slags. The research identified key components in the slags, developed technologies to separate the iron units and produce marketable products from the separation processes. Three products are generated from the technology developed in this research, including a high grade iron product containing about 90%Fe, a medium grade iron product containing about 60% Fe, and a low grade iron product containing less than 10% Fe. The high grade iron product contains primarily metallic iron and can be marketed as a replacement of pig iron or DRI (Direct Reduced Iron) for steel mills. The medium grade iron product contains both iron oxide and metallic iron and can be utilized as a substitute for the iron ore in the blast furnace. The low grade iron product is rich in calcium, magnesium and iron oxides and silicates. It has a sufficient lime value and

  5. Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Scott [Univ. of Colorado, Boulder, CO (United States)

    2010-07-31

    “Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

  6. Chromosome engineering for alien gene introgression in wheat: Progress and prospective

    Science.gov (United States)

    Chromosome engineering is a useful strategy for introgression of desirable genes from wild relatives into cultivated wheat. However, it has been a challenge to transfer a small amount of alien chromatin containing the gene of interest from one genome to another non-homologous genome through classic...

  7. Epstein-Barr virus BGLF4 kinase retards cellular S-phase progression and induces chromosomal abnormality.

    Directory of Open Access Journals (Sweden)

    Yu-Hsin Chang

    Full Text Available Epstein-Barr virus (EBV induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus. The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1. However, the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression. Here, we investigated the regulatory effects of BGLF4 on cell cycle progression and found that S-phase progression and DNA synthesis were interrupted by BGLF4 in mammalian cells. Expression of BGLF4 did not compensate Cdk1 defects for DNA replication in S. cerevisiae. Using time-lapse microscopy, we found the fate of individual HeLa cells was determined by the expression level of BGLF4. In addition to slight cell growth retardation, BGLF4 elicits abnormal chromosomal structure and micronucleus formation in 293 and NCP-TW01 cells. In Saos-2 cells, BGLF4 induced the hyperphosphorylation of co-transfected RB, while E2F1 was not released from RB-E2F1 complexes. The E2F1 regulated activities of the cyclin D1 and ZBRK1 promoters were suppressed by BGLF4 in a dose dependent manner. Detection with phosphoamino acid specific antibodies revealed that, in addition to Ser780, phosphorylation of the DNA damage-responsive Ser612 on RB was enhanced by BGLF4. Taken together, our study indicates that BGLF4 may directly or indirectly induce a DNA damage signal that eventually interferes with host DNA synthesis and delays S-phase progression.

  8. Structural studies of chromatin and chromosomes. Progress report, March 15--September 15, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, E.M.

    1997-11-01

    This study focused on the following: (1) the structure of chromatin and chromosomes by neutron and x-ray scatter and atomic force microscope; (2) the architecture of human sperm and the structure of sperm by atomic force microscopy (AFM); (3) genome-architecture and higher-order structures in human sperm nuclei; and (4) the effects of histone modifications on the structure of nucleosomes by protein DNA crosslinking method.

  9. X Chromosome Inactivation and Breast Cancer: Epigenetic Alteration in Tumor Initiation and Progression

    Science.gov (United States)

    2007-09-01

    types of mammary tumors, but not others. For instance, X chromosomal abnormalities appear to be associated with basal-like human breast cancer (BLC...andDNA damage-repair pathways to ensure genome integrity (Deng, 2006; Venkitaraman, 2002). In addition, BRCA1 plays a role in meiotic XY inactivation...find- ing that meiotic XY silencing proceeds by a mechanism involving silencing of unsynapsed DNA (Turner et al., 2006), which is distinct from X

  10. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13

    Energy Technology Data Exchange (ETDEWEB)

    Balciuniene, J.; Holmgren, G.; Forsman, K. [University Hospital, Umea (Sweden)] [and others

    1995-11-20

    Inherited retinal dystrophy is a common cause of visual impairment. Cone dystrophy affects the cone function and is manifested as progressive loss of the central vision, defective color vision, and photophobia. Linkage was demonstrated between progressive cone dystrophy (CORD5) and genetic markers on chromosome 17p12-p13 in a five-generation family. Multipoint analysis gave a maximum lod score of 7.72 at the marker D17S938. Recombinant haplotypes in the family suggest that the cone dystrophy locus is located in a 25-cM interval between the markers D17S926/D17S849 and D17S804/D17S945. Furthermore, one recombination was detected between the disease locus and a microsatellite marker in the candidate gene RCV1, encoding the retinal protein recoverin. Two additional candidate genes encoding retinal guanylate cyclase (GUC2D) and pigment epithelium-derived factor (PEDF) are located at 17p13.1. Moreover, loci for retinitis pigmentosa and Leber congenital amaurosis have been mapped to the same region. Identification of the cone dystrophy locus may be of importance not only for identifying functional genes in the cone system, but also for identifying genes for other retinal disorders. 34 refs., 3 figs., 2 tabs.

  11. The GTPase Gem and its partner Kif9 are required for chromosome alignment, spindle length control, and mitotic progression.

    Science.gov (United States)

    Andrieu, Guillaume; Quaranta, Muriel; Leprince, Corinne; Hatzoglou, Anastassia

    2012-12-01

    Within the Ras superfamily, Gem is a small GTP-binding protein that plays a role in regulating Ca(2+) channels and cytoskeletal remodeling in interphase cells. Here, we report for the first time that Gem is a spindle-associated protein and is required for proper mitotic progression. Functionally, loss of Gem leads to misaligned chromosomes and prometaphase delay. On the basis of different experimental approaches, we demonstrate that loss of Gem by RNA interference induces spindle elongation, while its enforced expression results in spindle shortening. The spindle length phenotype is generated through deregulation of spindle dynamics on Gem depletion and requires the expression of its downstream effector, the kinesin Kif9. Loss of Kif9 induces spindle abnormalities similar to those observed when Gem expression is repressed by siRNA. We further identify Kif9 as a new regulator of spindle dynamics. Kif9 depletion increases the steady-state levels of spindle α-tubulin by increasing the rate of microtubule polymerization. Overall, this study demonstrates a novel mechanism by which Gem contributes to the mitotic progression by maintaining correct spindle length through the kinesin Kif9.

  12. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

    Science.gov (United States)

    Jansen, M.; Mohapatra, G.; Betensky, R.A.; Keohane, C.; Louis, D.N.

    2013-01-01

    Aims Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Postoperative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. PMID:21988727

  13. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

    LENUS (Irish Health Repository)

    2012-02-01

    Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

  14. Human genome libraries. Final progress report, February 1, 1994--August 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Fa-Ten

    1998-01-01

    The goal of this program is to use a novel technology of chromosome microdissection and microcloning to construct chromosome region-specific libraries as resources for various human genome program studies. Region specific libraries have been constructed for the entire human chromosomes 2 and 18.

  15. Correlation of physical and genetic maps of human chromosome 16. Annual progress report, October 1, 1990--July 31, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1991-12-31

    This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentially 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.

  16. Nonlinear and Nonideal MHD. Final annual progress report, January 1, 2003 through December 31, 2003

    Energy Technology Data Exchange (ETDEWEB)

    Callen, James D

    2003-04-30

    This is the third and final annual progress report on the current 3-year ''Nonlinear and Nonideal MHD'' DoE grand DE-FG02-86ER53218 for the six months since the November 2002 progress report. During this grant year the funding level was $309k. The participating personnel and their approximate degree of funded involvement in this research project this grant year has been as follows: Professor J. D. Callen (PI, 1.8 months during academic year, 2.2 summer months); Professor C.C. Hegna (Co-PI: 2.3 months during academic year, 1.5 summer months); postdoc Dr. S. Gupta (100%); and graduate students A.L. Garcia-Perciante (50% RA) and X. Liu (50% RA).

  17. Flow-induced vibration for light water reactors. Final progress report, July 1981-September 1981

    Energy Technology Data Exchange (ETDEWEB)

    Torres, M.R.

    1981-11-01

    Flow-Induced Vibration for Light Water Reactors (FIV for LWRs) is a program designed to improve the FIV performance of light water reactors through the development of design criteria, analytical models for predicting behavior of components, and general scaling laws to improve the accuracy of reduced-scale tests, and through the identification of high FIV risk areas. The program is managed by the General Electric Nuclear Power Systems Engineering Department and has three major contributors: General Electric Nuclear Power Systems Engineering Department (NPSED), General Electric Corporate Research and Development (CR and D) and Argonne National Laboratory (ANL). The program commenced December 1, 1976. This progress report summarizes the accomplishments achieved during the final period from July 1981 to September 1981. This is the last quarterly progress report to be issued for this program.

  18. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer.

    Science.gov (United States)

    Ling, Hui; Spizzo, Riccardo; Atlasi, Yaser; Nicoloso, Milena; Shimizu, Masayoshi; Redis, Roxana S; Nishida, Naohiro; Gafà, Roberta; Song, Jian; Guo, Zhiyi; Ivan, Cristina; Barbarotto, Elisa; De Vries, Ingrid; Zhang, Xinna; Ferracin, Manuela; Churchman, Mike; van Galen, Janneke F; Beverloo, Berna H; Shariati, Maryam; Haderk, Franziska; Estecio, Marcos R; Garcia-Manero, Guillermo; Patijn, Gijs A; Gotley, David C; Bhardwaj, Vikas; Shureiqi, Imad; Sen, Subrata; Multani, Asha S; Welsh, James; Yamamoto, Ken; Taniguchi, Itsuki; Song, Min-Ae; Gallinger, Steven; Casey, Graham; Thibodeau, Stephen N; Le Marchand, Loïc; Tiirikainen, Maarit; Mani, Sendurai A; Zhang, Wei; Davuluri, Ramana V; Mimori, Koshi; Mori, Masaki; Sieuwerts, Anieta M; Martens, John W M; Tomlinson, Ian; Negrini, Massimo; Berindan-Neagoe, Ioana; Foekens, John A; Hamilton, Stanley R; Lanza, Giovanni; Kopetz, Scott; Fodde, Riccardo; Calin, George A

    2013-09-01

    The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.

  19. Extreme Performance Scalable Operating Systems Final Progress Report (July 1, 2008 - October 31, 2011)

    Energy Technology Data Exchange (ETDEWEB)

    Malony, Allen D; Shende, Sameer

    2011-10-31

    This is the final progress report for the FastOS (Phase 2) (FastOS-2) project with Argonne National Laboratory and the University of Oregon (UO). The project started at UO on July 1, 2008 and ran until April 30, 2010, at which time a six-month no-cost extension began. The FastOS-2 work at UO delivered excellent results in all research work areas: * scalable parallel monitoring * kernel-level performance measurement * parallel I/0 system measurement * large-scale and hybrid application performance measurement * onlne scalable performance data reduction and analysis * binary instrumentation

  20. Kinesin 5B (KIF5B is required for progression through female meiosis and proper chromosomal segregation in mitotic cells.

    Directory of Open Access Journals (Sweden)

    Dawit Kidane

    Full Text Available The fidelity of chromosomal segregation during cell division is important to maintain chromosomal stability in order to prevent cancer and birth defects. Although several spindle-associated molecular motors have been shown to be essential for cell division, only a few chromosome arm-associated motors have been described. Here, we investigated the role of Kinesin 5b (Kif5b during female mouse meiotic cell development and mitotic cell division. RNA interference (RNAi-mediated silencing of Kif5b in mouse oocytes induced significant delay in germinal vesicle breakdown (GVBD and failure in extrusion of the first polar body (PBE. In mitotic cells, knockdown of Kif5b leads to centrosome amplification and a chromosomal segregation defect. These data suggest that KIF5B is critical in suppressing chromosomal instability at the early stages of female meiotic cell development and mitotic cell division.

  1. Kinesin 5B (KIF5B) is required for progression through female meiosis and proper chromosomal segregation in mitotic cells.

    Science.gov (United States)

    Kidane, Dawit; Sakkas, Denny; Nottoli, Timothy; McGrath, James; Sweasy, Joann B

    2013-01-01

    The fidelity of chromosomal segregation during cell division is important to maintain chromosomal stability in order to prevent cancer and birth defects. Although several spindle-associated molecular motors have been shown to be essential for cell division, only a few chromosome arm-associated motors have been described. Here, we investigated the role of Kinesin 5b (Kif5b) during female mouse meiotic cell development and mitotic cell division. RNA interference (RNAi)-mediated silencing of Kif5b in mouse oocytes induced significant delay in germinal vesicle breakdown (GVBD) and failure in extrusion of the first polar body (PBE). In mitotic cells, knockdown of Kif5b leads to centrosome amplification and a chromosomal segregation defect. These data suggest that KIF5B is critical in suppressing chromosomal instability at the early stages of female meiotic cell development and mitotic cell division.

  2. The use of whole genome amplification to study chromosomal changes in prostate cancer: insights into genome-wide signature of preneoplasia associated with cancer progression

    Directory of Open Access Journals (Sweden)

    Squire Jeremy A

    2006-03-01

    Full Text Available Abstract Background Prostate cancer (CaP is a disease with multifactorial etiology that includes both genetic and environmental components. The knowledge of the genetic basis of CaP has increased over the past years, mainly in the pathways that underlie tumourigenesis, progression and drug resistance. The vast majority of cases of CaP are adenocarcinomas that likely develop through a pre-malignant lesion and high-grade prostatic intraepithelial neoplasia (HPIN. Histologically, CaP is a heterogeneous disease consisting of multiple, discrete foci of invasive carcinoma and HPIN that are commonly interspersed with benign glands and stroma. This admixture with benign tissue can complicate genomic analyses in CaP. Specifically, when DNA is bulk-extracted the genetic information obtained represents an average for all of the cells within the sample. Results To minimize this problem, we obtained DNA from individual foci of HPIN and CaP by laser capture microdissection (LCM. The small quantities of DNA thus obtained were then amplified by means of multiple-displacement amplification (MDA, for use in genomic DNA array comparative genomic hybridisation (gaCGH. Recurrent chromosome copy number abnormalities (CNAs were observed in both HPIN and CaP. In HPIN, chromosomal imbalances involving chromosome 8 where common, whilst in CaP additional chromosomal changes involving chromosomes 6, 10, 13 and 16 where also frequently observed. Conclusion An overall increase in chromosomal changes was seen in CaP compared to HPIN, suggesting a universal breakdown in chromosomal stability. The accumulation of CNAs, which occurs during this process is non-random and may indicate chromosomal regions important in tumourigenesis. It is therefore likely that the alterations in copy number are part of a programmed cycle of events that promote tumour development, progression and survival. The combination of LCM, MDA and gaCGH is ideally suited for the identification of CNAs from

  3. High-resolution array comparative genomic hybridization of chromosome 8q: evaluation of putative progression markers for gastroesophageal junction adenocarcinomas.

    Science.gov (United States)

    van Duin, M; van Marion, R; Vissers, K J; Hop, W C J; Dinjens, W N M; Tilanus, H W; Siersema, P D; van Dekken, H

    2007-01-01

    Amplification of 8q is frequently found in gastroesophageal junction (GEJ) cancer. It is usually detected in high-grade, high-stage GEJ adenocarcinomas. Moreover, it has been implicated in tumor progression in other cancer types. In this study, a detailed genomic analysis of 8q was performed on a series of GEJ adenocarcinomas, including 22 primary adenocarcinomas, 13 cell lines and two xenografts, by array comparative genomic hybridization (aCGH) with a whole chromosome 8q contig array. Of the 37 specimens, 21 originated from the esophagus and 16 were derived from the gastric cardia. Commonly overrepresented regions were identified at distal 8q, i.e. 124-125 Mb (8q24.13), at 127-128 Mb (8q24.21), and at 141-142 Mb (8q24.3). From these regions six genes were selected with putative relevance to cancer: ANXA13, MTSS1, FAM84B (alias NSE2), MYC, C8orf17 (alias MOST-1) and PTK2 (alias FAK). In addition, the gene EXT1 was selected since it was found in a specific amplification in cell line SK-GT-5. Quantitative RT-PCR analysis of these seven genes was subsequently performed on a panel of 24 gastroesophageal samples, including 13 cell lines, two xenografts and nine normal stomach controls. Significant overexpression was found for MYC and EXT1 in GEJ adenocarcinoma cell lines and xenografts compared to normal controls. Expression of the genes MTSS1, FAM84B and C8orf17 was found to be significantly decreased in this set of cell lines and xenografts. We conclude that, firstly, there are other genes than MYC involved in the 8q amplification in GEJ cancer. Secondly, the differential expression of these genes contributes to unravel the biology of GEJ adenocarcinomas.

  4. 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.

  5. Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Bender, W.

    2013-01-01

    Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

  6. Improved methods for water shutoff. Final technical progress report, October 1, 1997--September 30, 1998

    Energy Technology Data Exchange (ETDEWEB)

    Seright, R.S.; Liang, J.T.; Schrader, R.; Hagstrom, J. II; Liu, J.; Wavrik, K.

    1998-10-01

    In the United States, more than 20 billion barrels of salt water are produced each year during oilfield operations. A tremendous economic incentive exists to reduce water production if that can be accomplished without significantly sacrificing hydrocarbon production. This three-year research project had three objectives. The first objective was to identify chemical blocking agents that will (a) during placement, flow readily through fractures without penetrating significantly into porous rock and with screening out or developing excessive pressure gradients and (b) at a predictable and controllable time, become immobile and resistant breakdown upon exposure to moderate to high pressure gradients. The second objective was to identify schemes that optimize placement of the above blocking agents. The third objective was to explain why gels and other chemical blocking agents reduce permeability to one phase (e.g., water) more than that to another phase (e.g., oil or gas). The authors also wanted to identify conditions that maximize this phenomenon. This project consisted of three tasks, each of which addressed one of the above objectives. This report describes work performed during the third and final period of the project. During this three-year project, they: (1) Developed a procedure and software for sizing gelant treatments in hydraulically fractured production wells; (2) Developed a method (based on interwell tracer results) to determine the potential for applying gel treatments in naturally fractured reservoirs; (3) Characterized gel properties during extrusion through fractures; (4) Developed a method to predict gel placement in naturally fractured reservoirs; (5) Made progress in elucidating the mechanism for why some gels can reduce permeability to water more than that to oil; (6) Demonstrated the limitations of using water/oil ratio diagnostic plots to distinguish between channeling and coning; and (7) Proposed a philosophy for diagnosing and attacking water

  7. Characterizing the Final Steps of Chromosomal Replication at the Single-molecule Level in the Model System Escherichia coli

    KAUST Repository

    Elshenawy, Mohamed M.

    2015-12-01

    In the circular Escherichia coli chromosome, two replisomes are assembled at the unique origin of replication and drive DNA synthesis in opposite directions until they meet in the terminus region across from the origin. Despite the difference in rates of the two replisomes, their arrival at the terminus is synchronized through a highly specialized system consisting of the terminator protein (Tus) bound to the termination sites (Ter). This synchronicity is mediated by the polarity of the Tus−Ter complex that stops replisomes from one direction (non-permissive face) but not the other (permissive face). Two oppositely oriented clusters of five Tus–Ters that each block one of the two replisomes create a “replication fork trap” for the first arriving replisome while waiting for the late arriving one. Despite extensive biochemical and structural studies, the molecular mechanism behind Tus−Ter polar arrest activity remained controversial. Moreover, none of the previous work provided answers for the long-standing discrepancy between the ability of Tus−Ter to permanently stop replisomes in vitro and its low efficiency in vivo. Here, I spearheaded a collaborative project that combined single-molecule DNA replication assays, X-ray crystallography and binding studies to provide a true molecular-level understanding of the underlying mechanism of Tus−Ter polar arrest activity. We showed that efficiency of Tus−Ter is determined by a head-to-head kinetic competition between rate of strand separation by the replisome and rate of rearrangement of Tus−Ter interactions during the melting of the first 6 base pairs of Ter. This rearrangement maintains Tus’s strong grip on the DNA and stops the advancing replisome from breaking into Tus−Ter central interactions, but only transiently. We further showed how this kinetic competition functions within the context of two mechanisms to impose permanent fork stoppage. The rate-dependent fork arrest activity of Tus

  8. A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

    Directory of Open Access Journals (Sweden)

    Cigudosa Juan C

    2011-05-01

    Full Text Available Abstract Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs, will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents. With the extension of this analysis to an Array-CGH dataset (glioblastomas from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.

  9. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Comprehensive progress report, July 1991--June 1994

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1994-06-01

    This comprehensive progress report provides a synopsis of major research accomplishments during the years of 1991-1994, including the technical aspects of the project. The objectives and accomplishments are as follows: 1. Defining the chromosome segments associated with radiation and chemically-induced leukemogenesis (treatment-related acute myeloid leukemia, t-AML); A. Continued genetic analysis of chromosomes 5 and 7, B. Correlation of treatment with balanced and unbalanced translocations. 2. Cloning the breakpoints in balanced translocations in t-AML; A. Clone the t(9;11) and t(11;19) breakpoints, B. Clone the t(3,21)(q26,q22) breakpoint, C. Determine the relationship of these translocations to prior exposure to topoisomerase II inhibitors. 3. Compare the breakpoint junctions in patients who have the same translocations in t-AML and AML de novo. 4. Map the scaffold attachment regions in the genes that are involved in balanced translocations in t-AML. Plans for the continuation of present objectives and possible new objectives in consideration of past results are also provided.

  10. Episodic vertical oscillopsia with progressive gait ataxia: clinical description of a new episodic syndrome and evidence of linkage to chromosome 13q.

    Science.gov (United States)

    Cha, Y H; Lee, H; Jen, J C; Kattah, J C; Nelson, S F; Baloh, R W

    2007-11-01

    We describe four families with late onset episodic vertical oscillopsia and progressive gait ataxia. Probands presented between the ages of 40 and 64 years with initial symptoms of episodic vertical oscillopsia and interictal downbeat nystagmus. A mild gait ataxia developed over several years. Triggers included physical exertion, alcohol and caffeine. Patients did not respond to acetazolamide. Genetic screening for episodic ataxia types 1 and 2, and spinocerebellar ataxias 1, 2, 3 and 6 were negative. Using ancestral identity by descent analysis and dense single nucleotide polymorphism (SNP) genotyping throughout the genome, an interval of 28.6 cM (approximately 14.2 Mb) on chromosome 13q12.11-q13.3, composed of 1259 SNPs, was shared between affected individuals in two of the four families and highlighted a region of suggestive linkage (LOD >2.7).

  11. Bacterial chromosome segregation.

    Science.gov (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier

    2012-01-01

    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  12. Novel methods for physical mapping of the human genome applied to the long arm of chromosome 5. Final report

    Energy Technology Data Exchange (ETDEWEB)

    McClelland, M.

    1991-12-01

    The object of our current grant is to develop novel methods for mapping of the human genome. The techniques to be assessed were: (1) three methods for the production of unique sequence clones from the region of interest; (2) novel methods for the production and separation of multi-megabase DNA fragments; (3) methods for the production of ``physical linking clones`` that contain rare restriction sites; (4) application of these methods and available resources to map the region of interest. Progress includes: In the first two years methods were developed for physical mapping and the production of arrayed clones; We have concentrated on developing rare- cleavage tools based or restriction endonucleases and methylases; We studied the effect of methylation on enzymes used for PFE mapping of the human genome; we characterized two new isoschizomers of rare cutting endonucleases; we developed a reliable way to produce partial digests of DNA in agarose plugs and applied it to the human genome; and we applied a method to double the apparent specificity of the ``rare-cutter`` endonucleases.

  13. "Chromosome": a knowledge-based system for the chromosome classification.

    Science.gov (United States)

    Ramstein, G; Bernadet, M

    1993-01-01

    Chromosome, a knowledge-based analysis system has been designed for the classification of human chromosomes. Its aim is to perform an optimal classification by driving a tool box containing the procedures of image processing, pattern recognition and classification. This paper presents the general architecture of Chromosome, based on a multiagent system generator. The image processing tool box is described from the met aphasic enhancement to the fine classification. Emphasis is then put on the knowledge base intended for the chromosome recognition. The global classification process is also presented, showing how Chromosome proceeds to classify a given chromosome. Finally, we discuss further extensions of the system for the karyotype building.

  14. FINAL Progress Report DOE Grant DE-FG02-04ER15587

    Energy Technology Data Exchange (ETDEWEB)

    Mullins, Charles Buddie [Univ. of Texas, Austin, TX (United States)

    2016-11-03

    Catalysis Program - Viviane Schwartz Program Manager This Final Report discusses several archival journal articles that have been published that present and discuss the results that were discovered through this DOE grant.

  15. Development of Career Progression Systems for Employees in the Foodservice Industry. Final Report.

    Science.gov (United States)

    National Restaurant Association, Chicago, IL.

    Firms representing four segments of the foodservice industry (institutional foodservice (9 jobs), commercial restaurants (19 jobs), hotel foodservice (100 jobs), and airline foodservice (10 jobs), participated in a career and training study to test the feasibility of designing and implementing career progression (c.p.) systems within these…

  16. Study of private enterprise development on the Raft River KGRA. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Green, S.J.; Brown, W.S.; Meldrum, P.D.

    1977-07-01

    Information, analysis, and conclusions based on the small for-profit venture business model are presented. The necessary tasks are described and progress is reviewed. Water availability and business analysis problems are described. Included in the appendix are materials on land availability, characterization of geothermal resources under Idaho law, and greenhouse analysis and geothermal applications. (MHR)

  17. National Assessment of Educational Progress Grade 12 Preparedness Research College Course Content Analysis Study: Final Report

    Science.gov (United States)

    Educational Policy Improvement Center, 2014

    2014-01-01

    The National Assessment Governing Board is an independent, bipartisan organization that sets policy for the National Assessment of Educational Progress (NAEP). The Governing Board established the NAEP Program of 12th Grade Preparedness Research to assess what NAEP can report on the academic preparedness of 12th grade students entering college and…

  18. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  19. Strategies for cloning and manipulating natural and synthetic chromosomes.

    Science.gov (United States)

    Karas, Bogumil J; Suzuki, Yo; Weyman, Philip D

    2015-02-01

    Advances in synthetic biology methods to assemble and edit DNA are enabling genome engineering at a previously impracticable scale and scope. The synthesis of the Mycoplasma mycoides genome followed by its transplantation to convert a related cell into M. mycoides has transformed strain engineering. This approach exemplifies the combination of newly emerging chromosome-scale genome editing strategies that can be defined in three main steps: (1) chromosome acquisition into a microbial engineering platform, (2) alteration and improvement of the acquired chromosome, and (3) installation of the modified chromosome into the original or alternative organism. In this review, we outline recent progress in methods for acquiring chromosomes and chromosome-scale DNA molecules in the workhorse organisms Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae. We present overviews of important genetic strategies and tools for each of the three organisms, point out their respective strengths and weaknesses, and highlight how the host systems can be used in combination to facilitate chromosome assembly or engineering. Finally, we highlight efforts for the installation of the cloned/altered chromosomes or fragments into the target organism and present remaining challenges in expanding this powerful experimental approach to a wider range of target organisms.

  20. Experimental and Theoretical Progress of Linear Collider Final Focus Design and ATF2 Facility

    CERN Document Server

    Seryi, Andrei; Zimmermann, Frank; Kubo, Kiyoshi; Kuroda, Shigeru; Okugi, Toshiyuki; Tauchi, Toshiaki; Terunuma, Nobuhiro; Urakawa, Junji; White, Glen; Woodley, Mark; Angal-Kalinin, Deepa

    2014-01-01

    In this brief overview we will reflect on the process of the design of the linear collider (LC) final focus (FF) optics, and will also describe the theoretical and experimental efforts on design and practical realisation of a prototype of the LC FF optics implemented in the ATF2 facility at KEK, Japan, presently being commissioned and operated.

  1. Final Report on Models, Periodic Progress, Report No D1.3, Globeman21, ESPRIT 26509

    DEFF Research Database (Denmark)

    Pedersen, Jens Dahl; Tølle, Martin; Vesterager, Johan

    1999-01-01

    This deliverable D1.3 is the third and final deliverable of WP1 - Global Manufacturing Concept of the European part of the Globeman21 project. The report essentially presents the final models on generic Extended Enterprise Management (EEM) and generic Product Life Cycle Management (PLCM), a colle......This deliverable D1.3 is the third and final deliverable of WP1 - Global Manufacturing Concept of the European part of the Globeman21 project. The report essentially presents the final models on generic Extended Enterprise Management (EEM) and generic Product Life Cycle Management (PLCM......), a collection of practical experiences, and requirements for enhanced methods and tools for modelling. First, the deliverable outlines the GM21 understanding regarding extended enterprises and virtual enterprises. This is done by extracting and synthesising the essence of key definitions and concepts...... enterprise context. Through the set of recommended activities for individual life cycle phases of respectively the network entity, the VE entity, and the product entity of the Extended Enterprise Framework, the methodology supports realisation of extended enterprises. The time sequenced planning...

  2. Status of the KLOE Electromagnetic Calorimeter: final optimization, progress in construction and first calibration

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, M.; Anulli, F.; Barbiellini, G.; Bertolucci, S.; Bini, C.; Bloise, C.; Caloi, R.; Cabibbo, G.; Campana, P.; Cervelli, F.; De Zorzi, G.; Di Cosimo, G.; Di Domenico, A.; Erriquez, O.; Di Falco, S.; Farilla, A.; Ferrari, A.; Franzini, P.; Gauzzi, P.; Giovannella, S.; Graziani, E.; Han, S.W.; Incagli, M.; Kim, W.; Lanfranchi, G.; Lee-Franzini, J.; Lomtadze, T.; Miscetti, S.; Murtas, F.; Scuri, F.; Spiriti, E.; Tortora, L.; Venanzoni, G.; Woelfle, S.; Zhang, J.Q. [Bari Univ. (Italy). Dipt. di Fisica]|[INFN, Bari (Italy)]|[Institute of High Energy Physics of Academica Sinica, Beijing (China)]|[Laboratori Nazionali di Frascati dell`INFN, Frascati (Italy)]|[Physics Department, Columbia University, New York (United States)]|[Dipartimento di Fisica dell`Universita e Sezione INFN, Pisa (Italy)]|[Dipartimento di Fisica dell`Universita e Sezione INFN, Roma I (Italy)]|[Dipartimento di Fisica dell`Universita e Sezione INFN, Roma II (Italy)]|[Istituto Superiore di Sanita and Sezione INFN, ISS, Roma (Italy)]|[Physics Department, State University of New York at Stony Brook, Stony Brook, NY (United States)]|[Dipartimento di Fisica dell`Universita e Sezione INFN, Trieste/Udine (Italy)

    1997-03-01

    The design and the status of construction of the KLOE electromagnetic calorimeter are described in this report. 18 out of 24 barrel modules have been fully assembled and more than 50% of the end-cap modules are built. All experimental specifications are fulfilled as shown by the test beam results of the final size prototype. Since the quality of fibers and photomultipliers have gone through improvements, the final calorimeter performances will exceed our expectations. The main parameters of each calorimeter module (light yield, attenuation length and time resolution) are fully surveyed using cosmic rays. Extrapolating the results to electromagnetic showers, a time resolution of 55 ps/{radical}(E(GeV)) and a resolution of 0.9 cm/{radical}(E(GeV)) on the coordinate along the fibers are obtained. An energy resolution of 4.7%/{radical}(E(GeV)) can also be quoted. (orig.).

  3. Final Report on Models, Periodic Progress, Report No D1.3, Globeman21, ESPRIT 26509

    DEFF Research Database (Denmark)

    Pedersen, Jens Dahl; Tølle, Martin; Vesterager, Johan

    1999-01-01

    This deliverable D1.3 is the third and final deliverable of WP1 - Global Manufacturing Concept of the European part of the Globeman21 project. The report essentially presents the final models on generic Extended Enterprise Management (EEM) and generic Product Life Cycle Management (PLCM...... accomplished during the GM21EU project. Especially the Extended Enterprise Framework should be accentuated as a key concept of WP1. Building on ISO/DIS 15704 GERAM, the framework constitutes a generic reference model for extended enterprises and hereunder for EEM and PLCM issues. The Extended Enterprise...... classification schema for work preparation in extended enterprises. The classification schema is applied as support for a mapping of the EEM and PLCM pilot projects onto the Extended Enterprise Framework. By mapping the industrial pilot work onto a common reference model experiences have been collected from GM21...

  4. Experimental Program Final Technical Progress Report: 15 February 2007 to 30 September 2012

    Energy Technology Data Exchange (ETDEWEB)

    Kinney, Edward R. [University of Colorado, Boulder, CO

    2014-09-12

    This is the final technical report of the grant DE-FG02-04ER41301 to the University of Colorado at Boulder entitled "Intermediate Energy Nuclear Physics" and describes the results of our funded activities during the period 15 February 2007 to 30 September 2012. These activities were primarily carried out at Fermilab, RHIC, and the German lab DESY. Significant advances in these experiments were carried out by members of the Colorado group and are described in detail.

  5. [Tampa Electric Company IGCC project]. Final public design report; Technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-01

    This final Public Design Report (PDR) provides completed design information about Tampa Electric Company`s Polk Power Station Unit No. 1, which will demonstrate in a commercial 250 MW unit the operating parameters and benefits of the integration of oxygen-blown, entrained-flow coal gasification with advanced combined cycle technology. Pending development of technically and commercially viable sorbent for the Hot Gas Cleanup System, the HGCU also is demonstrated. The report is organized under the following sections: design basis description; plant descriptions; plant systems; project costs and schedule; heat and material balances; general arrangement drawings; equipment list; and miscellaneous drawings.

  6. Progress Report for DOE FG02-08ER64510 (Final, April 2014)

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Robert

    2014-04-01

    Over the course of five years we have established a long-term array of warming chambers at Duke and Harvard Forest that simulate future conditions with regard to temperature. In these chambers, we have studied, ants, other animal taxa, fungi, bacteria and plants and their responses to the treatments. We have coupled these studies with lab experiments, large-scale observations, and models to contextualize our results. Finally, we have developed integrative models of the future distribution of species and their consequences as a result of warming in eastern North America and more generally.

  7. International workshop on Chromosome 12 held at St. Catherine`s College, Oxford, England, September 18--20, 1992. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Gemmill, R.

    1992-12-31

    The First International Mapping Workshop on Human Chromosome 12 was held on Sept. 18--20, 1992, at St Catherine`s College, Oxford, UK. The meeting was hosted by Ian Craig and organized by Drs. Craig, Gemmill and Kutcherlapati. It was attended by 50 participants primarily from Europe and the USA. The workshop was highly successful and achieved the major goal of fostering direct and personal interactions between investigators with strong research interests in this chromosome. Participants reviewed the status of several critical aspects of chromosome mapping and prepared consensus views of the current state of knowledge. In addition, lists of resources available for this chromosome including somatic cell hybrids, individual DNA clones and libraries and genetic markers were prepared.

  8. CRM1 and chromosomal passenger complex component survivin are essential to normal mitosis progress and to preserve keratinocytes from mitotic abnormalities.

    Science.gov (United States)

    Labarrade, F; Botto, J-M; Domloge, N

    2016-10-01

    Human epidermis provides the body a barrier against environmental assaults. To assume this function, the epidermis needs the renewal of keratinocytes allowed by constant mitosis, which replace the exfoliating corneocytes. Keratinocyte stem cells (KSCs) located in the basal epidermis are mitotically active, self-renewing and govern the epithelial stratification by producing renewed source of keratinocytes. Protein complex such as the chromosomal passenger complex (CPC) allows the correct development of this process. The CPC is composed of four members: INCENP, survivin, borealin and aurora kinase B, and the disruption of the CPC during cell division induces mitotic spindle defects and improper repartition of chromosomes. The aim of our study was to investigate the implication of CRM1 and survivin in the progress of mitosis in skin keratinocytes. Cultured human keratinocytes and skin biopsies were used in this study. KSCs-enriched population of keratinocytes was isolated from total keratinocytes by differential attachment to a type IV collagen matrix. Survivin and CRM1 expression levels were assessed by immunofluorescence and immunoblotting. Specific siRNAs for each CPC member and for CRM1 were used to determine the relationship between these proteins. Survivin-specific siRNA was used to induce the apparition of mitotic abnormalities in cultured keratinocytes. We demonstrated the ability of our compound 'IV08.009' to modulate the expression level of survivin and CRM1 in keratinocytes and in skin biopsies. We observed that members of the CPC are interdependent: siRNA-induced inhibition of one component caused a decrease in the expression of all other CPC members. Downregulation of survivin or CRM1 induced mitotic abnormalities in keratinocytes. However, decreased number of mitotic abnormalities was observed in keratinocytes after 'IV08.009' application. Basal keratinocytes may divide frequently during skin lifespan, and signs of deterioration could appear such as loss

  9. Advanced Coal Conversion Process Demonstration Project. Final technical progress report, January 1, 1995--December 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-05-01

    This report describes the technical progress made on the Advanced Coal Conversion Process (ACCP) Demonstration Project from January 1, 1995 through December 31, 1995. This project demonstrates an advanced, thermal, coal upgrading process, coupled with physical cleaning techniques, that is designed to upgrade high-moisture, low-rank coals to a high-quality, low-sulfur fuel, registered as the SynCoal Process. The coal is processed through three stages (two heating stages followed by an inert cooling stage) of vibrating fluidized bed reactors that remove chemically bound water, carboxyl groups, and volatile sulfur compounds. After thermal upgrading, the coal is put through a deep-bed stratifier cleaning process to separate the pyrite-rich ash from the coal. The SynCoal Process enhances low-rank, western coals, usually with a moisture content of 25 to 55 percent, sulfur content of 0.5 to 1.5 percent, and heating value of 5,5000 to 9,000 British thermal units per pound (Btu/lb), by producing a stable, upgraded, coal product with a moisture content as low as 1 percent, sulfur content as low as 0.3 percent, and heating value up to 12,000 Btu/lb. During this reporting period, the primary focus for the ACCP Demonstration Project team was to expand SynCoal market awareness and acceptability for both the products and the technology. The ACCP Project team continued to focus on improving the operation, developing commercial markets, and improving the SynCoal products as well as the product`s acceptance.

  10. Theoretical studies in nuclear structure. Final progress report, June 1, 1991--July 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Marshalek, E.R.

    1997-06-01

    The general purview of the project is the theory of collective motion in atomic nuclei. The chief aim is to elucidate the phenomena of (1) anharmonic multiphonon excitations, and (2) collective tilted rotation, both of which are topics of considerable current interest. In the primary stage of an investigation it is often necessary to develop appropriate mathematical tools, as was the case here. In the next stage, the formalism must be tested on simple soluble models. The work described here is mainly concerned with these two stages. The final stage of realistic applications will require more time, manpower and, of course, the necessary funding. Some planning for this last stage has been carried out and anticipated problems axe briefly discussed. As it turns out, both of the above topics can be approached within the unified framework of a theorem that I developed, called the Cranking Bifurcation Theorem (CBT) to be described below. The CBT can be regarded as an outgrowth of the boson expansion method, which provides a general, and, in principal, exact formalism for treating collective excitations. We begin with a brief discussion of the CBT and then continue on to the applications.

  11. Novel catalysts for methane activation. Final progress report, September 30, 1992--April 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Hirschon, A.S.; Du, Y.; Wu, H.J.; Malhotra, R.; Wilson, R.B.

    1996-06-11

    This final report summarizes the results of our research under Contract No. DE-AC22-92PC92112, Novel Catalysts for Methane Activation. In this research we prepared and tested fullerene soots for converting methane into higher hydrocarbons. We conducted the methane conversions using dehydrocoupling conditions, primarily in the temperature regimes of 600{degrees}-1000{degrees}C and atmospheric pressures. The research was divided into three sections. The first section focused on comparing fullerene soots with other forms of carbon such as acetylene black and Norit-A. We found that the fullerene soot was indeed more reactive than the other forms of carbon. However, due to its high reactivity, it was not selective. The second section focused on the effect of metals on the reactivity of the soots, including both transition metals and alkali metals. We found that potassium could enhance the selectivities of fullerene soot to higher hydrocarbons, but the effect was unique to fullerene soot and did not improve the performance of other forms of carbon. The third part focused on the use of co-feeds for methane activation to enhance the selectivities and lower the temperature threshold of methane activation.

  12. The Cryogenic AntiCoincidence detector for ATHENA: the progress towards the final pixel design

    Science.gov (United States)

    Macculi, Claudio; Piro, Luigi; Cea, Donatella; Colasanti, Luca; Lotti, Simone; Natalucci, Lorenzo; Gatti, Flavio; Bagliani, Daniela; Biasotti, Michele; Corsini, Dario; Pizzigoni, Giulio; Torrioli, Guido; Barbera, Marco; Mineo, Teresa; Perinati, Emanuele

    2014-07-01

    related to one of the last sample produced (namely AC-S5), and steps to reach the final detector design will be discussed.

  13. Final Progress Report for the NASA Inductrack Model Rocket Launcher at the Lawrence Livermore National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Tung, L S; Post, R F; Martinez-Frias, J

    2001-06-27

    The Inductrack magnetic levitation system, developed at the Lawrence Livermore National Laboratory, was studied for its possible use for launching rockets. Under NASA sponsorship, a small model system was constructed at the Laboratory to pursue key technical aspects of this proposed application. The Inductrack is a passive magnetic levitation system employing special arrays of high-field permanent magnets (Halbach arrays) on the levitating cradle, moving above a ''track'' consisting of a close-packed array of shorted coils with which are interleaved with special drive coils. Halbach arrays produce a strong spatially periodic magnetic field on the front surface of the arrays, while canceling the field on their back surface. Relative motion between the Halbach arrays and the track coils induces currents in those coils. These currents levitate the cradle by interacting with the horizontal component of the magnetic field. Pulsed currents in the drive coils, synchronized with the motion of the carrier, interact with the vertical component of the magnetic field to provide acceleration forces. Motional stability, including resistance to both vertical and lateral aerodynamic forces, is provided by having Halbach arrays that interact with both the upper and the lower sides of the track coils. At present, a 7.8 meter track composed of drive and levitation coils has been built and the electronic drive circuitry performs as designed. A 9 kg cradle that carries the Halbach array of permanent magnets has been built. A mechanical launcher is nearly complete which will provide an initial cradle velocity of 9 m/s into the electronic drive section. We have found that the drag forces from the levitation coils were higher than in our original design. However, measurements of drag force at velocities less than 1 m/s are exactly as predicted by theory. Provided here are recommended design changes to improve the track's performance so that a final velocity of 40

  14. A new autosomal recessive non-progressive congenital cerebellar ataxia associated with mental retardation, optic atrophy, and skin abnormalities (CAMOS) maps to chromosome 15q24-q26 in a large consanguineous Lebanese Druze Family.

    Science.gov (United States)

    Delague, Valérie; Bareil, Corinne; Bouvagnet, Patrice; Salem, Nabiha; Chouery, Eliane; Loiselet, Jacques; Mégarbané, André; Claustres, Mireille

    2002-03-01

    Congenital cerebellar ataxias are a heterogeneous group of non-progressive disorders characterized by hypotonia and developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We report the mapping of a disease gene in a large inbred Lebanese Druze family, with five cases of a new form of non-progressive autosomal recessive congenital ataxia associated with optic atrophy, severe mental retardation, and structural skin abnormalities, to a 3.6-cM interval on chromosome 15q24-15q26.

  15. NO-sensitive guanylyl cyclase beta1 subunit is peripherally associated to chromosomes during mitosis. Novel role in chromatin condensation and cell cycle progression.

    Science.gov (United States)

    Pifarré, Paula; Baltrons, María Antonia; Földi, Istvan; García, Agustina

    2009-01-01

    NO-sensitive guanylyl cyclase (GC(NO)), the major NO target, is involved in important regulatory functions in the cardiovascular, gastrointestinal and central nervous systems. GC(NO) exists as heterodimers of alpha(1/2) and beta1 subunits. Deletion of the obligate beta1 dimerizing partner abrogates NO/cGMP signaling and shortens the life span of KO mice. Localization studies in the CNS have shown that beta1 is more widespread than alpha subunits and in some areas is the only GC(NO) subunit expressed, suggesting that beta1 may have GC(NO)-independent functions. GC(NO) is predominantly cytosolic, but association to membranes and other intracellular structures has been described. Here, we show localization of beta1 in cytoplasm and nucleus of cells expressing alpha subunits and GC(NO) activity (astrocytes, C6 cells), as well as in cells devoid of alpha subunits and GC(NO) activity (microglia). In both cell types beta1 associates peripherally to chromosomes in all phases of mitosis. Immunodepletion of beta1 in C6 cells enhances chromatin condensation in an in vitro assay. Moreover, silencing beta1 by siRNA induces cell cycle re-entry as determined by flow cytometry, and increases proliferation rate in a MTT-assay, whereas infection with beta1-containing adenovirus has the opposite effect. These actions are independent of cGMP formation. We postulate that beta1 is a multifunctional protein that regulates chromatin condensation and cell cycle progression, in addition to being an obligate monomer in functional GC(NO) heterodimers.

  16. Myopia and Late-Onset Progressive Cone Dystrophy Associate to LVAVA/MVAVA Exon 3 Interchange Haplotypes of Opsin Genes on Chromosome X.

    Science.gov (United States)

    Orosz, Orsolya; Rajta, István; Vajas, Attila; Takács, Lili; Csutak, Adrienne; Fodor, Mariann; Kolozsvári, Bence; Resch, Miklós; Sényi, Katalin; Lesch, Balázs; Szabó, Viktória; Berta, András; Balogh, István; Losonczy, Gergely

    2017-03-01

    Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes). A multigenerational family with X-linked high myopia and cone dystrophy was investigated. Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively. Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.

  17. Chromosomal mosaicism goes global

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B

    2008-11-01

    Full Text Available Intercellular differences of chromosomal content in the same individual are defined as chromosomal mosaicism (alias intercellular or somatic genomic variations or, in a number of publications, mosaic aneuploidy. It has long been suggested that this phenomenon poorly contributes both to intercellular (interindividual diversity and to human disease. However, our views have recently become to change due to a series of communications demonstrated a higher incidence of chromosomal mosaicism in diseased individuals (major psychiatric disorders and autoimmune diseases as well as depicted chromosomal mosaicism contribution to genetic diversity, the central nervous system development, and aging. The later has been produced by significant achievements in the field of molecular cytogenetics. Recently, Molecular Cytogenetics has published an article by Maj Hulten and colleagues that has provided evidences for chromosomal mosaicism to underlie formation of germline aneuploidy in human female gametes using trisomy 21 (Down syndrome as a model. Since meiotic aneuploidy is suggested to be the leading genetic cause of human prenatal mortality and postnatal morbidity, these data together with previous findings define chromosomal mosaicism not as a casual finding during cytogenetic analyses but as a more significant biological phenomenon than previously recognized. Finally, the significance of chromosomal mosaicism can be drawn from the fact, that this phenomenon is involved in genetic diversity, normal and abnormal prenatal development, human diseases, aging, and meiotic aneuploidy, the intrinsic cause of which remains, as yet, unknown.

  18. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Kotov, Valeri [Univ. of Vermont, Burlington, VT (United States)

    2016-05-29

    The research in this program involves theoretical investigations of electronic, optical and mechanical properties of graphene and its derivatives, such as bi-layer graphene, graphene-based van der Waals heterostructures, strained graphene, as well as graphene on various surfaces. One line of research has been development of theoretical models that support graphene’s large array of possible technological applications. For example one of our goals has been the understanding of surface plasmons and spin relaxation mechanisms in graphene, related to novel optoelectronics and spintronics applications. Our current research focus is on understanding the role of correlations in graphene under mechanical deformations, such as strain. The main goal is to describe the mutual interplay between strain and electron-electron interactions which could lead to the formation of novel elec- tronic phases with strongly modified electronic, magnetic and optical properties. This direction of research contributes to deeper understanding of interactions in graphene and related atomically-thin materials - a subject at the forefront of research on graphene and its derivatives.

  19. Final Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    J.Y. Hwang; R.C. Greenlund

    2002-12-31

    Michigan Technological University has demonstrated major inroads in establishing the viability of utilizing aluminum smelting by-product waste materials in lightweight concrete product applications. The research identified key elements of producing various forms of lightweight concrete products through utilizing various procedures and mixture components with the by-product materials. A process was developed through pilot plant testing that results in additional aluminum recovery at finer sizes, a clean returnable salt product through spray drying technology, and a low-salt-content oxide product with enough aluminum metal content that it can be used to form lightweight cementitious mixtures. Having three distinct products aids in generating favorable process economics. Revenue projections from aluminum recovery and salt recovery are enough to cover processing costs and create a cost-free oxide product to market for lightweight concrete applications. This supply side commercialization strategy offers aluminum by-product recyclers a potentially no cost product, which has been demonstrated through this project to create desirable and marketable lightweight concrete products of various forms. Environmental benefits to the public are tremendous. At best, all dross and salt cake materials have the potential to be completely recycled and utilized. At worst, disposal sites would see a reduced amount of material: a post processed oxide product with little salt and no hydrogen sulfide or ammonia gas generating capability, which, if isolated from high alkali conditions, would pose no reactivity concerns. The US aluminum industry has historically, along with the steel industry, been a leader in recycling metal. The findings from this project, increased metal recovery, improved salt recycling, and demonstrated end uses for oxide residues, will go a long way in helping the aluminum industry obtain 100% material utilization and zero discharge.

  20. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, Herbert J

    2012-02-06

    The BIOMOL grant was for 'Local System Support for PDB Biological Unit Search and Display' to augment Rasmol's [Bernstein 2000] [Sayle, Milner-White 1995] existing macromolecular display functions with new capabilities by taking advantage of recent increases in local computing power in order to move functionality that is now scattered among various local and remote systems into one local package. Work included new algorithms for molecular surface display, an extended format for Protein Data Bank Entries, work on issues relating to the integration of multiple diffraction images formats.

  1. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, Herbert J

    2012-02-06

    The BIOMOL grant was for 'Local System Support for PDB Biological Unit Search and Display' to augment Rasmol's [Bernstein 2000] [Sayle, Milner-White 1995] existing macromolecular display functions with new capabilities by taking advantage of recent increases in local computing power in order to move functionality that is now scattered among various local and remote systems into one local package. Work included new algorithms for molecular surface display, an extended format for Protein Data Bank Entries, work on issues relating to the integration of multiple diffraction images formats.

  2. [Sex chromosomes and meiosis].

    Science.gov (United States)

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C

    2009-01-01

    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  3. Modeling Chromosomes

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

  4. B chromosomes and sex in animals.

    Science.gov (United States)

    Camacho, J P M; Schmid, M; Cabrero, J

    2011-01-01

    Supernumerary (B) chromosomes are dispensable elements found in many eukaryote genomes in addition to standard (A) chromosomes. In many respects, B chromosomes resemble sex chromosomes, so that a common ancestry for them has frequently been suggested. For instance, B chromosomes in grasshoppers, and other insects, show a pycnotic cycle of condensation-decondensation during meiosis remarkably similar to that of the X chromosome. In some cases, B chromosome size is even very similar to that of the X chromosome. These resemblances have led to suggest the X as the B ancestor in many cases. In addition, sex chromosome origin from B chromosomes has also been suggested. In this article, we review the existing evidence for both evolutionary pathways, as well as sex differences for B frequency at adult and embryo progeny levels, B chromosome effects or B chromosome transmission. In addition, we review cases found in the literature showing sex-ratio distortion associated with B chromosome presence, the most extreme case being the paternal sex ratio (PSR) chromosomes in some Hymenoptera. We finally analyse the possibility of B chromosome regularisation within the host genome and, as a consequence of it, whether B chromosomes can become regular members of the host genome.

  5. An improved method for producing radiation hybrids applied to human chromosome 19. Technical progress report, March 1, 1991--February 28, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, C.L.

    1992-04-01

    At the initiation of the grant we had just produced radiation hybrids from a monochromosomal microcell hybrid containing human chromosome 19 as its only human component. Radiation hybrids were produced using doses of radiation ranging from 1000--8000 rads. Lethally irradiated cells were then fused to hamster recipients (CHTG49) and selected for growth in histidinol. Approximately 240 clones were isolated and 75 clones were expanded for the isolation of DNA. This report describes in situ hybridization studies and the introduction of markers into human chromosome 19.

  6. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Comprehensive progress report, January 1, 1980-December 31, 1982

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1982-06-01

    The observations that two particular translocations are consistently associated with specific differentiation stages of acute nonlymphocytic leukemia were confirmed. These are the translocation between chromosomes 8 and 21 in acute myeloblastic leukemia with maturation and the translocation between chromosomes 15 and 17 in acute promyelocytic leukemia. The observation of others that structural rearrangements involving the long arm of No. 11 are frequently seen in acute monoblastic leukemia was also confirmed. The chromosome aberrations that are observed in the great majority of patients with acute leukemia secondary to cytotoxic therapy were defined. Thus of 47 patients with secondary acute nonlymphocytic leukemia, an aneuploid clone was seen in 44, and 39 of the 44 had a loss of part or all of No. 5 and/or No. 7. I have been able to localize the region of chromosome No. 7, loss of which is important for the development of leukemia was localized. Patients with ANLL de novo whose occupational histories suggest exposure to potentially mutagenic agents have a higher frequency of aberrations involving Nos. 5 and/or 7, than do patients not so exposed. Thus 50% of exposed versus 10% of nonexposed patients had aberrations of Nos. 5 or 7.

  7. CtrA response regulator binding to the Caulobacter chromosome replication origin is required during nutrient and antibiotic stress as well as during cell cycle progression.

    Science.gov (United States)

    Bastedo, D Patrick; Marczynski, Gregory T

    2009-04-01

    The Caulobacter crescentus chromosome replication origin (Cori) has five binding sites for CtrA, an OmpR/PhoB family 'response regulator'. CtrA is degraded in replicating 'stalked' cells but is abundant in the non-replicating 'swarmer' cells, where it was proposed to repress replication by binding to Cori. We systematically mutated all Cori CtrA binding sites, and examined their consequences in the contexts of autonomous Cori-plasmid replication and in the natural chromosome locus. Remarkably, the C. crescentus chromosome tolerates severe mutations in all five CtrA binding sites, demonstrating that CtrA is not essential for replication. Further physiological and cell cycle experiments more rigorously supported the original hypothesis that CtrA represses replication. However, our experiments argued against another hypothesis that residual and/or replenished CtrA protein in stalked cells might prevent extra or unscheduled chromosome replication before cell division. Surprisingly, we also demonstrated that Cori CtrA binding sites are very advantageous and can become essential when cells encounter nutrients and antibiotics. Therefore, the CtrA cell cycle regulator co-ordinates replication with viable cell growth in stressful and rapidly changing environments. We argue that this new role for CtrA provided the primary selective pressure for evolving control by CtrA.

  8. Radiochemical and radioecological studies on Brazilian areas of high natural background. Progress report, October 30, 1974--October 30, 1975. [Etiology of radioinduced chromosomal aberrations in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Costa-Ribeiro, C.; Penna-Franca, E.; Rocha-Nogueira, A.; Christian-Pfeiffer, W.

    1975-11-01

    The absorption of /sup 212/Pb and/or /sup 212/Bi by ertythrocytes was investigated in an attempt to explain the in vivo genesis of somatic chromosomal aberrations of the type detected in peripheral blood lymphocytes of workers professionally exposed to /sup 220/Rn and its decay products, as well as in dwellers of Brazilian areas of high natural radioactivity. (auth)

  9. 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.

  10. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Final report, January 1--December 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1998-03-01

    It has been clear for the last 15 years that cloning translocation breakpoints in both AML de novo and t-AML would provide the DNA probes required to determine whether the breakpoints in cytogenetically apparently similar translocations were identical at the level of DNA. Therefore the author has pursued an analysis of rearrangements in both types of leukemia simultaneously. She has also cloned and sequenced several translocations in acute lymphoblastic leukemia and in chronic lymphatic leukemia. Recently she cloned the breakpoint in a number of translocations involving chromosome bands 11q23 and 21q22. She has cloned the gene which she called MLL, that is located in 11q23 that is involved in the 6;11, 9;11, and 11;19 translocations that are seen in AML de novo as well as in t-AML. She has evidence that the breakpoint in 11q23 and in the t(9;11) is relatively similar in de novo and secondary AML. In addition, she has cloned the gene at the breakpoint in chromosome 21 in the t(3;21). These studies have provided DNA probes that will be very important for diagnosis and for monitoring the patient`s response to treatment.

  11. A QTL on chromosome 6A in bread wheat (Triticum aestivum) is associated with longer coleoptiles, greater seedling vigour and final plant height.

    Science.gov (United States)

    Spielmeyer, W; Hyles, J; Joaquim, P; Azanza, F; Bonnett, D; Ellis, M E; Moore, C; Richards, R A

    2007-06-01

    Wheat crops with greater early vigour shade the soil surface more rapidly and reduce water loss. Evaporative losses affect water-use efficiency particularly in drier regions where most of the rainfall occurs early in the growing season before canopy closure. Greater seedling leaf area and longer coleoptiles are major determinants of increased vigour and better crop establishment. A previously developed high vigour breeding line 'Vigour 18' was used to establish a large recombinant inbred family and framework map to identify a QTL on chromosome 6A that accounted for up to 8% of the variation for coleoptile length, 14% of seedling leaf width and was associated with increased plant height. The SSR marker NW3106, nearest to the 6A QTL, was also associated with greater leaf width in a breeding population that was also derived from a cross involving the high vigour donor line 'Vigour18'. The association between the NW3106 marker and coleoptile length was validated in a second breeding population which was developed using an unrelated long coleoptile donor line. The 'Vigour18' allele of the QTL on chromosome 6A promoted coleoptile length and leaf width during early plant growth but was also associated with increased plant height at maturity. Markers linked to the QTL are being used to increase the frequency of increased vigour and long coleoptile alleles in early generations of breeding populations.

  12. 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.

  13. Mapping and ordered cloning of the human X chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Caskey, C.T.; Nelson, D.L.

    1992-12-01

    Progress is reported on gathering X chromosome specific libraries and integrating those with the library produced in this project. Further studies on understanding Fragile X Syndrome and other hereditary diseases related to the X chromosome are described. (DT)

  14. Chromosome choreography: the meiotic ballet.

    Science.gov (United States)

    Page, Scott L; Hawley, R Scott

    2003-08-08

    The separation of homologous chromosomes during meiosis in eukaryotes is the physical basis of Mendelian inheritance. The core of the meiotic process is a specialized nuclear division (meiosis I) in which homologs pair with each other, recombine, and then segregate from each other. The processes of chromosome alignment and pairing allow for homolog recognition. Reciprocal meiotic recombination ensures meiotic chromosome segregation by converting sister chromatid cohesion into mechanisms that hold homologous chromosomes together. Finally, the ability of sister kinetochores to orient to a single pole at metaphase I allows the separation of homologs to two different daughter cells. Failures to properly accomplish this elegant chromosome dance result in aneuploidy, a major cause of miscarriage and birth defects in human beings.

  15. Formation of Chromosomal Domains by Loop Extrusion

    Directory of Open Access Journals (Sweden)

    Geoffrey Fudenberg

    2016-05-01

    Full Text Available Topologically associating domains (TADs are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms of TAD formation remain unclear. Here, we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, we show that this model produces TADs and finer-scale features of Hi-C data. Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. Loop extrusion both explains diverse experimental observations—including the preferential orientation of CTCF motifs, enrichments of architectural proteins at TAD boundaries, and boundary deletion experiments—and makes specific predictions for the depletion of CTCF versus cohesin. Finally, loop extrusion has potentially far-ranging consequences for processes such as enhancer-promoter interactions, orientation-specific chromosomal looping, and compaction of mitotic chromosomes.

  16. Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma. Final report of a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Balducci, M.; Diletto, B.; Chiesa, S.; D' Agostino, G.R.; Gambacorta, M.A.; Ferro, M.; Valentini, V. [Catholic University of the Sacred Heart, Department of Radiation Oncology, Rome (Italy); Colosimo, C. [Catholic University of the Sacred Heart, Department of Radiology, Rome (Italy); Maira, G.; Anile, C. [Catholic University of the Sacred Heart, Department of Neurosurgery, Rome (Italy)

    2014-04-15

    Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM). Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m{sup 2} on days 1, 8, 15), fotemustine (FTM; 40 mg/m{sup 2} on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m{sup 2} on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity. A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7% of patients and G3-4 in 9.4%. One patient (3.1%) had complete response, 3 (9.4%) had partial response, 8 (25%) had stable disease for at least 8 weeks, while 20 patients (62.5%) experienced progressive disease. The clinical benefit was 37.5%. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8%. LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted. (orig.)

  17. Chromosomal aberrations related to metastasis of human solid tumors

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin

    2002-01-01

    The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic alterations.So does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor genes.During the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have occurred.There is still controversial with the association

  18. 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.

  19. Final Technical Progress Report; Closeout Certifications; CSSV Newsletter Volume I; CSSV Newsletter Volume II; CSSV Activity Journal; CSSV Final Financial Report

    Energy Technology Data Exchange (ETDEWEB)

    Houston, Johnny L [PI; Geter, Kerry [Division of Business and Finance

    2013-08-23

    This Project?s third year of implementation in 2007-2008, the final year, as designated by Elizabeth City State University (ECSU), in cooperation with the National Association of Mathematicians (NAM) Inc., in an effort to promote research and research training programs in computational science ? scientific visualization (CSSV). A major goal of the Project was to attract the energetic and productive faculty, graduate and upper division undergraduate students of diverse ethnicities to a program that investigates science and computational science issues of long-term interest to the Department of Energy (DoE) and the nation. The breadth and depth of computational science?scientific visualization and the magnitude of resources available are enormous for permitting a variety of research activities. ECSU?s Computational Science-Science Visualization Center will serve as a conduit for directing users to these enormous resources.

  20. Procedures for Handling Retaliation Complaints Under Section 31307 of the Moving Ahead for Progress in the 21st Century Act (MAP-21). Final rule.

    Science.gov (United States)

    2016-12-14

    On March 16, 2016, the Occupational Safety and Health Administration (OSHA) of the U.S. Department of Labor (Department) issued an interim final rule (IFR) that provided procedures for the Department's processing of complaints under the employee protection (retaliation or whistleblower) provisions of Section 31307 of the Moving Ahead for Progress in the 21st Century Act (MAP-21). The IFR established procedures and time frames for the handling of retaliation complaints under MAP-21, including procedures and time frames for employee complaints to OSHA, investigations by OSHA, appeals of OSHA determinations to an administrative law judge (ALJ) for a hearing de novo, hearings by ALJs, review of ALJ decisions by the Administrative Review Board (ARB) (acting on behalf of the Secretary of Labor) and judicial review of the Secretary's final decision. It also set forth the Department's interpretations of the MAP-21 whistleblower provisions on certain matters. This final rule adopts, without change, the IFR.

  1. Chromosome Analysis

    Science.gov (United States)

    1998-01-01

    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  2. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    of proteins and their co-operation in establishing the final mitotic chromosome structure.

  3. Final Progress Report for Collaborative Research: Aging of Black Carbon during Atmospheric Transport: Understanding Results from the DOE’s 2010 CARES and 2012 ClearfLo Campaigns

    Energy Technology Data Exchange (ETDEWEB)

    Mazzoleni, Claudio [Michigan Technological Univ., Houghton, MI (United States); Subramanian, R. [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    2016-08-31

    Over the course of this project, we have analyzed data and samples from the Carbonaceous Aerosol and Radiative Effects Study (CARES) and the Clear air for London (ClearfLo) campaign, as well as conducted or participated in laboratory experiments designed to better understand black carbon mixing state and climate-relevant properties. The laboratory campaigns took place at the Pacific Northwest National Laboratory and Carnegie Mellon University to study various climate-relevant aerosol properties of different sources of soot mixing with secondary organic aerosol precursors. Results from some of these activities were summarized in the previous progress report. This final report presents the manuscripts that have been published (many in the period since the last progress report), lists presentations at different conferences based on grant-related activities, and presents some results that are likely to be submitted for publication in the near future.

  4. Chimera-free, high copy number YAC libraries and efficient methods of analysis. Final technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    The first experiment involved a low chimera YAC library in recombination deficient host strains. To determine if the genetic background of the yeast host strain contributes to the formation of chimeric YACs the same YAC ligation mixture was introduced into three isogenic yeast hosts differing only in their recombination abilities. To prepare YACs, human genomic DNA was partially digested with EcoR1 and then ligated to YAC vector pCGS966 arms. DNA was size fractionated before and after ligation by preparative pulsed field gel electrophoresis (CHEF), selecting for fragments greater than 400 kb, and introduced into competent spheroplasts. CHEF gel Southern blots of resulting colony-purified YACs were probed with human DNA to determine if multiple YACs or YAC fragments were present in the same cell. The frequency of chimeric YACs was measured by fluorescence in situ hybridization (FISH) of YACs to human prometaphase spreads. YACs that hybridized to more than one location were assumed to be chimeric. In the second experiment new YAC vectors featuring tags for capture of YACs and YAC inserts were constructed. Yeast Artificial Chromosomes (YACs) have been of tremendous value in the physical mapping of the human genome. Because they can carry very large inserts, YACs are likely not only to contain entire genes but also their control elements. However, the only mode of purification of YAC DNA from current commonly used YAC libraries such as the CEPH library is by pulsed field gel electrophoresis. This is an inefficient, time consuming process and due to the single copy nature of these YACs, often result in poor yields. The vector pCGS1000 was designed to test new efficient ways of YAC DNA purification.

  5. Chimera-free, high copy number YAC libraries and efficient methods of analysis. Final technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    The first experiment involved a low chimera YAC library in recombination deficient host strains. To determine if the genetic background of the yeast host strain contributes to the formation of chimeric YACs the same YAC ligation mixture was introduced into three isogenic yeast hosts differing only in their recombination abilities. To prepare YACs, human genomic DNA was partially digested with EcoR1 and then ligated to YAC vector pCGS966 arms. DNA was size fractionated before and after ligation by preparative pulsed field gel electrophoresis (CHEF), selecting for fragments greater than 400 kb, and introduced into competent spheroplasts. CHEF gel Southern blots of resulting colony-purified YACs were probed with human DNA to determine if multiple YACs or YAC fragments were present in the same cell. The frequency of chimeric YACs was measured by fluorescence in situ hybridization (FISH) of YACs to human prometaphase spreads. YACs that hybridized to more than one location were assumed to be chimeric. In the second experiment new YAC vectors featuring tags for capture of YACs and YAC inserts were constructed. Yeast Artificial Chromosomes (YACs) have been of tremendous value in the physical mapping of the human genome. Because they can carry very large inserts, YACs are likely not only to contain entire genes but also their control elements. However, the only mode of purification of YAC DNA from current commonly used YAC libraries such as the CEPH library is by pulsed field gel electrophoresis. This is an inefficient, time consuming process and due to the single copy nature of these YACs, often result in poor yields. The vector pCGS1000 was designed to test new efficient ways of YAC DNA purification.

  6. Fusion reactor systems studies. Progress report for the period November 1, 1996--October 31, 1997, and final report

    Energy Technology Data Exchange (ETDEWEB)

    El-Guebaly, L.A.; Blanchard, J.P.; Kulcinski, G.L.

    1997-08-01

    During FY97, the University of Wisconsin Fusion Technology Institute personnel have participated in the ARIES-RS and the ARIES-ST projects. The main areas of effort are: (1) neutronics analysis; (2) shielding of components and personnel; (3) neutron wall loading distribution; (4) radiation damage to in-vessel components; (5) components lifetimes; (6) embrittled materials designs issues; (7) stress and structural analysis; (8) activation, LOCA, and safety analysis; (9) support and fabrication of components; (10) vacuum system; and (11) maintenance. Progress made in these areas are summarized.

  7. GSK-3 inhibitors induce chromosome instability

    Directory of Open Access Journals (Sweden)

    Staples Oliver D

    2007-08-01

    Full Text Available Abstract Background Several mechanisms operate during mitosis to ensure accurate chromosome segregation. However, during tumour evolution these mechanisms go awry resulting in chromosome instability. While several lines of evidence suggest that mutations in adenomatous polyposis coli (APC may promote chromosome instability, at least in colon cancer, the underlying mechanisms remain unclear. Here, we turn our attention to GSK-3 – a protein kinase, which in concert with APC, targets β-catenin for proteolysis – and ask whether GSK-3 is required for accurate chromosome segregation. Results To probe the role of GSK-3 in mitosis, we inhibited GSK-3 kinase activity in cells using a panel of small molecule inhibitors, including SB-415286, AR-A014418, 1-Azakenpaullone and CHIR99021. Analysis of synchronised HeLa cells shows that GSK-3 inhibitors do not prevent G1/S progression or cell division. They do, however, significantly delay mitotic exit, largely because inhibitor-treated cells have difficulty aligning all their chromosomes. Although bipolar spindles form and the majority of chromosomes biorient, one or more chromosomes often remain mono-oriented near the spindle poles. Despite a prolonged mitotic delay, anaphase frequently initiates without the last chromosome aligning, resulting in chromosome non-disjunction. To rule out the possibility of "off-target" effects, we also used RNA interference to selectively repress GSK-3β. Cells deficient for GSK-3β exhibit a similar chromosome alignment defect, with chromosomes clustered near the spindle poles. GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 inhibitors may induce unwanted side effects by inducing chromosome instability.

  8. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study.

    Science.gov (United States)

    Baccarani, Michele; Druker, Brian J; Branford, Susan; Kim, Dong-Wook; Pane, Fabrizio; Mongay, Lidia; Mone, Manisha; Ortmann, Christine-Elke; Kantarjian, Hagop M; Radich, Jerald P; Hughes, Timothy P; Cortes, Jorge E; Guilhot, François

    2014-01-01

    The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival(PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR.Adverse events were more frequent with high-dose imatinib. Patients with B1 treatment interruption (vs [1) and those able to maintain imatinib C600 mg/day (vs\\600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with longterm clinical outcomes.

  9. The DNA sequence of the human X chromosome

    OpenAIRE

    Ross, Mark T.; Grafham, Darren V.; Coffey, Alison J; Scherer, Steven; McLay, Kirsten; Muzny, Donna; Platzer, Matthias; Howell, Gareth R.; Burrows, Christine; Bird, Christine P.; Frankish, Adam; Lovell, Frances L.; Howe, Kevin L; Jennifer L Ashurst; Fulton, Robert S.

    2005-01-01

    The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a...

  10. Final Progress Report: FRACTURE AND SUBCRITICAL DEBONDING IN THIN LAYERED STRUCTURES: EXPERIMENTS AND MULTI-SCALE MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Reinhold H. Dauskardt

    2005-08-30

    Final technical report detailing unique experimental and multi-scale computational modeling capabilities developed to study fracture and subcritical cracking in thin-film structures. Our program to date at Stanford has studied the mechanisms of fracture and fatigue crack-growth in structural ceramics at high temperature, bulk and thin-film glasses in selected moist environments where we demonstrated the presence of a true mechanical fatigue effect in some glass compositions. We also reported on the effects of complex environments and fatigue loading on subcritical cracking that effects the reliability of MEMS and other micro-devices using novel micro-machined silicon specimens and nanomaterial layers.

  11. SMC complexes in bacterial chromosome condensation and segregation.

    Science.gov (United States)

    Strunnikov, Alexander V

    2006-03-01

    Bacterial chromosomes segregate via a partition apparatus that employs a score of specialized proteins. The SMC complexes play a crucial role in the chromosome partitioning process by organizing bacterial chromosomes through their ATP-dependent chromatin-compacting activity. Recent progress in the composition of these complexes and elucidation of their structural and enzymatic properties has advanced our comprehension of chromosome condensation and segregation mechanics in bacteria.

  12. SMC complexes in bacterial chromosome condensation and segregation

    OpenAIRE

    Strunnikov, Alexander V.

    2005-01-01

    Bacterial chromosomes segregate via a partition apparatus that employs a score of specialized proteins. The SMC complexes play a crucial role in the chromosome partitioning process by organizing bacterial chromosomes through their ATP-dependent chromatin-compacting activity. Recent progress in the composition of these complexes and elucidation of their structural and enzymatic properties has advanced our comprehension of chromosome condensation and segregation mechanics in bacteria.

  13. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.

    1997-02-01

    The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both {sup 18}F and {sup 124}I; however, the lack of its availability (until quite recently) prevented experiments with {sup 124}I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with {sup 18}F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models.

  14. Measurement and apportionment of radon source terms for modeling indoor environments. Final progress report, March 1990--August 1992

    Energy Technology Data Exchange (ETDEWEB)

    Harley, N.H.

    1992-12-31

    During the present 2 1/2 year contract period, we have made significant Progress in modeling the source apportionment of indoor {sup 222}Rn and in {sup 222}Rn decay product dosimetry. Two additional areas were worked on which we believe are useful for the DOE Radon research Program. One involved an analysis of the research house data, grouping the hourly house {sup 222}Rn measurements into 2 day, 7 day and 90 day intervals to simulate the response of passive monitors. Another area requiring some attention resulted in a publication of 3 years of our indoor/outdoor measurements in a high-rise apartment. Little interest has been evinced in apartment measurements yet 20% of the US population lives in multiple-family dwellings, not in contact with the ground. These data together with a summary of all other published data on apartments showed that apartments have only about 50% greater {sup 222}Rn concentration than the measured outdoor {sup 222}Rn. Apartment dwellers generally represent a low risk group regarding {sup 222}Rn exposure. The following sections describe the main projects in some detail.

  15. Zfy genes are required for efficient meiotic sex chromosome inactivation (MSCI) in spermatocytes.

    Science.gov (United States)

    Vernet, Nadège; Mahadevaiah, Shantha K; de Rooij, Dirk G; Burgoyne, Paul S; Ellis, Peter J I

    2016-10-13

    During spermatogenesis, germ cells that fail to synapse their chromosomes or fail to undergo meiotic sex chromosome inactivation (MSCI) are eliminated via apoptosis during mid-pachytene. Previous work showed that Y-linked genes Zfy1 and Zfy2 act as 'executioners' for this checkpoint, and that wrongful expression of either gene during pachytene triggers germ cell death. Here, we show that in mice, Zfy genes are also necessary for efficient MSCI and the sex chromosomes are not correctly silenced in Zfy-deficient spermatocytes. This unexpectedly reveals a triple role for Zfy at the mid-pachytene checkpoint in which Zfy genes first promote MSCI, then monitor its progress (since if MSCI is achieved, Zfy genes will be silenced), and finally execute cells with MSCI failure. This potentially constitutes a negative feedback loop governing this critical checkpoint mechanism.

  16. Construction of a genome-wide human BAC-Unigene resource. Final progress report, 1989--1996

    Energy Technology Data Exchange (ETDEWEB)

    Lim, C.S.; Xu, R.X.; Wang, M. [and others

    1996-12-31

    Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes (non-redundant, unigene sets of cDNA representing EST clusters) are available for human alone. A total of 44,000 Unigene cDNA clones have been supplied by Research Genetics. Unigenes, or cDNAs are excellent resource for map building for two reasons. Firstly, they exist in two alternative forms -- as both sequence information for PCR primer pairs, and cDNA clones -- thus making library screening by colony hybridization as well as pooled library PCR possible. The authors have developed an efficient and robust procedure to screen genomic libraries with large number of DNA probes. Secondly, the linkage and order of expressed sequences, or genes are highly conserved among human, mouse and other mammalian species. Therefore, mapping with cDNA markers rather than random anonymous STSs will greatly facilitate comparative, evolutionary studies as well as physical map building. They have currently deconvoluted over 10,000 Unigene probes against a 4X coverage human BAC clones from the approved library D by high density colony hybridization method. 10,000 batches of Unigenes are arrayed in an imaginary 100 X 100 matrix from which 100 row pools and 100 column pools are obtained. Library filters are hybridized with pooled probes, thus reducing the number of hybridization required for addressing the positives for each Unigene from 10,000 to 200. Details on the experimental scheme as well as daily progress report is posted on the Web site (http://www.tree.caltech.edu).

  17. Development of a Coal Quality Expert. Final technical progress report No. 11, [October 1--December 31, 1992

    Energy Technology Data Exchange (ETDEWEB)

    1993-05-20

    Task 3 provides detailed characterization of fuel properties of the test coals and in-depth evaluation of their performance characteristics under controlled pilot-scale combustion testing. Results from this task provide fundamental information required to develop some of the improved algorithms for the CQE. Both bench-scale fuel characterization and test furnace performance evaluations are being performed under this task. All pilot-scale combustion tests under this task have been completed. Topical reports for the coals evaluated under the Public Service Oklahoma`s Northeastern Unit 4 and Northern States Power`s King Unit 1 test series have been issued. Work continued during the past quarter on preparation of the final report for the Mississippi Power Company`s Watson Unit 4 tests (to be completed first quarter 1993) and analyzing pilot-scale combustion data from the Alabama Power Company`s Gaston tests; a topical report for the Gaston study will also be issued in 1993. Bench-scale testing and data analyses continued in support of the development of the slagging and fouling models. Data obtained from the analysis of samples of deposits, inflame solids, fly ash, and coal from CQE pilot-scale and drop tube combustion tests were evaluated for use in devising and verifying the slagging and fouling algorithms.

  18. Highly nucleophilic acetylide, vinyl, and vinylidene complexes. Final progress report, 1 January 1991--31 March 1994

    Energy Technology Data Exchange (ETDEWEB)

    Geoffroy, G.L.

    1994-10-04

    In the course of this research the authors found that the anionic alkynyl complex [Cp{prime}(CO)(PPh{sub 3})Mn-C{triple_bond}C-CH{sub 3}]{sup {minus}} can be generated in situ by the addition of two equivalents of n-BuLi to a solution of the carbene complex Cp{prime}(CO)(PPh{sub 3})Mn{double_bond}C(OMe)CH{sub 2}CH{sub 3}. It was also found that the highly nucleophilic propynyl complex [Cp(CO)(PPh{sub 3})Mn-C{triple_bond}C-Me]{sup {minus}} reacts with a variety of aldehydes and ketones in the presence of BF{sub 3}{center_dot}Et{sub 2}O to give, after quenching with MeOH, a series of cationic vinylcarbyne complexes of the general form [Cp(CO)(PPh{sub 3})Mn{triple_bond}C-C(Me){double_bond}C(R)(R{prime})]BF{sub 4}. The cationic alkylidyne complexes [Cp(CO){sub 2}M{triple_bond}C-CH{sub 2}R]{sup +} [M = Re, R = H, M = Mn, R = H, Me, Ph] have been found to undergo facile deprotonation to give the corresponding neutral vinylidene complexes Cp(CO){sub 2}M{double_bond}C{double_bond}C(H)R. The authors have also investigated reactions relevant to the halide promoted Fe and Ru catalyzed carbonylation of nitroaromatics. The final part of this work has involved investigations of metal-oxo complexes.

  19. Final design and progress of WEAVE: the next generation wide-field spectroscopy facility for the William Herschel Telescope

    Science.gov (United States)

    Dalton, Gavin; Trager, Scott; Abrams, Don Carlos; Bonifacio, Piercarlo; Aguerri, J. Alfonso L.; Middleton, Kevin; Benn, Chris; Dee, Kevin; Sayède, Frédéric; Lewis, Ian; Pragt, Johannes; Pico, Sergio; Walton, Nic; Rey, Jeurg; Allende Prieto, Carlos; Peñate, José; Lhome, Emilie; Agócs, Tibor; Alonso, José; Terrett, David; Brock, Matthew; Gilbert, James; Schallig, Ellen; Ridings, Andy; Guinouard, Isabelle; Verheijen, Marc; Tosh, Ian; Rogers, Kevin; Lee, Martin; Steele, Iain; Stuik, Remko; Tromp, Niels; Jaskó, Attila; Carrasco, Esperanza; Farcas, Szigfrid; Kragt, Jan; Lesman, Dirk; Kroes, Gabby; Mottram, Chris; Bates, Stuart; Rodriguez, Luis Fernando; Gribbin, Frank; Delgado, José Miguel; Herreros, José Miguel; Martin, Carlos; Cano, Diego; Navarro, Ramon; Irwin, Mike; Lewis, Jim; Gonzalez Solares, Eduardo; Murphy, David; Worley, Clare; Bassom, Richard; O'Mahoney, Neil; Bianco, Andrea; Zurita, Christina; ter Horst, Rik; Molinari, Emilio; Lodi, Marcello; Guerra, José; Martin, Adrian; Vallenari, Antonella; Salasnich, Bernardo; Baruffolo, Andrea; Jin, Shoko; Hill, Vanessa; Smith, Dan; Drew, Janet; Poggianti, Bianca; Pieri, Mat; Dominquez Palmero, Lillian; Farina, Cecilia

    2016-08-01

    We present the Final Design of the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT), together with a status update on the details of manufacturing, integration and the overall project schedule now that all the major fabrication contracts are in place. We also present a summary of the current planning behind the 5-year initial phase of survey operations. WEAVE will provide optical ground-based follow up of ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 integral field units, or a single large IFU for each observation. The fibres are fed to a single (dual-beam) spectrograph, with total of 16k spectral pixels, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R 5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R 20000. The project is now in the manufacturing and integration phase with first light expected for early of 2018.

  20. Central receiver solar thermal power system, phase 1. Quarterly progress report (final) for period ending June 30, 1976

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-10-01

    During this report period, the major program activities were aimed toward the fabrication of the three major research experiments and continued evaluation of the Pilot Plant performance and operating modes. The detail designs were completed early in this period. Effort was continued in the evaluation of Pilot Plant start transients. Both warm and hot starts from thermal storage were evaluated as was a cold start from the Receiver. In the Collector Subsystem Experiment the heliostat structures and drive mechanisms were completed and delivered. The detail design of the 5 MW Receiver Experiment was completed at Foster Wheeler. In the Thermal Storage Subsystem the detail design of the experiment was completed early in the period. A final selection of the heat transport media was made with Hitec selected as the molten salt and Caloria HT-43 selected as the hydrocarbon oil. During this period Bechtel continued its efforts in the optimization of the Electrical Power Generation Subsystem. Work was also continued on the completion of data that will be used in the Electrical Power Generation Subsystem analytical model being prepared by Martin as a part of the overall Pilot Plant Simulation Model. (WDM)

  1. The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.; Garte, S.J.

    1992-12-31

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.

  2. Hybrid solar thermal-photovoltaic systems demonstration, Phase I and II. Final technical progress report, July 5, 1979-December 1982

    Energy Technology Data Exchange (ETDEWEB)

    Loferski, J.J. (ed.)

    1983-12-01

    The purpose of the project is to investigate a system based on combined photovoltaic/thermal (PV/T) panels to supply the energy needs of a small single family residence. The system finally selected and constructed uses PV/T panels which utilize air as the heat transfer medium. Optimization of thermal performance was accomplished by attaching metal fins to the back surface of each cell which significantly increased the heat transfer coefficient from the solar cells to the air stream. The other major components of the selected system are an air-to-air heat pump, a rock bin thermal energy storage bin, a synchronous dc-to-ac converter, a microprocessor to control the system, a heat exchanger for the domestic hot water system and of course the building itself which is a one story, well insulated structure having a floor area of 1200 ft/sup 2/. A prototype collector was constructed and tested. Based on this experience, twenty collectors, containing 2860 four inch diameter solar cells, were constructed and installed on the building. Performance of the system was simulated using a TRNSYS-derived program, modified to accommodate PV/T panels and to include the particular components included in the selected system. Simulation of the performance showed that about 65 percent of the total annual energy needs of the building would be provided by the PV/T system. Of this total, about one half is produced at a time when it can be used in the building and one half must be sold back to the utility.

  3. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Lalioti, M.D.; Rossier, C.; Antonarakis, S.E. [Univ. of Geneva Medical School (Switzerland)] [and others

    1996-04-15

    We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.

  4. CHROMOSOME ABNORMALITIES IN INFERTILITY

    Directory of Open Access Journals (Sweden)

    Mateja Smogavec

    2009-08-01

    Conclusions Chromosomal analysis is an important method in diagnostic procedures of infertility, because chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions. Sex chromosome aneuploidies are highly correlated to infertility of females and males.

  5. Bacterial Chromosome Organization and Segregation

    OpenAIRE

    Toro, Esteban; Shapiro, Lucy

    2010-01-01

    Bacterial chromosomes are generally ∼1000 times longer than the cells in which they reside, and concurrent replication, segregation, and transcription/translation of this crowded mass of DNA poses a challenging organizational problem. Recent advances in cell-imaging technology with subdiffraction resolution have revealed that the bacterial nucleoid is reliably oriented and highly organized within the cell. Such organization is transmitted from one generation to the next by progressive segrega...

  6. 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.

  7. Abnormal Chromosome Segregation May Trigger Tumors

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Cancer is a primary threat to human health as it kills millions of people each year.Scientists have shown that 75% of human cancers have an abnormal number of chromosomes in cells,and the proportion of the cells with an abnormal chromosome number is tightly and positively related to malignance progression and metastasis of cancers. But the pathological mechanism behind the anomaly still remains unknown.

  8. [Dosage compensation mechanism of X chromosome].

    Science.gov (United States)

    Wang, Yan-Yun; Chen, Mei; Li, Bin

    2012-08-01

    Dosage compensation mechanism is crucial for the balance expression of X chromosome genes, which ensures the protein or enzyme encoded by the X chromosome to be equal or almost equal expression amounts between males and females. However, different organisms have evolved distinct dosage compensation strategies, and so far three kinds of dosage compensation strategies among organisms have been reported. The first strategy is that the single male X chromosome expression is doubly activated; the second one is to inactivate one female X chromosome by leaving both sexes with one active allele; and the third one is to reduce the expression to half activity in both X chromosomes of the female. The study of dosage compensation will be useful to reveal the mechanism of regulation of X-linked genes as well as the evolution and the differentiation progress of the sex chromosome, and it can also contribute to illustrate mutation and distortion of sex chromosome. Therefore, this paper briefly reviewed and discussed the progresses and prospects of the important mechanism of dosage compensation.

  9. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  10. ROCK DEFORMATION. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-05-24

    The Gordon Research Conference (GRC) on ROCK DEFORMATION was held at II Ciocco from 5/19/02 thru 5/24/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  11. Shorebird Project Final Progress Report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This study documented the habitats, hydrology, vegetation communities and weather patterns that create or destroy shorebird habitat. This project examined shorebird...

  12. Polymer physics of chromosome large-scale 3D organisation.

    Science.gov (United States)

    Chiariello, Andrea M; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

    2016-07-13

    Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

  13. Polymer physics of chromosome large-scale 3D organisation

    Science.gov (United States)

    Chiariello, Andrea M.; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

    2016-07-01

    Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

  14. Separation of DNA replication from the assembly of break-competent meiotic chromosomes.

    Directory of Open Access Journals (Sweden)

    Hannah G Blitzblau

    Full Text Available The meiotic cell division reduces the chromosome number from diploid to haploid to form gametes for sexual reproduction. Although much progress has been made in understanding meiotic recombination and the two meiotic divisions, the processes leading up to recombination, including the prolonged pre-meiotic S phase (meiS and the assembly of meiotic chromosome axes, remain poorly defined. We have used genome-wide approaches in Saccharomyces cerevisiae to measure the kinetics of pre-meiotic DNA replication and to investigate the interdependencies between replication and axis formation. We found that replication initiation was delayed for a large number of origins in meiS compared to mitosis and that meiotic cells were far more sensitive to replication inhibition, most likely due to the starvation conditions required for meiotic induction. Moreover, replication initiation was delayed even in the absence of chromosome axes, indicating replication timing is independent of the process of axis assembly. Finally, we found that cells were able to install axis components and initiate recombination on unreplicated DNA. Thus, although pre-meiotic DNA replication and meiotic chromosome axis formation occur concurrently, they are not strictly coupled. The functional separation of these processes reveals a modular method of building meiotic chromosomes and predicts that any crosstalk between these modules must occur through superimposed regulatory mechanisms.

  15. Chromosome Disorder Outreach

    Science.gov (United States)

    ... BLOG Join Us Donate You are not alone. Chromosome Disorder Outreach, Inc. is a non-profit organization, ... Support For all those diagnosed with any rare chromosome disorder. Since 1992, CDO has supported the parents ...

  16. 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

  17. ZEBRAFISH CHROMOSOME-BANDING

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1995-01-01

    Banding techniques were carried out on metaphase chromosomes of zebrafish (Danio rerio) embryos. The karyotypes with the longest chromosomes consist of 12 metacentrics, 26 submetacentrics, and 12 subtelocentrics (2n = 50). All centromeres are C-band positive. Eight chromosomes have a pericentric C-b

  18. 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

  19. Chromosome region-specific libraries for human genome analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Fa-Ten.

    1991-01-01

    We have made important progress since the beginning of the current grant year. We have further developed the microdissection and PCR- assisted microcloning techniques using the linker-adaptor method. We have critically evaluated the microdissection libraries constructed by this microtechnology and proved that they are of high quality. We further demonstrated that these microdissection clones are useful in identifying corresponding YAC clones for a thousand-fold expansion of the genomic coverage and for contig construction. We are also improving the technique of cloning the dissected fragments in test tube by the TDT method. We are applying both of these PCR cloning technique to human chromosomes 2 and 5 to construct region-specific libraries for physical mapping purposes of LLNL and LANL. Finally, we are exploring efficient procedures to use unique sequence microclones to isolate cDNA clones from defined chromosomal regions as valuable resources for identifying expressed gene sequences in the human genome. We believe that we are making important progress under the auspices of this DOE human genome program grant and we will continue to make significant contributions in the coming year. 4 refs., 4 figs.

  20. Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis

    OpenAIRE

    Gascoigne, Karen E; Cheeseman, Iain M.

    2013-01-01

    Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a “dicentric” chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cel...

  1. Mapping strategies: Chromosome 16 workshop

    Energy Technology Data Exchange (ETDEWEB)

    1989-01-01

    The following topics from a workshop on chromosome 16 are briefly discussed: genetic map of chromosome 16; chromosome breakpoint map of chromosome 16; integrated physical/genetic map of chromosome 16; pulsed field map of the 16p13.2--p13.3 region (3 sheets); and a report of the HGM10 chromosome 16 committee.

  2. Control of chromosome replication in caulobacter crescentus.

    Science.gov (United States)

    Marczynski, Gregory T; Shapiro, Lucy

    2002-01-01

    Caulobacter crescentus permits detailed analysis of chromosome replication control during a developmental cell cycle. Its chromosome replication origin (Cori) may be prototypical of the large and diverse class of alpha-proteobacteria. Cori has features that both affiliate and distinguish it from the Escherichia coli chromosome replication origin. For example, requirements for DnaA protein and RNA transcription affiliate both origins. However, Cori is distinguished by several features, and especially by five binding sites for the CtrA response regulator protein. To selectively repress and limit chromosome replication, CtrA receives both protein degradation and protein phosphorylation signals. The signal mediators, proteases, response regulators, and kinases, as well as Cori DNA and the replisome, all show distinct patterns of temporal and spatial organization during cell cycle progression. Future studies should integrate our knowledge of biochemical activities at Cori with our emerging understanding of cytological dynamics in C. crescentus and other bacteria.

  3. Engineering of plant chromosomes.

    Science.gov (United States)

    Mette, Michael Florian; Houben, Andreas

    2015-02-01

    Engineered minimal chromosomes with sufficient mitotic and meiotic stability have an enormous potential as vectors for stacking multiple genes required for complex traits in plant biotechnology. Proof of principle for essential steps in chromosome engineering such as truncation of chromosomes by T-DNA-mediated telomere seeding and de novo formation of centromeres by cenH3 fusion protein tethering has been recently obtained. In order to generate robust protocols for application in plant biotechnology, these steps need to be combined and supplemented with additional methods such as site-specific recombination for the directed transfer of multiple genes of interest on the minichromosomes. At the same time, the development of these methods allows new insight into basic aspects of plant chromosome functions such as how centromeres assure proper distribution of chromosomes to daughter cells or how telomeres serve to cap the chromosome ends to prevent shortening of ends over DNA replication cycles and chromosome end fusion.

  4. The X chromosome and immune associated genes.

    Science.gov (United States)

    Bianchi, Ilaria; Lleo, Ana; Gershwin, M Eric; Invernizzi, Pietro

    2012-05-01

    The X chromosome is known to contain the largest number of immune-related genes of the whole human genome. For this reason, X chromosome has recently become subject of great interest and attention and numerous studies have been aimed at understanding the role of genes on the X chromosome in triggering and maintaining the autoimmune aggression. Autoimmune diseases are indeed a growing heath burden affecting cumulatively up to 10% of the general population. It is intriguing that most X-linked primary immune deficiencies carry significant autoimmune manifestations, thus illustrating the critical role played by products of single gene located on the X chromosome in the onset, function and homeostasis of the immune system. Again, the plethora of autoimmune stigmata observed in patients with Turner syndrome, a disease due to the lack of one X chromosome or the presence of major X chromosome deletions, indicate that X-linked genes play a unique and major role in autoimmunity. There have been several reports on a role of X chromosome gene dosage through inactivation or duplication in women with autoimmune diseases, for example through a higher rate of circulating cells with a single X chromosome (i.e. with X monosomy). Finally, a challenge for researchers in the coming years will be to dissect the role for the large number of X-linked microRNAs from the perspective of autoimmune disease development. Taken together, X chromosome might well constitute the common trait of the susceptibility to autoimmune diseases, other than to explain the female preponderance of these conditions. This review will focus on the available evidence on X chromosome changes and discuss their potential implications and limitations.

  5. In silico detection of phylogenetic informative Y-chromosomal single nucleotide polymorphisms from whole genome sequencing data.

    Science.gov (United States)

    Van Geystelen, Anneleen; Wenseleers, Tom; Decorte, Ronny; Caspers, Maarten J L; Larmuseau, Maarten H D

    2014-11-01

    A state-of-the-art phylogeny of the human Y-chromosome is an essential tool for forensic genetics. The explosion of whole genome sequencing (WGS) data due to the rapid progress of next-generation sequencing facilities is useful to optimize and to increase the resolution of the phylogenetic Y-chromosomal tree. The most interesting Y-chromosomal variants to increase the phylogeny are SNPs (Y-SNPs) especially since the software to call them in WGS data and to genotype them in forensic assays has been optimized over the past years. The PENNY software presented here detects potentially phylogenetic interesting Y-SNPs in silico based on SNP calling data files and classifies them into different types according to their position in the currently used Y-chromosomal tree. The software utilized 790 available male WGS samples of which 172 had a high SNP calling quality. In total, 1269 Y-SNPs potentially capable of increasing the resolution of the Y-chromosomal phylogenetic tree were detected based on a first run with PENNY. Based on a test panel of 57 high-quality and 618 low-quality WGS samples, we could prove that these newly added Y-SNPs indeed increased the resolution of the phylogenetic Y-chromosomal analysis substantially. Finally, we performed a second run with PENNY whereby all samples including those of the test panel are used and this resulted in 509 additional phylogenetic promising Y-SNPs. By including these additional Y-SNPs, a final update of the present phylogenetic Y-chromosomal tree which is useful for forensic applications was generated. In order to find more convincing forensic interesting Y-SNPs with this PENNY software, the number of samples and variety of the haplogroups to which these samples belong needs to increase. The PENNY software (inclusive the user manual) is freely available on the website http://bio.kuleuven.be/eeb/lbeg/software.

  6. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division...

  7. Particle-induced chromosome aberrations and mutations: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, S. [Gesellschaft fuer Schwerionenforschung, Darmstadt (Germany)

    1997-09-01

    This overview will focus on progress in chromosome and mutation studies achieved by the application of new techniques. Furthermore, recent relevant data on longterm genetic effects of densely ionizing radiation will be summarized. (orig./MG)

  8. Chromosomal instability in meningiomas.

    Science.gov (United States)

    van Tilborg, Angela A G; Al Allak, Bushra; Velthuizen, Sandra C J M; de Vries, Annie; Kros, Johan M; Avezaat, Cees J J; de Klein, Annelies; Beverloo, H Berna; Zwarthoff, Ellen C

    2005-04-01

    Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumor suppressor gene on chromosome 22. No causative gene is known for the remaining 40%. Cytogenetic analysis shows that meningiomas caused by inactivation of the NF2 gene can be divided into tumors that show monosomy 22 as the sole abnormality and tumors with a more complex karyotype. Meningiomas not caused by the NF2 gene usually have a diploid karyotype. Here we report that, besides the clonal chromosomal aberrations, the chromosome numbers in many meningiomas varied from one metaphase spread to the other, a feature that is indicative of chromosomal instability. Unexpectedly and regardless of genotype, a subgroup of tumors was observed with an average number of 44.9 chromosomes and little variation in the number of chromosomes per metaphase spread. In addition, a second subgroup was recognized with a hyperdiploid number of chromosomes (average 48.5) and considerable variation in numbers per metaphase. However, this numerical instability resulted in a clonal karyotype with chromosomal gains and losses in addition to loss of chromosome 22 only in meningiomas caused by inactivation of the NF2 gene. In cultured cells of all tumor groups, bi- and multinucleated cells were seen, as well as anaphase bridges, residual chromatid strings, multiple spindle poles, and unseparated chromatids, suggesting defects in the mitotic apparatus or kinetochore. Thus, we conclude that even a benign and slow-growing tumor like a meningioma displays chromosomal instability.

  9. Neo-sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes

    DEFF Research Database (Denmark)

    Zhou, Qi; Wang, Jun; Huang, Ling

    2008-01-01

    SNX22 abolished a microRNA target site. Finally, expression analyses revealed complex patterns of expression divergence between neo-Y and neo-X alleles. CONCLUSION: The nascent neo-sex chromosome system of black muntjacs is a valuable model in which to study the evolution of sex chromosomes in mammals......BACKGROUND: The regular mammalian X and Y chromosomes diverged from each other at least 166 to 148 million years ago, leaving few traces of their early evolution, including degeneration of the Y chromosome and evolution of dosage compensation. RESULTS: We studied the intriguing case of black...... muntjac, in which a recent X-autosome fusion and a subsequent large autosomal inversion within just the past 0.5 million years have led to inheritance patterns identical to the traditional X-Y (neo-sex chromosomes). We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene...

  10. Delimiting the origin of a B chromosome by FISH mapping, chromosome painting and DNA sequence analysis in Astyanax paranae (Teleostei, Characiformes.

    Directory of Open Access Journals (Sweden)

    Duílio M Z de A Silva

    Full Text Available Supernumerary (B chromosomes have been shown to contain a wide variety of repetitive sequences. For this reason, fluorescent in situ hybridisation (FISH is a useful tool for ascertaining the origin of these genomic elements, especially when combined with painting from microdissected B chromosomes. In order to investigate the origin of B chromosomes in the fish species Astyanax paranae, these two approaches were used along with PCR amplification of specific DNA sequences obtained from the B chromosomes and its comparison with those residing in the A chromosomes. Remarkably, chromosome painting with the one-arm metacentric B chromosome probe showed hybridization signals on entire B chromosome, while FISH mapping revealed the presence of H1 histone and 18S rDNA genes symmetrically placed in both arms of the B chromosome. These results support the hypothesis that the B chromosome of A. paranae is an isochromosome. Additionally, the chromosome pairs Nos. 2 or 23 are considered the possible B chromosome ancestors since both contain syntenic H1 and 18S rRNA sequences. The analysis of DNA sequence fragments of the histone and rRNA genes obtained from the microdissected B chromosomes showed high similarity with those obtained from 0B individuals, which supports the intraspecific origin of B chromosomes in A. paranae. Finally, the population hereby analysed showed a female-biased B chromosome presence suggesting that B chromosomes in this species could influence sex determinism.

  11. Delimiting the origin of a B chromosome by FISH mapping, chromosome painting and DNA sequence analysis in Astyanax paranae (Teleostei, Characiformes).

    Science.gov (United States)

    Silva, Duílio M Z de A; Pansonato-Alves, José Carlos; Utsunomia, Ricardo; Araya-Jaime, Cristian; Ruiz-Ruano, Francisco J; Daniel, Sandro Natal; Hashimoto, Diogo Teruo; Oliveira, Cláudio; Camacho, Juan Pedro M; Porto-Foresti, Fábio; Foresti, Fausto

    2014-01-01

    Supernumerary (B) chromosomes have been shown to contain a wide variety of repetitive sequences. For this reason, fluorescent in situ hybridisation (FISH) is a useful tool for ascertaining the origin of these genomic elements, especially when combined with painting from microdissected B chromosomes. In order to investigate the origin of B chromosomes in the fish species Astyanax paranae, these two approaches were used along with PCR amplification of specific DNA sequences obtained from the B chromosomes and its comparison with those residing in the A chromosomes. Remarkably, chromosome painting with the one-arm metacentric B chromosome probe showed hybridization signals on entire B chromosome, while FISH mapping revealed the presence of H1 histone and 18S rDNA genes symmetrically placed in both arms of the B chromosome. These results support the hypothesis that the B chromosome of A. paranae is an isochromosome. Additionally, the chromosome pairs Nos. 2 or 23 are considered the possible B chromosome ancestors since both contain syntenic H1 and 18S rRNA sequences. The analysis of DNA sequence fragments of the histone and rRNA genes obtained from the microdissected B chromosomes showed high similarity with those obtained from 0B individuals, which supports the intraspecific origin of B chromosomes in A. paranae. Finally, the population hereby analysed showed a female-biased B chromosome presence suggesting that B chromosomes in this species could influence sex determinism.

  12. Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis.

    Science.gov (United States)

    Gascoigne, Karen E; Cheeseman, Iain M

    2013-07-01

    Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a "dicentric" chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cells. Here, we tested the ability of a single dicentric chromosome to contribute to genomic instability and neoplastic conversion in vertebrate cells. We developed a system to transiently and reversibly induce dicentric chromosome formation on a single chromosome with high temporal control. We find that induced dicentric chromosomes are frequently damaged and mis-segregated during mitosis, and that this leads to extensive chromosomal rearrangements including translocations with other chromosomes. Populations of pre-neoplastic cells in which a single dicentric chromosome is induced acquire extensive genomic instability and display hallmarks of cellular transformation including anchorage-independent growth in soft agar. Our results suggest that a single dicentric chromosome could contribute to tumor initiation.

  13. The prevalence of chromosomal abnormalities in subgroups of infertile men.

    Science.gov (United States)

    Dul, E C; Groen, H; van Ravenswaaij-Arts, C M A; Dijkhuizen, T; van Echten-Arends, J; Land, J A

    2012-01-01

    The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men. In a retrospective cohort of 1223 azoospermic men and men eligible for ICSI treatment, we studied sperm parameters, hormone levels and medical history for an association with chromosomal abnormalities. The prevalence of chromosomal abnormalities in the cohort was 3.1%. No association was found between chromosomal abnormalities and sperm volume, concentration, progressive motility or total motile sperm count. Azoospermia was significantly associated with the presence of a chromosomal abnormality [15.2%, odds ratio (OR) 7.70, P chromosomal abnormalities (OR 2.96, P = 0.013). Azoospermic men with a positive andrologic history had a lower prevalence of chromosomal abnormalities than azoospermic men with an uneventful history (OR 0.28, P = 0.047). In non-azoospermic men, we found that none of the studied variables were associated with the prevalence of chromosomal abnormalities. We show that the highest prevalence of chromosomal abnormalities is found in hypergonadotrophic azoospermic men with an uneventful andrologic history.

  14. Analysis of plant meiotic chromosomes by chromosome painting.

    Science.gov (United States)

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  15. Mechanisms for chromosome segregation.

    Science.gov (United States)

    Bouet, Jean-Yves; Stouf, Mathieu; Lebailly, Elise; Cornet, François

    2014-12-01

    Bacteria face the problem of segregating their gigantic chromosomes without a segregation period restricted in time and space, as Eukaryotes do. Segregation thus involves multiple activities, general or specific of a chromosome region and differentially controlled. Recent advances show that these various mechanisms conform to a “pair and release” rule, which appears as a general rule in DNA segregation. We describe the latest advances in segregation of bacterial chromosomes with emphasis on the different pair and release mechanisms.

  16. The Precarious Prokaryotic Chromosome

    OpenAIRE

    Kuzminov, Andrei

    2014-01-01

    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the t...

  17. Small supernumerary marker chromosomes (sSMC in humans; are there B chromosomes hidden among them

    Directory of Open Access Journals (Sweden)

    Ogilvie Caroline

    2008-06-01

    Full Text Available Abstract Background Small supernumerary marker chromosomes (sSMC and B-chromosomes represent a heterogeneous collection of chromosomes added to the typical karyotype, and which are both small in size. They may consist of heterochromatic and/or euchromatic material. Also a predominance of maternal transmission was reported for both groups. Even though sSMC and B-chromosomes show some similarity it is still an open question if B-chromosomes are present among the heterogeneous group of sSMC. According to current theories, sSMC would need drive, drift or beneficial effects to increase in frequency in order to become B chromosome. However, up to now no B-chromosomes were described in human. Results Here we provide first evidence and discuss, that among sSMC B-chromosomes might be hidden. We present two potential candidates which may already be, or may in future evolve into B chromosomes in human: (i sSMC cases where the marker is stainable only by DNA derived from itself; and (ii acrocentric-derived inverted duplication sSMC without associated clinical phenotype. Here we report on the second sSMC stainable exclusively by its own DNA and show that for acrocentric derived sSMC 3.9× more are familial cases than reported for other sSMC. Conclusion The majority of sSMC are not to be considered as B-chromosomes. Nonetheless, a minority of sSMC show similarities to B-chromosomes. Further studies are necessary to come to final conclusions for that problem.

  18. Chromosome oscillations in mitosis

    Science.gov (United States)

    Campas, Otger

    2008-03-01

    Successful cell division necessitates a tight regulation of chromosome movement via the activity of molecular motors. Many of the key players at the origin of the forces generating the motion have been identified, but their spatial and temporal organization remains elusive. In animal cells, chromosomes periodically switch between phases of movement towards and away from the pole. This characteristic oscillatory behaviour cannot be explained by the current models of chromosome positioning and congression. We perform a self-contained theoretical analysis in which the motion of mono-oriented chromosomes results from the competition between the activity of the kinetochore and chromokinesin motors on the chromosome arms. Our analysis, consistent with the available experimental data, proposes that the interplay between the aster-like morphology of the spindle and the collective kinetics of molecular motors is at the origin of chromosome oscillations, positioning and congression. It provides a natural explanation for the so-called chromosome directional instability and for the mechanism by which chromosomes sense their position in space. In addition, we estimate the in vivo velocity of chromokinesins at vanishing load and propose new experiments to assess the mechanism at the origin of chromosome movement in cell division.

  19. Coordination between chromosome replication, segregation, and cell division in Caulobacter crescentus

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

    Progression through the Caulobacter crescentus cell cycle is coupled to a cellular differentiation program. The swarmer cell is replicationally quiescent, and DNA replication initiates at the swarmer-to-stalked cell transition. There is a very short delay between initiation of DNA replication......, and the completely replicated terminus regions stay associated with each other after chromosome replication is completed, disassociating very late in the cell cycle shortly before the final cell division event. Invagination of the cytoplasmic membrane occurs earlier than separation of the replicated terminus regions...

  20. Possible origin of B chromosome in Dichotomius sericeus (Coleoptera).

    Science.gov (United States)

    Amorim, Igor Costa; Milani, Diogo; Cabral-de-Mello, Diogo Cavalcanti; Rocha, Marília França; Moura, Rita Cássia

    2016-08-01

    B chromosomes have so far been described in about 80 species of Coleoptera, mainly using conventional staining analysis. In this study, 152 individuals of the dung beetle Dichotomius sericeus (Coleoptera), collected from three isolated geographical areas in the State of Pernambuco, Brazil, were analyzed to determine the frequency, prevalence, distribution, meiotic behavior, and possible B chromosome origin. The cytogenetic analysis consisted of conventional staining, C-banding, triple fluorochrome staining (CMA3/DA/DAPI), and fluorescent in situ hybridization using ribosomal DNAs (rDNAs) and H3 histone gene as probes, as well as microdissection and chromosome painting of the B chromosome. The B chromosomes were detected in all populations analyzed. Analysis revealed the heterochromatic nature and the presence of G+C-rich blocks and 18S rDNA on the B chromosome. FISH with DNA from microdissected B chromosome painted the entire extension of the B chromosome for all populations, besides the pericentromeric regions of all the autosomes, as well as the X chromosome. Finally, cross-hybridization in nine related species of Dichotomius using the microdissected B chromosome as probe did not reveal any hybridization signal. The results suggest an intraspecific and monophyletic origin for B chromosomes in D. sericeus, probably from the second or third autosomal pair.

  1. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J

    1983-01-01

    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...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...... with women without elevated risk. Spontaneous abortion rate and prematurity rate did not differ from rates expected without amniocentesis. It is concluded that current indications may be characterized as a mixture of evident high risk factors and factors with only a minor influence on risk. Indications...

  2. 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

  3. 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

  4. Genetic modification of mammalian genome at chromosome level

    Directory of Open Access Journals (Sweden)

    OLEG L. SEROV

    2000-09-01

    Full Text Available The review is concerned with a progress in genetic modification of a mammalian genome in vitro and in vivo at chromosomal level. Recently three new approaches for the chromosome biotechnology have been developed: Using Cre/loxP-system a researcher is able to produce targeted rearrangements of whole chromosomes or their segments or particular genes within the genome, and therefore to modify the set, position and copy number of the endogenous elements of the genome. Mammalian artificial chromosomes (MACs provide a possibility to introduce into genome relatively large segments of alien chromosome material, either artificially constructed or derived from the genome of different species. Using ES-somatic cell hybrids allows to transfer whole chromosomes or their fragments between different genomes within and between species. Advantages and limitations of these approaches are discussed.

  5. Dynamics of Escherichia coli chromosome segregation during multifork replication.

    Science.gov (United States)

    Nielsen, Henrik J; Youngren, Brenda; Hansen, Flemming G; Austin, Stuart

    2007-12-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks.

  6. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication▿

    Science.gov (United States)

    Nielsen, Henrik J.; Youngren, Brenda; Hansen, Flemming G.; Austin, Stuart

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks. PMID:17905986

  7. XYY chromosome anomaly and schizophrenia.

    Science.gov (United States)

    Rajagopalan, M; MacBeth, R; Varma, S L

    1998-02-07

    Sex chromosome anomalies have been associated with psychoses, and most of the evidence is linked to the presence of an additional X chromosome. We report a patient with XYY chromosome anomaly who developed schizophrenia.

  8. 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 chromoso...

  9. Origin of B chromosomes in the genus Astyanax (Characiformes, Characidae) and the limits of chromosome painting.

    Science.gov (United States)

    de A Silva, Duílio M Z; Daniel, Sandro Natal; Camacho, Juan Pedro M; Utsunomia, Ricardo; Ruiz-Ruano, Francisco J; Penitente, Manolo; Pansonato-Alves, José Carlos; Hashimoto, Diogo Teruo; Oliveira, Claudio; Porto-Foresti, Fábio; Foresti, Fausto

    2016-06-01

    Eukaryote genomes are frequently burdened with the presence of supernumerary (B) chromosomes. Their origin is frequently investigated by chromosome painting, under the hypothesis that sharing the repetitive DNA sequences contained in the painting probes is a sign of common descent. However, the intragenomic mobility of many anonymous DNA sequences contained in these probes (e.g., transposable elements) adds high uncertainty to this conclusion. Here we test the validity of chromosome painting to investigate B chromosome origin by comparing its results for seven B chromosome types in two fish species genus Astyanax, with those obtained (1) by means of the physical mapping of 18S ribosomal DNA (rDNA), H1 histone genes, the As51 satellite DNA and the (AC)15 microsatellite, and (2) by comparing the nucleotide sequence of one of these families (ITS regions from ribosomal DNA) between genomic DNA from B-lacking individuals in both species and the microdissected DNA from two metacentric B chromosomes found in these same species. Intra- and inter-specific painting suggested that all B chromosomes that were assayed shared homologous DNA sequences among them, as well as with a variable number of A chromosomes in each species. This finding would be consistent with a common origin for all seven B chromosomes analyzed. By contrast, the physical mapping of repetitive DNA sequences failed to give support to this hypothesis, as no more than two B-types shared a given repetitive DNA. Finally, sequence analysis of the ITS regions suggested that at least some of the B chromosomes could have had a common origin.

  10. Chromosomal organization and segregation in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Isabelle Vallet-Gely

    2013-05-01

    Full Text Available The study of chromosomal organization and segregation in a handful of bacteria has revealed surprising variety in the mechanisms mediating such fundamental processes. In this study, we further emphasized this diversity by revealing an original organization of the Pseudomonas aeruginosa chromosome. We analyzed the localization of 20 chromosomal markers and several components of the replication machinery in this important opportunistic γ-proteobacteria pathogen. This technique allowed us to show that the 6.3 Mb unique circular chromosome of P. aeruginosa is globally oriented from the old pole of the cell to the division plane/new pole along the oriC-dif axis. The replication machinery is positioned at mid-cell, and the chromosomal loci from oriC to dif are moved sequentially to mid-cell prior to replication. The two chromosomal copies are subsequently segregated at their final subcellular destination in the two halves of the cell. We identified two regions in which markers localize at similar positions, suggesting a bias in the distribution of chromosomal regions in the cell. The first region encompasses 1.4 Mb surrounding oriC, where loci are positioned around the 0.2/0.8 relative cell length upon segregation. The second region contains at least 800 kb surrounding dif, where loci show an extensive colocalization step following replication. We also showed that disrupting the ParABS system is very detrimental in P. aeruginosa. Possible mechanisms responsible for the coordinated chromosomal segregation process and for the presence of large distinctive regions are discussed.

  11. Female meiotic sex chromosome inactivation in chicken.

    Science.gov (United States)

    Schoenmakers, Sam; Wassenaar, Evelyne; Hoogerbrugge, Jos W; Laven, Joop S E; Grootegoed, J Anton; Baarends, Willy M

    2009-05-01

    During meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI) leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (ZW), whereas males have the homogametic ZZ constitution. During chicken oogenesis, the heterologous ZW pair reaches a state of complete heterologous synapsis, and this might enable maintenance of transcription of Z- and W chromosomal genes during meiotic prophase. Herein, we show that the ZW pair is transiently silenced, from early pachytene to early diplotene using immunocytochemistry and gene expression analyses. We propose that ZW inactivation is most likely achieved via spreading of heterochromatin from the W on the Z chromosome. Also, persistent meiotic DNA double-strand breaks (DSBs) may contribute to silencing of Z. Surprisingly, gammaH2AX, a marker of DSBs, and also the earliest histone modification that is associated with XY body formation in mammalian and marsupial spermatocytes, does not cover the ZW during the synapsed stage. However, when the ZW pair starts to desynapse, a second wave of gammaH2AX accumulates on the unsynapsed regions of Z, which also show a reappearance of the DSB repair protein RAD51. This indicates that repair of meiotic DSBs on the heterologous part of Z is postponed until late pachytene/diplotene, possibly to avoid recombination with regions on the heterologously synapsed W chromosome. Two days after entering diplotene, the Z looses gammaH2AX and shows reactivation. This is the first report of meiotic sex chromosome inactivation in a species with female heterogamety, providing evidence that this mechanism is not specific to spermatogenesis. It also indicates the presence of an evolutionary force that drives meiotic sex chromosome inactivation independent of the final achievement of synapsis.

  12. Female meiotic sex chromosome inactivation in chicken.

    Directory of Open Access Journals (Sweden)

    Sam Schoenmakers

    2009-05-01

    Full Text Available During meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (ZW, whereas males have the homogametic ZZ constitution. During chicken oogenesis, the heterologous ZW pair reaches a state of complete heterologous synapsis, and this might enable maintenance of transcription of Z- and W chromosomal genes during meiotic prophase. Herein, we show that the ZW pair is transiently silenced, from early pachytene to early diplotene using immunocytochemistry and gene expression analyses. We propose that ZW inactivation is most likely achieved via spreading of heterochromatin from the W on the Z chromosome. Also, persistent meiotic DNA double-strand breaks (DSBs may contribute to silencing of Z. Surprisingly, gammaH2AX, a marker of DSBs, and also the earliest histone modification that is associated with XY body formation in mammalian and marsupial spermatocytes, does not cover the ZW during the synapsed stage. However, when the ZW pair starts to desynapse, a second wave of gammaH2AX accumulates on the unsynapsed regions of Z, which also show a reappearance of the DSB repair protein RAD51. This indicates that repair of meiotic DSBs on the heterologous part of Z is postponed until late pachytene/diplotene, possibly to avoid recombination with regions on the heterologously synapsed W chromosome. Two days after entering diplotene, the Z looses gammaH2AX and shows reactivation. This is the first report of meiotic sex chromosome inactivation in a species with female heterogamety, providing evidence that this mechanism is not specific to spermatogenesis. It also indicates the presence of an evolutionary force that drives meiotic sex chromosome inactivation independent of the final achievement of synapsis.

  13. Independent stratum formation on the avian sex chromosomes reveals inter-chromosomal gene conversion and predominance of purifying selection on the W chromosome.

    Science.gov (United States)

    Wright, Alison E; Harrison, Peter W; Montgomery, Stephen H; Pointer, Marie A; Mank, Judith E

    2014-11-01

    We used a comparative approach spanning three species and 90 million years to study the evolutionary history of the avian sex chromosomes. Using whole transcriptomes, we assembled the largest cross-species dataset of W-linked coding content to date. Our results show that recombination suppression in large portions of the avian sex chromosomes has evolved independently, and that long-term sex chromosome divergence is consistent with repeated and independent inversions spreading progressively to restrict recombination. In contrast, over short-term periods we observe heterogeneous and locus-specific divergence. We also uncover four instances of gene conversion between both highly diverged and recently evolved gametologs, suggesting a complex mosaic of recombination suppression across the sex chromosomes. Lastly, evidence from 16 gametologs reveal that the W chromosome is evolving with a significant contribution of purifying selection, consistent with previous findings that W-linked genes play an important role in encoding sex-specific fitness.

  14. Chromosomal Instability Confers Intrinsic Multidrug Resistance

    DEFF Research Database (Denmark)

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

    2011-01-01

    their diploid parental cells only with increasing chromosomal heterogeneity and isogenic cell line models of CIN+ displayed multidrug resistance relative to their CIN- parental cancer cell line derivatives. In a meta-analysis of CRC outcome following cytotoxic treatment, CIN+ predicted worse 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(5); 1858-70. (c......Aneuploidy is associated with poor prognosis in solid tumors. Spontaneous chromosome missegregation events in aneuploid cells promote chromosomal instability (CIN) that may contribute to the acquisition of multidrug resistance in vitro and heighten risk for tumor relapse in animal models...

  15. Sequential cloning of chromosomes

    Science.gov (United States)

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. 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 (class IIS) 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. 9 figs.

  16. 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.

  17. Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies

    Energy Technology Data Exchange (ETDEWEB)

    Pampalona, J.; Soler, D.; Genesca, A. [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra E-08193 (Spain); Tusell, L., E-mail: laura.tusell@uab.es [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra E-08193 (Spain)

    2010-01-05

    The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16{sup INK4a} protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and

  18. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, January 1, 1980-Dec 31, 1980. [Consequences of radiotherapy and/or chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J. D.

    1980-09-01

    The relationship of the chromosome pattern in leukemic cells to prior disease and to the type of therapy are summarized. Although the karyotype seen in secondary ANLL is distinctly different from that seen in the primary malignancy, the nature of the primary disease may influence the pattern of karyotypic changes seen in the leukemic cell. This notion is very speculative and is based on limited observations. Two of three patients with leukemia following multiple myeloma were unique in that they were the only ones whose leukemic cells had more than 48 chromosomes, with +1, +6, +8, +21; this constellation of abnormalities was not seen in any of the other patients. Since most of the patients had received both radiotherapy and chemotherapy, it is difficult to determine whether specific chromosome changes are related more closely to one rather than the other of these types of therapy. It appears, however, that combined therapy is much more likely to result in abnormalities of both No. 5 and No. 7 (9/15 patients) than is either modality used alone (1/12). (ERB)

  19. CHROMOSOMES OF AMERICAN MARSUPIALS.

    Science.gov (United States)

    BIGGERS, J D; FRITZ, H I; HARE, W C; MCFEELY, R A

    1965-06-18

    Studies of the chromosomes of four American marsupials demonstrated that Caluromys derbianus and Marmosa mexicana have a diploid number of 14 chromosomes, and that Philander opossum and Didelphis marsupialis have a diploid number of 22. The karyotypes of C. derbianus and M. mexicana are similar, whereas those of P. opossum and D. marsupialis are dissimilar. If the 14-chromosome karyotype represents a reduction from a primitive number of 22, these observations suggest that the change has occurred independently in the American and Australasian forms.

  20. Evidence for different origin of sex chromosomes in snakes, birds, and mammals and step-wise differentiation of snake sex chromosomes.

    Science.gov (United States)

    Matsubara, Kazumi; Tarui, Hiroshi; Toriba, Michihisa; Yamada, Kazuhiko; Nishida-Umehara, Chizuko; Agata, Kiyokazu; Matsuda, Yoichi

    2006-11-28

    All snake species exhibit genetic sex determination with the ZZ/ZW type of sex chromosomes. To investigate the origin and evolution of snake sex chromosomes, we constructed, by FISH, a cytogenetic map of the Japanese four-striped rat snake (Elaphe quadrivirgata) with 109 cDNA clones. Eleven of the 109 clones were localized to the Z chromosome. All human and chicken homologues of the snake Z-linked genes were located on autosomes, suggesting that the sex chromosomes of snakes, mammals, and birds were all derived from different autosomal pairs of the common ancestor. We mapped the 11 Z-linked genes of E. quadrivirgata to chromosomes of two other species, the Burmese python (Python molurus bivittatus) and the habu (Trimeresurus flavoviridis), to investigate the process of W chromosome differentiation. All and 3 of the 11 clones were localized to both the Z and W chromosomes in P. molurus and E. quadrivirgata, respectively, whereas no cDNA clones were mapped to the W chromosome in T. flavoviridis. Comparative mapping revealed that the sex chromosomes are only slightly differentiated in P. molurus, whereas they are fully differentiated in T. flavoviridis, and E. quadrivirgata is at a transitional stage of sex-chromosome differentiation. The differentiation of sex chromosomes was probably initiated from the distal region on the short arm of the protosex chromosome of the common ancestor, and then deletion and heterochromatization progressed on the sex-specific chromosome from the phylogenetically primitive boids to the more advanced viperids.

  1. Molecular mapping of chromosomes 17 and X

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1991-01-15

    Progress toward the construction of high density genetic maps of chromosomes 17 and X has been made by isolating and characterizing a relatively large set of polymorphic probes for each chromosome and using these probes to construct genetic maps. We have mapped the same polymorphic probes against a series of chromosome breakpoints on X and 17. The probes could be assigned to over 30 physical intervals on the X chromosome and 7 intervals on 17. In many cases, this process resulted in improved characterization of the relative locations of the breakpoints with respect to each other and the definition of new physical intervals. The strategy for isolation of the polymorphic clones utilized chromosome specific libraries of 1--15 kb segments from each of the two chromosomes. From these libraries, clones were screened for those detecting restriction fragment length polymorphisms. The markers were further characterized, the chromosomal assignments confirmed and in most cases segments of the original probes were subcloned into plasmids to produce probes with improved signal to noise ratios for use in the genetic marker studies. The linkage studies utilize the CEPH reference families and other well-characterized families in our collection which have been used for genetic disease linkage work. Preliminary maps and maps of portions of specific regions of 17 and X are provided. We have nearly completed a map of the 1 megabase Mycoplasma arthritidis genome by applying these techniques to a lambda phage library of its genome. We have found bit mapping to be an efficient means to organize a contiguous set of overlapping clones from a larger genome.

  2. Correlation of physical and genetic maps of human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1990-01-01

    This project is now progressing strongly. Thirteen somatic cell hybrids containing rearranged {number sign}16 chromosomes have been constructed, bringing the total number of hybrids constructed by the group to 27 which divides chromosome 16 into 29 regions. 170 probes have been mapped into these regions. Although this is the second progress report for this contract it essentially contains all the work carried out since the first progress report covered a period of less than three months during which little had been done other than setting up. The project has been progressing very well and has led to numerous collaborations with other groups involved in mapping this chromosome or studying genes on it. 7 refs., 1 fig., 2 tabs.

  3. 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.

  4. Chromosome doubling method

    Science.gov (United States)

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  5. Activation of X Chromosome Inactivation

    NARCIS (Netherlands)

    C.M. Maduro (Cheryl)

    2016-01-01

    markdownabstractIn mammals, males are the heterogametic sex having an X chromosome and a Y chromosome whereas females have two X chromosomes. Despite originating from an ancient homologous autosomal pair, the X and Y chromosome now differ greatly in size and gene content after ~180 MY of evolution.

  6. Activation of X Chromosome Inactivation

    NARCIS (Netherlands)

    C.M. Maduro (Cheryl)

    2016-01-01

    markdownabstractIn mammals, males are the heterogametic sex having an X chromosome and a Y chromosome whereas females have two X chromosomes. Despite originating from an ancient homologous autosomal pair, the X and Y chromosome now differ greatly in size and gene content after ~180 MY of evolution.

  7. The Philadelphia chromosome in leukemogenesis

    Institute of Scientific and Technical Information of China (English)

    ZhiJieKang; JinSongYan; QuentinLiu; YuFeiLiu; LingZhiXu; ZiJieLong; DanHuang; YaYang; BingLiu; JiuXingFeng; YuJiaPan

    2016-01-01

    The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Phila‑delphia chromosome (Ph) and is a hallmark of chronic myeloid leukemia (CML). In leukemia cells, Ph not only impairs the physiological signaling pathways but also disrupts genomic stability. This aberrant fusion gene encodes the breakpoint cluster region‑proto‑oncogene tyrosine‑protein kinase (BCR‑ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. The kinase activity is responsible for maintaining proliferation, inhibiting differentia‑tion, and conferring resistance to cell death. During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase, the expression patterns of different BCR‑ABL1 transcripts vary. Each BCR‑ABL1 transcript is present in a distinct leukemia phenotype, which predicts both response to therapy and clinical outcome. Besides CML, the Ph is found in acute lymphoblastic leukemia, acute myeloid leukemia, and mixed‑phenotype acute leukemia. Here, we provide an overview of the clinical presentation and cellular biology of different phenotypes of Ph‑positive leukemia and highlight key ifndings regarding leukemogenesis.

  8. 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.

  9. Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.

    Directory of Open Access Journals (Sweden)

    Yuval Tabach

    Full Text Available Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification.

  10. Experimental verification of a progressive damage model for composite laminates based on continuum damage mechanics. M.S. Thesis Final Report

    Science.gov (United States)

    Coats, Timothy William

    1994-01-01

    Progressive failure is a crucial concern when using laminated composites in structural design. Therefore the ability to model damage and predict the life of laminated composites is vital. The purpose of this research was to experimentally verify the application of the continuum damage model, a progressive failure theory utilizing continuum damage mechanics, to a toughened material system. Damage due to tension-tension fatigue was documented for the IM7/5260 composite laminates. Crack density and delamination surface area were used to calculate matrix cracking and delamination internal state variables, respectively, to predict stiffness loss. A damage dependent finite element code qualitatively predicted trends in transverse matrix cracking, axial splits and local stress-strain distributions for notched quasi-isotropic laminates. The predictions were similar to the experimental data and it was concluded that the continuum damage model provided a good prediction of stiffness loss while qualitatively predicting damage growth in notched laminates.

  11. APC and chromosome instability in colorectal cancer

    Directory of Open Access Journals (Sweden)

    C. M. Cabrera

    Full Text Available Colon cancer is a common disease that can be sporadic or familial. An inactivated adenomatous polyposis coli (APC suppressor gene is found in over 80% of colorectal tumors, this being an early alteration in the development of adenomatous polyps. APC function is not only critical for tumor initiation and progression, and chromosome instability (CIN is another characteristic dependent at least partly on APC mutations.

  12. 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.

  13. Energy Landscapes of Folding Chromosomes

    Science.gov (United States)

    Zhang, Bin

    The genome, the blueprint of life, contains nearly all the information needed to build and maintain an entire organism. A comprehensive understanding of the genome is of paramount interest to human health and will advance progress in many areas, including life sciences, medicine, and biotechnology. The overarching goal of my research is to understand the structure-dynamics-function relationships of the human genome. In this talk, I will be presenting our efforts in moving towards that goal, with a particular emphasis on studying the three-dimensional organization, the structure of the genome with multi-scale approaches. Specifically, I will discuss the reconstruction of genome structures at both interphase and metaphase by making use of data from chromosome conformation capture experiments. Computationally modeling of chromatin fiber at atomistic level from first principles will also be presented as our effort for studying the genome structure from bottom up.

  14. Federal Assistance Program Quarterly Project Progress Report. Geothermal Energy Program: Information Dissemination, Public Outreach, and Technical Analysis Activities. Reporting Period: January 1 - March 31, 2001 [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Lund, John W.

    2002-03-22

    The final report of the accomplishments of the geothermal energy program: information dissemination, public outreach and technical analysis activities by the project team consisting of the Geo-Heat Center, Geothermal Resources Council, Geothermal Education Office, Geothermal Energy Association and the Washington State University Energy Program.

  15. Evolution and survival on eutherian sex chromosomes.

    Directory of Open Access Journals (Sweden)

    Melissa A Wilson

    2009-07-01

    Full Text Available Since the two eutherian sex chromosomes diverged from an ancestral autosomal pair, the X has remained relatively gene-rich, while the Y has lost most of its genes through the accumulation of deleterious mutations in nonrecombining regions. Presently, it is unclear what is distinctive about genes that remain on the Y chromosome, when the sex chromosomes acquired their unique evolutionary rates, and whether X-Y gene divergence paralleled that of paralogs located on autosomes. To tackle these questions, here we juxtaposed the evolution of X and Y homologous genes (gametologs in eutherian mammals with their autosomal orthologs in marsupial and monotreme mammals. We discovered that genes on the X and Y acquired distinct evolutionary rates immediately following the suppression of recombination between the two sex chromosomes. The Y-linked genes evolved at higher rates, while the X-linked genes maintained the lower evolutionary rates of the ancestral autosomal genes. These distinct rates have been maintained throughout the evolution of X and Y. Specifically, in humans, most X gametologs and, curiously, also most Y gametologs evolved under stronger purifying selection than similarly aged autosomal paralogs. Finally, after evaluating the current experimental data from the literature, we concluded that unique mRNA/protein expression patterns and functions acquired by Y (versus X gametologs likely contributed to their retention. Our results also suggest that either the boundary between sex chromosome strata 3 and 4 should be shifted or that stratum 3 should be divided into two strata.

  16. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress

    DEFF Research Database (Denmark)

    Lukas, Claudia; Savic, Velibor; Bekker-Jensen, Simon

    2011-01-01

    Completion of genome duplication is challenged by structural and topological barriers that impede progression of replication forks. Although this can seriously undermine genome integrity, the fate of DNA with unresolved replication intermediates is not known. Here, we show that mild replication...... bodies shield chromosomal fragile sites sequestered in these compartments against erosion. Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations....... increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear...

  17. DNA double strand break repair, chromosome synapsis and transcriptional silencing in meiosis.

    Science.gov (United States)

    Inagaki, Akiko; Schoenmakers, Sam; Baarends, Willy M

    2010-05-16

    Chromosome pairing and synapsis during meiotic prophase requires the formation and repair of DNA double-strand breaks (DSBs) by the topoisomerase-like enzyme SPO11. Chromosomes, or chromosomal regions, that lack a pairing partner, such as the largely heterologous X and Y chromosomes, show delayed meiotic DSB repair and are transcriptionally silenced. Herein, we review meiosis-specific aspects of DSB repair in relation to homology recognition and meiotic silencing of heterologous regions. We propose a dynamic interplay between progression of synapsis and persistent meiotic DSBs. Signaling from these persistent breaks could inhibit heterologous synapsis and stimulate meiotic silencing of the X and Y chromosomes.

  18. Molecular mapping of chromosomes 17 and X

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1989-01-01

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  19. [A new method employing homologous recombination and YAC rescue to expedite gap filling long range mapping]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-31

    We have embarked on three areas of research relevant to the telomere rescue strategy mediated by homologous recombination described in this proposal. First, we have constructed the telomere rescue vector. Second, we have carried out tests in yeast and mammalian cells to ascertain whether the various crucial components function. Finally, we have begun to develop the molecular reagents required to target the telomeric regions of chromosome 16. The specific progress in each area is described briefly below.

  20. 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.

  1. The DNA sequence of the human X chromosome.

    Science.gov (United States)

    Ross, Mark T; Grafham, Darren V; Coffey, Alison J; Scherer, Steven; McLay, Kirsten; Muzny, Donna; Platzer, Matthias; Howell, Gareth R; Burrows, Christine; Bird, Christine P; Frankish, Adam; Lovell, Frances L; Howe, Kevin L; Ashurst, Jennifer L; Fulton, Robert S; Sudbrak, Ralf; Wen, Gaiping; Jones, Matthew C; Hurles, Matthew E; Andrews, T Daniel; Scott, Carol E; Searle, Stephen; Ramser, Juliane; Whittaker, Adam; Deadman, Rebecca; Carter, Nigel P; Hunt, Sarah E; Chen, Rui; Cree, Andrew; Gunaratne, Preethi; Havlak, Paul; Hodgson, Anne; Metzker, Michael L; Richards, Stephen; Scott, Graham; Steffen, David; Sodergren, Erica; Wheeler, David A; Worley, Kim C; Ainscough, Rachael; Ambrose, Kerrie D; Ansari-Lari, M Ali; Aradhya, Swaroop; Ashwell, Robert I S; Babbage, Anne K; Bagguley, Claire L; Ballabio, Andrea; Banerjee, Ruby; Barker, Gary E; Barlow, Karen F; Barrett, Ian P; Bates, Karen N; Beare, David M; Beasley, Helen; Beasley, Oliver; Beck, Alfred; Bethel, Graeme; Blechschmidt, Karin; Brady, Nicola; Bray-Allen, Sarah; Bridgeman, Anne M; Brown, Andrew J; Brown, Mary J; Bonnin, David; Bruford, Elspeth A; Buhay, Christian; Burch, Paula; Burford, Deborah; Burgess, Joanne; Burrill, Wayne; Burton, John; Bye, Jackie M; Carder, Carol; Carrel, Laura; Chako, Joseph; Chapman, Joanne C; Chavez, Dean; Chen, Ellson; Chen, Guan; Chen, Yuan; Chen, Zhijian; Chinault, Craig; Ciccodicola, Alfredo; Clark, Sue Y; Clarke, Graham; Clee, Chris M; Clegg, Sheila; Clerc-Blankenburg, Kerstin; Clifford, Karen; Cobley, Vicky; Cole, Charlotte G; Conquer, Jen S; Corby, Nicole; Connor, Richard E; David, Robert; Davies, Joy; Davis, Clay; Davis, John; Delgado, Oliver; Deshazo, Denise; Dhami, Pawandeep; Ding, Yan; Dinh, Huyen; Dodsworth, Steve; Draper, Heather; Dugan-Rocha, Shannon; Dunham, Andrew; Dunn, Matthew; Durbin, K James; Dutta, Ireena; Eades, Tamsin; Ellwood, Matthew; Emery-Cohen, Alexandra; Errington, Helen; Evans, Kathryn L; Faulkner, Louisa; Francis, Fiona; Frankland, John; Fraser, Audrey E; Galgoczy, Petra; Gilbert, James; Gill, Rachel; Glöckner, Gernot; Gregory, Simon G; Gribble, Susan; Griffiths, Coline; Grocock, Russell; Gu, Yanghong; Gwilliam, Rhian; Hamilton, Cerissa; Hart, Elizabeth A; Hawes, Alicia; Heath, Paul D; Heitmann, Katja; Hennig, Steffen; Hernandez, Judith; Hinzmann, Bernd; Ho, Sarah; Hoffs, Michael; Howden, Phillip J; Huckle, Elizabeth J; Hume, Jennifer; Hunt, Paul J; Hunt, Adrienne R; Isherwood, Judith; Jacob, Leni; Johnson, David; Jones, Sally; de Jong, Pieter J; Joseph, Shirin S; Keenan, Stephen; Kelly, Susan; Kershaw, Joanne K; Khan, Ziad; Kioschis, Petra; Klages, Sven; Knights, Andrew J; Kosiura, Anna; Kovar-Smith, Christie; Laird, Gavin K; Langford, Cordelia; Lawlor, Stephanie; Leversha, Margaret; Lewis, Lora; Liu, Wen; Lloyd, Christine; Lloyd, David M; Loulseged, Hermela; Loveland, Jane E; Lovell, Jamieson D; Lozado, Ryan; Lu, Jing; Lyne, Rachael; Ma, Jie; Maheshwari, Manjula; Matthews, Lucy H; McDowall, Jennifer; McLaren, Stuart; McMurray, Amanda; Meidl, Patrick; Meitinger, Thomas; Milne, Sarah; Miner, George; Mistry, Shailesh L; Morgan, Margaret; Morris, Sidney; Müller, Ines; Mullikin, James C; Nguyen, Ngoc; Nordsiek, Gabriele; Nyakatura, Gerald; O'Dell, Christopher N; Okwuonu, Geoffery; Palmer, Sophie; Pandian, Richard; Parker, David; Parrish, Julia; Pasternak, Shiran; Patel, Dina; Pearce, Alex V; Pearson, Danita M; Pelan, Sarah E; Perez, Lesette; Porter, Keith M; Ramsey, Yvonne; Reichwald, Kathrin; Rhodes, Susan; Ridler, Kerry A; Schlessinger, David; Schueler, Mary G; Sehra, Harminder K; Shaw-Smith, Charles; Shen, Hua; Sheridan, Elizabeth M; Shownkeen, Ratna; Skuce, Carl D; Smith, Michelle L; Sotheran, Elizabeth C; Steingruber, Helen E; Steward, Charles A; Storey, Roy; Swann, R Mark; Swarbreck, David; Tabor, Paul E; Taudien, Stefan; Taylor, Tineace; Teague, Brian; Thomas, Karen; Thorpe, Andrea; Timms, Kirsten; Tracey, Alan; Trevanion, Steve; Tromans, Anthony C; d'Urso, Michele; Verduzco, Daniel; Villasana, Donna; Waldron, Lenee; Wall, Melanie; Wang, Qiaoyan; Warren, James; Warry, Georgina L; Wei, Xuehong; West, Anthony; Whitehead, Siobhan L; Whiteley, Mathew N; Wilkinson, Jane E; Willey, David L; Williams, Gabrielle; Williams, Leanne; Williamson, Angela; Williamson, Helen; Wilming, Laurens; Woodmansey, Rebecca L; Wray, Paul W; Yen, Jennifer; Zhang, Jingkun; Zhou, Jianling; Zoghbi, Huda; Zorilla, Sara; Buck, David; Reinhardt, Richard; Poustka, Annemarie; Rosenthal, André; Lehrach, Hans; Meindl, Alfons; Minx, Patrick J; Hillier, Ladeana W; Willard, Huntington F; Wilson, Richard K; Waterston, Robert H; Rice, Catherine M; Vaudin, Mark; Coulson, Alan; Nelson, David L; Weinstock, George; Sulston, John E; Durbin, Richard; Hubbard, Tim; Gibbs, Richard A; Beck, Stephan; Rogers, Jane; Bentley, David R

    2005-03-17

    The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

  2. Recovery of valuable chlorosilane intermediates by a novel waste conversion process. Technical report for phase IIIA (final) and phase IIIB (progress)

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, K.E.

    1998-10-01

    From July 1994 through May 1998, direct process residue (DPR) hydrogenolysis has been studied in the laboratory, at a small Pilot Plant, and finally at a larger Pilot Plant within Dow Corning`s Carrollton, Kentucky plant. The system reacts filtered DPR with monomer at high temperature and pressure. The process demonstrates DPR conversion up to 86%. The reaction product contains high concentrations of valuable monomers such as dimethyldichlorosilane and methyldichlorosilane. A larger DPR hydrogenolysis reactor based on these results is being designed for operation in Europe at Dow Corning`s Barry, Wales site.

  3. 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.

  4. Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes.

    Science.gov (United States)

    Schvarzstein, Mara; Wignall, Sarah M; Villeneuve, Anne M

    2010-02-01

    Organisms that reproduce sexually must reduce their chromosome number by half during meiosis to generate haploid gametes. To achieve this reduction in ploidy, organisms must devise strategies to couple sister chromatids so that they stay together during the first meiotic division (when homologous chromosomes separate) and then segregate away from one another during the second division. Here we review recent findings that shed light on how Caenorhabditis elegans, an organism with holocentric chromosomes, deals with these challenges of meiosis by differentiating distinct chromosomal subdomains and remodeling chromosome structure during prophase. Furthermore, we discuss how features of chromosome organization established during prophase affect later chromosome behavior during the meiotic divisions. Finally, we illustrate how analysis of holocentric meiosis can inform our thinking about mechanisms that operate on monocentric chromosomes.

  5. Chromosomal Mapping of Repetitive DNAs in the Grasshopper Abracris flavolineata Reveal Possible Ancestry of the B Chromosome and H3 Histone Spreading.

    Directory of Open Access Journals (Sweden)

    Danilo Bueno

    Full Text Available Supernumerary chromosomes (B chromosomes occur in approximately 15% of eukaryote species. Although these chromosomes have been extensively studied, knowledge concerning their specific molecular composition is lacking in most cases. The accumulation of repetitive DNAs is one remarkable characteristic of B chromosomes, and the occurrence of distinct types of multigene families, satellite DNAs and some transposable elements have been reported. Here, we describe the organization of repetitive DNAs in the A complement and B chromosome system in the grasshopper species Abracris flavolineata using classical cytogenetic techniques and FISH analysis using probes for five multigene families, telomeric repeats and repetitive C0t-1 DNA fractions. The 18S rRNA and H3 histone multigene families are highly variable and well distributed in A. flavolineata chromosomes, which contrasts with the conservation of U snRNA genes and less variable distribution of 5S rDNA sequences. The H3 histone gene was an extensively distributed with clusters occurring in all chromosomes. Repetitive DNAs were concentrated in C-positive regions, including the pericentromeric region and small chromosomal arms, with some occurrence in C-negative regions, but abundance was low in the B chromosome. Finally, the first demonstration of the U2 snRNA gene in B chromosomes in A. flavolineata may shed light on its possible origin. These results provide new information regarding chromosomal variability for repetitive DNAs in grasshoppers and the specific molecular composition of B chromosomes.

  6. Chromosomal rearrangement interferes with meiotic X chromosome inactivation

    OpenAIRE

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-01-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X–autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencin...

  7. Regulation of chromosomal replication in Caulobacter crescentus.

    Science.gov (United States)

    Collier, Justine

    2012-03-01

    The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. 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.

  9. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B;

    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...

  10. 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…

  11. Why Chromosome Palindromes?

    Directory of Open Access Journals (Sweden)

    Esther Betrán

    2012-01-01

    Full Text Available We look at sex-limited chromosome (Y or W evolution with particular emphasis on the importance of palindromes. Y chromosome palindromes consist of inverted duplicates that allow for local recombination in an otherwise nonrecombining chromosome. Since palindromes enable intrachromosomal gene conversion that can help eliminate deleterious mutations, they are often highlighted as mechanisms to protect against Y degeneration. However, the adaptive significance of recombination resides in its ability to decouple the evolutionary fates of linked mutations, leading to both a decrease in degeneration rate and an increase in adaptation rate. Our paper emphasizes the latter, that palindromes may exist to accelerate adaptation by increasing the potential targets and fixation rates of incoming beneficial mutations. This hypothesis helps reconcile two enigmatic features of the “palindromes as protectors” view: (1 genes that are not located in palindromes have been retained under purifying selection for tens of millions of years, and (2 under models that only consider deleterious mutations, gene conversion benefits duplicate gene maintenance but not initial fixation. We conclude by looking at ways to test the hypothesis that palindromes enhance the rate of adaptive evolution of Y-linked genes and whether this effect can be extended to palindromes on other chromosomes.

  12. 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…

  13. Chromosome Variations And Human Behavior

    Science.gov (United States)

    Soudek, D.

    1974-01-01

    Article focused on the science of cytogenetics, which studied the transmission of the units of heredity called chromosomes, and considered the advantage of proper diagnosis of genetic diseases, treated on the chromosomal level. (Author/RK)

  14. Pelletizing/reslurrying as a means of distributing and firing clean coal. Final quarterly technical progress report No. 7, January 1, 1992-- March 31, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Conkle, H.N.

    1992-06-09

    Work in this quarter focused on completing (1) the final batch of pilot-scale disk pellets, (2) storage, handling, and transportation evaluation, (3) pellet reslurrying and atomization studies, and (4) cost estimation for pellet and slurry production. Disk pelletization of Elkhorn coal was completed this quarter. Pellets were approximately 1/2- to 3/4-in. in diameter. Pellets, after thermal curing were strong and durable and exceeded the pellet acceptance criteria. Storage and handling tests indicate a strong, durable pellet can be prepared from all coals, and these pellets (with the appropriate binder) can withstand outdoor, exposed storage for at least 4 weeks. Pellets in unexposed storage show no deterioration in pellet properties. Real and simulated transportation tests indicate truck transportation should generate less than 5 percent fines during transport. Continuous reslurrying testing and subsequent atomization evaluation were performed this quarter in association with University of Alabama and Jim Walter Resources. Four different slurries of approximately 55-percent-solids with viscosities below 500 cP (at 100 sec{sup {minus}1}) were prepared. Both continuous pellet-to-slurry production and atomization testing was successfully demonstrated. Finally, an in depth evaluation of the cost to prepare pellets, transport, handle, store, and convert the pellet into Coal Water Fuel (CWF) slurries was completed. Cost of the pellet-CWF option are compared with the cost to directly convert clean coal filter cake into slurry and transport, handle and store it at the user site. Findings indicate that in many circumstances, the pellet-CWF option would be the preferred choice. The decision depends on the plant size and transportation distance, and to a lesser degree on the pelletization technique and the coal selected.

  15. Engineering development of coal-fired high performance power systems, Phases 2 and 3. Quarterly progress report, October 1--December 31, 1996. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The goals of this program are to develop a coal-fired high performance power generation system (HIPPS) by the year 2000 that is capable of: {gt} 47% efficiency (HHV); NO{sub x}, SO{sub x}, and particulates {gt} 10% NSPS; coal providing {ge} 65% of heat input; all sold wastes benign; and cost of electricity 90% of present plant. Work reported herein is from Task 1.3 HIPPS Commercial Plant Design, Task 2,2 HITAF Air Heater, and Task 2.4 Duct Heater Design. The impact on cycle efficiency from the integration of various technology advances is presented. The criteria associated with a commercial HIPPS plant design as well as possible environmental control options are presented. The design of the HITAF air heaters, both radiative and convective, is the most critical task in the program. In this report, a summary of the effort associated with the radiative air heater designs that have been considered is provided. The primary testing of the air heater design will be carried out in the UND/EERC pilot-scale furnace; progress to date on the design and construction of the furnace is a major part of this report. The results of laboratory and bench scale activities associated with defining slag properties are presented. Correct material selection is critical for the success of the concept; the materials, both ceramic and metallic, being considered for radiant air heater are presented. The activities associated with the duct heater are also presented.

  16. [Dicentric Y chromosome].

    Science.gov (United States)

    Abdelmoula, N Bouayed; Amouri, A

    2005-01-01

    Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

  17. 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

  18. Dynamics of X Chromosome Inactivation

    NARCIS (Netherlands)

    F. Loos (Friedemann)

    2015-01-01

    markdownabstract__Abstract__ Dosage compensation evolved to account for the difference in expression of sex chromosome-linked genes. In mammals dosage compensation is achieved by inactivation of one X chromosome during early female embryogenesis in a process called X chromosome inactivation (XCI).

  19. Chromosomal redistribution of male-biased genes in mammalian evolution with two bursts of gene gain on the X chromosome.

    Science.gov (United States)

    Zhang, Yong E; Vibranovski, Maria D; Landback, Patrick; Marais, Gabriel A B; Long, Manyuan

    2010-10-05

    Mammalian X chromosomes evolved under various mechanisms including sexual antagonism, the faster-X process, and meiotic sex chromosome inactivation (MSCI). These forces may contribute to nonrandom chromosomal distribution of sex-biased genes. In order to understand the evolution of gene content on the X chromosome and autosome under these forces, we dated human and mouse protein-coding genes and miRNA genes on the vertebrate phylogenetic tree. We found that the X chromosome recently acquired a burst of young male-biased genes, which is consistent with fixation of recessive male-beneficial alleles by sexual antagonism. For genes originating earlier, however, this pattern diminishes and finally reverses with an overrepresentation of the oldest male-biased genes on autosomes. MSCI contributes to this dynamic since it silences X-linked old genes but not X-linked young genes. This demasculinization process seems to be associated with feminization of the X chromosome with more X-linked old genes expressed in ovaries. Moreover, we detected another burst of gene originations after the split of eutherian mammals and opossum, and these genes were quickly incorporated into transcriptional networks of multiple tissues. Preexisting X-linked genes also show significantly higher protein-level evolution during this period compared to autosomal genes, suggesting positive selection accompanied the early evolution of mammalian X chromosomes. These two findings cast new light on the evolutionary history of the mammalian X chromosome in terms of gene gain, sequence, and expressional evolution.

  20. Chromosomal redistribution of male-biased genes in mammalian evolution with two bursts of gene gain on the X chromosome.

    Directory of Open Access Journals (Sweden)

    Yong E Zhang

    Full Text Available Mammalian X chromosomes evolved under various mechanisms including sexual antagonism, the faster-X process, and meiotic sex chromosome inactivation (MSCI. These forces may contribute to nonrandom chromosomal distribution of sex-biased genes. In order to understand the evolution of gene content on the X chromosome and autosome under these forces, we dated human and mouse protein-coding genes and miRNA genes on the vertebrate phylogenetic tree. We found that the X chromosome recently acquired a burst of young male-biased genes, which is consistent with fixation of recessive male-beneficial alleles by sexual antagonism. For genes originating earlier, however, this pattern diminishes and finally reverses with an overrepresentation of the oldest male-biased genes on autosomes. MSCI contributes to this dynamic since it silences X-linked old genes but not X-linked young genes. This demasculinization process seems to be associated with feminization of the X chromosome with more X-linked old genes expressed in ovaries. Moreover, we detected another burst of gene originations after the split of eutherian mammals and opossum, and these genes were quickly incorporated into transcriptional networks of multiple tissues. Preexisting X-linked genes also show significantly higher protein-level evolution during this period compared to autosomal genes, suggesting positive selection accompanied the early evolution of mammalian X chromosomes. These two findings cast new light on the evolutionary history of the mammalian X chromosome in terms of gene gain, sequence, and expressional evolution.

  1. Chromosomal breakpoints characterization of two supernumerary ring chromosomes 20.

    Science.gov (United States)

    Guediche, N; Brisset, S; Benichou, J-J; Guérin, N; Mabboux, P; Maurin, M-L; Bas, C; Laroudie, M; Picone, O; Goldszmidt, D; Prévot, S; Labrune, P; Tachdjian, G

    2010-02-01

    The occurrence of an additional ring chromosome 20 is a rare chromosome abnormality, and no common phenotype has been yet described. We report on two new patients presenting with a supernumerary ring chromosome 20 both prenatally diagnosed. The first presented with intrauterine growth retardation and some craniofacial dysmorphism, and the second case had a normal phenotype except for obesity. Conventional cytogenetic studies showed for each patient a small supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization, these SMCs corresponded to ring chromosomes 20 including a part of short and long arms of chromosome 20. Detailed molecular cytogenetic characterization showed different breakpoints (20p11.23 and 20q11.23 for Patient 1 and 20p11.21 and 20q11.21 for Patient 2) and sizes of the two ring chromosomes 20 (13.6 Mb for case 1 and 4.8 Mb for case 2). Review of the 13 case reports of an extra r(20) ascertained postnatally (8 cases) and prenatally (5 cases) showed varying degrees of phenotypic abnormalities. We document a detailed molecular cytogenetic chromosomal breakpoints characterization of two cases of supernumerary ring chromosomes 20. These results emphasize the need to characterize precisely chromosomal breakpoints of supernumerary ring chromosomes 20 in order to establish genotype-phenotype correlation. This report may be helpful for prediction of natural history and outcome, particularly in prenatal diagnosis.

  2. Familial complex chromosomal rearrangement resulting in a recombinant chromosome.

    Science.gov (United States)

    Berend, Sue Ann; Bodamer, Olaf A F; Shapira, Stuart K; Shaffer, Lisa G; Bacino, Carlos A

    2002-05-15

    Familial complex chromosomal rearrangements (CCRs) are rare and tend to involve fewer breakpoints and fewer chromosomes than CCRs that are de novo in origin. We report on a CCR identified in a child with congenital heart disease and dysmorphic features. Initially, the child's karyotype was thought to involve a straightforward three-way translocation between chromosomes 3, 8, and 16. However, after analyzing the mother's chromosomes, the mother was found to have a more complex rearrangement that resulted in a recombinant chromosome in the child. The mother's karyotype included an inverted chromosome 2 and multiple translocations involving chromosomes 3, 5, 8, and 16. No evidence of deletion or duplication that could account for the clinical findings in the child was identified.

  3. Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways

    OpenAIRE

    Ichijima, Yosuke; Sin, Ho-Su; Satoshi H Namekawa

    2012-01-01

    Sex chromosome inactivation in male germ cells is a paradigm of epigenetic programming during sexual reproduction. Recent progress has revealed the underlying mechanisms of sex chromosome inactivation in male meiosis. The trigger of chromosome-wide silencing is activation of the DNA damage response (DDR) pathway, which is centered on the mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX). This DDR pathway shares features with the somatic DDR p...

  4. An SMC ATPase mutant disrupts chromosome segregation in Caulobacter.

    Science.gov (United States)

    Schwartz, Monica A; Shapiro, Lucy

    2011-12-01

    Accurate replication and segregation of the bacterial genome are essential for cell cycle progression. We have identified a single amino acid substitution in the Caulobacter structural maintenance of chromosomes (SMC) protein that disrupts chromosome segregation and cell division. The E1076Q point mutation in the SMC ATPase domain caused a dominant-negative phenotype in which DNA replication was able to proceed, but duplicated parS centromeres, normally found at opposite cell poles, remained at one pole. The cellular positions of other chromosomal loci were in the wild-type order relative to the parS centromere, but chromosomes remained unsegregated and appeared to be stacked upon one another. Purified SMC-E1076Q was deficient in ATP hydrolysis and exhibited abnormally stable binding to DNA. We propose that SMC spuriously links the duplicated chromosome immediately after passage of the replication fork. In wild-type cells, ATP hydrolysis opens the SMC dimer, freeing one chromosome to segregate to the opposite pole. The loss of ATP hydrolysis causes the SMC-E1076Q dimer to remain bound to both chromosomes, inhibiting segregation.

  5. Studies of transport pathways of Th, U, rare earths, Ra-228, and Ra-226 from soil to plants and farm animals: Final progress report, 1983-1988

    Energy Technology Data Exchange (ETDEWEB)

    Linsalata, P

    1988-07-01

    This report consists of three parts. Part 1 discusses a field study conducted in an area of enhanced, natural radioactivity to assess the soil to edible vegetable concentration ratios (CR = concentration in dry vegetable/concentration in dry soil) of Th-232, Th-230, Ra-226, Ra-228, and the light rare earth elements (REE's), La, Ce, and Nd. Twenty-eight soil, and approximately 42 vegetable samples consisting of relatively equal numbers of seven varieties, were obtained from 11 farms on the Pocos de Caldas Plateau in the state of Minas Gerais, Brazil. This region is the site of a major natural analogue study to assess the mobilization and retardation processes affecting thorium and the REE's at the Morro do Ferro ore body, and uranium series radionuclides at the Osamu Utsumi open pit uranium mine. Thorium (IV) serves as a chemical analogue for quadrivalent plutonium, the light REE's (III) as chemical analogues for trivalent americium and curium, and uranium (VI) as an analogue for transuranics with stable oxidation states above IV, e.g., Pu(VI). Part 2 includes our final measurement results for naturally occurring light rare earth elements (REE's include La, Ce, Nd, and SM), U-series and Th-series radionuclides in adult farm animal tissues, feeds and soils. Our findings on soil-to-tissue concentration ratios (CR's) and the comparative behavior of these elements in farm animals raised under natural conditions by local farmers are presented. Part 3 summarizes our findings to date on the distribution and mobilization of Th-232, light rare earth elements (LREE), U-238 and Ra-228 in the MF basin. Estimates of first order, present day, mobilization rate constants resulting from ground water solubilization and seepage/stream transport are calculated using revised inventory estimates for the occurrence of these elements in the ore body and annual flux estimates for the transport of these elements away from the ore body. 151 refs., 20 figs., 40 tabs.

  6. Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

    Directory of Open Access Journals (Sweden)

    Mohr Brigitte

    2003-01-01

    Full Text Available Abstract Background The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression. Results We developed a simplified computer readable cytogenetic notation (SCCN by which chromosome findings are normalised at a resolution of 400 bands. Lost or gained chromosomes or chromosome segments are specified in detail, and ranges of chromosome breakpoint assignments are recorded. Software modules were written to summarise the recorded chromosome changes with regard to the respective chromosome involvement. To assess the degree of karyotype alterations the ploidy levels and numbers of numerical and structural changes were recorded separately, and summarised in a complex karyotype aberration score (CKAS. The SCCN and CKAS were used to analyse the extend and the spectrum of additional chromosome aberrations in 94 patients with Philadelphia chromosome positive (Ph-positive acute lymphoblastic leukemia (ALL and secondary chromosome anomalies. Dosage changes of chromosomal material represented 92.1% of all additional events. Recurring regions of chromosome losses were identified. Structural rearrangements affecting (pericentromeric chromosome regions were recorded in 24.6% of the cases. Conclusions SCCN and CKAS provide unifying elements between karyotypes and computer processable data formats. They proved to be useful in the investigation of additional chromosome aberrations in Ph-positive ALL, and may represent a step towards full automation of the analysis of large and complex karyotype databases.

  7. Risk of Gonadoblastoma Development in Patients with Turner Syndrome with Cryptic Y Chromosome Material.

    Science.gov (United States)

    Kwon, Ahreum; Hyun, Sei Eun; Jung, Mo Kyung; Chae, Hyun Wook; Lee, Woo Jung; Kim, Tae Hyuk; Kim, Duk Hee; Kim, Ho-Seong

    2017-06-01

    Current guidelines recommend that testing for Y chromosome material should be performed only in patients with Turner syndrome harboring a marker chromosome and exhibiting virilization in order to detect individuals who are at high risk of gonadoblastoma. However, cryptic Y chromosome material is suggested to be a risk factor for gonadoblastoma in patients with Turner syndrome. Here, we aimed to estimate the frequency of cryptic Y chromosome material in patients with Turner syndrome and determine whether Y chromosome material increased the risk for development of gonadoblastoma. A total of 124 patients who were diagnosed with Turner syndrome by conventional cytogenetic techniques underwent additional molecular analysis to detect cryptic Y chromosome material. In addition, patients with Turner syndrome harboring Y chromosome cell lines had their ovaries removed prophylactically. Finally, we assessed the occurrence of gonadoblastoma in patients with Turner syndrome. Molecular analysis demonstrated that 10 patients had Y chromosome material among 118 patients without overt Y chromosome (8.5%). Six patients with overt Y chromosome and four patients with cryptic Y chromosome material underwent oophorectomy. Histopathological analysis revealed that the occurrence of gonadoblastoma in the total group was 2.4%, and gonadoblastoma occurred in one of six patients with an overt Y chromosome (16.7%) and 2 of 10 patients with cryptic Y chromosome material (20.0%). The risk of developing gonadoblastoma in patients with cryptic Y chromosome material was similar to that in patients with overt Y chromosome. Therefore, molecular screening for Y chromosome material should be recommended for all patients with Turner syndrome to detect individuals at a high risk of gonadoblastoma and to facilitate proper management of the disease.

  8. Rapid chromosome evolution in recently formed polyploids in Tragopogon (Asteraceae.

    Directory of Open Access Journals (Sweden)

    K Yoong Lim

    Full Text Available BACKGROUND: Polyploidy, frequently termed "whole genome duplication", is a major force in the evolution of many eukaryotes. Indeed, most angiosperm species have undergone at least one round of polyploidy in their evolutionary history. Despite enormous progress in our understanding of many aspects of polyploidy, we essentially have no information about the role of chromosome divergence in the establishment of young polyploid populations. Here we investigate synthetic lines and natural populations of two recently and recurrently formed allotetraploids Tragopogon mirus and T. miscellus (formed within the past 80 years to assess the role of aberrant meiosis in generating chromosomal/genomic diversity. That diversity is likely important in the formation, establishment and survival of polyploid populations and species. METHODOLOGY/PRINCIPAL FINDINGS: Applications of fluorescence in situ hybridisation (FISH to natural populations of T. mirus and T. miscellus suggest that chromosomal rearrangements and other chromosomal changes are common in both allotetraploids. We detected extensive chromosomal polymorphism between individuals and populations, including (i plants monosomic and trisomic for particular chromosomes (perhaps indicating compensatory trisomy, (ii intergenomic translocations and (iii variable sizes and expression patterns of individual ribosomal DNA (rDNA loci. We even observed karyotypic variation among sibling plants. Significantly, translocations, chromosome loss, and meiotic irregularities, including quadrivalent formation, were observed in synthetic (S(0 and S(1 generations polyploid lines. Our results not only provide a mechanism for chromosomal variation in natural populations, but also indicate that chromosomal changes occur rapidly following polyploidisation. CONCLUSIONS/SIGNIFICANCE: These data shed new light on previous analyses of genome and transcriptome structures in de novo and establishing polyploid species. Crucially our

  9. [Dicentric Y chromosomes. First part: cytogenetic and molecular aspects].

    Science.gov (United States)

    Bouayed Abdelmoula, N; Amouri, A

    2005-01-01

    Dicentric Y chromosomes have been reviewed twice in 1994 by Hsu et al. and in 1995 by Tuck-Muller et al. who showed that dic(Y) are the most common Y structural abnormalities and that their influence on gonadal and somatic development is extremely variable. The prediction of their phenotypic consequences is often difficult because of the variety of genomic sequences concerned by duplications and deletions, because of the variable degrees of mosaicism (cell line 45,X in particular) and at the end, because of identification and analysis technical difficulties of the structure of the rearranged Y chromosome. The clinical specter of this cytogenetic abnormality is rather wide going from almost-normal or infertile males, to females with or without stigmas of Turner syndrome. Middle phenotypes consist of various degrees of genital ambiguities. However, clinical expression seems to be related to the genomic capital of the Y chromosome, mainly the Y genes involved in the control of the process of the determination of gonads (Yp) and spermatogenesis (Yq) as well as control of the growth and the skeletal development (Yp). Here, we report a third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. In the light of previous reviews as well as the recent data of the genetic cartography of the Y chromosome, we try, in this first part, to determine characteristics of reported dicentric Y chromosomes as well as their chromosomal mechanics, their mitotic stability and finally their cytogenetic and molecular investigations.

  10. Geometric correction of deformed chromosomes for automatic Karyotyping.

    Science.gov (United States)

    Khan, Shadab; DSouza, Alisha; Sanches, João; Ventura, Rodrigo

    2012-01-01

    Automatic Karyotyping is the process of classifying chromosomes from an unordered karyogram into their respective classes to create an ordered karyogram. Automatic karyotyping algorithms typically perform geometrical correction of deformed chromosomes for feature extraction; these features are used by classifier algorithms for classifying the chromosomes. Karyograms of bone marrow cells are known to have poor image quality. An example of such karyograms is the Lisbon-K(1) (LK(1)) dataset that is used in our work. Thus, to correct the geometrical deformation of chromosomes from LK(1), a robust method to obtain the medial axis of the chromosome was necessary. To address this problem, we developed an algorithm that uses the seed points to make a primary prediction. Subsequently, the algorithm computes the distance of boundary from the predicted point, and the gradients at algorithm-specified points on the boundary to compute two auxiliary predictions. Primary prediction is then corrected using auxiliary predictions, and a final prediction is obtained to be included in the seed region. A medial axis is obtained this way, which is further used for geometrical correction of the chromosomes. This algorithm was found capable of correcting geometrical deformations in even highly distorted chromosomes with forked ends.

  11. Perichromosomal protein Ki67 supports mitotic chromosome architecture.

    Science.gov (United States)

    Takagi, Masatoshi; Natsume, Toyoaki; Kanemaki, Masato T; Imamoto, Naoko

    2016-10-01

    Although the condensin complexes and topoisomerase IIα (TopoIIα) are the central players in mitotic chromosome formation, they are insufficient for its completion, and additional factors involved in the process have been extensively sought. In this study, we examined the possibility that Ki67, a perichromosomal protein widely used as a cell proliferation marker, is one such factor. Using a combination of auxin-inducible degron and CRISPR-Cas9-based gene editing technologies, we generated a human HCT116 cell line in which Ki67 is rapidly depleted in a few hours. The removal of Ki67 before mitotic entry did not impact the early mitotic chromosome assembly observed in prophase but subsequently resulted in the formation of misshapen mitotic chromosomes. When Ki67 was removed after mitotic entry, preassembled rod-shaped mitotic chromosomes became disorganized. In addition, we show that Ki67 and TopoIIα are reciprocally coimmunoprecipitated from mitotic cell extracts. These observations indicate that Ki67 aids the finalization of mitotic chromosome formation and helps maintain rod-shaped chromosome architecture, likely in collaboration with TopoIIα. Together, these findings represent a new model in which mitotic chromosome architecture is supported both internally and externally. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  12. Stable morphology, but dynamic internal reorganisation, of interphase human chromosomes in living cells.

    Directory of Open Access Journals (Sweden)

    Iris Müller

    Full Text Available Despite the distinctive structure of mitotic chromosomes, it has not been possible to visualise individual chromosomes in living interphase cells, where chromosomes spend over 90% of their time. Studies of interphase chromosome structure and dynamics use fluorescence in-situ hybridisation (FISH on fixed cells, which potentially damages structure and loses dynamic information. We have developed a new methodology, involving photoactivation of labelled histone H3 at mitosis, to visualise individual and specific human chromosomes in living interphase cells. Our data revealed bulk chromosome volume and morphology are established rapidly after mitosis, changing only incrementally after the first hour of G1. This contrasted with the behaviour of specific loci on labelled chromosomes, which showed more progressive reorganisation, and revealed that "looping out" of chromatin from chromosome territories is a dynamic state. We measured considerable heterogeneity in chromosome decondensation, even between sister chromatids, which may reflect local structural impediments to decondensation and could potentially amplify transcriptional noise. Chromosome structure showed tremendous resistance to inhibitors of transcription, histone deacetylation and chromatin remodelling. Together, these data indicate steric constraints determine structure, rather than innate chromosome architecture or function-driven anchoring, with interphase chromatin organisation governed primarily by opposition between needs for decondensation and the space available for this to happen.

  13. Chromosomal instability in near-diploid colorectal cancer: a link between numbers and structure.

    Directory of Open Access Journals (Sweden)

    Martine Muleris

    Full Text Available Chromosomal instability (CIN plays a crucial role in tumor development and occurs mainly as the consequence of either missegregation of normal chromosomes (MSG or structural rearrangement (SR. However, little is known about the respective chromosomal targets of MSG and SR and the way these processes combined within tumors to generate CIN. To address these questions, we karyotyped a consecutive series of 96 near-diploid colorectal cancers (CRCs and distinguished chromosomal changes generated by either MSG or SR in tumor cells. Eighty-three tumors (86% presented with chromosomal abnormalities that contained both MSGs and SRs to varying degrees whereas all 13 others (14% showed normal karyotype. Using a maximum likelihood statistical method, chromosomes affected by MSG or SR and likely to represent changes that are selected for during tumor progression were found to be different and mostly mutually exclusive. MSGs and SRs were not randomly associated within tumors, delineating two major pathways of chromosome alterations that consisted of either chromosome gains by MSG or chromosomal losses by both MSG and SR. CRCs showing microsatellite instability (MSI presented with either normal karyotype or chromosome gains whereas MSS (microsatellite stable CRCs exhibited a combination of the two pathways. Taken together, these data provide new insights into the respective involvement of MSG and SR in near-diploid colorectal cancers, showing how these processes target distinct portions of the genome and result in specific patterns of chromosomal changes according to MSI status.

  14. Chromosome assortment in Saccharum.

    Science.gov (United States)

    Al-Janabi, S M; Honeycutt, R J; Sobral, B W

    1994-12-01

    Recent work has revealed random chromosome pairing and assortment in Saccharum spontaneum L., the most widely distributed, and morphologically and cytologically variable of the species of Saccharum. This conclusion was based on the analysis of a segregating population from across between S. spontaneum 'SES 208' and a spontaneously-doubled haploid of itself, derived from anther culture. To determine whether polysomic inheritance is common in Saccharum and whether it is observed in a typical biparental cross, we studied chromosome pairing and assortment in 44 progeny of a cross between euploid, meiotically regular, 2n=80 forms of Saccharum officinarum 'LA Purple' and Saccharum robustum ' Mol 5829'. Papuan 2n=80 forms of S. robustum have been suggested as the immediate progenitor species for cultivated sugarcane (S. officinarum). A total of 738 loci in LA Purple and 720 loci in Mol 5829 were amplified and typed in the progeny by arbitrarily primed PCR using 45 primers. Fifty and 33 single-dose polymorphisms were identified in the S. officinarum and S. robustum genomes, respectively (χ 2 at 98%). Linkage analysis of single-dose polymorphisms in both genomes revealed linkages in repulsion and coupling phases. In the S. officinarum genome, a map hypothesis gave 7 linkage groups with 17 linked and 33 unlinked markers. Four of 13 pairwise linkages were in repulsion phase and 9 were in coupling phase. In the S. robustum genome, a map hypothesis gave 5 linkage groups, defined by 12 markers, with 21 markers unlinked, and 2 of 9 pairwise linkages were in repulsion phase. Therefore, complete polysomic inheritance was not observed in either species, suggesting that chromosomal behavior is different from that observed by linkage analysis of over 500 markers in the S. spontaneum map. Implications of this finding for evolution and breeding are discussed.

  15. Cytogenetics and chromosomes of tapeworms (Platyhelminthes, Cestoda).

    Science.gov (United States)

    Spakulová, Marta; Orosová, Martina; Mackiewicz, John S

    2011-01-01

    Tapeworms (Cestoda, Platyhelminthes) are a highly diversified group of parasites that can have significant veterinary importance as well as medical impact as disease agents of human alveococcosis, hydatidosis, taeniosis/cysticercosis/neurocysticercosis, hymenolepidosis or diphyllobothriasis. Because of their great diversity, there has been keen interest in their phylogenetic relationships to other obligate parasitic platyhelminthes, as well as within the group itself. Recent phylogenetic analyses of cestodes, however, have focused on morphological, molecular, life cycle, embryology and host-specificity features and conspicuously omitted inclusion of karyological data. Here we review the literature from 1907 to 2010 and the current status of knowledge of the chromosomes and cytogenetics within all of the cestode orders and place it within an evolutionary perspective. Karyological data are discussed and tabulated for 115 species from nine eucestode orders with ideograms of 46 species, and a comparison of cytogenetic patterns between acetabulate and bothriate cestode lineages is made. Attention is drawn to gaps in our knowledge for seven remaining orders and cestodarian groups Gyrocotylidea and Amphilinidea. Among the cytogenetic aspects covered are: chromosome number, triploidy, classical karyotype cytogenetics (banding patterns, karyotype asymmetry, secondary constrictions), as well as advanced karyotype techniques allowing location of genes on chromosomes by fluorescence in situ hybridization. We demonstrate that further progress in cestode karyosystematics rests with new molecular approaches and the application of advanced cytogenetic markers facilitating intimate karyotype analysis.

  16. Mapping genes on human chromosome 20

    Energy Technology Data Exchange (ETDEWEB)

    Keith, T.; Phipps, P.; Serino, K. [Collaborative Research, Inc., Waltham, MA (United States)] [and others

    1994-09-01

    While a substantial number of genes have been physically localized to human chromosome 20, few have been genetically mapped. In the process of developing a genetic linkage map of chromosome 20, we have mapped microsatellite polymorphisms associated with six genes. Three of these had highly informative polymorphisms (greater than 0.70) that were originally identified by other investigators. These include avian sarcoma oncogene homolog (SRC), ribophorin II (RPN2), and phosphoenolpyruvate carboxykinase (PCK1). Polymorphisms associated with two genes were determined following a screen of their DNA sequences in GenBank. These include dinucleotide polymorphisms in introl II of cystatin c (CST3) and in the promoter region of neuroendocrine convertase 2 (NEC2) with heterozygosities of 0.52 and 0.54, respectively. A sixth gene, prodynorphin (PDYN) was mapped following the identification of a dinucleotide repeat polymorphism (heterozygosity of 0.35) in a cosmid subclone from a YAC homologous to the original phage clone. CA-positive cosmid subclones from a YAC for an additional gene, guanine nucleotide binding protein, alpha (GNAS10), have been identified and sequencing is in progress. Similar efforts were utilized to identify a microsatellite polymorphism from a half-YAC cloned by W. Brown and localized by FISH to 20pter. This polymorphism is highly informative, with a heterozygosity of 0.83, and serves to delimit the genetic map of the short arm of this chromosome.

  17. Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63 is amplified in early carcinogenesis but down-regulated as disease progressed

    Institute of Scientific and Technical Information of China (English)

    Chueh-Chuan Yen; Liang-Shun Wang; Min-Hsiung Huang; Biing-Shiung Huang; Cheng-Po Hu; Po-Min Chen; Chi-Hung Lin; Yann-Jang Chen; Chin-Chen Pan; Kai-Hsi Lu; Paul Chih-Hsueh Chen; Jiun-Yi Hsia; Jung-Ta Chen; Yu-Chung Wu; Wen-Hu Hsu

    2005-01-01

    AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear.METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status.RESULTS: The average copy numbers (±SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3:4.19 (±0.69); CCNL1:5.24 (±0.67); SvC4L1: 2.01 (±0.16); EVI1: 2.02 (±0.12);hTERC: 5.28 (±0.54); SKIL: 2.71 (±0.14); EIF5A2: 1.95(±0.12); ECT2:9.18 (±1.68); PIK3CA: 8.13 (±1.17);EIF4G1:1.07 (±0.05); SST: 3.07 (±0.25); TP63: 2.51(±0.22); TFRC: 2.42 (±0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC andSKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and SST, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis.CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes(SSR3, SMC4L1, ECT2, and SST) were

  18. Breakage-fusion-bridge cycles and large insertions contribute to the rapid evolution of accessory chromosomes in a fungal pathogen.

    Directory of Open Access Journals (Sweden)

    Daniel Croll

    2013-06-01

    Full Text Available Chromosomal rearrangements are a major driver of eukaryotic genome evolution, affecting speciation, pathogenicity and cancer progression. Changes in chromosome structure are often initiated by mis-repair of double-strand breaks in the DNA. Mis-repair is particularly likely when telomeres are lost or when dispersed repeats misalign during crossing-over. Fungi carry highly polymorphic chromosomal complements showing substantial variation in chromosome length and number. The mechanisms driving chromosome polymorphism in fungi are poorly understood. We aimed to identify mechanisms of chromosomal rearrangements in the fungal wheat pathogen Zymoseptoria tritici. We combined population genomic resequencing and chromosomal segment PCR assays with electrophoretic karyotyping and resequencing of parents and offspring from experimental crosses to show that this pathogen harbors a highly diverse complement of accessory chromosomes that exhibits strong global geographic differentiation in numbers and lengths of chromosomes. Homologous chromosomes carried highly differentiated gene contents due to numerous insertions and deletions. The largest accessory chromosome recently doubled in length through insertions totaling 380 kb. Based on comparative genomics, we identified the precise breakpoint locations of these insertions. Nondisjunction during meiosis led to chromosome losses in progeny of three different crosses. We showed that a new accessory chromosome emerged in two viable offspring through a fusion between sister chromatids. Such chromosome fusion is likely to initiate a breakage-fusion-bridge (BFB cycle that can rapidly degenerate chromosomal structure. We suggest that the accessory chromosomes of Z. tritici originated mainly from ancient core chromosomes through a degeneration process that included BFB cycles, nondisjunction and mutational decay of duplicated sequences. The rapidly evolving accessory chromosome complement may serve as a cradle for

  19. Breakage-fusion-bridge cycles and large insertions contribute to the rapid evolution of accessory chromosomes in a fungal pathogen.

    Science.gov (United States)

    Croll, Daniel; Zala, Marcello; McDonald, Bruce A

    2013-06-01

    Chromosomal rearrangements are a major driver of eukaryotic genome evolution, affecting speciation, pathogenicity and cancer progression. Changes in chromosome structure are often initiated by mis-repair of double-strand breaks in the DNA. Mis-repair is particularly likely when telomeres are lost or when dispersed repeats misalign during crossing-over. Fungi carry highly polymorphic chromosomal complements showing substantial variation in chromosome length and number. The mechanisms driving chromosome polymorphism in fungi are poorly understood. We aimed to identify mechanisms of chromosomal rearrangements in the fungal wheat pathogen Zymoseptoria tritici. We combined population genomic resequencing and chromosomal segment PCR assays with electrophoretic karyotyping and resequencing of parents and offspring from experimental crosses to show that this pathogen harbors a highly diverse complement of accessory chromosomes that exhibits strong global geographic differentiation in numbers and lengths of chromosomes. Homologous chromosomes carried highly differentiated gene contents due to numerous insertions and deletions. The largest accessory chromosome recently doubled in length through insertions totaling 380 kb. Based on comparative genomics, we identified the precise breakpoint locations of these insertions. Nondisjunction during meiosis led to chromosome losses in progeny of three different crosses. We showed that a new accessory chromosome emerged in two viable offspring through a fusion between sister chromatids. Such chromosome fusion is likely to initiate a breakage-fusion-bridge (BFB) cycle that can rapidly degenerate chromosomal structure. We suggest that the accessory chromosomes of Z. tritici originated mainly from ancient core chromosomes through a degeneration process that included BFB cycles, nondisjunction and mutational decay of duplicated sequences. The rapidly evolving accessory chromosome complement may serve as a cradle for adaptive evolution in

  20. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO) terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different "Molecular Function" GO categories were found for chromosome 1......We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...

  1. Chromosomal instability in the lymphocytes of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Harsimran Kaur

    2009-01-01

    Full Text Available Genomic instability in the tumor tissue has been correlated with tumor progression. In the present study, chromosomal aberrations (CAs in peripheral blood lymphocytes (PBLs of breast tumor patients were studied to assess whether chromosomal instability (CIN in PBLs correlates with aggressiveness of breast tumor (i.e., disease stage and has any prognostic utility. Cultured blood lymphocyte metaphases were scored for aberrations in 31 breast cancer patients and 20 healthy age and sex-matched controls. A variety of CAs, including aneuploidy, polyploidy, terminal deletions, acentric fragments, double minutes, chromatid separations, ring chromosome, marker chromosome, chromatid gaps, and breaks were seen in PBLs of the patients. The CAs in patients were higher than in controls. A comparison of the frequency of metaphases with aberrations by grouping the patients according to the stage of advancement of disease did not reveal any consistent pattern of variation in lymphocytic CIN. Neither was any specific chromosomal abnormality found to be associated with the stage of cancer. This might be indicative of the fact that cancer patients have constitutional CIN, which predisposes them to the disease, and this inherent difference in the level of genomic instability might play a role in disease progression and response to treatment.

  2. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

    Directory of Open Access Journals (Sweden)

    Sarah Derks

    2006-01-01

    Full Text Available Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps, 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively. P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10. Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development.

  3. ESG-CET Final Progress Title

    Energy Technology Data Exchange (ETDEWEB)

    Don Middleton

    2011-10-06

    Drawing to a close after five years of funding from DOE's ASCR and BER program offices, the SciDAC-2 project called the Earth System Grid (ESG) Center for Enabling Technologies has successfully established a new capability for serving data from distributed centers. The system enables users to access, analyze, and visualize data using a globally federated collection of networks, computers and software. The ESG software - now known as the Earth System Grid Federation (ESGF) - has attracted a broad developer base and has been widely adopted so that it is now being utilized in serving the most comprehensive multi-model climate data sets in the world. The system is used to support international climate model intercomparison activities as well as high profile U.S. DOE, NOAA, NASA, and NSF projects. It currently provides more than 25,000 users access to more than half a petabyte of climate data (from models and from observations) and has enabled over a 1,000 scientific publications.

  4. Biorefinery Demonstration Project Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, David [University of Georgia Research Foundation, Inc., Athens, GA (United States)

    2015-10-20

    In this project we focused on various aspects of biorefinery technology development including algal-biorefinery technology, thermochemical conversion of biomass to bio-oils and biochar; we tested characteristics and applications of biochars and evaluated nutrient cycling with wastewater treatment by the coupling of algal culture systems and anaerobic digestion. Key results include a method for reducing water content of bio-oil through atomized alcohol addition. The effect included increasing the pH and reducing the viscosity and cloud point of the bio-oil. Low input biochar production systems were evaluated via literature reviews and direct experimental work. Additionally, emissions were evaluated and three biochar systems were compared via a life cycle analysis. Attached growth systems for both algal cultivation and algal harvesting were found to be superior to suspended growth cultures. Nutrient requirements for algal cultivation could be obtained by the recycling of anaerobic digester effluents, thus experimentally showing that these two systems could be directly coupled. Twenty-two journal articles and six intellectual property applications resulted from the cumulative work that this project contributed to programmatically.

  5. Water & Aqueous Solutions. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-08-09

    The Gordon Research Conference (GRC) on Water & Aqueous Solutions was held at Holderness School, New Hampshire, 8/4/02 thru 8/9/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  6. Chemical Reactions at Surfaces. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2003-02-21

    The Gordon Research Conference (GRC) on Chemical Reactions at Surfaces was held at Holiday Inn, Ventura, California, 2/16-21/03. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  7. Studies in genetic discrimination. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  8. Innovative conservation housing. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Nuttle, D.A.

    1983-01-01

    A new passive solar thermal storage brick was developed and tested. A new insulating curtain concept was developed to assist in passive solar heating and cooling. A steel truss was designed to replace the wood truss in solar attic applications where the wood truss typically suffers some 50% loss of structural strength. Improvements were made of the dry composting toilet and grey water recycling for homes. An algae cultivation system was created for production of food, feed, fertilizer, or biomass as needed for home, farm, or industry. New concepts were explored in the areas of economy shelter, solar hot water heating, home generation of electricity, edible landscapes and other home food production, growing of fiber crops for cottage industry, storage, insulation, solar cooking, and solar refrigeration. (LEW)

  9. Electron Donor Acceptor Interactions. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-08-16

    The Gordon Research Conference (GRC) on Electron Donor Acceptor Interactions was held at Salve Regina University, Newport, Rhode Island, 8/11-16/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  10. DNA-damage response during mitosis induces whole-chromosome missegregation.

    Science.gov (United States)

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

    2014-11-01

    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, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

  11. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    Science.gov (United States)

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-10-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  12. Affected chromosome homeostasis and genomic instability of clonal yeast cultures.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Panek, Anita; Golec, Ewelina; Lewinska, Anna; Wnuk, Maciej

    2016-05-01

    Yeast cells originating from one single colony are considered genotypically and phenotypically identical. However, taking into account the cellular heterogeneity, it seems also important to monitor cell-to-cell variations within a clone population. In the present study, a comprehensive yeast karyotype screening was conducted using single chromosome comet assay. Chromosome-dependent and mutation-dependent changes in DNA (DNA with breaks or with abnormal replication intermediates) were studied using both single-gene deletion haploid mutants (bub1, bub2, mad1, tel1, rad1 and tor1) and diploid cells lacking one active gene of interest, namely BUB1/bub1, BUB2/bub2, MAD1/mad1, TEL1/tel1, RAD1/rad1 and TOR1/tor1 involved in the control of cell cycle progression, DNA repair and the regulation of longevity. Increased chromosome fragility and replication stress-mediated chromosome abnormalities were correlated with elevated incidence of genomic instability, namely aneuploid events-disomies, monosomies and to a lesser extent trisomies as judged by in situ comparative genomic hybridization (CGH). The tor1 longevity mutant with relatively balanced chromosome homeostasis was found the most genomically stable among analyzed mutants. During clonal yeast culture, spontaneously formed abnormal chromosome structures may stimulate changes in the ploidy state and, in turn, promote genomic heterogeneity. These alterations may be more accented in selected mutated genetic backgrounds, namely in yeast cells deficient in proper cell cycle regulation and DNA repair.

  13. 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…

  14. Double-strand break repair on sex chromosomes: challenges during male meiotic prophase.

    Science.gov (United States)

    Lu, Lin-Yu; Yu, Xiaochun

    2015-01-01

    During meiotic prophase, DNA double-strand break (DSB) repair-mediated homologous recombination (HR) occurs for exchange of genetic information between homologous chromosomes. Unlike autosomes or female sex chromosomes, human male sex chromosomes X and Y share little homology. Although DSBs are generated throughout male sex chromosomes, homologous recombination does not occur for most regions and DSB repair process is significantly prolonged. As a result, male sex chromosomes are coated with many DNA damage response proteins and form a unique chromatin structure known as the XY body. Interestingly, associated with the prolonged DSB repair, transcription is repressed in the XY body but not in autosomes, a phenomenon known as meiotic sex chromosome inactivation (MSCI), which is critical for male meiosis. Here using mice as model organisms, we briefly summarize recent progress on DSB repair in meiotic prophase and focus on the mechanism and function of DNA damage response in the XY body.

  15. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Wu, C.B.; Jones, S.M.; Lesicki, A.; Reinglass, T. [Univ. of Michigan, Ann Arbor, MI (United States); Sharp, G.B.; Lange, B.M. [Arkansas Children`s Hospital, Little Rock, AR (United States); Varvil, T.; Otterud, B.; Leppert, M. [Univ. of Utah, Salt Lake City, UT (United States)

    1995-01-01

    Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; {theta} = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparing clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder. 34 refs., 1 fig., 1 tab.

  16. Studies of Tumor Suppressor Genes via Chromosome Engineering

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kugoh

    2015-12-01

    Full Text Available The development and progression of malignant tumors likely result from consecutive accumulation of genetic alterations, including dysfunctional tumor suppressor genes. However, the signaling mechanisms that underlie the development of tumors have not yet been completely elucidated. Discovery of novel tumor-related genes plays a crucial role in our understanding of the development and progression of malignant tumors. Chromosome engineering technology based on microcell-mediated chromosome transfer (MMCT is an effective approach for identification of tumor suppressor genes. The studies have revealed at least five tumor suppression effects. The discovery of novel tumor suppressor genes provide greater understanding of the complex signaling pathways that underlie the development and progression of malignant tumors. These advances are being exploited to develop targeted drugs and new biological therapies for cancer.

  17. Studies of Tumor Suppressor Genes via Chromosome Engineering.

    Science.gov (United States)

    Kugoh, Hiroyuki; Ohira, Takahito; Oshimura, Mitsuo

    2015-12-30

    The development and progression of malignant tumors likely result from consecutive accumulation of genetic alterations, including dysfunctional tumor suppressor genes. However, the signaling mechanisms that underlie the development of tumors have not yet been completely elucidated. Discovery of novel tumor-related genes plays a crucial role in our understanding of the development and progression of malignant tumors. Chromosome engineering technology based on microcell-mediated chromosome transfer (MMCT) is an effective approach for identification of tumor suppressor genes. The studies have revealed at least five tumor suppression effects. The discovery of novel tumor suppressor genes provide greater understanding of the complex signaling pathways that underlie the development and progression of malignant tumors. These advances are being exploited to develop targeted drugs and new biological therapies for cancer.

  18. Mechanisms of telomere loss and their consequences for chromosome instability

    Directory of Open Access Journals (Sweden)

    Keiko eMuraki

    2012-10-01

    Full Text Available The ends of chromosomes in mammals, called telomeres, are composed of a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

  19. 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.

  20. Direct ChromOSOme Analysis and FISH Detection of Primary Gastric cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate chromosome aberrations and their role in the genesis and development of primary gastric cancer. Methods: An improved, direct chromosome preparation from solid tumors was adopted for G-banding analysis followed by FISH on decolored G-banding chromosomes so that chromosome aberrations could be confirmed at DNA level. Results: A total of 28 primary gastric cancer specimens were studies. Case 1 and case 2 had simple chromosome numerical changes: 49, XY, +2, +8, +9 and 48, +8, +20, respectively. All but case 1 and 2 had complicated chromosome abnormalities. Chromosome structural of frequent occurrence involved del(7q)(21/26), del(3p)(14/26), del(lp)(l1/26) and del(17p)(10/26). The chromosome abnormalities could be simple and complicated. In former, numerical changes involving 1 to 3 chromosome could be observed. Trisomies 8 and 9 might represent a cytogenetic subgroup of primary gastric cancer. In the later, the del(7q) was the most consistent aberration. 7q32-qter was the commonly lost segment. Conclusion: Numerical and structural alterations of chromosomes are present in primary gastric cancer. Del(7q) is one of the structural change characteristic of primary gastric cancer. In the 7q32-qter fragment, a tumor suppressor gene probably exists and it may have close relation to the genesis and progression of gastric cancer.

  1. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others

    1995-06-01

    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  2. Genetics Home Reference: Y chromosome infertility

    Science.gov (United States)

    ... Home Health Conditions Y chromosome infertility Y chromosome infertility Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Y chromosome infertility is a condition that affects the production of ...

  3. 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.

  4. Farnesyltransferase inhibitor treatment restores chromosome territory positions and active chromosome dynamics in Hutchinson-Gilford progeria syndrome cells

    Science.gov (United States)

    2011-01-01

    Background Hutchinson-Gilford progeria syndrome (HGPS) is a premature ageing syndrome that affects children leading to premature death, usually from heart infarction or strokes, making this syndrome similar to normative ageing. HGPS is commonly caused by a mutation in the A-type lamin gene, LMNA (G608G). This leads to the expression of an aberrant truncated lamin A protein, progerin. Progerin cannot be processed as wild-type pre-lamin A and remains farnesylated, leading to its aberrant behavior during interphase and mitosis. Farnesyltransferase inhibitors prevent the accumulation of farnesylated progerin, producing a less toxic protein. Results We have found that in proliferating fibroblasts derived from HGPS patients the nuclear location of interphase chromosomes differs from control proliferating cells and mimics that of control quiescent fibroblasts, with smaller chromosomes toward the nuclear interior and larger chromosomes toward the nuclear periphery. For this study we have treated HGPS fibroblasts with farnesyltransferase inhibitors and analyzed the nuclear location of individual chromosome territories. We have found that after exposure to farnesyltransferase inhibitors mis-localized chromosome territories were restored to a nuclear position akin to chromosomes in proliferating control cells. Furthermore, not only has this treatment afforded chromosomes to be repositioned but has also restored the machinery that controls their rapid movement upon serum removal. This machinery contains nuclear myosin 1β, whose distribution is also restored after farnesyltransferase inhibitor treatment of HGPS cells. Conclusions This study not only progresses the understanding of genome behavior in HGPS cells but demonstrates that interphase chromosome movement requires processed lamin A. PMID:21838864

  5. Sex chromosome evolution: historical insights and future perspectives

    Science.gov (United States)

    Nordén, Anna K.

    2017-01-01

    Many separate-sexed organisms have sex chromosomes controlling sex determination. Sex chromosomes often have reduced recombination, specialized (frequently sex-specific) gene content, dosage compensation and heteromorphic size. Research on sex determination and sex chromosome evolution has increased over the past decade and is today a very active field. However, some areas within the field have not received as much attention as others. We therefore believe that a historic overview of key findings and empirical discoveries will put current thinking into context and help us better understand where to go next. Here, we present a timeline of important conceptual and analytical models, as well as empirical studies that have advanced the field and changed our understanding of the evolution of sex chromosomes. Finally, we highlight gaps in our knowledge so far and propose some specific areas within the field that we recommend a greater focus on in the future, including the role of ecology in sex chromosome evolution and new multilocus models of sex chromosome divergence. PMID:28469017

  6. Micromechanical study of protein-DNA interactions and chromosomes

    Science.gov (United States)

    Marko, John

    I will discuss micromechanics experiments that our group has used to analyze protein-DNA interactions and chromosome organization. In single-DNA experiments we have found that a feature of protein-DNA complexes is that their dissociation rates can depend strikingly on bulk solution concentrations of other proteins and DNA segments; I will describe experiments which demonstrate this effect, which can involve tens-fold changes in off-rates with submicromolar changes in solution concentrations. Second, I will discuss experiments aimed at analyzing large-scale human chromosome structure; we isolate metaphase chromosomes, which in their native form behave as remarkably elastic networks of chromatin. Exposure to DNA-cutting restriction enzymes completely eliminates this elasticity, indicating that there is not a mechanically contiguous protein ''scaffold'' from which the chromosome gains its stability. I will show results of siRNA experiments indicating that depletion of condensin proteins leads to destabilization of chromosome mechanics, indicating condensin's role as the major chromatin ''cross-linker'' in metaphase chromosomes. Finally I will discuss similar experiments on human G1 nuclei, where we use genetic and chemical modifications to separate the contributions of the nuclear lamina and chromatin to the mechanical stiffness of the nucleus as a whole. Supported by the NSF (DMR-1206868, MCB-1022117) and the NIH (GM105847, CA193419).

  7. Comparative Sex Chromosome Genomics in Snakes: Differentiation, Evolutionary Strata, and Lack of Global Dosage Compensation

    Science.gov (United States)

    Zektser, Yulia; Mahajan, Shivani; Bachtrog, Doris

    2013-01-01

    Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females). Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae), but completely heteromorphic sex chromosomes in both garter snakes (Colubridae) and pygmy rattlesnake (Viperidae). Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases). This demonstrates that mutation rates are male-biased in snakes (male-driven evolution), but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex chromosomes

  8. Comparative sex chromosome genomics in snakes: differentiation, evolutionary strata, and lack of global dosage compensation.

    Directory of Open Access Journals (Sweden)

    Beatriz Vicoso

    Full Text Available Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females. Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae, but completely heteromorphic sex chromosomes in both garter snakes (Colubridae and pygmy rattlesnake (Viperidae. Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases. This demonstrates that mutation rates are male-biased in snakes (male-driven evolution, but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex

  9. 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...

  10. 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...

  11. CHROMOSOMAL MAPPING IN STRAINS OF STAPHYLOCOCCUS AUREUS,

    Science.gov (United States)

    STAPHYLOCOCCUS AUREUS , CHROMOSOMES), (*CHROMOSOMES, MAPPING), NITROSO COMPOUNDS, GUANIDINES, GENETICS, MUTATIONS, DRUGS, TOLERANCES(PHYSIOLOGY), TEST METHODS, DEOXYRIBONUCLEIC ACIDS, INHIBITION, RESISTANCE(BIOLOGY).

  12. 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.;

    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...... 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, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows...... chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumors. Finally, a genome-doubling event is independently predictive of poor relapse-free survival in early-stage disease in two independent cohorts in multivariate analyses...

  13. Genes and chromosomes: control of development

    Directory of Open Access Journals (Sweden)

    Oleg Serov

    2004-09-01

    Full Text Available The past decade has witnessed immense progress in research into the molecular basis behind the developmental regulation of genes. Sets of genes functioning under hierarchical control have been identified, evolutionary conserved systems of genes effecting the cell-to-cell transmission of transmembrane signals and assigned a central role in morphogenesis have been intensively studied; the concept of genomic regulatory networks coordinating expression of many genes has been introduced, to mention some of the major breakthroughs. It should be noted that the temporal and tissue-specific parameters of gene expression are correctly regulated in development only in the context of the chromosome and that they are to a great extent dependent on the position of the gene on the chromosome or the interphase nucleus. Moreover epigenetic inheritance of the gene states through successive cell generations has been conducted exclusively at the chromosome level by virtue of cell or chromosome memory. The ontogenetic memory is an inherent property of the chromosome and cis-regulation has a crucial role in its maintenance.Durante a última década houve imenso progresso na pesquisa sobre as bases moleculares da regulação gênica durante o desenvolvimento. Foram identificados grupos de genes funcionando sob controle hierárquico, sistemas de genes conservados ao longo da evolução atuando na transmissão célula a célula de sinais transmembrana e com uma função central na morfogênese foram intensamente estudados e o conceito de redes genômicas regulatórias coordenando a expressão de diversos genes foi introduzido, para citar apenas alguns dos principais avanços. Deve-se notar que os parâmetros tempo e tecido-específicos da expressão gênica são corretamente regulados durante o desenvolvimento apenas no contexto do cromossomo e que são amplamente dependentes da posição do gene no cromossomo ou no núcleo em interfase. Além do mais, a herança epigen

  14. Origin and evolution of B chromosomes in the cichlid fish Astatotilapia latifasciata based on integrated genomic analyses.

    Science.gov (United States)

    Valente, Guilherme T; Conte, Matthew A; Fantinatti, Bruno E A; Cabral-de-Mello, Diogo C; Carvalho, Robson F; Vicari, Marcelo R; Kocher, Thomas D; Martins, Cesar

    2014-08-01

    Approximately 15% of eukaryotes contain supernumerary B chromosomes. When present, B chromosomes frequently represent as much as 5% of the genome. Despite thousands of reports describing the distribution of supernumeraries in various taxa, a comprehensive theory for the origin, maintenance, and evolution of B chromosomes has not emerged. Here, we sequence the complete genomes of individual cichlid fish (Astatotilapia latifasciata) with and without B chromosomes, as well as microdissected B chromosomes, to identify DNA sequences on the B. B sequences were further analyzed through quantitative polymerase chain reaction and in situ hybridization. We find that the B chromosome contains thousands of sequences duplicated from essentially every chromosome in the ancestral karyotype. Although most genes on the B chromosome are fragmented, a few are largely intact, and we detect evidence that at least three of them are transcriptionally active. We propose a model in which the B chromosome originated early in the evolutionary history of Lake Victoria cichlids from a small fragment of one autosome. DNA sequences originating from several autosomes, including protein-coding genes and transposable elements, subsequently inserted into this proto-B. We propose that intact B chromosome genes involved with microtubule organization, kinetochore structure, recombination and progression through the cell cycle may play a role in driving the transmission of the B chromosome. Furthermore, our work suggests that karyotyping is an essential step prior to genome sequencing to avoid problems in genome assembly and analytical biases created by the presence of high copy number sequences on the B chromosome.

  15. Mealybug Chromosome Cycle as a Paradigm of Epigenetics

    Directory of Open Access Journals (Sweden)

    Giorgio Prantera

    2012-01-01

    Full Text Available Recently, epigenetics has had an ever-growing impact on research not only for its intrinsic interest but also because it has been implied in biological phenomena, such as tumor emergence and progression. The first epigenetic phenomenon to be described in the early 1960s was chromosome imprinting in some insect species (sciaridae and coccoideae. Here, we discuss recent experimental results to dissect the phenomenon of imprinted facultative heterochromatinization in Lecanoid coccids (mealybugs. In these insect species, the entire paternally derived haploid chromosome set becomes heterochromatic during embryogenesis in males. We describe the role of known epigenetic marks, such as DNA methylation and histone modifications, in this phenomenon. We then discuss the models proposed to explain the noncanonical chromosome cycle of these species.

  16. Development of Triticum aestivum-Leymus racemosus translocation lines using gametocidal chromosomes

    Institute of Scientific and Technical Information of China (English)

    袁建华; 陈佩度; 刘大钧

    2003-01-01

    Specific chromosomes of certain Aegilops species introduced into wheat genome background may often facilitate chromosome breakage and refusion, and finally result in a variety of chromosome restructuring. Such a phenomenon is commonly called gametocidal effect of the chromosomes. The chromosome 2C of Ae. cylindrica is one of such chromosomes. In the present study, scab resistant wheat-L. racemosus addition lines involving chromosomes Lr.2 and Lr.7 were crossed to wheat-Ae. cylindrica disomic addition line Add2C. Then F1 hybrids were subsequently backcrossed with wheat cv "Chinese Spring". BC1 plants with chromosome structural aberration were identified by C-banding. In the self-pollinated progenies of these plants, three translocation lines were developed and characterized by mitotic and meiotic analysis combined with C-banding and fluorescent in situ hybridization (FISH) using biotin-labeled genomic DNA of L. racemosus as probe. Some other putative translocation lines to be further characterized were also found. The practicability and efficiency of the translocation between wheat and alien chromosomes induced by gametocidal chromosomes, as well as the potential use of the developed alien translocation lines were also discussed.

  17. 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

    2013-07-08

    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.

  18. Chromosome segregation in Vibrio cholerae.

    Science.gov (United States)

    Ramachandran, Revathy; Jha, Jyoti; Chattoraj, Dhruba K

    2014-01-01

    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae compare with those in other bacteria, and highlight some of the remaining questions regarding the process of bacterial chromosome segregation.

  19. Numerous transitions of sex chromosomes in Diptera.

    Science.gov (United States)

    Vicoso, Beatriz; Bachtrog, Doris

    2015-04-01

    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.

  20. 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.

  1. Average-12.9 chromosome imbalances coupling with 15 differential expression genes possibly involved in the carcinogenesis, progression and metastasis of supraglottic laryngeal squamous cell cancer%声门上喉癌的染色体异常和重要相关基因的研究

    Institute of Scientific and Technical Information of China (English)

    富伟能; 尚超; 黄带发; 徐振明; 孙兴和; 孙开来

    2006-01-01

    Objective With the objective of discovering novel putative chromosomal regions and special genes involved in the carcinogenesis, progression and metastasis of laryngeal squamous cell cancer (LSCC). Methods DNA copy profile of LSCC were obtained and analyzed by comparative genomic hybridization (CGH) and a computerized digital image analysis system. cDNA microarray of LSCC was performed and the profile was analyzed by Hierarchical clustering. Results CGH analysis showed average-12.9 gains and losses of chromosomes in LSCC. Relatively high frequencies of gains were found at 3q15-21 (14/18), 5p12-13 (11/18), 8q22-24 (6/18), 11q12-13 (8/18), 15q21-23 (7/18) and 18p11 (8/18), while those of losses at 1p13-21 (8/18), 3p21-23 (14/18), 5q21-22 (14/18), 9p12-pter (11/18) and 13q21-31 (8/18). Hierarchical clustering analysis showed that the differentially expressed genes were segregated into three groups. Three genes differentially expressed in processⅠ( normal tissue to cancer) and processⅡ(cancer to lymph node metastasis), and the Cy5/Cy3 ratios of twelve genes were either higher than 5.0 or lower than 0.2 in processⅠor processⅡ. The fifteen special genes were first reported possibly to be the relationships with LSCC. In particular, 4 genes of them, which were cytochrome C oxidase Ⅴa, PPBP,EPHX2 andPON1, were first reported to correlate with tumorigenesis.SH3GL2, which was one of the 15 special genes, was located at one of the special chromosome regions, 9p12-pter. Conclusion The important genes and special chromosomal aberrances might provide us a clue for further investigation of carcinogenesis, progression and metastasis in LSCC.%目的筛查声门上喉癌发生、发展及转移相关的异常染色体和重要基因. 方法应用比较基因组杂交(comparative genomic hybridization, CGH)分析喉声门上鳞状细胞癌(laryngeal squamous cell cancer, LSCC)癌组织和癌旁组织DNA拷贝数的差异.应用cDNA芯片结合聚类分析研究喉声门上

  2. Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy.

    Science.gov (United States)

    Zucca, Emanuele; Conconi, Annarita; Martinelli, Giovanni; Bouabdallah, Reda; Tucci, Alessandra; Vitolo, Umberto; Martelli, Maurizio; Pettengell, Ruth; Salles, Gilles; Sebban, Catherine; Guillermo, Armando Lopez; Pinotti, Graziella; Devizzi, Liliana; Morschhauser, Franck; Tilly, Hervé; Torri, Valter; Hohaus, Stefan; Ferreri, Andrés J M; Zachée, Pierre; Bosly, André; Haioun, Corinne; Stelitano, Caterina; Bellei, Monica; Ponzoni, Maurilio; Moreau, Anne; Jack, Andrew; Campo, Elias; Mazzucchelli, Luca; Cavalli, Franco; Johnson, Peter; Thieblemont, Catherine

    2017-06-10

    Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m(2)/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m(2) intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

  3. Lack of response to unaligned chromosomes in mammalian female gametes.

    Science.gov (United States)

    Sebestova, Jaroslava; Danylevska, Anna; Novakova, Lucia; Kubelka, Michal; Anger, Martin

    2012-08-15

    Chromosome segregation errors are highly frequent in mammalian female meiosis, and their incidence gradually increases with maternal age. The fate of aneuploid eggs is obviously dependent on the stringency of mechanisms for detecting unattached or repairing incorrectly attached kinetochores. In case of their failure, the newly formed embryo will inherit the impaired set of chromosomes, which will have severe consequences for its further development. Whether spindle assembly checkpoint (SAC) in oocytes is capable of arresting cell cycle progression in response to unaligned kinetochores was discussed for a long time. It is known that abolishing SAC increases frequency of chromosome segregation errors and causes precocious entry into anaphase; SAC, therefore, seems to be essential for normal chromosome segregation in meiosis I. However, it was also reported that for anaphase-promoting complex (APC) activation, which is a prerequisite for entering anaphase; alignment of only a critical mass of kinetochores on equatorial plane is sufficient. This indicates that the function of SAC and of cooperating chromosome attachment correction mechanisms in oocytes is different from somatic cells. To analyze this phenomenon, we used live cell confocal microscopy to monitor chromosome movements, spindle formation, APC activation and polar body extrusion (PBE) simultaneously in individual oocytes at various time points during first meiotic division. Our results, using oocytes from aged animals and interspecific crosses, demonstrate that multiple unaligned kinetochores and severe congression defects are tolerated at the metaphase to anaphase transition, although such cells retain sensitivity to nocodazole. This indicates that checkpoint mechanisms, operating in oocytes at this point, are essential for accurate timing of APC activation in meiosis I, but they are insufficient in detection or correction of unaligned chromosomes, preparing thus conditions for propagation of the aneuploidy

  4. Chromosomal mapping of microsatellite repeats in the rock bream fish Oplegnathus fasciatus, with emphasis of their distribution in the neo-Y chromosome.

    Science.gov (United States)

    Xu, Dongdong; Lou, Bao; Bertollo, Luiz Antonio Carlos; Cioffi, Marcelo de Bello

    2013-03-19

    Despite the theoretical and experimental progress, our understanding on sex chromosome differentiation is still diagrammatic. The accumulation of repetitive DNA sequences is believed to occur in early stages of such differentiation. As fish species present a wide range of sex chromosome systems they are excellent models to examine the differentiation of these chromosomes. In the present study, the chromosomal distribution of 9 mono-, di- and tri-nucleotide microsatellites were analyzed using fluorescence in situ hybrization (FISH) in rock bream fish (Oplegnathus fasciatus), which is characterized by an X1X2Y sex chromosome system. Generally, the males and females exhibited the same autosomal pattern of distribution for a specific microsatellite probe. The male specific Y chromosome displays a specific amount of distinct microsatellites repeats along both arms. However, the accumulation of these repetitive sequences was not accompanied by a huge heterochromatinization process. The present data provide new insights into the chromosomal constitution of the multiple sex chromosomes and allow further investigations on the true role of the microsatellite repeats in the differentiation process of this sex system.

  5. 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.

  6. 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.

  7. Chromosome Segregation in Vibrio cholerae

    OpenAIRE

    Ramachandran, R.; Jha, J.; Chattoraj, DK

    2014-01-01

    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae com...

  8. Origin and domestication of papaya Yh chromosome

    Science.gov (United States)

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XYh). The hermaphrodite-specific region of the Yh chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previo...

  9. 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.

  10. Organization of the R chromosome region in maize. [Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Kermicle, J.

    1992-03-01

    The maize R gene is said to show more phenotypic variation than any other locus in higher plants. The locus is organized on a modular basis. Individual units -- termed ``genic elements`` since they function as independent genes -- differ by regulating the presence, intensity and timing of anthocyanin pigmentation in different plant parts. A given allele may comprise only one genic element or, more commonly, an allele comprises a complex of elements, organized as a small gene family. Different numbers and combinations of even a few genic elements gives a large number of possible complexes. Following molecular cloning of R we concentrated effort initially on a genic element that confers strong pigmentation only to the kernel. The functional limits of this gene (R-sc:124) had been defined genetically by extensive mutagenesis with the transposable element Dissociation. Subsequently, a set of contiguous probes were prepared from a genomic clone of R-sc:124. This set of probes distinguishes among various R-genic elements, providing physical evidence on gene complexes whose overall organization had been determined genetically. Some surprises were in store, as detailed below. These same tools made it possible to analyze the effect of position of Ds insertion within R-sc:124 on spotting phenotype, germinal reversion rate and frequency of Ds excision. Furthermore, we are now able to address in much more detail some of the unique phenomena of R action, such as a difference in kernel phenotype when certain alleles are transmitted by ovules relative to sperm. The last category of objectives is discussed in the section entitled ``updated research plan.``

  11. Flow karyotyping and sorting of human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Peters, D.; Pinkel, D.; Trask, B.; van den Engh, G.; Van Dilla, M.A.

    1986-07-16

    Flow cytometry and sorting are becoming increasingly useful as tools for chromosome classfication and for the detection of numerical and structural chromosome aberrations. Chromosomes of a single type can be purified with these tools to facilitate gene mapping or production of chromosome specific recombinant DNA libraries. For analysis of chromosomes with flow cytometry, the chromosomes are extracted from mitotic cells, stained with one or more fluorescent dyes and classified one-by-one according to their dye content(s). Thus, the flow approach is fundamentally different than conventional karyotyping where chromosomes are classified within the context of a metaphase spread. Flow sorting allows purification of chromosomes that can be distinguished flow cytometrically. The authors describe the basic principles of flow cytometric chromosome classification i.e. flow karyotyping, and chromosome sorting and describe several applications. 30 refs., 8 figs.

  12. Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

    OpenAIRE

    Spiegl-Kreinecker, S.; Pirker, C; Marosi, C; Buchroithner, J; Pichler, J; Silye, R; Fischer, J.; Micksche, M.; Berger, W

    2007-01-01

    Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustin...

  13. Human chromosomes: Structure, behavior, and effects

    Energy Technology Data Exchange (ETDEWEB)

    Therman, E.; Susman, M.

    1993-12-31

    The book `Human Chromosomes: Structure, Behavior, and Effects` covers the most important topics regarding human chromosomes and current research in cytogenetics. Attention is given both to structure and function of autosomes and sex chromosomes, as well as definitions and causes of chromosomal aberrations. This often involves discussion about various aspects of the cell cycle (both mitosis and meiosis). Methods and techniques involved in researching and mapping human chromosomes are also discussed.

  14. 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.

  15. Entropy-driven spatial organization of highly confined polymers: Lessons for the bacterial chromosome

    Science.gov (United States)

    Jun, Suckjoon; Mulder, Bela

    2006-08-01

    Despite recent progress in visualization experiments, the mechanism underlying chromosome segregation in bacteria still remains elusive. Here we address a basic physical issue associated with bacterial chromosome segregation, namely the spatial organization of highly confined, self-avoiding polymers (of nontrivial topology) in a rod-shaped cell-like geometry. Through computer simulations, we present evidence that, under strong confinement conditions, topologically distinct domains of a polymer complex effectively repel each other to maximize their conformational entropy, suggesting that duplicated circular chromosomes could partition spontaneously. This mechanism not only is able to account for the spatial separation per se but also captures the major features of the spatiotemporal organization of the duplicating chromosomes observed in Escherichia coli and Caulobacter crescentus. bacterial chromosome segregation | Caulobacter crescentus | Escherichia coli | polymer physics

  16. [Chromosome territories in the interphase nucleus in normal or pathological condition].

    Science.gov (United States)

    Lavrov, A V; Vol'dgorn, Ia I; Bochkov, N P

    2011-01-01

    The non-random arrangement of chromosomes in the interphase nucleus was observed for the first time in the late XIX century. However, considerable progress in studying chromosome territories became possible only in the end of the XX century mainly due to advances in microscopy and molecular biology. At present, chromosome territories are believed to play an important role in epigenetic regulation of genome activity during various cell processes including but not limited to cell cycle, differentiation, stress response. 3D structure of genome also plays an important role in pathogenesis of various hereditary diseases and cancer. This article describes main provisions of the chromosome territory theory and current trends toward further development of human genetics based on the new knowledge about the role of chromosome territories.

  17. A Link between Meiotic Prophase Progression and CrossoverControl

    Energy Technology Data Exchange (ETDEWEB)

    Carlton, Peter M.; Farruggio, Alfonso P.; Dernburg, Abby F.

    2005-07-06

    During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealed that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.

  18. A link between meiotic prophase progression and crossover control.

    Directory of Open Access Journals (Sweden)

    Peter M Carlton

    2006-02-01

    Full Text Available During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealed that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4 and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.

  19. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice.

    Science.gov (United States)

    Cox, Kimberly H; Quinnies, Kayla M; Eschendroeder, Alex; Didrick, Paula M; Eugster, Erica A; Rissman, Emilie F

    2015-01-01

    Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.e. fragile-X, autism). To investigate the role of X-chromosome genes in social behavior, we used a mouse model that has atypical sex chromosome configurations resembling Turner (45, XO) and Klinefelter syndromes (47, XXY). We examined a number of behaviors in juvenile mice. Mice with only one copy of most X-chromosome genes, regardless of gonadal sex, were less social in dyadic interaction and social preference tasks. In the elevated plus maze, mice with one X-chromosome spent less time in the distal ends of the open arms as compared to mice with two copies of X-chromosome genes. Using qRTPCR, we noted that amygdala from female mice with one X-chromosome had higher expression levels of vasopressin (Avp) as compared to mice in the other groups. Finally, in plasma from girls with Turner syndrome we detected reduced vasopressin (AVP) concentrations as compared to control patients. These novel findings link sex chromosome genes with social behavior via concentrations of AVP in brain, adding to our understanding of sex differences in neurobehavioral disorders.

  20. Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs).

    Science.gov (United States)

    Kim, Taehyun; Bershteyn, Marina; Wynshaw-Boris, Anthony

    2014-01-01

    The fusion of the short (p) and long (q) arms of a chromosome is referred to as a "ring chromosome." Ring chromosome disorders occur in approximately 1 in 50,000-100,000 patients. Ring chromosomes can result in birth defects, mental disabilities, and growth retardation if additional genes are deleted during the formation of the ring. Due to the severity of these large-scale aberrations affecting multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have so far been proposed. Our recent study (Bershteyn et al.) using patient-derived fibroblast lines containing ring chromosomes, found that cellular reprogramming of these fibroblasts into induced pluripotent stem cells (iPSCs) resulted in the cell-autonomous correction of the ring chromosomal aberration via compensatory uniparental disomy (UPD). These observations have important implications for studying the mechanism of chromosomal number control and may lead to the development of effective therapies for other, more common, chromosomal aberrations.

  1. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Gurney, Kevin R

    2015-01-12

    This document constitutes the final report under DOE grant DE-FG-08ER64649. The organization of this document is as follows: first, I will review the original scope of the proposed research. Second, I will present the current draft of a paper nearing submission to Nature Climate Change on the initial results of this funded effort. Finally, I will present the last phase of the research under this grant which has supported a Ph.D. student. To that end, I will present the graduate student’s proposed research, a portion of which is completed and reflected in the paper nearing submission. This final work phase will be completed in the next 12 months. This final workphase will likely result in 1-2 additional publications and we consider the results (as exemplified by the current paper) high quality. The continuing results will acknowledge the funding provided by DOE grant DE-FG-08ER64649.

  2. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    DeTar, Carleton [P.I.

    2012-12-10

    This document constitutes the Final Report for award DE-FC02-06ER41446 as required by the Office of Science. It summarizes accomplishments and provides copies of scientific publications with significant contribution from this award.

  3. Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

    NARCIS (Netherlands)

    Franssen, M. T. M.; Korevaar, J. C.; Tjoa, W. M.; Leschot, N. J.; Bossuyt, P. M. M.; Knegt, A. C.; Suykerbuyk, R. F.; Hochstenbach, R.; van der Veen, F.; Goddijn, M.

    2008-01-01

    Objective To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis. Methods From the databases of three centres for clinical genetics in the Netherlands, all cases of inherited unbalanced structural chromosome abnorma

  4. Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

    NARCIS (Netherlands)

    Franssen, M. T. M.; Korevaar, J. C.; Tjoa, W. M.; Leschot, N. J.; Bossuyt, P. M. M.; Knegt, A. C.; Suykerbuyk, R. F.; Hochstenbach, R.; van der Veen, F.; Goddijn, M.

    2008-01-01

    Objective To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis. Methods From the databases of three centres for clinical genetics in the Netherlands, all cases of inherited unbalanced structural chromosome abnorma

  5. Report of the Fourth International Workshop on human X chromosome mapping 1993

    Energy Technology Data Exchange (ETDEWEB)

    Schlessinger, D.; Mandel, J.L.; Monaco, A.P.; Nelson, D.L.; Willard, H.F. [eds.

    1993-12-31

    Vigorous interactive efforts by the X chromosome community have led to accelerated mapping in the last six months. Seventy-five participants from 12 countries around the globe contributed progress reports to the Fourth International X Chromosome Workshop, at St. Louis, MO, May 9-12, 1993. It became clear that well over half the chromosome is now covered by YAC contigs that are being extended, verified, and aligned by their content of STSs and other markers placed by cytogenetic or linkage mapping techniques. The major aim of the workshop was to assemble the consensus map that appears in this report, summarizing both consensus order and YAC contig information.

  6. Sex Chromosome Evolution, Heterochiasmy, and Physiological QTL in the Salmonid Brook Charr Salvelinus fontinalis

    Science.gov (United States)

    Sutherland, Ben J.G.; Rico, Ciro; Audet, Céline; Bernatchez, Louis

    2017-01-01

    Whole-genome duplication (WGD) can have large impacts on genome evolution, and much remains unknown about these impacts. This includes the mechanisms of coping with a duplicated sex determination system and whether this has an impact on increasing the diversity of sex determination mechanisms. Other impacts include sexual conflict, where alleles having different optimums in each sex can result in sequestration of genes into nonrecombining sex chromosomes. Sex chromosome development itself may involve sex-specific recombination rate (i.e., heterochiasmy), which is also poorly understood. The family Salmonidae is a model system for these phenomena, having undergone autotetraploidization and subsequent rediploidization in most of the genome at the base of the lineage. The salmonid master sex determining gene is known, and many species have nonhomologous sex chromosomes, putatively due to transposition of this gene. In this study, we identify the sex chromosome of Brook Charr Salvelinus fontinalis and compare sex chromosome identities across the lineage (eight species and four genera). Although nonhomology is frequent, homologous sex chromosomes and other consistencies are present in distantly related species, indicating probable convergence on specific sex and neo-sex chromosomes. We also characterize strong heterochiasmy with 2.7-fold more crossovers in maternal than paternal haplotypes with paternal crossovers biased to chromosome ends. When considering only rediploidized chromosomes, the overall heterochiasmy trend remains, although with only 1.9-fold more recombination in the female than the male. Y chromosome crossovers are restricted to a single end of the chromosome, and this chromosome contains a large interspecific inversion, although its status between males and females remains unknown. Finally, we identify quantitative trait loci (QTL) for 21 unique growth, reproductive, and stress-related phenotypes to improve knowledge of the genetic architecture of these

  7. Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation

    Indian Academy of Sciences (India)

    Jennifer A. Marshall Graves

    2015-12-01

    The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna—and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved.

  8. Systems-level chromosomal parameters represent a suprachromosomal basis for the non-random chromosomal arrangement in human interphase nuclei

    Science.gov (United States)

    Fatakia, Sarosh N.; Mehta, Ishita S.; Rao, Basuthkar J.

    2016-01-01

    Forty-six chromosome territories (CTs) are positioned uniquely in human interphase nuclei, wherein each of their positions can range from the centre of the nucleus to its periphery. A non-empirical basis for their non-random arrangement remains unreported. Here, we derive a suprachromosomal basis of that overall arrangement (which we refer to as a CT constellation), and report a hierarchical nature of the same. Using matrix algebra, we unify intrinsic chromosomal parameters (e.g., chromosomal length, gene density, the number of genes per chromosome), to derive an extrinsic effective gene density matrix, the hierarchy of which is dominated largely by extrinsic mathematical coupling of HSA19, followed by HSA17 (human chromosome 19 and 17, both preferentially interior CTs) with all CTs. We corroborate predicted constellations and effective gene density hierarchy with published reports from fluorescent in situ hybridization based microscopy and Hi-C techniques, and delineate analogous hierarchy in disparate vertebrates. Our theory accurately predicts CTs localised to the nuclear interior, which interestingly share conserved synteny with HSA19 and/or HSA17. Finally, the effective gene density hierarchy dictates how permutations among CT position represents the plasticity within its constellations, based on which we suggest that a differential mix of coding with noncoding genome modulates the same. PMID:27845379

  9. Chromosome segregation in plant meiosis

    Science.gov (United States)

    Zamariola, Linda; Tiang, Choon Lin; De Storme, Nico; Pawlowski, Wojtek; Geelen, Danny

    2014-01-01

    Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved. PMID:24987397

  10. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

    Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.

  11. Dean flow fractionation of chromosomes

    Science.gov (United States)

    Hockin, Matt; Sant, Himanshu J.; Capecchi, Mario; Gale, Bruce K.

    2016-03-01

    Efforts to transfer intact mammalian chromosomes between cells have been attempted for more than 50 years with the consistent result being transfer of sub unit length pieces regardless of method. Inertial microfluidics is a new field that has shown much promise in addressing the fractionation of particles in the 2-20 μm size range (with unknown limits) and separations are based upon particles being carried by curving confined flows (within a spiral shaped, often rectangular flow chamber) and migrating to stable "equilibrium" positions of varying distance from a chamber wall depending on the balance of dean and lift forces. We fabricated spiral channels for inertial microfluidic separations using a standard soft lithography process. The concentration of chromosomes, small contaminant DNA and large cell debris in each outlets were evaluated using microscope (60X) and a flow cytometer. Using Dean Flow Fractionation, we were able to focus 4.5 times more chromosomes in outlet 2 compared to outlet 4 where most of the large debris is found. We recover 16% of the chromosomes in outlet #1- 50% in 2, 23% in 3 and 11% in 4. It should be noted that these estimates of recovery do not capture one piece of information- it actually may be that the chromosomes at each outlet are physically different and work needs to be done to verify this potential.

  12. v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage.

    Science.gov (United States)

    Ikeuchi, Masayoshi; Fukumoto, Yasunori; Honda, Takuya; Kuga, Takahisa; Saito, Youhei; Yamaguchi, Naoto; Nakayama, Yuji

    2016-06-02

    An increase in Src activity is commonly observed in epithelial cancers. Aberrant activation of the kinase activity is associated with malignant progression. However, the mechanisms that underlie the Src-induced malignant progression of cancer are not completely understood. We show here that v-Src, an oncogene that was first identified from a Rous sarcoma virus and a mutant variant of c-Src, leads to an increase in the number of anaphase and telophase cells having chromosome bridges. v-Src increases the number of γH2AX foci, and this increase is inhibited by treatment with PP2, a Src kinase inhibitor. v-Src induces the phosphorylation of KAP1 at Ser824, Chk2 at Thr68, and Chk1 at Ser345, suggesting the activation of the ATM/ATR pathway. Caffeine decreases the number of cells having chromosome bridges at a concentration incapable of inhibiting Chk1 phosphorylation at Ser345. These results suggest that v-Src induces chromosome bridges via generation of DNA damage and the subsequent DNA damage response, possibly by homologous recombination. A chromosome bridge gives rise to the accumulation of DNA damage directly through chromosome breakage and indirectly through cytokinesis failure-induced multinucleation. We propose that v-Src-induced chromosome bridge formation is one of the causes of the v-Src-induced malignant progression of cancer cells.

  13. The Reduction of Chromosome Number in Meiosis Is Determined by Properties Built into the Chromosomes

    OpenAIRE

    Paliulis, Leocadia V.; Nicklas, R. Bruce

    2000-01-01

    In meiosis I, two chromatids move to each spindle pole. Then, in meiosis II, the two are distributed, one to each future gamete. This requires that meiosis I chromosomes attach to the spindle differently than meiosis II chromosomes and that they regulate chromosome cohesion differently. We investigated whether the information that dictates the division type of the chromosome comes from the whole cell, the spindle, or the chromosome itself. Also, we determined when chromosomes can switch from ...

  14. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Science.gov (United States)

    Mengoli, Valentina; Bucciarelli, Elisabetta; Lattao, Ramona; Piergentili, Roberto; Gatti, Maurizio; Bonaccorsi, Silvia

    2014-10-01

    Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on slight differences

  15. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Directory of Open Access Journals (Sweden)

    Valentina Mengoli

    2014-10-01

    Full Text Available Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on

  16. An integrated molecular cytogenetic map of Cucumis sativus L. chromosome 2

    Directory of Open Access Journals (Sweden)

    Huang Sanwen

    2011-01-01

    Full Text Available Abstract Background Integration of molecular, genetic and cytological maps is still a challenge for most plant species. Recent progress in molecular and cytogenetic studies created a basis for developing integrated maps in cucumber (Cucumis sativus L.. Results In this study, eleven fosmid clones and three plasmids containing 45S rDNA, the centromeric satellite repeat Type III and the pericentriomeric repeat CsRP1 sequences respectively were hybridized to cucumber metaphase chromosomes to assign their cytological location on chromosome 2. Moreover, an integrated molecular cytogenetic map of cucumber chromosomes 2 was constructed by fluorescence in situ hybridization (FISH mapping of 11 fosmid clones together with the cucumber centromere-specific Type III sequence on meiotic pachytene chromosomes. The cytogenetic map was fully integrated with genetic linkage map since each fosmid clone was anchored by a genetically mapped simple sequence repeat marker (SSR. The relationship between the genetic and physical distances along chromosome was analyzed. Conclusions Recombination was not evenly distributed along the physical length of chromosome 2. Suppression of recombination was found in centromeric and pericentromeric regions. Our results also indicated that the molecular markers composing the linkage map for chromosome 2 provided excellent coverage of the chromosome.

  17. Loss of pRB causes centromere dysfunction and chromosomal instability.

    Science.gov (United States)

    Manning, Amity L; Longworth, Michelle S; Dyson, Nicholas J

    2010-07-01

    Chromosome instability (CIN) is a common feature of tumor cells. By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells. The retinoblastoma tumor suppressor is frequently inactivated in human cancers and is best known for its regulation of the G1/S-phase transition. Recent studies have shown that pRB inactivation also slows mitotic progression and promotes aneuploidy, but reasons for these phenotypes are not well understood. Here we describe the underlying mitotic defects of pRB-deficient cells that cause chromosome missegregation. Analysis of mitotic cells reveals that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to an increase in intercentromeric distance and deformation of centromeric structure. These defects promote merotelic attachment, resulting in failure of chromosome congression and an increased propensity for lagging chromosomes following mitotic delay. While complete loss of centromere function or chromosome cohesion would have catastrophic consequences, these more moderate defects allow pRB-deficient cells to proliferate but undermine the fidelity of mitosis, leading to whole-chromosome gains and losses. These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer.

  18. Quarterly Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Ayman I. Hawari

    2002-12-30

    This report presents the progress made during the first quarter of phase 2 for the project entitled ''Development and Validation of Thermal Neutron Scattering Laws from Applications and Safety Implications in Generation IV Reactor Designs.'' (B204) THIS IS NOT A FINAL REPORT

  19. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Baron, Edward [Univ. of Oklahoma

    2014-04-28

    The progress over the course of the grant period was excellent. We went from 3-D test codes to full 3-D production codes. We studied several SNe Ia. Most of the support has gone for the 3 years of support of OU graduate student Brian Friesen, who is now mature in his fourth year of research. It is unfortunate that there will be no further DOE support to see him through to the completion of his PhD.

  20. Chromosome-specific families in Vibrio genomes

    Directory of Open Access Journals (Sweden)

    Oksana eLukjancenko

    2014-03-01

    Full Text Available We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown. Of the chromosome specific core protein families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different `Molecular Function` GO categories were found for chromosome 1 specific protein families, and these include several broad activities: pyridoxine 5' phosphate synthetase, glucosylceramidase, heme transport, DNA ligase, amino acid binding, and ribosomal components; in contrast, chromosome 2 specific protein families have only 66 Molecular Function GO terms and include many membrane-associated activities, such as ion channels, transmembrane transporters, and electron transport chain proteins. Thus, it appears that whilst there are many 'housekeeping systems' encoded in chromosome 1, there are far fewer core functions found in chromosome 2. However, the presence of many membrane-associated encoded proteins in chromosome 2 is surprising.

  1. Final Report

    DEFF Research Database (Denmark)

    Heiselberg, Per; Brohus, Henrik; Nielsen, Peter V.

    This final report for the Hybrid Ventilation Centre at Aalborg University describes the activities and research achievement in the project period from August 2001 to August 2006. The report summarises the work performed and the results achieved with reference to articles and reports published...

  2. Positive and purifying selection on the Drosophila Y chromosome.

    Science.gov (United States)

    Singh, Nadia D; Koerich, Leonardo B; Carvalho, Antonio Bernardo; Clark, Andrew G

    2014-10-01

    Y chromosomes, with their reduced effective population size, lack of recombination, and male-limited transmission, present a unique collection of constraints for the operation of natural selection. Male-limited transmission may greatly increase the efficacy of selection for male-beneficial mutations, but the reduced effective size also inflates the role of random genetic drift. Together, these defining features of the Y chromosome are expected to influence rates and patterns of molecular evolution on the Y as compared with X-linked or autosomal loci. Here, we use sequence data from 11 genes in 9 Drosophila species to gain insight into the efficacy of natural selection on the Drosophila Y relative to the rest of the genome. Drosophila is an ideal system for assessing the consequences of Y-linkage for molecular evolution in part because the gene content of Drosophila Y chromosomes is highly dynamic, with orthologous genes being Y-linked in some species whereas autosomal in others. Our results confirm the expectation that the efficacy of natural selection at weakly selected sites is reduced on the Y chromosome. In contrast, purifying selection on the Y chromosome for strongly deleterious mutations does not appear to be compromised. Finally, we find evidence of recurrent positive selection for 4 of the 11 genes studied here. Our results thus highlight the variable nature of the mode and impact of natural selection on the Drosophila Y chromosome. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Chromosome synteny in cucumis species

    Science.gov (United States)

    Cucumber, Cucumis sativus L. (2n = 2x = 14) and melon, C. melo L. (2n = 2x = 24) are two important vegetable species in the genus Cucumis (family Cucurbitaceae). Two inter-fertile botanical varieties with 14 chromosomes, the cultivated C. sativus var. sativus L. and the wild C. sativus var. hardwick...

  4. Chromosome Territory Modeller and Viewer.

    Science.gov (United States)

    Tkacz, Magdalena A; Chromiński, Kornel; Idziak-Helmcke, Dominika; Robaszkiewicz, Ewa; Hasterok, Robert

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi-a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license.

  5. Chromosomal disorders and male infertility

    Institute of Scientific and Technical Information of China (English)

    Gary L Harton; Helen G Tempest

    2012-01-01

    infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family.Despite this,the molecular and genetic factors underlying the cause of infertility remain largely undiscovered.Nevertheless,more and more genetic factors associated with infertility are being identified.This review will focus on our current understanding of the chromosomal basis of male infertility specifically:chromosomal aneuploidy,structural and numerical karyotype abnormalities and Y chromosomal microdeletions.Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans.Aneuploidy is predominantly maternal in origin,but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts.Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm.Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed,as well as the application of preimplantation genetic diagnosis (PGD) in such cases.Clinical recommendations where possible will be made,as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

  6. Chromosome 5 and Parkinson disease.

    Science.gov (United States)

    Foroud, Tatiana; Pankratz, Nathan; Martinez, Maria

    2006-10-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder. Despite the identification of five causative genes, the majority of PD etiology is still unknown. A region on chromosome 5q is one of the few regions of the genome found linked in multiple studies of familial PD. Analyses were performed using genotypic data from two independent research studies to evaluate rigorously the evidence of linkage on chromosome 5. The combined sample consisting of 1238 affected individuals from 569 multiplex PD families were genotyped for a common set of 20 microsatellite markers spanning an 80 cM region on chromosome 5q. Two disease models were employed and model-free linkage analyses were performed to detect linkage to a PD susceptibility gene and also to detect linkage to a quantitative phenotype, age of onset of PD. There was little evidence of linkage using either a narrower or broader disease definition (lod <0.5). Analyses employing age of onset of PD as the phenotype produced a lod score of 1.8. These results in a very large sample of familial PD suggest that it is unlikely that a PD susceptibility gene is located on chromosome 5q. Evidence for a locus contributing to the age of onset of PD is modest at best (empirical P-value=0.07).

  7. CHROMOSOMAL MULTIPLICITY IN BURKHOLDERIA CEPACIA

    Science.gov (United States)

    We have used CHEF gel electrophoresis to screen preparations of large DNA from different Burkholderia cepacia isolates for the presence of DNA species corresponding to the linearized forms of the three chromosomes of 3.4,2.5, and 0.9 Mb identified in B. cepacia strain 17616. DNA ...

  8. Chromosomal disorders and male infertility.

    Science.gov (United States)

    Harton, Gary L; Tempest, Helen G

    2012-01-01

    Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically: chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis (PGD) in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

  9. Sex chromosome rearrangements in Polyphaga beetles.

    Science.gov (United States)

    Dutrillaux, A M; Dutrillaux, B

    2009-01-01

    The presence of a parachute sex chromosome bivalent (Xyp) at metaphase I of male meiosis is a well-known characteristic of Coleoptera, present in almost all families of this order and assumed to represent their ancestral sex chromosome formula. Sex chromosomes appear to be manifold more frequently involved in inter-chromosomal rearrangements than the average of the nine autosomal pairs usually forming their karyotype. This leads to various formulae such as neo-sex, multiple sex and perhaps unique sex chromosomes. These rearrangements alter the intimate association between sex chromosomes and nucleolar proteins, which are usual components of the Xyp. Different situations, selected in a series of 125 mitotic and meiotic cytogenetic studies of Polyphaga beetle species, are reported and discussed, with the aim to improve our knowledge on the mechanisms of sex chromosome rearrangements, the relationships with nucleoli and the consequences on dosage compensation and chromosome segregation.

  10. Association of recurrent pregnancy loss with chromosomal ...

    African Journals Online (AJOL)

    EB

    Results: Parental chromosomal abnormality was detected in 28 cases (2.8% of all cases, 5.7% of the couples) most of which ... Key words: chromosomal abnormality, recurrent pregnancy loss, thrombophilia ..... significant role in infertility.

  11. X microchromosome with additional chromosome anomalies found in Ullrich-Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wydner, K.L.; Sciorra, L.J. [Univ. of Medicine and Dentistry, New Brunswick, NJ (United States); Singer-Granick, C. [Hahnemann Univ., Philadelphia, PA (United States)] [and others

    1995-03-27

    Using standard cytogenetic methods coupled with molecular techniques, the following karyotype mos 45,X/46,XXq+/46,X-mar(X)/47,XXq+, +mar(X), was identified in a patient with Ullrich-Turner syndrome (UTS). High-resolution banding (n = 650) of the metaphase chromosomes yielded a breakpoint at q28 on the Xq+ rearranged chromosome. FISH was used to determine the presence of Y-containing DNA in the Xq+ and the mar(X) chromosomes. The following molecular probes were used: DYZ1, DYZ3, and spectrum orange WCP Y. The lack of specific hybridization of these probes was interpreted as a low risk of gonadoblastoma in this patient. Using X-chromosome- and centromere-specific probes, FISH demonstrated the presence of hybridizing material on both rearranged chromosomes, the Xq+ and mar(X). Finally, we determined that the mar(X) and Xq+ chromosomes contained telomeres in the absence of any interstitial telomeric hybridizing material. A micro-X chromosome is present in this UTS patient. Delineation of events leading toward the mechanisms responsible for the multiple DNA rearrangements required to generate the micro-X and Xq+ chromosomes awaits future studies. 25 refs., 6 figs., 1 tab.

  12. Novel Integrated Lab-on-Chip System for Chromosome Translocations Analysis

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Lange, Jacob Moresco; Shah, Pranjul Jaykumar

    2009-01-01

    This presentation will focus on the development of a chromosome total analysis system (C-TAS) starting from the design strategy and simulations to the integration into a final monolithic plug and play device. Individual modules which perform the sample preprocessing and analysis tasks like - cell...... isolation, cell culture, cell lysing, chromosome extraction and Fluorescence In-Situ Hybridization will be presented. How we solved connecting the individual chips and adjusting the microfluidic flows, by using simulations will be discussed....

  13. Chromosome protein framework from proteome analysis of isolated human metaphase chromosomes.

    Science.gov (United States)

    Fukui, Kiichi; Uchiyama, Susumu

    2007-01-01

    We have presented a structural model of the chromosome based on its constituent proteins. Development of a method of mass isolation for intact human metaphase chromosomes and proteome analysis by mass spectrometry of the isolated chromosomal proteins enabled us to develop a four-layer structural model of human metaphase chromosomes. The model consists of four layers, each with different chromosomal protein sets, i.e., chromosome coating proteins (CCPs), chromosome peripheral proteins (CPPs), chromosome structural proteins (CSPs), and chromosome fibrous proteins (CFPs). More than 200 identified proteins have been classified and assigned to the four layers with each layer occupying a distinct region of the chromosome. CCPs are localized at the most outer regions of the chromosomes and they attach to the regions tentatively and occasionally. CCPs include mostly mitochondrial and cytoplasmic proteins, e.g., 70 kDa heat shock protein 9B and Hsp60. CPPs are also localized at the peripheral regions of the chromosomes, but as the essential part of the chromosomes. CPPs include nucleolin, lamin A/C, fibrillarin, etc. CSPs are the primary chromosomal structure proteins, and include topoisomerase IIalpha, condensin subunits, histones, etc. CFPs have a fibrous nature, e.g., beta-actin, vimentin, myosin II, tublin, etc. A data set of these proteins, which we developed, contains essential chromosome proteins with classified information based on this four-layer model and presents useful leads for further studies on chromosomal structure and function.

  14. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    1987-01-01

    A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented...... and discussed, and the previously reported cases of familially transmitted G-group ring chromosomes are reviewed....

  15. Female meiotic sex chromosome inactivation in chicken

    NARCIS (Netherlands)

    S. Schoenmakers (Sam); E. Wassenaar (Evelyne); J.W. Hoogerbrugge (Jos); J.S.E. Laven (Joop); J.A. Grootegoed (Anton); W.M. Baarends (Willy)

    2009-01-01

    textabstractDuring meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI) leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (Z

  16. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Stinis, Panos [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-08-07

    This is the final report for the work conducted at the University of Minnesota (during the period 12/01/12-09/18/14) by PI Panos Stinis as part of the "Collaboratory on Mathematics for Mesoscopic Modeling of Materials" (CM4). CM4 is a multi-institution DOE-funded project whose aim is to conduct basic and applied research in the emerging field of mesoscopic modeling of materials.

  17. A Plain English Map of the Human Chromosomes.

    Science.gov (United States)

    Offner, Susan

    1992-01-01

    Presents a chromosome map for 19 known chromosomes in human genetics. Describes the characteristics attributed to the genetic codes for each of the chromosomes and discusses the teaching applications of the chromosome map. (MDH)

  18. S phase progression in human cells is dictated by the genetic continuity of DNA foci.

    Directory of Open Access Journals (Sweden)

    Apolinar Maya-Mendoza

    2010-04-01

    Full Text Available DNA synthesis must be performed with extreme precision to maintain genomic integrity. In mammalian cells, different genomic regions are replicated at defined times, perhaps to preserve epigenetic information and cell differentiation status. However, the molecular principles that define this S phase program are unknown. By analyzing replication foci within discrete chromosome territories during interphase, we show that foci which are active during consecutive intervals of S phase are maintained as spatially adjacent neighbors throughout the cell cycle. Using extended DNA fibers, we demonstrate that this spatial continuity of replication foci correlates with the genetic continuity of adjacent replicon clusters along chromosomes. Finally, we used bioinformatic tools to compare the structure of DNA foci with DNA domains that are seen to replicate during discrete time intervals of S phase using genome-wide strategies. Data presented show that a major mechanism of S phase progression involves the sequential synthesis of regions of the genome because of their genetic continuity along the chromosomal fiber.

  19. A History of the Discovery of Random X Chromosome Inactivation in the Human Female and its Significance

    Directory of Open Access Journals (Sweden)

    Sophia Balderman

    2011-07-01

    Full Text Available Genetic determinants of sex in placental mammals developed by the evolution of primordial autosomes into the male and female sex chromosomes. The Y chromosome determines maleness by the action of the gene SRY, which encodes a protein that initiates a sequence of events prompting the embryonic gonads to develop into testes. The X chromosome in the absence of a Y chromosome results in a female by permitting the conversion of the embryonic gonads into ovaries. We trace the historical progress that resulted in the discovery that one X chromosome in the female is randomly inactivated in early embryogenesis, accomplishing approximate equivalency of X chromosome gene dosage in both sexes. This event results in half of the somatic cells in a tissue containing proteins encoded by the genes of the maternal X chromosome and half having proteins encoded by the genes of the paternal X chromosome, on average, accounting for the phenotype of a female heterozygote with an X chromosome mutation. The hypothesis of X chromosome inactivation as a random event early in embryogenesis was first described as a result of studies of variegated coat color in female mice. Similar results were found in women using the X chromosome-linked gene, glucose-6-phosphate dehydrogenase, studied in red cells. The random inactivation of the X chromosome-bearing genes for isoenzyme types A and B of glucose-6-phosphate dehydrogenase was used to establish the clonal origin of neoplasms in informative women with leiomyomas. Behind these discoveries are the stories of the men and women scientists whose research enlightened these aspects of X chromosome function and their implication for medicine.

  20. Human Chromosome 21: Mapping of the chromosomes and cloning of cDNAs

    Energy Technology Data Exchange (ETDEWEB)

    Antonarakis, S.E.

    1991-09-01

    The objective of the research funded by DOE grant DE-FG02-89ER60857 from 6/15/89 to 8/31/91 was to contribute to the physical mapping of human chromosome 21 (HC21) by cloning large fragments of DNA into Yeast Artificial Chromosomes (YACs) and identify YACs that map on HC21. A total of 54 sequence tagged sites (STS) have been developed and mapped in our laboratory to HC21 and can be used as initial reference points for YAC identification and construction of overlapping clones. A small YAC library was constructed which is HC21 specific. DNA from somatic cell hybrid WAV17 or from flow-sorted HC21 was partially digested with EcoRI, ligated into vectors PJS97, PJS98, and YACs have been obtained with average size insert of more than 300 kb. This library has been deposited in D. Patterson's lab for the Joint YAC screening effort. Additional YAC libraries from ICI Pharmaceuticals or from Los Alamos National Laboratories have been screened with several STS and positive YACs have been identified. Work in progress includes screening of YAC libraries in order to construct overlapping clones, characterization of the cloning ends of YACs, characterization of additional STS and cloning of HC21 specific cDNAs. 15 refs., 2 figs., 5 tabs.

  1. 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.

  2. Neurophysiological findings in a newborn with chromosome 10 trisomy.

    Science.gov (United States)

    Vidale, Simone; Di Palma, Franco; Sironi, Luigi; Arnaboldi, Marco

    2014-01-01

    The trisomy of the short arm of chromosome 10 is a rare condition. The phenotypic expression of this genetic aberration is characterised by growth and mental retardation with several neurological signs. We report the neurophysiological findings in a newborn affected by 10p chromosome trisomy who developed seizures. Serial EEGs showed a progressive reduction in burst-suppression activity and a slow rhythmic basal activity. At 1 year of age the recording showed for the first time spikes of high amplitude (up to 800 μV) in bilateral frontal regions. These findings could be related to an asymmetrical cerebral maturation in the context of perinatal sufferance and brain malformation due to the genetic aberration.

  3. A spindle-like apparatus guides bacterial chromosome segregation.

    Science.gov (United States)

    Ptacin, Jerod L; Lee, Steven F; Garner, Ethan C; Toro, Esteban; Eckart, Michael; Comolli, Luis R; Moerner, W E; Shapiro, Lucy

    2010-08-01

    Until recently, a dedicated mitotic apparatus that segregates newly replicated chromosomes into daughter cells was believed to be unique to eukaryotic cells. Here we demonstrate that the bacterium Caulobacter crescentus segregates its chromosome using a partitioning (Par) apparatus that has surprising similarities to eukaryotic spindles. We show that the C. crescentus ATPase ParA forms linear polymers in vitro and assembles into a narrow linear structure in vivo. The centromere-binding protein ParB binds to and destabilizes ParA structures in vitro. We propose that this ParB-stimulated ParA depolymerization activity moves the centromere to the opposite cell pole through a burnt bridge Brownian ratchet mechanism. Finally, we identify the pole-specific TipN protein as a new component of the Par system that is required to maintain the directionality of DNA transfer towards the new cell pole. Our results elucidate a bacterial chromosome segregation mechanism that features basic operating principles similar to eukaryotic mitotic machines, including a multivalent protein complex at the centromere that stimulates the dynamic disassembly of polymers to move chromosomes into daughter compartments.

  4. Y-chromosome polymorphism: Possible largest Y chromosome in man?

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, D.S.K.; Al-Awadi, S.A.; Bastaki, L. [Kuwait Medical Genetics Centre, Sulaibikat (Kuwait)] [and others

    1994-09-01

    The role of variations (inversions/deletion or duplication) in the heterochromatin in gonadal development and function, reproductive fitness, and malignant disease has been extensively studied. However, the causal-relationship of large Y (Yqh+) and repeated fetal loss has not been established unequivocally. An Arab couple (?Bedouin origin) with a history of repeated abortions were investigated. Karyotype analysis of the husband showed a very large Y chromosome, confirmed by GTG-, QFQ- and CBG-banding techniques. C-banding showed discontinuous distribution of the heterochromatin blocks separated by pale bands. The origin of the large heterochromatin segment could be due to tandem duplication of the Yq region or translocation (Yq:Yq). No other relatives (males) of the propositus have been available for investigation. Polymorphism of the Y chromosome could be attributed to evolutionary changes from an ancestral type, either by deletion or duplication of the heterochromatin segment. More detailed studies on isolated, aboriginal/tribal human populations will enable us to better understand the significance of the Y chromosome polymorphism.

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

    Directory of Open Access Journals (Sweden)

    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

  6. The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary

    OpenAIRE

    Wienberg, Johannes; Jauch, Anna; Lüdecke, H J; Senger, G.; Horsthemke, B; Claussen, U.; Cremer, Thomas; Arnold, N; Lengauer, Christoph

    1994-01-01

    Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of ...

  7. Responses of chromosome segregation machinery to mechanical perturbations.

    Science.gov (United States)

    Itabashi, Takeshi; Takagi, Jun; Suzuki, Kazuya; Ishiwata, Shin'ichi

    2013-01-01

    For genome stability, the proper segregation of chromosomes is required. The exquisite process of chromosome segregation has charmed a lot of cell- and molecular biologists into watching what happens inside a mitotic cell and how each molecule contributes to this process for the accomplishment of accurate cell division1. The process to partition the duplicated genome to the daughter cells in each cell division is mediated by a self-organized structure called the mitotic spindle. It is well known that the mitotic spindle is a multi-component macromolecular machine composed of microtubules, molecular motors (kinesins, cytoplasmic dynein), and other regulatory molecules (microtubule-associated proteins, kinases, etc.). In recent years, most of the protein components of the mitotic spindle have been identified and the functions of these proteins have been characterized using molecular perturbations2,3. Thus, the mechanisms for spindle assembly and chromosome segregation are being revealed rapidly. However, the chromosome segregation machinery is poorly understood from the mechanical point of view, such as how the mitotic spindle within a cell responds to a variety of mechanical forces, originating from cell-cell interactions or environmental fluctuations. Recent advances in the controlled mechanical perturbation have indicated that the mitotic spindle possesses a structural pliability, size adaptability to the applied external forces, and a strong self-organizing ability. Mechanical perturbations revealed also the mechanochemical regulation of chromosome segregation machinery, which responds to the applied forces. Here, we discuss the current progress in the biophysical research on the architectural and functional dynamics of the mitotic spindle.

  8. Single chromosomal abnormalities in Philadelphia-negative chronic myeloproliferative disorders.

    Science.gov (United States)

    Panani, Anna D

    2007-01-01

    In Philadelphia-negative chronic myeloproliferative disorders (CMPD), increased proliferation with effective maturation of the myeloid lineage is present, while peripheral leukocytosis, thrombocytosis or elevated red blood cell mass are found. This group of disorders includes polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Furthermore, cases that cannot be clearly defined are regarded as unclassified CMPD. In Philadelphia-negative CMPD, recurrent cytogenetic abnormalities occur, but no specific abnormality has been defined to date. Chromosomal abnormalities detected in a neoplastic disease as a sole anomaly are of major importance, possibly constituting primary changes implicated in the initiation or progression of the neoplastic process. The aim of this study was to investigate the frequency and the type of single chromosomal changes in Philadelphia-negative CMPD patients. By conventional cytogenetics, 245 Philadelphia-negative CMPD cases at diagnosis were investigated for the frequency and the type of single chromosomal aberrations. Seventeen patients presented single chromosomal changes. These aberrations were, according to frequency, +8 (in 3 PV cases, 2 IMF and 2 unclassified myeloproliferative diseases), +13 in 3 cases (IMF, ET and unclassified myeloproliferative disease), monosomy 10 in 2 PV cases, monosomy 14 in one ET patient, +3, -4 and del(11)(q13) in 1 unclassified myeloproliferative disease each and monosomy 7 in 1 IMF case. It is unclear whether these abnormalities found at the time of diagnosis play a role in CMPD. However, since an isolated chromosomal abnormality may be implicated in the initiation of the neoplastic process, the documentation of more cases of CMPD with single abnormalities at the time of diagnosis would facilitate the identification of candidate genes involved in the neoplastic process.

  9. The Chromosomes of Birds during Meiosis.

    Science.gov (United States)

    Pigozzi, María I

    2016-01-01

    The cytological analysis of meiotic chromosomes is an exceptional tool to approach complex processes such as synapsis and recombination during the division. Chromosome studies of meiosis have been especially valuable in birds, where naturally occurring mutants or experimental knock-out animals are not available to fully investigate the basic mechanisms of major meiotic events. This review highlights the main contributions of synaptonemal complex and lampbrush chromosome research to the current knowledge of avian meiosis, with special emphasis on the organization of chromosomes during prophase I, the impact of chromosome rearrangements during meiosis, and distinctive features of the ZW pair.

  10. Chromosome congression explained by nanoscale electrostatics.

    Science.gov (United States)

    Gagliardi, L John; Shain, Daniel H

    2014-02-24

    Nanoscale electrostatic microtubule disassembly forces between positively charged molecules in kinetochores and negative charges on plus ends of microtubules have been implicated in poleward chromosome motions and may also contribute to antipoleward chromosome movements. We propose that chromosome congression can be understood in terms of antipoleward nanoscale electrostatic microtubule assembly forces between negatively charged microtubule plus ends and like-charged chromosome arms, acting in conjunction with poleward microtubule disassembly forces. Several other aspects of post-attachment prometaphase chromosome motions, as well as metaphase oscillations, are consistently explained within this framework.

  11. Polymer models of chromosome (re)organization

    Science.gov (United States)

    Mirny, Leonid

    Chromosome Conformation Capture technique (Hi-C) provides comprehensive information about frequencies of spatial interactions between genomic loci. Inferring 3D organization of chromosomes from these data is a challenging biophysical problem. We develop a top-down approach to biophysical modeling of chromosomes. Starting with a minimal set of biologically motivated interactions we build ensembles of polymer conformations that can reproduce major features observed in Hi-C experiments. I will present our work on modeling organization of human metaphase and interphase chromosomes. Our works suggests that active processes of loop extrusion can be a universal mechanism responsible for formation of domains in interphase and chromosome compaction in metaphase.

  12. Progress Report

    DEFF Research Database (Denmark)

    Duer, Karsten

    1999-01-01

    Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999.......Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999....

  13. Chromosome painting of Z and W sex chromosomes in Characidium (Characiformes, Crenuchidae).

    Science.gov (United States)

    Pazian, Marlon F; Shimabukuro-Dias, Cristiane Kioko; Pansonato-Alves, José Carlos; Oliveira, Claudio; Foresti, Fausto

    2013-03-01

    Some species of the genus Characidium have heteromorphic ZZ/ZW sex chromosomes with a totally heterochromatic W chromosome. Methods for chromosome microdissection associated with chromosome painting have become important tools for cytogenetic studies in Neotropical fish. In Characidium cf. fasciatum, the Z chromosome contains a pericentromeric heterochromatin block, whereas the W chromosome is completely heterochromatic. Therefore, a probe was produced from the W chromosome through microdissection and degenerate oligonucleotide-primed polymerase chain reaction amplification. FISH was performed using the W probe on the chromosomes of specimens of this species. This revealed expressive marks in the pericentromeric region of the Z chromosome as well as a completely painted W chromosome. When applying the same probe on chromosome preparations of C. cf. gomesi and Characidium sp., a pattern similar to C. cf. fasciatum was found, while C. cf. zebra, C. cf. lagosantense and Crenuchus spilurus species showed no hybridization signals. Structural changes in the chromosomes of an ancestral sexual system in the group that includes the species C. cf. gomesi, C. cf. fasciatum and Characidium sp., could have contributed to the process of speciation and could represent a causal mechanism of chromosomal diversification in this group. The heterochromatinization process possibly began in homomorphic and homologous chromosomes of an ancestral form, and this process could have given rise to the current patterns found in the species with sex chromosome heteromorphism.

  14. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    R Paul Drake

    2004-01-12

    OAK-B135 This is the final report from the project Hydrodynamics by High-Energy-Density Plasma Flow and Hydrodynamics and Radiation Hydrodynamics with Astrophysical Applications. This project supported a group at the University of Michigan in the invention, design, performance, and analysis of experiments using high-energy-density research facilities. The experiments explored compressible nonlinear hydrodynamics, in particular at decelerating interfaces, and the radiation hydrodynamics of strong shock waves. It has application to supernovae, astrophysical jets, shock-cloud interactions, and radiative shock waves.

  15. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Jarillo-Herrero, Pablo [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2017-02-07

    This is the final report of our research program on electronic transport experiments on Topological Insulator (TI) devices, funded by the DOE Office of Basic Energy Sciences. TIbased electronic devices are attractive as platforms for spintronic applications, and for detection of emergent properties such as Majorana excitations , electron-hole condensates , and the topological magneto-electric effect . Most theoretical proposals envision geometries consisting of a planar TI device integrated with materials of distinctly different physical phases (such as ferromagnets and superconductors). Experimental realization of physics tied to the surface states is a challenge due to the ubiquitous presence of bulk carriers in most TI compounds as well as degradation during device fabrication.

  16. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Yelton, John Martin [UF; Mitselmakher, Guenakh [UF; Korytov, Andrey [UF; Avery, Paul [UF; Furic, Ivan [UF; Acosta, Darin [UF; Konigsberg, Jacobo [UF; Field, Richard [UF; Matchev, Konstantin [UF; Ramond, Pierre [UF; Thorn, Richard [UF; Sikivie, Pierre [UF; Ray, Heather [UF; Tanner, David [UF

    2013-10-10

    We report on progress in a series of different directions within high energy physics research. 1. Neutrino research in hardware and software on the Minerva and MiniBooNE experiments 2. Experimental particle physics at the hadron colliders, with emphasis on research and development and data analysis on the CMS experiment operating at the CERN LHC. This includes research on the discovery and properties on the Higgs Boson. 3. Educational outreach through the Quarknet program, taking physics research into High School classrooms. 4. Theoretical and Phenomenological High Energy research, covering a broad range of activities ranging from fundamental theoretical issues to areas of immediate phenomenological importance. 5. Experiment searches for the Axion, as part of the ADMX experiment.

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

    Directory of Open Access Journals (Sweden)

    Ruth N. MacKinnon

    2011-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Considerations for comparing radiation-induced chromosome aberration data with predictions from biophysical models

    Science.gov (United States)

    Wu, H.; Furusawa, Y.; George, K.; Kawata, T.; Cucinotta, F.

    Biophysical models addressing the formation of radiation-induced chromosome aberrations are usually based on the assumption that chromosome aberrations are formed by DNA double strand break (DSB) misrejoining, via either the homologous or the non-homologous repair pathway. However, comparing chromosome aberration data with model predictions is not always straightforward. In this paper we discuss some of the aspects that must be considered to make these comparisons meaningful. Firstly, biophysical models are usually applied to DSB rejoining and misrejoining in the G0/G1 phase of the cell cycle, while most chromosome aberration data reported in the literature are analyzed in metaphase. Since cells must progress through the cell cycle check points in order to reach mitosis, model predictions that differ from the metaphase chromosome analysis may actually agree with the aberration data in chromosomes collected in interphase. Secondly, high- LET radiation generally produces more complex aberrations involving exchanges between three or more DSB. While some models have successfully provided quantitative predictions of high-LET radiation induced complex aberrations in human lymphocytes, applying such models to other cell types requires special considerations due to the lack of geometric symmetry of the nucleus. Chromosome aberration data for non-spherical human fibroblast cells bombarded from various directions by high-LET charged particles will be presented, and their implication on physical modeling will be discussed.

  20. Artificially introduced aneuploid chromosomes assume a conserved position in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Kundan Sengupta

    Full Text Available BACKGROUND: Chromosomal aneuploidy is a defining feature of carcinomas. For instance, in colon cancer, an additional copy of Chromosome 7 is not only observed in early pre-malignant polyps, but is faithfully maintained throughout progression to metastasis. These copy number changes show a positive correlation with average transcript levels of resident genes. An independent line of research has also established that specific chromosomes occupy a well conserved 3D position within the interphase nucleus. METHODOLOGY/PRINCIPAL FINDINGS: We investigated whether cancer-specific aneuploid chromosomes assume a 3D-position similar to that of its endogenous homologues, which would suggest a possible correlation with transcriptional activity. Using 3D-FISH and confocal laser scanning microscopy, we show that Chromosomes 7, 18, or 19 introduced via microcell-mediated chromosome transfer into the parental diploid colon cancer cell line DLD-1 maintain their conserved position in the interphase nucleus. CONCLUSIONS: Our data is therefore consistent with the model that each chromosome has an associated zip code (possibly gene density that determines its nuclear localization. Whether the nuclear localization determines or is determined by the transcriptional activity of resident genes has yet to be ascertained.

  1. Structural Chromosomal Alterations Induced by Dietary Bioflavonoids in Fanconi Anemia Lymphocytes

    Directory of Open Access Journals (Sweden)

    Gonzalo Guevara

    2007-06-01

    Full Text Available IntroductionFanconi anemia is an autosomal recessive diseasecharacterized by a variety of congenital abnormalities,progressive bone marrow failure,increased chromosomal instability and higherrisk to acute myeloid leukemia, solid tumors. Thisentity can be considered an appropriate biologicalmodel to analyze natural substances with possiblegenotoxic effect. The aims of this study wereto describe and quantify structural chromosomalaberrations induced by 5 flavones, 2 isoflavonesand a topoisomerase II chemotherapeutic inhibitorin Fanconi anemia lymphocytes in order todetermine chromosomal numbers changes and/or type of chromosomal damage.Materials and methodsChromosomes stimulated by phytohaemagglutininM, from Fanconi anemia lymphocytes,were analysed by conventional cytogenetic culture.For each chemical substance and controls,one hundred metaphases were evaluated. Chromosomalalterations were documented by photographyand imaging analyzer. To statisticalanalysis was used chi square test to identify significantdifferences between frequencies of chromosomaldamage of basal and exposed cellcultured a P value less than 0.05.ResultsThere were 431 chromosomal alterations in1000 metaphases analysed; genistein was themore genotoxic bioflavonoid, followed in descendentorder by genistin, fisetin, kaempferol,quercetin, baicalein and miricetin. Chromosomalaberrations observed were: chromatidbreaks, chromosomal breaks, cromatid andchromosomal gaps, quadriratials exchanges,dicentrics chromosome and complex rearrangements.ConclusionBioflavonoids as genistein, genistin and fisetin,which are commonly present in the human diet,showed statistical significance in the number ofchromosomal aberrations in Fanconi anemialymphocytes, regarding the basal damage.

  2. 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.

  3. Centromeric Non-coding Transcription: Opening the Black Box of Chromosomal Instability?

    Science.gov (United States)

    Cáceres-Gutiérrez, Rodrigo; Herrera, Luis A

    2017-06-01

    In eukaryotes, mitosis is tightly regulated to avoid the generation of numerical chromosome aberrations, or aneuploidies. The aneuploid phenotype is a consequence of chromosomal instability (CIN), i.e., an enhanced rate of chromosome segregation errors, which is frequently found in cancer cells and is associated with tumor aggressiveness and increased tumor cell survival potential. To avoid the generation of aneuploidies, cells rely on the spindle assembly checkpoint (SAC), a widely conserved mechanism that protects the genome against this type of error. This signaling pathway stops mitotic pro-gression before anaphase until all chromosomes are correctly attached to spindle microtubules. Howev-er, impairment of the SAC cannot account for the establishment of CIN because cells bearing this phe-notype have a functional SAC. Hence, in cells with CIN, anaphase is not triggered until all chromo-somes are correctly attached to spindle microtubules and congressed at the metaphase plate. Thus, an in-teresting question arises: What mechanisms actually mediate CIN in cancer cells? Recent research has shown that some pathways involved in chromosome segregation are closely associated to centromere-encoded non-coding RNA (cencRNA) and that these RNAs are deregulated in abnormal conditions, such as cancer. These mechanisms may provide new explanations for chromosome segregation errors. The present review discusses some of these findings and proposes novel mechanisms for the establish-ment of CIN based on regulation by cencRNA.

  4. Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways.

    Science.gov (United States)

    Ichijima, Yosuke; Sin, Ho-Su; Namekawa, Satoshi H

    2012-08-01

    Sex chromosome inactivation in male germ cells is a paradigm of epigenetic programming during sexual reproduction. Recent progress has revealed the underlying mechanisms of sex chromosome inactivation in male meiosis. The trigger of chromosome-wide silencing is activation of the DNA damage response (DDR) pathway, which is centered on the mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX). This DDR pathway shares features with the somatic DDR pathway recognizing DNA replication stress in the S phase. Additionally, it is likely to be distinct from the DDR pathway that recognizes meiosis-specific double-strand breaks. This review article extensively discusses the underlying mechanism of sex chromosome inactivation.

  5. Chromosome X aneuploidy in Brazilian schizophrenic patients.

    Science.gov (United States)

    de Moraes, Leopoldo Silva; Khayat, André Salim; de Lima, Patrícia Danielle Lima; Lima, Eleonidas Moura; Pinto, Giovanny Rebouças; Leal, Mariana Ferreira; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2010-01-01

    The identification of cytogenetic abnormalities in schizophrenic patients may provide clues to the genes involved in this disease. For this reason, a chromosomal analysis of samples from 62 schizophrenics and 70 controls was performed with trypsin-Giemsa banding and fluorescence in situ hybridization of the X chromosome. A clonal pericentric inversion on chromosome 9 was detected in one male patient, and we also discovered mosaicism associated with X chromosome aneuploidy in female patients, primarily detected in schizophrenic and normal female controls over 40 years old. When compared with age-matched female controls, the frequency of X chromosome loss was not significantly different between schizophrenics and controls, except for the 40- to 49-year-old age group. Our findings suggest that the X chromosome loss seen in schizophrenic patients is inherent to the normal cellular aging process. However, our data also suggest that X chromosome gain may be correlated with schizophrenia in this Brazilian population.

  6. Flow cytometric detection of aberrant chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Yu, L.C.; Langlois, R.

    1983-05-11

    This report describes the quantification of chromosomal aberrations by flow cytometry. Both homogeneously and heterogeneously occurring chromosome aberrations were studied. Homogeneously occurring aberrations were noted in chromosomes isolated from human colon carcinoma (LoVo) cells, stained with Hoechst 33258 and chromomycin A3 and analyzed using dual beam flow cytometry. The resulting bivariate flow karyotype showed a homogeneously occurring marker chromosome of intermediate size. Heterogeneously occurring aberrations were quantified by slit-scan flow cytometry in chromosomes isolated from control and irradiated Chinese hamster cells and stained with propidium iodide. Heterogeneously occurring dicentric chromosomes were detected by their shapes (two centrometers). The frequencies of such chromosomes estimated by slit-scan flow cytometry correlated well with the frequencies determined by visual microscopy.

  7. Dynamics of chromosome segregation in Escherichia coli

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck

    2007-01-01

    in the cell by labeling specific parts of it. Later the dynamics of chromosome segregation was included. Investigating chromosome organization by labeling of specific loci was already a widely used technique when I started on this thesis, but the data acquisition and treatment was slow and generally poorly......, and it is obvious that structured cellular actions are required to unpack it, as required for its replication, and refold the two daughter chromosomes separately without getting them entangled in the process each generation. The intention of the study was initially to find out how the chromosome is organized....... Adding the results of the thesis together with known data results in the following description of the chromosome dynamics of slowly growing E.coli cells: The chromosome of slow growing cells is organized with the origin at the cell center when it is newborn. It has one chromosomal arm on one side...

  8. Chromosomal patterns in human malignant astrocytomas.

    Science.gov (United States)

    Rey, J A; Bello, M J; de Campos, J M; Kusak, M E; Ramos, C; Benitez, J

    1987-12-01

    Cytogenetic analysis by direct and/or in vitro preparations was performed on 34 malignant astrocytomas. Thirty tumors showed near-diploid chromosome numbers, whereas, tritetraploid chromosome complements were present in four tumors. The most frequent chromosomal changes implied numerical deviations by a gain of chromosomes #7, #19, and #20, and by losses of #10, #22, and Y. Structural rearrangements were present in stem- or side lines of 24 tumors. Although no common chromosomal rearrangement seems to exist among those tumors, chromosomes #1, #6, #7, and #9 were predominantly involved. Polysomy and structural rearrangements of chromosome #7 could be related to the overexpression of epidermal growth factor gene, previously observed in some malignant gliomas.

  9. Entropy as the driver of chromosome segregation.

    Science.gov (United States)

    Jun, Suckjoon; Wright, Andrew

    2010-08-01

    We present a new physical biology approach to understanding the relationship between the organization and segregation of bacterial chromosomes. We posit that replicated Escherichia coli daughter strands will spontaneously demix as a result of entropic forces, despite their strong confinement within the cell; in other words, we propose that entropy can act as a primordial physical force which drives chromosome segregation under the right physical conditions. Furthermore, proteins implicated in the regulation of chromosome structure and segregation may in fact function primarily in supporting such an entropy-driven segregation mechanism by regulating the physical state of chromosomes. We conclude that bacterial chromosome segregation is best understood in terms of spontaneous demixing of daughter strands. Our concept may also have important implications for chromosome segregation in eukaryotes, in which spindle-dependent chromosome movement follows an extended period of sister chromatid demixing and compaction.

  10. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    Directory of Open Access Journals (Sweden)

    Daniela Mierla

    2012-06-01

    Full Text Available Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, karyotype analysis by G-banding was performed from peripheral blood in 967 women infertility. Results: Chromosomal abnormalities were found to 79 women (8,17%. The percentage of chromosomal abnormalities in the studied population correlates with the data in the literature. Chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions.

  11. Environmental pollution, chromosomes, and health

    Science.gov (United States)

    Bell, Peter M.

    In mid-May, 1980, President Carter declared a state of emergency at the Love Canal area, near Niagara Falls, New York. The reason for this was for the U.S. to underwrite the relocation costs ($3-5 million) of some 2500 residents who, according to a report by the EPA (Environmental Protection Agency) may have suffered damaged chromosomes. These injuries were apparently caused by contact with toxic wastes that had been dumped in the area in the years prior to development for housing.That the toxic compounds exist in the Love Canal and Niagara Falls subsurface zones, including public water supplies, appears to be established fact. That the residents of the Love Canal area suffered chromosomal damage may be established fact as well. Whether or not these two findings can be linked to ill health of the residents is another matter. Recently, the EPA report has been described as having ‘close to zero scientific significance,’ and has been ‘discredited’(Science, 208, 123a, 1980). The reasons for this disparity go beyond differences of opinion, beyond possible inadequacies of the EPA study, and even beyond problems that probably will arise from future studies, including those now in the planning stages. The problem is that even if victims have easily recognizable injuries from toxic substances (injury that apparently has not occurred to Love Canal residents), medical science usually cannot show a causal relationship. Even chromosomal damage is, at best, difficult to interpret. In ideal studies of significant populations and control groups, the association of toxic chemical to chromosome damage and to cancer and birth defects is indirect and, up to now, has been shown to have little or no significance to an individual member of the exposed population.

  12. Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium

    Science.gov (United States)

    The chromosome painting is an efficient tool for chromosome research. However, plant chromosome painting is relatively underdeveloped. In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat-Thinopyrum intermedium addition line, and chromosomes of...

  13. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.

    1982-01-01

    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  14. Chromosome segregation and aneuploidy. I

    Energy Technology Data Exchange (ETDEWEB)

    Vig, B.K. [Univ. of Nevada, Reno, NV (United States)

    1993-12-31

    Of all genetic afflictions of man, aneuploidy ranks as the most prevalent. Among liveborn babies aneuploidy exist to the extent of about 0.3%, to about 0.5% among stillborns and a dramatic 25% among miscarriages. The burden is too heavy to be taken lightly. Whereas cytogeneticists are capable of tracing the origin of the extra or missing chromosome to the contributing parent, it is not certain what factors are responsible for this {open_quote}epidemic{close_quote} affecting the human genome. The matter is complicated by the observation that, to the best of our knowledge, all chromosomes do not malsegregate with equal frequency. Chromosome number 16, for example, is the most prevalent among abortuses - one-third of all aneuploid miscarriages are due to trisomy 16 - yet it never appears in aneuploid constitution among the liveborn. Some chromsomes, number 1, for example, appear only rarely, if at all. In the latter case painstaking efforts have to be made to karyotype very early stages of embryonic development, as early as the 8-cell stage. Even though no convincing data are yet available, it is conceivable that the product of most aneuploid zygotes is lost before implantation.

  15. Mechanisms of Chromosome Congression during Mitosis

    Science.gov (United States)

    Maiato, Helder; Gomes, Ana Margarida; Sousa, Filipe; Barisic, Marin

    2017-01-01

    Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E) that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle microtubule

  16. Mechanisms of Chromosome Congression during Mitosis

    Directory of Open Access Journals (Sweden)

    Helder Maiato

    2017-02-01

    Full Text Available Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle

  17. The origin of an unusual sex chromosome constitution in Acomys sp. (Rodentia, Muridae) from Tanzania.

    Science.gov (United States)

    Castiglia, Riccardo; Makundi, Rhodes; Corti, Marco

    2007-10-01

    This paper describes a case which presents an evident variation from the "standard" XX/XY sex chromosomal constitution in a rodent, Acomys sp. This species known to be found in three localities of East Africa has only recently been separated from A. spinosissimus, its closest relative. In our study, five specimens of Acomys sp. and eight specimens of A. spinosissimus were live-trapped in five localities. Comparisons between the two taxa assed by G-banding show a complete homology in the chromosomal shape and banding pattern for 29 pairs of chromosomes corresponding to the complete autosomal set of A. spinosissimus. However, while all the A. spinosissimus analysed have 2n = 60 and a XY-XX system, in Acomys sp. males and females constitute mosaics for sex chromosomes in the bone marrow cells. Females (2n = 59, 60) have an excess (97%) of aneuploid cells with one single giant X chromosome, and males (2n = 60, 61) show X0/XY cells occurring in somatic tissues and XY cells in the germinal lineage. In addition, an odd heterochromatic submetacentric chromosome was identified in all the cells examined in two males and a female of Acomys sp. Since this chromosome was not related to sex determination and it is not present in all the analysed specimens, it can be considered as a B chromosome. Finally, the in situ fluorescence hybridisation (FISH) with telomeric probes showed a very intense interstitial telomeric signal (ITS) at the medial part on the long heterochromatic arm of the X chromosome. This could be due to recent chromosomal rearrangement.

  18. Genetic Diversity on the Human X Chromosome Does Not Support a Strict Pseudoautosomal Boundary.

    Science.gov (United States)

    Cotter, Daniel J; Brotman, Sarah M; Wilson Sayres, Melissa A

    2016-05-01

    Unlike the autosomes, recombination between the X chromosome and the Y chromosome is often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. PAR1 spans the first 2.7 Mb of the proximal arm of the human sex chromosomes, whereas the much smaller PAR2 encompasses the distal 320 kb of the long arm of each sex chromosome. In addition to PAR1 and PAR2, there is a human-specific X-transposed region that was duplicated from the X to the Y chromosome. The X-transposed region is often not excluded from X-specific analyses, unlike the PARs, because it is not thought to routinely recombine. Genetic diversity is expected to be higher in recombining regions than in nonrecombining regions because recombination reduces the effect of linked selection. In this study, we investigated patterns of genetic diversity in noncoding regions across the entire X chromosome of a global sample of 26 unrelated genetic females. We found that genetic diversity in PAR1 is significantly greater than in the nonrecombining regions (nonPARs). However, rather than an abrupt drop in diversity at the pseudoautosomal boundary, there is a gradual reduction in diversity from the recombining through the nonrecombining regions, suggesting that recombination between the human sex chromosomes spans across the currently defined pseudoautosomal boundary. A consequence of recombination spanning this boundary potentially includes increasing the rate of sex-linked disorders (e.g., de la Chapelle) and sex chromosome aneuploidies. In contrast, diversity in PAR2 is not significantly elevated compared to the nonPARs, suggesting that recombination is not obligatory in PAR2. Finally, diversity in the X-transposed region is higher than in the surrounding nonPARs, providing evidence that recombination may occur with some frequency between the X and Y chromosomes in the X-transposed region.

  19. Chromosomal imbalances in nasopharyngeal carcinoma: a meta-analysis of comparative genomic hybridization results

    Directory of Open Access Journals (Sweden)

    Jin Ping

    2006-01-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a highly prevalent disease in Southeast Asia and its prevalence is clearly affected by genetic background. Various theories have been suggested for its high incidence in this geographical region but to these days no conclusive explanation has been identified. Chromosomal imbalances identifiable through comparative genomic hybridization may shed some light on common genetic alterations that may be of relevance to the onset and progression of NPC. Review of the literature, however, reveals contradictory results among reported findings possibly related to factors associated with patient selection, stage of disease, differences in methodological details etc. To increase the power of the analysis and attempt to identify commonalities among the reported findings, we performed a meta-analysis of results described in NPC tissues based on chromosomal comparative genomic hybridization (CGH. This meta-analysis revealed consistent patters in chromosomal abnormalities that appeared to cluster in specific "hot spots" along the genome following a stage-dependent progression.

  20. Whole chromosome painting of B chromosomes of the red-eye tetra Moenkhausia sanctaefilomenae (Teleostei, Characidae)

    Science.gov (United States)

    Scudeler, Patricia Elda Sobrinho; Diniz, Débora; Wasko, Adriane Pinto; Oliveira, Claudio; Foresti, Fausto

    2015-01-01

    Abstract B chromosomes are dispensable genomic elements found in different groups of animals and plants. In the present study, a whole chromosome probe was generated from a specific heterochromatic B chromosome occurring in cells of the characidae fish Moenkhausia sanctaefilomenae (Steindachner, 1907). The chromosome painting probes were used in fluorescence in situ hybridization (FISH) experiments for the assessment of metaphase chromosomes obtained from individuals from three populations of Moenkhausia sanctaefilomenae. The results revealed that DNA sequences were shared between a specific B chromosome and many chromosomes of the A complement in all populations analyzed, suggesting a possible intra-specific origin of these B chromosomes. However, no hybridization signals were observed in other B chromosomes found in the same individuals, implying a possible independent origin of B chromosome variants in this species. FISH experiments using 18S rDNA probes revealed the presence of non-active ribosomal genes in some B chromosomes and in some chromosomes of the A complement, suggesting that at least two types of B chromosomes had an independent origin. The role of heterochromatic segments and ribosomal sequences in the origin of B chromosomes were discussed. PMID:26753081

  1. Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

    Directory of Open Access Journals (Sweden)

    Sebastian Pita

    2013-05-01

    Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

  2. Whole chromosome painting of B chromosomes of the red-eye tetra Moenkhausia sanctaefilomenae (Teleostei, Characidae).

    Science.gov (United States)

    Scudeler, Patricia Elda Sobrinho; Diniz, Débora; Wasko, Adriane Pinto; Oliveira, Claudio; Foresti, Fausto

    2015-01-01

    B chromosomes are dispensable genomic elements found in different groups of animals and plants. In the present study, a whole chromosome probe was generated from a specific heterochromatic B chromosome occurring in cells of the characidae fish Moenkhausia sanctaefilomenae (Steindachner, 1907). The chromosome painting probes were used in fluorescence in situ hybridization (FISH) experiments for the assessment of metaphase chromosomes obtained from individuals from three populations of Moenkhausia sanctaefilomenae. The results revealed that DNA sequences were shared between a specific B chromosome and many chromosomes of the A complement in all populations analyzed, suggesting a possible intra-specific origin of these B chromosomes. However, no hybridization signals were observed in other B chromosomes found in the same individuals, implying a possible independent origin of B chromosome variants in this species. FISH experiments using 18S rDNA probes revealed the presence of non-active ribosomal genes in some B chromosomes and in some chromosomes of the A complement, suggesting that at least two types of B chromosomes had an independent origin. The role of heterochromatic segments and ribosomal sequences in the origin of B chromosomes were discussed.

  3. Chromosome aberrations induced by zebularine in triticale.

    Science.gov (United States)

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  4. The importance of having two X chromosomes.

    Science.gov (United States)

    Arnold, Arthur P; Reue, Karen; Eghbali, Mansoureh; Vilain, Eric; Chen, Xuqi; Ghahramani, Negar; Itoh, Yuichiro; Li, Jingyuan; Link, Jenny C; Ngun, Tuck; Williams-Burris, Shayna M

    2016-02-19

    Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes.

  5. Chromosome analysis of arsenic affected cattle

    Directory of Open Access Journals (Sweden)

    S. Shekhar

    2014-10-01

    Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.

  6. Progressive Business

    DEFF Research Database (Denmark)

    Christiansen, Christian O.

    2016-01-01

    Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015.......Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015....

  7. Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes.

    Science.gov (United States)

    Gui, Liming; Homer, Hayden

    2012-06-01

    The spindle assembly checkpoint (SAC) averts aneuploidy by coordinating proper bipolar chromosomal attachment with anaphase-promoting complex/cyclosome (APC/C)-mediated securin and cyclin B1 destruction required for anaphase onset. The generation of a Mad2-based signal at kinetochores is central to current models of SAC-based APC/C inhibition. During mitosis, kinetochores of polar-displaced chromosomes, which are at greatest risk of mis-segregating, recruit the highest levels of Mad2, thereby ensuring that SAC activation is proportionate to aneuploidy risk. Paradoxically, although an SAC operates in mammalian oocytes, meiosis I (MI) is notoriously error prone and polar-displaced chromosomes do not prevent anaphase onset. Here we find that Mad2 is not preferentially recruited to the kinetochores of polar chromosomes of wild-type mouse oocytes, in which polar chromosomes are rare, or of oocytes depleted of the kinesin-7 motor CENP-E, in which polar chromosomes are more abundant. Furthermore, in CENP-E-depleted oocytes, although polar chromosomal displacement intensified during MI and the capacity to form stable end-on attachments was severely compromised, all kinetochores nevertheless became devoid of Mad2. Thus, it is possible that the ability of the SAC to robustly discriminate chromosomal position might be compromised by the propensity of oocyte kinetochores to become saturated with unproductive attachments, thereby predisposing to aneuploidy. Our data also reveal novel functions for CENP-E in oocytes: first, CENP-E stabilises BubR1, thereby impacting MI progression; and second, CENP-E mediates bi-orientation by promoting kinetochore reorientation and preventing chromosomal drift towards the poles.

  8. Can corruption of chromosome cohesion create a conduit to cancer?

    Science.gov (United States)

    Xu, Huiling; Tomaszewski, Jonathan M; McKay, Michael J

    2011-03-01

    Cohesin is a conserved multisubunit protein complex with diverse cellular roles, making key contributions to the coordination of chromosome segregation, the DNA damage response and chromatin regulation by epigenetic mechanisms. Much has been learned in recent years about the roles of cohesin in a physiological context, whereas its potential and emerging role in tumour initiation and/or progression has received relatively little attention. In this Opinion article we examine how cohesin deregulation could contribute to cancer development on the basis of its physiological roles.

  9. Cockayne syndrome - A Clinical, Radiological, Audiological And Chromosomal Study

    Directory of Open Access Journals (Sweden)

    Ashraff V V

    2004-01-01

    Full Text Available We report two brothers of Cockayne syndrome (CS with progressive growth retardation, microcephaly, bird headed facies with sunken eyes, cutaneous photosensitivity, retinits pigmentosa, sensorineural deafness, spasticity ataxia, neuropathy and intracranial calcifiactions. These clinical with radiological features of cortical and cerebellar atrophy with basal ganglionic calcification and presence of consanguinity in parents and chromosome studies showing sister chromatid exchange in less than 6% strongly supported the diagnosis of Cockyne syndrome and differentiated it from Bloom′s syndrome and xeroderma pigmentosa. Without genetic analysis or tests for defective DNA repair, the diagnosis is mostly clinical.

  10. Cyclin G-associated kinase promotes microtubule outgrowth from chromosomes during spindle assembly.

    Science.gov (United States)

    Tanenbaum, Marvin E; Vallenius, Tea; Geers, Erica F; Greene, Lois; Mäkelä, Tomi P; Medema, Rene H

    2010-08-01

    During mitosis, all chromosomes must attach to microtubules of the mitotic spindle to ensure correct chromosome segregation. Microtubule attachment occurs at specialized structures at the centromeric region of chromosomes, called kinetochores. These kinetochores can generate microtubule attachments through capture of centrosome-derived microtubules, but in addition, they can generate microtubules themselves, which are subsequently integrated with centrosome-derived microtubules to form the mitotic spindle. Here, we have performed a large scale RNAi screen and identify cyclin G-associated kinase (GAK) as a novel regulator of microtubule generation at kinetochores/chromatin. This function of GAK requires its C-terminal J-domain, which is essential for clathrin recycling from endocytic vesicles. Consistently, cells lacking GAK show strongly reduced levels of clathrin on the mitotic spindle, and reduction of clathrin levels also inhibits microtubule generation at kinetochores/chromosomes. Finally, we present evidence that association of clathrin with the spindle is promoted by a signal coming from the chromosomes. These results identify a role for GAK and clathrin in microtubule outgrowth from kinetochores/chromosomes and suggest that GAK acts through clathrin to control microtubule outgrowth around chromosomes.

  11. The genetic content of chromosomal inversions across a wide latitudinal gradient.

    Directory of Open Access Journals (Sweden)

    Pedro Simões

    Full Text Available There is increasing evidence regarding the role of chromosomal inversions in relevant biological processes such as local adaptation and speciation. A classic example of the adaptive role of chromosomal polymorphisms is given by the clines of inversion frequencies in Drosophila subobscura, repeatable across continents. Nevertheless, not much is known about the molecular variation associated with these polymorphisms. We characterized the genetic content of ca. 600 individuals from nine European populations following a latitudinal gradient by analysing 19 microsatellite loci from two autosomes (J and U and the sex chromosome (A, taking into account their chromosomal inversions. Our results clearly demonstrate the molecular genetic uniformity within a given chromosomal inversion across a large latitudinal gradient, particularly from Groningen (Netherlands in the north to Málaga (Spain in the south, experiencing highly diverse environmental conditions. This low genetic differentiation within the same gene arrangement across the nine European populations is consistent with the local adaptation hypothesis for th evolutionof chromosomal polymorphisms. We also show the effective role of chromosomal inversions in maintaining different genetic pools within these inverted genomic regions even in the presence of high gene flow. Inversions represent thus an important barrier to gene flux and can help maintain specific allelic combinations with positive effects on fitness. Consistent patterns of microsatellite allele-inversion linkage disequilibrium particularly in loci within inversions were also observed. Finally, we identified areas within inversions presenting clinal variation that might be under selection.

  12. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Callis, Judy [Univ. of California, Davis, CA (United States)

    2016-11-30

    This report summarizes our research activities. In the award period, we have made significant progress on the first aim, with new discoveries reported in one published paper (1) and in one submitted manuscript (2) currently under review. The published manuscript reports on our discovery of plant ribokinase and the metabolic pathway in which it functions; the submitted manuscript is identification and characterization of the plant fructokinase family of enzymes from expression studies, sequence comparisons, subcellular localizations and enzymatic activities of recombinant proteins. Our study of loss-of-function mutants in the fructokinase family members (2) revealed that there were no phenotypic differences observed for the five genes analyzed, so we have adopted the Crispr/Cas9 system to isolate mutants in the two genes for which there are no currently available insertion mutants, and we are generating higher order mutants (double, triples, etc) to discern the relative roles and significance for each fructokinase. These mutants will be an important resource to understand regulation of carbohydrate movement and catabolism in plants. As studies from others indicate, alteration of fructokinases results in changes in cell walls and vasculatures, which have importance relative to biofuel yield and quality. In the second aim, we have characterized the protein-protein interactions for the pkfB proteins FLN1 and FLN2 that are localized to chloroplast transcriptional complexes and have proposed a new model for how chloroplast transcription is regulated. This work has been submitted for publication, been revised and will be re-submitted in December 2016

  13. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Robert C. [Texas A& M University; Kamon, Teruki [Texas A& M University; Toback, David [Texas A& M University; Safonov, Alexei [Texas A& M University; Dutta, Bhaskar [Texas A& M University; Dimitri, Nanopoulos [Texas A& M University; Pope, Christopher [Texas A& M University; White, James [Texas A& M University

    2013-11-18

    Overview The High Energy Physics Group at Texas A&M University is submitting this final report for our grant number DE-FG02-95ER40917. This grant has supported our wide range of research activities for over a decade. The reports contained here summarize the latest work done by our research team. Task A (Collider Physics Program): CMS & CDF Profs. T. Kamon, A. Safonov, and D. Toback co-lead the Texas A&M (TAMU) collider program focusing on CDF and CMS experiments. Task D: Particle Physics Theory Our particle physics theory task is the combined effort of Profs. B. Dutta, D. Nanopoulos, and C. Pope. Task E (Underground Physics): LUX & NEXT Profs. R. Webb and J. White(deceased) lead the Xenon-based underground research program consisting of two main thrusts: the first, participation in the LUX two-phase xenon dark matter search experiment and the second, detector R&D primarily aimed at developing future detectors for underground physics (e.g. NEXT and LZ).

  14. Physical Model of Segregation of E.coli Chromosomes using Molecular Dynamics

    Science.gov (United States)

    Alnahhas, Faisal; Kharel, Savan

    2016-03-01

    Chromosome segregation is one of the most interesting physical processes during a bacterial cell cycle. We will use molecular dynamics simulations which will help us understand how strongly confined polymer segregates. In the presentation, we will discuss how segregation of initially overlapping circular chromosome occurs during a cell cycle. In particular, we will describe the role played by entropic mechanism in the demixing of overlapping circular polymer confined in a cylindrical boundary. We discuss how our polymer chains modeled as an E-coli chromosome experiences an effective repulsion, which ultimately leads to partition driven by the entropic forces. Also, we will also discuss how the segregation of circular chromosome in cylindrical confinement differs from a spherical confinement. Finally, we will discuss the role played by proteins and supercoiling in during the segregation process.

  15. Organization of some repetitive DNAs and B chromosomes in the grasshopper Eumastusia koebelei koebelei (Rehn, 1909) (Orthoptera, Acrididae, Leptysminae)

    Science.gov (United States)

    Anjos, Allison; Loreto, Vilma; Cabral-de-Mello, Diogo C.

    2016-01-01

    Abstract B chromosomes occur in approximately 15% of eukaryotes and are usually heterochromatic and rich in repetitive DNAs. Here we describe characteristics of a B chromosome in the grasshopper Eumastusia koebelei koebelei (Rehn, 1909) through classical cytogenetic methods and mapping of some repetitive DNAs, including multigene families, telomeric repeats and a DNA fraction enriched with repetitive DNAs obtained from DOP-PCR. Eumastusia koebelei koebelei presented 2n=23, X0 and, in one individual, two copies of the same variant of a B chromosome were noticed, which are associated during meiosis. The C-positive blocks were located in the pericentromeric regions of the standard complement and along the entire length of the B chromosomes. Some G+C-rich heterochromatic blocks were noticed, including conspicuous blocks in the B chromosomes. The mapping of 18S rDNA and U2 snDNA revealed only autosomal clusters, and the telomeric probe hybridized in terminal regions. Finally, the DOP-PCR probe obtained from an individual without a B chromosome revealed signals in the heterochromatic regions, including the entire length of the B chromosome. The possible intraspecific origin of the B chromosomes, due to the shared pool of repetitive DNAs between the A and B chromosomes and the possible consequences of their association are discussed. PMID:27551344

  16. Deciphering evolutionary strata on plant sex chromosomes and fungal mating-type chromosomes through compositional segmentation.

    Science.gov (United States)

    Pandey, Ravi S; Azad, Rajeev K

    2016-03-01

    Sex chromosomes have evolved from a pair of homologous autosomes which differentiated into sex determination systems, such as XY or ZW system, as a consequence of successive recombination suppression between the gametologous chromosomes. Identifying the regions of recombination suppression, namely, the "evolutionary strata", is central to understanding the history and dynamics of sex chromosome evolution. Evolution of sex chromosomes as a consequence of serial recombination suppressions is well-studied for mammals and birds, but not for plants, although 48 dioecious plants have already been reported. Only two plants Silene latifolia and papaya have been studied until now for the presence of evolutionary strata on their X chromosomes, made possible by the sequencing of sex-linked genes on both the X and Y chromosomes, which is a requirement of all current methods that determine stratum structure based on the comparison of gametologous sex chromosomes. To circumvent this limitation and detect strata even if only the sequence of sex chromosome in the homogametic sex (i.e. X or Z chromosome) is available, we have developed an integrated segmentation and clustering method. In application to gene sequences on the papaya X chromosome and protein-coding sequences on the S. latifolia X chromosome, our method could decipher all known evolutionary strata, as reported by previous studies. Our method, after validating on known strata on the papaya and S. latifolia X chromosome, was applied to the chromosome 19 of Populus trichocarpa, an incipient sex chromosome, deciphering two, yet unknown, evolutionary strata. In addition, we applied this approach to the recently sequenced sex chromosome V of the brown alga Ectocarpus sp. that has a haploid sex determination system (UV system) recovering the sex determining and pseudoautosomal regions, and then to the mating-type chromosomes of an anther-smut fungus Microbotryum lychnidis-dioicae predicting five strata in the non

  17. Scaling Chromosomes for an Evolutionary Karyotype: A Chromosomal Tradeoff between Size and Number across Woody Species.

    Science.gov (United States)

    Liang, Guolu; Chen, Hong

    2015-01-01

    This study aims to examine the expected scaling relationships between chromosome size and number across woody species and to clarify the importance of the scaling for the maintenance of chromosome diversity by analyzing the scaling at the inter- & intra-chromosomal level. To achieve for the goals, chromosome trait data were extracted for 191 woody species (including 56 evergreen species and 135 deciduous species) from the available literature. Cross-species analyses revealed a tradeoff among chromosomes between chromosome size and number, demonstrating there is selective mechanism crossing chromosomes among woody species. And the explanations for the result were presented from intra- to inter-chromosome contexts that the scaling may be compromises among scale symmetry, mechanical requirements, and resource allocation across chromosomes. Therein, a 3/4 scaling pattern was observed between total chromosomes and m-chromosomes within nucleus which may imply total chromosomes may evolve from more to less. In addition, the primary evolutionary trend of karyotype and the role of m-chromosomes in the process of karyotype evolution were also discussed.

  18. Microdissection and chromosome painting of X and B chromosomes in Locusta migratoria.

    Science.gov (United States)

    Teruel, María; Cabrero, Josefa; Montiel, Eugenia E; Acosta, Manuel J; Sánchez, Antonio; Camacho, Juan Pedro M

    2009-01-01

    Acquisition of knowledge of the nature and DNA content of B chromosomes has been triggered by a collection of molecular techniques, one of which, microdissection, has provided interesting results in a number of B chromosome systems. Here we provide the first data on the molecular composition of B chromosomes in Locusta migratoria, after microdissection of the B and X chromosomes, DNA amplification by one (B) or two (X) different methods, and chromosome painting. The results showed that B chromosomes share at least two types of repetitive DNA sequences with the A chromosomes, suggesting that Bs in this species most likely arose intraspecifically. One of these repetitive DNAs is located on the heterochromatic distal half of the B chromosome and in the pericentromeric regions of about half of the A chromosomes, including the X. The other type of repetitive DNA is located interspersedly over the non-centromeric euchromatic regions of all A chromosomes and in an interstitial part of the proximal euchromatic half of the B chromosome. Chromosome painting, however, did not provide results sufficiently reliable to determine, in this species, which A chromosome gave rise to the B; this might be done by detailed analysis of the microdissected DNA sequences.

  19. Chromosome-specific segmentation revealed by structural analysis of individually isolated chromosomes.

    Science.gov (United States)

    Kitada, Kunio; Taima, Akira; Ogasawara, Kiyomoto; Metsugi, Shouichi; Aikawa, Satoko

    2011-04-01

    Analysis of structural rearrangements at the individual chromosomal level is still technologically challenging. Here we optimized a chromosome isolation method using fluorescent marker-assisted laser-capture and laser-beam microdissection and applied it to structural analysis of two aberrant chromosomes found in a lung cancer cell line. A high-density array-comparative genomic hybridization (array-CGH) analysis of DNA samples prepared from each of the chromosomes revealed that these two chromosomes contained 296 and 263 segments, respectively, ranging from 1.5 kb to 784.3 kb in size, derived from different portions of chromosome 8. Among these segments, 242 were common in both aberrant chromosomes, but 75 were found to be chromosome-specific. Sequences of 263 junction sites connecting the ends of segments were determined using a PCR/Sanger-sequencing procedure. Overlapping microhomologies were found at 169 junction sites. Junction partners came from various portions of chromosome 8 and no biased pattern in the positional distribution of junction partners was detected. These structural characteristics suggested the occurrence of random fragmentation of the entire chromosome 8 followed by random rejoining of these fragments. Based on that, we proposed a model to explain how these aberrant chromosomes are formed. Through these structural analyses, it was demonstrated that the optimized chromosome isolation method described here can provide high-quality chromosomal DNA for high resolution array-CGH analysis and probably for massively parallel sequencing analysis.

  20. Early detection of emphysema progression

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin;

    2010-01-01

    more sensitive estimates of emphysema progression. The standard CT densitometric score of emphysema is the relative area of voxels below a threshold (RA). The RA score is a global measurement and reflects the overall emphysema progression. In this work, we propose a framework for estimation of local...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...... score. We applied the proposed algorithm on 27 patients with severe emphysema with CT scans acquired five time points, at baseline, after 3, after 12, after 21 and after 24 or 30 months. The results showed consistent emphysema progression with time and the overall progression score correlates...

  1. Sexual maldevelopment and sex reversal, chromosomal causes.

    Science.gov (United States)

    Magenis, R Ellen

    2006-01-01

    The SRY gene on the Y chromosome is the testis determining factor (TDF). It is therefore the initial male determining factor. However, phenotypic sex determination includes a cascade of genes located on autosomes as well as sex chromosomes. Aberrations of these genes may cause sexual maldevelopment or sex reversal. Abnormalities may include single gene mutations and gene loss or gain-changes may involve only sex organs or may be part of syndromes. These changes may also arise as chromosome abnormalities involving contiguous genes. Eight cases with chromosomal abnormalities involving different causative mechanisms are described herein. The most common cause is nondisjunction, including loss or gain of sex chromosomes. Less common causes are mispairing and crossing over in meiosis, chromosome breaks with repair, nonhomologous pairing due to low copy repeats and crossing over, and translocation (familial or de novo) with segregation. Cases include: [see: text].

  2. Chromosome engineering: power tools for plant genetics.

    Science.gov (United States)

    Chan, Simon W L

    2010-12-01

    The term "chromosome engineering" describes technologies in which chromosomes are manipulated to change their mode of genetic inheritance. This review examines recent innovations in chromosome engineering that promise to greatly increase the efficiency of plant breeding. Haploid Arabidopsis thaliana have been produced by altering the kinetochore protein CENH3, yielding instant homozygous lines. Haploid production will facilitate reverse breeding, a method that downregulates recombination to ensure progeny contain intact parental chromosomes. Another chromosome engineering success is the conversion of meiosis into mitosis, which produces diploid gametes that are clones of the parent plant. This is a key step in apomixis (asexual reproduction through seeds) and could help to preserve hybrid vigor in the future. New homologous recombination methods in plants will potentiate many chromosome engineering applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Building bridges within the bacterial chromosome.

    Science.gov (United States)

    Song, Dan; Loparo, Joseph J

    2015-03-01

    All organisms must dramatically compact their genomes to accommodate DNA within the cell. Bacteria use a set of DNA-binding proteins with low sequence specificity called nucleoid-associated proteins (NAPs) to assist in chromosome condensation and organization. By bending or bridging DNA, NAPs also facilitate chromosome segregation and regulate gene expression. Over the past decade, emerging single-molecule and chromosome conformation capture techniques have investigated the molecular mechanisms by which NAPs remodel and organize the bacterial chromosome. In this review we describe how such approaches reveal the biochemical mechanisms of three NAPs that are believed to facilitate DNA bridging: histone-like nucleoid structuring protein (H-NS), ParB, and structural maintenance of chromosomes (SMC). These three proteins form qualitatively different DNA bridges, leading to varied effects on transcription and chromosome segregation.

  4. Fast chromosome karyotyping by auction algorithm.

    Science.gov (United States)

    Wu, Xiaolin; Dumitrescu, Sorina; Biyani, Pravesh; Wu, Qiang

    2005-01-01

    We consider the problem of automated classification of human chromosomes or karyotyping and study discrete optimisation algorithms to solve the problem as one of joint maximum likelihood classification. We demonstrate that the auction algorithm offers a simpler and more efficient solution for chromosome karyotyping than the previously known transportation algorithm, while still guaranteeing global optimality. This improvement in algorithm efficiency is made possible by first casting chromosome karyotyping into a problem of optimal assignment and then exploiting the sparsity of the assignment problem due to the inherent properties of chromosome data. Furthermore, the auction algorithm also works when the chromosome data in a cell are incomplete due to the exclusion of overlapped or severely bent chromosomes, as often encountered in routine quality data.

  5. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Gentile, Thomas R.

    2014-03-14

    We propose to extend the technique of polarized neutron scattering into new domains by continued development and application of polarized 3He spin-filters. These devices are particularly relevant to the Spallation Neutron Source, as the polarizing monochromators historically used at reactor sources will usually not be suitable polarizers, and wide-angle polarization analysis will be essential. With prior support from the Office of Science, we have developed neutron spin-filters based on the large spin dependence of the cross section for neutron capture by 3He, and applied these devices to a small angle neutron scattering spectrometer (SANS), polarized neutron reflectometers, a thermal energy single crystal diffractometer (SCD), and a thermal energy triple-axis instrument. Our developments have been adopted for application on the magnetism reflectometer at the SNS and for the NIST Center for Neutron Research (NCNR) 3He user capability. Results from both these programs are emerging. We have made significant progress in the past grant period on wide-angle polarization analysis. We have also performed several studies relevant to continuous optical pumping, including collaboration on experiments that have revealed neutron beam effects on spin filters that are continuously pumped by spin-exchange optical pumping. We contributed to an experiment on a neutron interferometer, in which the successful results obtained are directly related to both 3He cell technology and high accuracy 3He -based neutron polarimetry. Implementation of wide-angle polarization analysis will continue to be key thrust for our work in this new proposal. We will also focus on continuous optical pumping and the fundamental issues that determine the achievable 3He polarization. This project will be carried out by a collaboration involving scientists at NIST, Indiana University, Hamilton College, and the Univ. of Wisconsin who are experts in 3He polarization techniques, and materials scientists from the

  6. FINAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    PETER, GARY F. [UNIVERSITY OF FLORIDA

    2014-07-16

    Excellent progress was made in standardizing three complementary methods: Magnetic resonance imaging, x-ray micro CT, and MALDI imaging linear ion trap mass spectroscopy to image biomass and chemical, anatomical and functional changes that occur during pretreatment and hydrolysis. Magnetic resonance microscopy provides excellent images with as low as 5 uM resolution with hydrated biomass samples. We visualized dramatic changes in signal associated with the hydrolysis of the carbohydrates by strong acids. Quantitative diffusion approaches were used to probe more subtle structural changes in biomass. Diffusion tensor calculations reflect diffusion anisotropy and fractional anisotropy maps clearly show the longer range diffusion within the vessels compared to within the fiber cells. The diffusion is increased along the cell walls of the vessels. Suggesting that further research with NMR imaging should be pursued. X-ray CT provides excellent images at as low as 3.5 uM resolution from dried biomass. Small increases in surface area, and decreases in local density have been quantified in with wood after mild pretreatments; these changes are expected to be underestimates of the hydrated wood, due to the ~12% shrinkage that occurs upon drying untreated wood. MALDI-MS spectra show high ion intensities at most mass to charge ratios in untreated and pretreated woody material. MALDI-MSn is required to improve specificity and reduce background for imaging. MALDI-TOF is not specific enough for carbohydrate identification. Using MALDI-LIT/MSn we can readily identify oligomeric glucans and xylans and their fragmentation patterns as well as those of the glucuronic acid side chains of birch 4-O-methyl glucuronxylan. Imaging of glucan and xylan oligomers show that many contain isobaric ions with different distributions, indicating again that MSn is needed for accurate imaging of lignocellulosic materials. We are now starting to integrate the three imaging methods by using the same set

  7. Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma.

    Science.gov (United States)

    Spiegl-Kreinecker, S; Pirker, C; Marosi, C; Buchroithner, J; Pichler, J; Silye, R; Fischer, J; Micksche, M; Berger, W

    2007-03-26

    Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustine but responded to temozolomide after re-operation to temozolomide. The primary tumour -derived BTL1 cells showed chromosomal imbalances typical of highly aggressive glioblastomas. Interestingly, BTL2 cells established from the first recurrence developed under therapy showed signs of enhanced chromosomal instability. In contrast, BTL3 cells from the second recurrence resembled a less aggressive subclone of the primary tumour. Although BTL2 cells exhibited a highly aggressive phenotype, BTL3 cells were characterised by reduced proliferative and migratory potential. Despite persistent methylation of the O6-methylguanine-DNA methyltransferase promoter, BTL3 cells exhibited the highest temozolomide sensitivity. A comparable situation was found in two out of five glioblastoma patients, both characterised by enhanced survival time, who also relapsed after surgery/chemotherapy with less aggressive recurrences. Taken together, our data suggest that pretreated glioblastoma patients may relapse with highly chemosensitive tumours confirming the feasibility of temozolomide treatment even in case of repeated recurrence.

  8. Formation of chromosomal domains in interphase by loop extrusion

    Science.gov (United States)

    Fudenberg, Geoffrey

    While genomes are often considered as one-dimensional sequences, interphase chromosomes are organized in three dimensions with an essential role for regulating gene expression. Recent studies have shown that Topologically Associating Domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes. Despite observations that architectural proteins, including CTCF, demarcate and maintain the borders of TADs, the mechanisms underlying TAD formation remain unknown. Here we propose that loop extrusion underlies the formation TADs. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops, but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. This process dynamically forms loops of various sizes within but not between TADs. Using polymer simulations, we find that loop extrusion can produce TADs as determined by our analyses of the highest-resolution experimental data. Moreover, we find that loop extrusion can explain many diverse experimental observations, including: the preferential orientation of CTCF motifs and enrichments of architectural proteins at TAD boundaries; TAD boundary deletion experiments; and experiments with knockdown or depletion of CTCF, cohesin, and cohesin-loading factors. Together, the emerging picture from our work is that TADs are formed by rapidly associating, growing, and dissociating loops, presenting a clear framework for understanding interphase chromosomal organization.

  9. Chromosomal rearrangements in Tourette syndrome

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Debes, Nanette Mol; Hjermind, Lena E

    2013-01-01

    Tourette syndrome (TS) is a childhood-onset complex neurobiological disorder characterized by a combination of persistent motor and vocal tics and frequent presence of other neuropsychiatric comorbidities. TS shares the fate of other complex disorders, where the genetic etiology is largely unknown......, and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has...

  10. Meiosis I: When Chromosomes Undergo Extreme Makeover

    OpenAIRE

    Miller, Matthew P; Amon, Angelika; Ünal, Elçin

    2013-01-01

    The ultimate success of cell division relies on the accurate partitioning of the genetic material. Errors in this process occur in nearly all tumors and are the leading cause of miscarriages and congenital birth defects in humans. Two cell divisions, mitosis and meiosis, use common as well as unique mechanisms to ensure faithful chromosome segregation. In mitosis, alternating rounds of DNA replication and chromosome segregation preserves the chromosome complement of the progenitor cell. In co...

  11. Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute myeloid leukemia after hematopoietic cell transplantation.

    Science.gov (United States)

    Kelemen, Katalin; Galani, Komal; Conley, Christopher R; Greipp, Patricia T

    2014-06-01

    The acquisition of the Philadelphia chromosome (Ph) as a secondary change during the course of hematopoietic malignancies is rare and is associated with poor prognosis. Few cases of secondary Ph have been reported after hematopoietic cell transplantation (HCT). A secondary Ph at relapse is of clinical importance because it provides a therapeutic target for tyrosine kinase inhibitors along with or in replacement of chemotherapy. We describe a case of relapsed acute myeloid leukemia (AML) after HCT that developed a BCR-ABL1 translocation along with erythrophagocytosis by blasts as a secondary change at the time of relapse. The progression of this patient's myeloid neoplasm from myelodysplastic syndrome to AML to relapsed AML after HCT was accompanied by a stepwise cytogenetic evolution: A deletion 20q abnormality subsequently acquired a deletion 7q and, finally, at relapse after HCT, a secondary Ph was gained. The relationship between the secondary Ph and the erythrophagocytosis by blasts is not clear. We review the possible pathogenesis and cytogenetic associations of erythrophagocytosis by blasts, a rare feature in acute leukemias.

  12. Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication.

    Science.gov (United States)

    Lori, C; Ozaki, S; Steiner, S; Böhm, R; Abel, S; Dubey, B N; Schirmer, T; Hiller, S; Jenal, U

    2015-07-01

    Fundamental to all living organisms is the capacity to coordinate cell division and cell differentiation to generate appropriate numbers of specialized cells. Whereas eukaryotes use cyclins and cyclin-dependent kinases to balance division with cell fate decisions, equivalent regulatory systems have not been described in bacteria. Moreover, the mechanisms used by bacteria to tune division in line with developmental programs are poorly understood. Here we show that Caulobacter crescentus, a bacterium with an asymmetric division cycle, uses oscillating levels of the second messenger cyclic diguanylate (c-di-GMP) to drive its cell cycle. We demonstrate that c-di-GMP directly binds to the essential cell cycle kinase CckA to inhibit kinase activity and stimulate phosphatase activity. An upshift of c-di-GMP during the G1-S transition switches CckA from the kinase to the phosphatase mode, thereby allowing replication initiation and cell cycle progression. Finally, we show that during division, c-di-GMP imposes spatial control on CckA to install the replication asymmetry of future daughter cells. These studies reveal c-di-GMP to be a cyclin-like molecule in bacteria that coordinates chromosome replication with cell morphogenesis in Caulobacter. The observation that c-di-GMP-mediated control is conserved in the plant pathogen Agrobacterium tumefaciens suggests a general mechanism through which this global regulator of bacterial virulence and persistence coordinates behaviour and cell proliferation.

  13. Research on automatic human chromosome image analysis

    Science.gov (United States)

    Ming, Delie; Tian, Jinwen; Liu, Jian

    2007-11-01

    Human chromosome karyotyping is one of the essential tasks in cytogenetics, especially in genetic syndrome diagnoses. In this thesis, an automatic procedure is introduced for human chromosome image analysis. According to different status of touching and overlapping chromosomes, several segmentation methods are proposed to achieve the best results. Medial axis is extracted by the middle point algorithm. Chromosome band is enhanced by the algorithm based on multiscale B-spline wavelets, extracted by average gray profile, gradient profile and shape profile, and calculated by the WDD (Weighted Density Distribution) descriptors. The multilayer classifier is used in classification. Experiment results demonstrate that the algorithms perform well.

  14. Movement of chromosomes with severed kinetochore microtubules.

    Science.gov (United States)

    Forer, Arthur; Johansen, Kristen M; Johansen, Jørgen

    2015-05-01

    Experiments dating from 1966 and thereafter showed that anaphase chromosomes continued to move poleward after their kinetochore microtubules were severed by ultraviolet microbeam irradiation. These observations were initially met with scepticism as they contradicted the prevailing view that kinetochore fibre microtubules pulled chromosomes to the pole. However, recent experiments using visible light laser microbeam irradiations have corroborated these earlier experiments as anaphase chromosomes again were shown to move poleward after their kinetochore microtubules were severed. Thus, multiple independent studies using different techniques have shown that chromosomes can indeed move poleward without direct microtubule connections to the pole, with only a kinetochore 'stub' of microtubules. An issue not yet settled is: what propels the disconnected chromosome? There are two not necessarily mutually exclusive proposals in the literature: (1) chromosome movement is propelled by the kinetochore stub interacting with non-kinetochore microtubules and (2) chromosome movement is propelled by a spindle matrix acting on the stub. In this review, we summarise the data indicating that chromosomes can move with severed kinetochore microtubules and we discuss proposed mechanisms for chromosome movement with severed kinetochore microtubules.

  15. Genome architecture: domain organization of interphase chromosomes.

    Science.gov (United States)

    Bickmore, Wendy A; van Steensel, Bas

    2013-03-14

    The architecture of interphase chromosomes is important for the regulation of gene expression and genome maintenance. Chromosomes are linearly segmented into hundreds of domains with different protein compositions. Furthermore, the spatial organization of chromosomes is nonrandom and is characterized by many local and long-range contacts among genes and other sequence elements. A variety of genome-wide mapping techniques have made it possible to chart these properties at high resolution. Combined with microscopy and computational modeling, the results begin to yield a more coherent picture that integrates linear and three-dimensional (3D) views of chromosome organization in relation to gene regulation and other nuclear functions.

  16. Meiotic chromosome abnormalities in human spermatogenesis.

    Science.gov (United States)

    Martin, Renée H

    2006-08-01

    The last few years have witnessed an explosion in the information about chromosome abnormalities in human sperm and the meiotic events that predispose to these abnormalities. We have determined that all chromosomes are susceptible to nondisjunction, but chromosomes 21 and 22 and, especially, the sex chromosomes have an increased frequency of aneuploidy. Studies are just beginning on the effects of potential mutagens on the chromosomal constitution of human sperm. The effects of pesticides and cancer therapeutic agents have been reviewed. In the last decade, there has been a great impetus to study chromosome abnormalities in sperm from infertile men because the advent of intracytoplasmic sperm injection (ICSI) made it possible for these men to father pregnancies. A large number of studies have demonstrated that infertile men have an increased frequency of chromosomally abnormal sperm and children, even when they have a normal somatic karyotype. Meiotic studies on the pachytene stage of spermatogenesis have demonstrated that infertile men have impaired chromosome synapsis, a significantly decreased frequency of recombination, and an increased frequency of chromosomes completely lacking a recombination site. Such errors make these cells susceptible to meiotic arrest and the production of aneuploid gametes.

  17. Abrupt evolution of Philadelphia chromosome-positive acute myeloid leukemia in myelodysplastic syndrome.

    Science.gov (United States)

    Fukunaga, Akiko; Sakoda, Hiroto; Iwamoto, Yoshihiro; Inano, Shojiro; Sueki, Yuki; Yanagida, Soshi; Arima, Nobuyoshi

    2013-03-01

    Myelodysplastic syndrome (MDS) is a clonal disorder arising from an alteration in multipotent stem cells, which lose the ability of normal proliferation and differentiation. Disease progression occurs in approximately 30% MDS cases. Specific chromosomal alterations seem responsible for each step in the evolution of acute myeloid leukemia (AML). Multiple genetic aberrations occur during the clonal evolution of MDS; however, few studies report the presence of the Philadelphia (Ph) chromosome. We report a rare case of Ph-positive AML, which evolved during the course of low-risk MDS. The patient, a 76-year-old man with mild leukocytopenia, was diagnosed with MDS, refractory neutropenia (RN). After 1.5 yr, his peripheral blood and bone marrow were suddenly occupied by immature basophils and myeloblasts, indicating the onset of AML. A bone marrow smear showed multilineage dysplasia, consistent with MDS evolution. Chromosomal analysis showed an additional t(9;22)(q34;q11) translocation. Because progression occurred concurrently with emergence of the Ph chromosome, we diagnosed this case as Ph-positive AML with basophilia arising from the clonal evolution of MDS. The patient was initially treated with nilotinib. A hematological response was soon achieved with disappearance of the Ph chromosome in the bone marrow. Emergence of Ph-positive AML in the course of low-risk MDS has rarely been reported. We report this case as a rare clinical course of MDS.

  18. Abnormal meiotic recombination with complex chromosomal rearrangement in an azoospermic man.

    Science.gov (United States)

    Wang, Liu; Iqbal, Furhan; Li, Guangyuan; Jiang, Xiaohua; Bukhari, Ihtisham; Jiang, Hanwei; Yang, Qingling; Zhong, Liangwen; Zhang, Yuanwei; Hua, Juan; Cooke, Howard J; Shi, Qinghua

    2015-06-01

    Spermatocyte spreading and immunostaining were applied to detect meiotic prophase I progression, homologous chromosome pairing, synapsis and recombination in an azoospermic reciprocal translocation 46, XY, t(5;7;9;13)(5q11;7p11;7p15;9q12;13p12) carrier. Histological examination of the haematoxylin and eosin stained testicular sections revealed reduced germ cells with no spermatids or sperm in the patient. TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay showed apoptotic cells in testicular sections of translocation carrier. Immnunofluorescence analysis indicated the presence of an octavalent in all the pachytene spermatocytes analysed in the patient. Meiotic progression was disturbed, as an increase in zygotene (P recombination frequency was observed on 5p, 5q, 7q, 9p and 13q in the translocation carrier compared with the reported controls. A significant reduction in XY recombination frequency was also found in the participants. Our results indicated that complex chromosomal rearrangements can impair synaptic integrity of translocated chromosomes, which may reduce chromosomal recombination on translocated as well as non-translocated chromosomes, a phenomenon commonly known as interchromosomal effect.

  19. Chromosomal replicons of higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Van' t Hof, J.

    1987-03-16

    This brief discussion of replicons of higher plants offers a glimpse into the properties of chromosomal DNA replication. It gives evidence that the S phase of unrelated plant species is comprised of temporally ordered replicon families that increase in number with genome size. This orderly process, which assures a normal inheritance of genetic material to recipient daughter cells, is maintained at the level of replicon clusters by two mutually exclusive mechanisms, one involving the rate at which single replicons replicate their allotment of DNA, and another by means of the tempo-pause. The same two mechanisms are used by cells to alter the pattern of chromosomal DNA replication just prior to and during normal development. Both mechanisms are genetically determined and produce genetic effects when disturbed of disrupted by additional non-conforming DNAs. Further insight into how these two mechanisms operate requires more molecular information about the nature of replicons and the factors that govern when a replicon family replicates. Plant material is a rich and ideal source for this information just awaiting exploitation. 63 refs.

  20. Increased chromosome radiosensitivity during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard [Commissariat a l`Energie Atomique, Laboratoire de Radiobiologie et Oncologie, DRR, DSV, Fontenay aux roses (France)

    1997-03-04

    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions.

  1. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  2. 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 chromos...... 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....... 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...

  3. The Evolutionary Tempo of Sex Chromosome Degradation in Carica papaya.

    Science.gov (United States)

    Wu, Meng; Moore, Richard C

    2015-06-01

    Genes on non-recombining heterogametic sex chromosomes may degrade over time through the irreversible accumulation of deleterious mutations. In papaya, the non-recombining male-specific region of the Y (MSY) consists of two evolutionary strata corresponding to chromosomal inversions occurring approximately 7.0 and 1.9 MYA. The step-wise recombination suppression between the papaya X and Y allows for a temporal examination of the degeneration progress of the young Y chromosome. Comparative evolutionary analyses of 55 X/Y gene pairs showed that Y-linked genes have more unfavorable substitutions than X-linked genes. However, this asymmetric evolutionary pattern is confined to the oldest stratum, and is only observed when recently evolved pseudogenes are included in the analysis, indicating a slow degeneration tempo of the papaya Y chromosome. Population genetic analyses of coding sequence variation of six Y-linked focal loci in the oldest evolutionary stratum detected an excess of nonsynonymous polymorphism and reduced codon bias relative to autosomal loci. However, this pattern was also observed for corresponding X-linked loci. Both the MSY and its corresponding X-specific region are pericentromeric where recombination has been shown to be greatly reduced. Like the MSY region, overall selective efficacy on the X-specific region may be reduced due to the interference of selective forces between highly linked loci, or the Hill-Robertson effect, that is accentuated in regions of low or suppressed recombination. Thus, a pattern of gene decay on the X-specific region may be explained by relaxed purifying selection and widespread genetic hitchhiking due to its pericentromeric location.

  4. Initiation of chromosomal replication in predatory bacterium Bdellovibrio bacteriovorus

    Directory of Open Access Journals (Sweden)

    Lukasz Makowski

    2016-11-01

    Full Text Available Bdellovibrio bacteriovorus is a small Gram-negative predatory bacterium that attacks other Gram-negative bacteria, including many animal, human, and plant pathogens. This bacterium exhibits a peculiar biphasic life cycle during which two different types of cells are produced: non-replicating highly motile cells (the free-living phase and replicating cells (the intracellular-growth phase. The process of chromosomal replication in B. bacteriovorus must therefore be temporally and spatially regulated to ensure that it is coordinated with cell differentiation and cell cycle progression. Recently, B. bacteriovorus has received considerable research interest due to its intriguing life cycle and great potential as a prospective antimicrobial agent. Although we know that chromosomal replication in bacteria is mainly regulated at the initiation step, no data exists about this process in B. bacteriovorus. We report the first characterization of key elements of initiation of chromosomal replication – DnaA protein and oriC region from the predatory bacterium, B. bacteriovorus. In vitro studies using different approaches demonstrate that the B. bacteriovorus oriC (BdoriC is specifically bound and unwound by the DnaA protein. Sequence comparison of the DnaA-binding sites enabled us to propose a consensus sequence for the B. bacteriovorus DnaA box (5’-NN(A/TTCCACA-3’. Surprisingly, in vitro analysis revealed that BdoriC is also bound and unwound by the host DnaA proteins (relatively distantly related from B. bacteriovorus. We compared the architecture of the DnaA–oriC complexes (orisomes in homologous (oriC and DnaA from B. bacteriovorus and heterologous (BdoriC and DnaA from prey, E. coli or P. aeruginosa systems. This work provides important new entry points toward improving our understanding of the initiation of chromosomal replication in this predatory bacterium.

  5. Chromosomal Instability Confers Intrinsic Multi-Drug Resistance

    Science.gov (United States)

    Lee, Alvin J X; Endesfelder, David; Rowan, Andrew J; Walther, Axel; Birkbak, Nicolai J; Futreal, P Andrew; Downward, Julian; Szallasi, Zoltan; Tomlinson, Ian P M; Kschischo, Maik; Swanton, Charles

    2011-01-01

    Aneuploidy is associated with poor prognosis in solid tumours. Spontaneous chromosome mis-segregation events in aneuploid cells promote Chromosomal Instability (CIN) that may contribute to the acquisition of multi-drug resistance in vitro and heighten risk for tumour relapse in animal models. Identification of distinct therapeutic agents that target tumour karyotypic complexity has important clinical implications. In order to identify distinct therapeutic approaches to specifically limit the growth of CIN tumours we focussed on a panel of colorectal cancer (CRC) cell lines, previously classified as either chromosomally-unstable (CIN+) or diploid/near-diploid (CIN−), and treated them individually with a library of kinase inhibitors targeting components of signal transduction, cell cycle and trans-membrane receptor signalling pathways. CIN+ cell lines displayed significant intrinsic multi-drug resistance compared to CIN− cancer cell lines and this appeared to be independent of somatic mutation status and proliferation rate. Confirming the association of CIN rather than ploidy status with multi-drug resistance, tetraploid isogenic cells that had arisen from diploid cell lines displayed lower drug sensitivity than their diploid parental cells only with increasing chromosomal heterogeneity, and isogenic cell line models of CIN+ displayed multi-drug resistance relative to their CIN− parental cancer cell line derivatives. In a meta-analysis of CRC outcome following cytotoxic treatment, CIN+ predicted worse progression-free or disease-free survival relative to patients with CIN− disease. Our results suggest that stratifying tumour responses according to CIN status should be considered within the context of clinical trials to minimize the confounding effects of tumour CIN status on drug sensitivity. PMID:21363922

  6. Three-dimensional genome architecture influences partner selection for chromosomal translocations in human disease.

    Directory of Open Access Journals (Sweden)

    Jesse M Engreitz

    Full Text Available Chromosomal translocations are frequent features of cancer genomes that contribute to disease progression. These rearrangements result from formation and illegitimate repair of DNA double-strand breaks (DSBs, a process that requires spatial colocalization of chromosomal breakpoints. The "contact first" hypothesis suggests that translocation partners colocalize in the nuclei of normal cells, prior to rearrangement. It is unclear, however, the extent to which spatial interactions based on three-dimensional genome architecture contribute to chromosomal rearrangements in human disease. Here we intersect Hi-C maps of three-dimensional chromosome conformation with collections of 1,533 chromosomal translocations from cancer and germline genomes. We show that many translocation-prone pairs of regions genome-wide, including the cancer translocation partners BCR-ABL and MYC-IGH, display elevated Hi-C contact frequencies in normal human cells. Considering tissue specificity, we find that translocation breakpoints reported in human hematologic malignancies have higher Hi-C contact frequencies in lymphoid cells than those reported in sarcomas and epithelial tumors. However, translocations from multiple tissue types show significant correlation with Hi-C contact frequencies, suggesting that both tissue-specific and universal features of chromatin structure contribute to chromosomal alterations. Our results demonstrate that three-dimensional genome architecture shapes the landscape of rearrangements directly observed in human disease and establish Hi-C as a key method for dissecting these effects.

  7. Conservation of chromosomes syntenic with avian autosomes in squamate reptiles revealed by comparative chromosome painting.

    Science.gov (United States)

    Pokorná, Martina; Giovannotti, Massimo; Kratochvíl, Lukáš; Caputo, Vincenzo; Olmo, Ettore; Ferguson-Smith, Malcolm A; Rens, Willem

    2012-08-01

    In contrast to mammals, birds exhibit a slow rate of chromosomal evolution. It is not clear whether high chromosome conservation is an evolutionary novelty of birds or was inherited from an earlier avian ancestor. The evolutionary conservatism of macrochromosomes between birds and turtles supports the latter possibility; however, the rate of chromosomal evolution is largely unknown in other sauropsids. In squamates, we previously reported strong conservatism of the chromosomes syntenic with the avian Z, which could reflect a peculiarity of this part of the genome. The chromosome 1 of iguanians and snakes is largely syntenic with chromosomes 3, 5 and 7 of the avian ancestral karyotype. In this project, we used comparative chromosome painting to determine how widely this synteny is conserved across nine families covering most of the main lineages of Squamata. The results suggest that the association of the avian ancestral chromosomes 3, 5 and 7 can be dated back to at least the early Jurassic and could be an ancestral characteristic for Unidentata (Serpentes, Iguania, Anguimorpha, Laterata and Scinciformata). In Squamata chromosome conservatism therefore also holds for the parts of the genome which are homologous to bird autosomes, and following on from this, a slow rate of chromosomal evolution could be a common characteristic of all sauropsids. The large evolutionary stasis in chromosome organization in birds therefore seems to be inherited from their ancestors, and it is particularly striking in comparison with mammals, probably the only major tetrapod lineage with an increased rate of chromosomal rearrangements as a whole.

  8. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Wu, C.T.B.; Jones, S.M.

    1994-09-01

    Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North American kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.

  9. GAT 3 - fuel cells and their management (PACoGES). Progress report; GAT 3 - piles a combustible et leur gestion (PACoGES). Rapport final (juillet 2002 a juin 2004)

    Energy Technology Data Exchange (ETDEWEB)

    Lamy, C.

    2005-07-01

    The Topic Analysis Group PACoGES ('Piles a Combustible et leur Gestion') has conducted thoughts on fuel cells and their management with all the searchers concern with researches and developments on fuel cells and in particular on solid oxide fuel cells (SOFC, ITSOFC) running at high temperature (600 to 1000 C). This has concerned about 200 searchers working in about fifty laboratories (CNRS, CEA, EDF, GDF, INRETS, CNAM, Armines, and several industrial teams). Here is given the final report 2002-2004 concerning all the researches carried out by this Group. (O.M.)

  10. Effects of catalytic mineral matter on CO/CO{sub 2} temperature and burning time for char combustion. Quarterly progress report No. 15 (Final report), October 1993--December 1993

    Energy Technology Data Exchange (ETDEWEB)

    Longwell, J.P.; Sarofim, A.F.; Lee, C.H.

    1993-12-31

    The high temperature oxidation of char is of interest in a number of applications in which coal must be burned in confined spaces including the conversion of oil-fired boilers to coal using coal-water slurries, the development of a new generation of pulverized-coal-fired cyclone burners, the injection of coal into the tuyeres of blast furnaces, the use of coal as a fuel in direct-fired gas turbines and in large-bore low-speed diesels, and entrained flow gasifiers. There is a need to understand the temperature history of char particles in conventional pulverized-coal-fired boilers to better explain the processes governing the formation of pollutants and the transformation of mineral matter. The temperature of char particle burning is the product of a strongly coupled balance between particle physical properties, heat and mass transfer, surface reaction, and CO/CO{sub 2} ratio. Particle temperature has major effects not only on the burning rate but also on ash properties and mineral matter vaporization. Measurements of the temperature of individual burning char particles have clearly demonstrated large particle-to-particle temperature variations which depend strongly on particle size and on particle composition. This report consists of two major parts. In the first part, experimental measurements of CO/CO{sub 2} ratio for a single spherocarb particle is presented along with a kinetic model which allows estimation of CO/CO{sub 2} generated at a carbon surface for temperatures higher than those reported in the experimental work. In the second part, modeling of a temperature profile during a char combustion is reported, and also progress in modeling the complex sets of coupled phenomena involving full gas phase reaction kinetics, heat transfer, and mass transfer is summarized. In the appendix progress on construction and testing of an improved electrodynamic balance is presented.

  11. Chromosomal rearrangements and the pathogenesis of differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Stefan K.G. Grebe

    2011-12-01

    Full Text Available The majority of thyroid cancers arise from the follicular cells of the thyroid gland, which yield a wide variety of distinct morphotypes, ranging from relatively indolent lesions to the most malignant forms of cancer known. The remaining primary thyroid cancers arise from C cells within the gland and result primarily from mutations of the RET protooncogene, germ line mutations of which give rise to the various forms of multiple endocrine neoplasia. The most common of the follicular cell-derived cancers are papillary carcinomas, (PTC, followed by follicular carcinomas (FTC and its Hurthle cell variant (HCC and finally anaplastic carcinomas (ATC. The pathogenesis of many thyroid cancers, of both PTC and FTC morphotype, involves chromosomal translocations. Rearrangements of the RET protoconcogene are known to be involved in the pathogenesis of ca. 50% of PTC. A similar proportion of FTC have been associated with a t(2;3(q13;p25 translocation, fusing the thyroid-specific transcription factor PAX8 with the peroxisome proliferator-activated receptor gamma (PPARγ nuclear receptor, a ubiquitously expressed transcription factor. These rearrangements have analogy with translocations in erythropoetic cells, which form the only other known group of human malignancies that are largely the result of chromosomal translocation events. In this review we compare and contrast the oncogenic properties of thyroid and erythroid chromosomal transformations and speculate on mechanisms leading to their formation.

  12. Refining the Y chromosome phylogeny with southern African sequences.

    Science.gov (United States)

    Barbieri, Chiara; Hübner, Alexander; Macholdt, Enrico; Ni, Shengyu; Lippold, Sebastian; Schröder, Roland; Mpoloka, Sununguko Wata; Purps, Josephine; Roewer, Lutz; Stoneking, Mark; Pakendorf, Brigitte

    2016-05-01

    The recent availability of large-scale sequence data for the human Y chromosome has revolutionized analyses of and insights gained from this non-recombining, paternally inherited chromosome. However, the studies to date focus on Eurasian variation, and hence the diversity of early-diverging branches found in Africa has not been adequately documented. Here, we analyze over 900 kb of Y chromosome sequence obtained from 547 individuals from southern African Khoisan- and Bantu-speaking populations, identifying 232 new sequences from basal haplogroups A and B. We identify new clades in the phylogeny, an older age for the root, and substantially older ages for some individual haplogroups. Furthermore, while haplogroup B2a is traditionally associated with the spread of Bantu speakers, we find that it probably also existed in Khoisan groups before the arrival of Bantu speakers. Finally, there is pronounced variation in branch length between major haplogroups; in particular, haplogroups associated with Bantu speakers have significantly longer branches. Technical artifacts cannot explain this branch length variation, which instead likely reflects aspects of the demographic history of Bantu speakers, such as recent population expansion and an older average paternal age. The influence of demographic factors on branch length variation has broader implications both for the human Y phylogeny and for similar analyses of other species.

  13. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae

    Directory of Open Access Journals (Sweden)

    Artoni Roberto F

    2011-07-01

    Full Text Available Abstract Background The Characidium (a Neotropical fish group have a conserved diploid number (2n = 50, but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR. In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.

  14. Aberrations of chromosome 8 in myelodysplastic syndromes: Clinical and biological significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2006-01-01

    Full Text Available Introduction: Rearrangements of any single chromosome in human karyotype have been reported in patients with pMDS. Objective: To examine the role of aberrations of chromosome 8 in pathogenesis, clinical presentation and progression of myelodysplastic syndromes. Method: Cytogenetic analysis of bone marrow cells was carried out by direct method and by means of 24- and/or 48-hour unstimulated cell culture. Chromosomes were obtained by modified method of HG-bands. Results: On presentation, 109 out of 271 successfully karyotyped patients (40,2% had abnormal karyotypes. Among them, 22 patients (10.9% had aberrations of chromosome 8. Ten patients had trisomy 8 as "simple" aberration whilst additional three cases had trisomy 8 included in "complex" karyotypes (≥3 chromosomes. Cases with constitutional trisomy 8 mosaicism (CT8M were excluded using the chromosome analyses of PHA-stimulated blood cultures. On the contrary, monosomy (seven patients or deletion of chromosome 8 (two patients were exclusively found in "complex" karyotypes. During prolonged cytogenetic follow-up, trisomy 8 was not recorded in evolving karyotypes. In contrast, trisomy 8 disappeared in two cases during subsequent cytogenetic studies, i.e. 23 and 72 months from diagnosis, accompanied in one patient with complete hematological remission. No difference regarding age, sex, cytopenia, blood and marrow blast count or response to treatment was found between patients with trisomy 8 as the sole aberration compared to those with normal cytogenetics. Median survival of patients with trisomy 8 as the sole aberration was 27 months, as compared to 32 months in patients with normal cytogenetics (p=0.468, whilst median survival of patients with aberrations of chromosome 8 included in "complex" karyotypes was only 4 months. Conclusion: Aberrations of chromosome 8 are common in patients with pMDS. The presence of a clone with trisomy 8 is not always the sign of disease progression or poor

  15. Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome integrity are linked to telomere function.

    Directory of Open Access Journals (Sweden)

    Kaitlin M Stimpson

    Full Text Available The short arms of the ten acrocentric human chromosomes share several repetitive DNAs, including ribosomal RNA genes (rDNA. The rDNA arrays correspond to nucleolar organizing regions that coalesce each cell cycle to form the nucleolus. Telomere disruption by expressing a mutant version of telomere binding protein TRF2 (dnTRF2 causes non-random acrocentric fusions, as well as large-scale nucleolar defects. The mechanisms responsible for acrocentric chromosome sensitivity to dysfunctional telomeres are unclear. In this study, we show that TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal changes occur. We used the controllable dnTRF2 system to precisely dissect the timing and progression of nucleolar and chromosomal instability induced by telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage and morphological changes that occur at acrocentric short arms. The rDNA repeat arrays on the short arms decondense, and are coated by RNA polymerase I transcription binding factor UBF, physically linking acrocentrics to one another as they become fusogenic. These results highlight the importance of telomere function in nucleolar stability and structural integrity of acrocentric chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to cause DNA damage at chromosome ends, but our findings suggest that it also disrupts chromosome structure beyond the telomere region, specifically within the rDNA arrays located on acrocentric chromosomes. These results have relevance for Robertsonian translocation formation in humans and mechanisms by which acrocentric-acrocentric fusions are promoted by DNA damage and repair.

  16. 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.

  17. Inheritance of a ring 14 chromosome.

    Science.gov (United States)

    Riley, S B; Buckton, K E; Ratcliffe, S G; Syme, J

    1981-06-01

    A family is described in which the mother, her two live offspring, and a therapeutically aborted fetus each had a ring 14 chromosomes. The two children were mentally retarded and the mother's intelligence was at the lower end of the normal range. In addition, the mother had two spontaneous abortions, one of which was shown to be chromosomally normal.

  18. Inheritance of a ring 14 chromosome.

    OpenAIRE

    Riley, S B; Buckton, K E; Ratcliffe, S G; Syme, J.

    1981-01-01

    A family is described in which the mother, her two live offspring, and a therapeutically aborted fetus each had a ring 14 chromosomes. The two children were mentally retarded and the mother's intelligence was at the lower end of the normal range. In addition, the mother had two spontaneous abortions, one of which was shown to be chromosomally normal.

  19. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    Directory of Open Access Journals (Sweden)

    Maria Maurer

    2015-07-01

    Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

  20. Genomic Dark Matter Illuminated: Anopheles Y Chromosomes.

    Science.gov (United States)

    Redmond, Seth N; Neafsey, Daniel E

    2016-08-01

    Hall et al. have strategically used long-read sequencing technology to characterize the structure and highly repetitive content of the Y chromosome in Anopheles malaria mosquitoes. Their work confirms that this important but elusive heterochromatic sex chromosome is evolving extremely rapidly and harbors a remarkably small number of genes.

  1. Non-disjunction of chromosome 13

    DEFF Research Database (Denmark)

    Bugge, Merete; Collins, Andrew; Hertz, Jens Michael

    2007-01-01

    recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms...

  2. Chromosome condensation: weaving an untangled web.

    Science.gov (United States)

    Thadani, Rahul; Uhlmann, Frank

    2015-08-03

    The compaction of diffuse interphase chromatin into stable mitotic chromosomes enables the segregation of replicated DNA to daughter cells. Two new studies characterise, both in vivo and in vitro, the essential contribution of the vertebrate condensin complex to chromosome organisation.

  3. Chromosome Segregation: Organizing Overlap at the Midzone

    NARCIS (Netherlands)

    Janson, M.E.; Tran, P.T.

    2008-01-01

    Sets of overlapping microtubules support the segregation of chromosomes by linking the poles of mitotic spindles. Recent work examines the effect of putting these linkages under pressure by the activation of dicentric chromosomes and sheds new light on the structural role of several well-known spind

  4. Paradigm Lost: The Human Chromosome Story.

    Science.gov (United States)

    Unger, Lawrence; Blystone, Robert V.

    1996-01-01

    Discusses whether the discovery in 1956 that humans have a chromosome number of 46, as opposed to 47 or 48 as previously thought, fits into a paradigm shift of the Kuhnian type. Concludes that Kuhn probably would not have considered the chromosome number shift to be large enough to be a focus for one of his paradigms. (AIM)

  5. Human male meiotic sex chromosome inactivation

    NARCIS (Netherlands)

    Vries, M. de; Vosters, S.; Merkx, G.F.M.; Hauwers, K.W.M. d'; Wansink, D.G.; Ramos, L.; Boer, P. de

    2012-01-01

    In mammalian male gametogenesis the sex chromosomes are distinctive in both gene activity and epigenetic strategy. At first meiotic prophase the heteromorphic X and Y chromosomes are placed in a separate chromatin domain called the XY body. In this process, X,Y chromatin becomes highly phosphorylate

  6. Human male meiotic sex chromosome inactivation

    NARCIS (Netherlands)

    Vries, M. de; Vosters, S.; Merkx, G.F.M.; Hauwers, K.W.M. d'; Wansink, D.G.; Ramos, L.; Boer, P. de

    2012-01-01

    In mammalian male gametogenesis the sex chromosomes are distinctive in both gene activity and epigenetic strategy. At first meiotic prophase the heteromorphic X and Y chromosomes are placed in a separate chromatin domain called the XY body. In this process, X,Y chromatin becomes highly

  7. Chromosome morphometry in opisthorchiid species (Platyhelminthes, Trematoda).

    Science.gov (United States)

    Zadesenets, Kira S; Polyakov, Andrey V; Katokhin, Alexey V; Mordvinov, Viatcheslav A; Rubtsov, Nikolay B

    2017-08-01

    Few existing studies have dealt with cytogenetics in trematodes, largely due to the attendant technical difficulty of chromosome preparation. We performed a comparative analysis of chromosomes in five opistorchiid species, including Opisthorchis felineus Rivolta, 1884, Opisthorchis viverrini Poirier, 1886, Clonorchis sinensis Cobbold, 1875, Metorchis xanthosomus Creplin 1846, and Metorchis bilis (Braun, 1790) Odening, 1962. For some of these species, no detailed morphometric description of their karyotypes has yet been published; for the karyotype of Metorchis bilis this is the first-ever description. We found that opisthorchiids, like other trematodes, are characterized by karyotypic conservatism (N=6-7) and karyotype asymmetry, although comparison of chromosome morphometric traits did reveal differences between the karyotypes of the species. Moreover, to address certain a methodological issue in trematode chromosome preparation, we analyzed how the source of chromosomal material (partenitae or mature flukes) and the chromosome preparation techniques used (air-drying and cell suspension methods) affected chromosome spreading and size, concluding that the most reliable comparative method involves comparing relative parameters (relative length, arm ratio, centromeric index) of chromosomes prepared using the same technique. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. [CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH INFERTILITY].

    Science.gov (United States)

    Pylyp, L Y; Spinenko, L O; Verhoglyad, N V; Kashevarova, O O; Zukin, V D

    2015-01-01

    To assess the frequency and structure of chromosomal abnormalities in patients with infertility, a retrospective analysis of cytogenetic studies of 3414 patients (1741 females and 1673 males), referred to the Clinic of reproductive medicine "Nadiya" from 2007 to 2012, was performed. Chromosomal abnormalities were detected in 2.37% patients: 2.79% in males and 1.95% in females. Balanced structural chromosomal abnormalities prevailed over numerical abnormalities and corresponded to 80.2% of all chromosomal abnormalities detected in the studied group. Sex chromosome abnormalities made up 23.5% of chromosomal pathology (19/81) and included gonosomal aneuploidies in 84% of cases (16/19) and structural abnormalities of chromosome Y in 16% of cases (3/19). The low level sex chromosome mosaicism was detected with the frequency of 0.55%. Our results highlight the importance of cytogenetic studies in patients seeking infertility treatment by assisted reproductive technologies, since an abnormal finding not only provide a firm diagnosis to couples with infertility, but also influences significantly the approach to infertility treatment in such patients.

  9. Small supernumerary marker chromosomes (sSMC) in humans; are there B chromosomes hidden among them

    OpenAIRE

    Ogilvie Caroline; Kosyakova Nadezda; Mrasek Kristin; Liehr Thomas; Vermeesch Joris; Trifonov Vladimir; Rubtsov Nikolai

    2008-01-01

    Abstract Background Small supernumerary marker chromosomes (sSMC) and B-chromosomes represent a heterogeneous collection of chromosomes added to the typical karyotype, and which are both small in size. They may consist of heterochromatic and/or euchromatic material. Also a predominance of maternal transmission was reported for both groups. Even though sSMC and B-chromosomes show some similarity it is still an open question if B-chromosomes are present among the heterogeneous group of sSMC. Ac...

  10. DETECTION OF CHROMOSOME ABERRATIONS IN TWELVE PRIMARY GASTRIC CANCERS BY DIRECT CHROMOSOME ANALYSIS AND FISH

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Direct chromosome analysis and FISH were performed on twelve primary gastric carcinomas. Two of them had simple chromosome changes: 48,XX, +8, +20, and 49, XY, +2, +8, +9, and the others had complicated chromosome changes, which includes much more numerical and structural chromosome aberrations. Frequent structural changes in the complicated types involved chromosome 7, 3, 1, 5 and 12 etc. The del 7q was noted in eight cases. The del (3p) and del (1p) were noted in six and five cases, respectively. The results provide some important clues for isolation of the genes related to gastric cancer.

  11. Advances in understanding paternally transmitted Chromosomal Abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate the types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.

  12. Review of the Y chromosome and hypertension

    Directory of Open Access Journals (Sweden)

    D. Ely

    2000-06-01

    Full Text Available The Y chromosome from spontaneously hypertensive rats (SHR has a locus that raises blood pressure 20-25 mmHg. Associated with the SHR Y chromosome effect is a 4-week earlier pubertal rise of testosterone and dependence upon the androgen receptor for the full blood pressure effect. Several indices of enhanced sympathetic nervous system (SNS activity are also associated with the SHR Y chromosome. Blockade of SNS outflow reduced the blood pressure effect. Salt sensitivity was increased by the Y chromosome as was salt appetite which was SNS dependent. A strong correlation (r = 0.57, P<0.001 was demonstrable between plasma testosterone and angiotensin II. Coronary collagen increased with blood pressure and the presence of the SHR Y chromosome. A promising candidate gene for the Y effect is the Sry locus (testis determining factor, a transcription factor which may also have other functions.

  13. Temporal genomic evolution of bird sex chromosomes

    DEFF Research Database (Denmark)

    Wang, Zongji; Zhang, Jilin; Yang, Wei;

    2014-01-01

    BACKGROUND: Sex chromosomes exhibit many unusual patterns in sequence and gene expression relative to autosomes. Birds have evolved a female heterogametic sex system (male ZZ, female ZW), through stepwise suppression of recombination between chrZ and chrW. To address the broad patterns and complex...... driving forces of Z chromosome evolution, we analyze here 45 newly available bird genomes and four species' transcriptomes, over their course of recombination loss between the sex chromosomes. RESULTS: We show Z chromosomes in general have a significantly higher substitution rate in introns and synonymous...... changes with that of introns, between chrZ and autosomes or regions with increasing ages of becoming Z-linked, therefore codon usage bias in birds is probably driven by the mutational bias. On the other hand, Z chromosomes also evolve significantly faster at nonsynonymous sites relative to autosomes...

  14. Structure and dynamics of interphase chromosomes.

    Directory of Open Access Journals (Sweden)

    Angelo Rosa

    Full Text Available During interphase chromosomes decondense, but fluorescent in situ hybridization experiments reveal the existence of distinct territories occupied by individual chromosomes inside the nuclei of most eukaryotic cells. We use computer simulations to show that the existence and stability of territories is a kinetic effect that can be explained without invoking an underlying nuclear scaffold or protein-mediated interactions between DNA sequences. In particular, we show that the experimentally observed territory shapes and spatial distances between marked chromosome sites for human, Drosophila, and budding yeast chromosomes can be reproduced by a parameter-free minimal model of decondensing chromosomes. Our results suggest that the observed interphase structure and dynamics are due to generic polymer effects: confined Brownian motion conserving the local topological state of long chain molecules and segregation of mutually unentangled chains due to topological constraints.

  15. Unusual maternal uniparental isodisomic x chromosome mosaicism with asymmetric y chromosomal rearrangement.

    Science.gov (United States)

    Lee, B Y; Kim, S Y; Park, J Y; Choi, E Y; Kim, D J; Kim, J W; Ryu, H M; Cho, Y H; Park, S Y; Seo, J T

    2014-01-01

    Infertile men with azoospermia commonly have associated microdeletions in the azoospermia factor (AZF) region of the Y chromosome, sex chromosome mosaicism, or sex chromosome rearrangements. In this study, we describe an unusual 46,XX and 45,X mosaicism with a rare Y chromosome rearrangement in a phenotypically normal male patient. The patient's karyotype was 46,XX[50]/45,X[25]/46,X,der(Y)(pter→q11.222::p11.2→pter)[25]. The derivative Y chromosome had a deletion at Yq11.222 and was duplicated at Yp11.2. Two copies of the SRY gene were confirmed by fluorescence in situ hybridization analysis, and complete deletion of the AZFb and AZFc regions was shown by multiplex-PCR for microdeletion analysis. Both X chromosomes of the predominant mosaic cell line (46,XX) were isodisomic and derived from the maternal gamete, as determined by examination of short tandem repeat markers. We postulate that the derivative Y chromosome might have been generated during paternal meiosis or early embryogenesis. Also, we suggest that the very rare mosaicism of isodisomic X chromosomes might be formed during maternal meiosis II or during postzygotic division derived from the 46,X,der(Y)/ 45,X lineage because of the instability of the derivative Y chromosome. To our knowledge, this is the first confirmatory study to verify the origin of a sex chromosome mosaicism with a Y chromosome rearrangement.

  16. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men.

    Science.gov (United States)

    Fu, Li; Xiong, Da-Ke; Ding, Xian-Ping; Li, Chuang; Zhang, Li-Yuan; Ding, Min; Nie, Shuang-Shuang; Quan, Qiang

    2012-06-01

    To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men. This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia. Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls. There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

  17. Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos.

    Science.gov (United States)

    Rodrigo, Lorena; Peinado, Vanessa; Mateu, Emilia; Remohí, José; Pellicer, Antonio; Simón, Carlos; Gil-Salom, Manuel; Rubio, Carmen

    2010-09-01

    To evaluate the effect of sperm chromosome abnormalities--disomy for sex chromosomes and diploidy--in the chromosomal constitution of preimplantation embryos. Retrospective cohort study. Infertility clinic. Three groups: 46,XY infertile men with increased incidence of sex chromosome disomy in sperm; 46,XY infertile men with increased diploidy rates in sperm; 47,XYY infertile men with increased sex chromosome disomy and diploidy rates in sperm. Sperm collection for fluorescence in situ hybridization analysis. Embryo biopsy for preimplantation genetic screening. Frequencies of numerical abnormalities in sperm for chromosomes 13, 18, 21, X, and Y, and in embryos for chromosomes 13, 16, 18, 21, 22, X, and Y. A significant increase of chromosomally abnormal and mosaic embryos was observed in the three study groups compared with controls. Those sperm samples with increased sex chromosome disomy rates produced significantly higher percentages of aneuploid embryos, with a threefold increase for sex chromosomes. Sperm samples with increased diploidy rates were mainly associated to the production of triploid embryos. A strong correlation between sperm and embryo chromosomal constitution has been shown in infertile men with 46,XY and 47,XYY karyotypes. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Comparative analysis by chromosome painting of the sex chromosomes in arvicolid rodents.

    Science.gov (United States)

    Acosta, M J; Romero-Fernández, I; Sánchez, A; Marchal, J A

    2011-01-01

    Sex chromosome evolution in mammals has been extensively investigated through chromosome-painting analyses. In some rodent species from the subfamily Arvicolinae the sex chromosomes contain remarkable features such as giant size, a consequence of heterochromatic enlargement, or asynaptic behaviour during male meiosis. Here, we have made a comparative study of the sex chromosomes in 6 arvicolid species using different probes from the X and Y chromosomes of 3 species, in order to gain knowledge about intra- or interspecific preservation of euchromatic regions. Our results clearly reveal poor conservation of the euchromatic region of the Y chromosome within these species, while the euchromatin on the X chromosome is extremely well preserved. Furthermore, we detected no clear correlation between the synaptic/asynaptic behaviour of the sex chromosomes, and the presence or absence of sequence homology within their euchromatic regions. Notably, our study has shown a new relationship between the giant sex chromosomes of 2 species, Microtus agrestis and Microtus cabrerae, that is, both X and Y share a novel region of common sequences in the euchromatin that is not present in the other species analysed. This interspecific euchromatic conservation, limited to the giant sex chromosomes, could point towards a common evolutionary origin for the heterochromatic enlargement process that has characterized the evolution of the sex chromosomes in some arvicolid species.

  19. Productization and Manufacturing Scaling of High-Efficiency Solar Cell and Module Products Based on a Disruptive Low-Cost, Mono-Crystalline Technology: Final Technical Progress Report, April 1, 2009 - December 30, 2010

    Energy Technology Data Exchange (ETDEWEB)

    Fatemi, H.

    2012-07-01

    Final report for PV incubator subcontract with Solexel, Inc. The purpose of this project was to develop Solexel's Unique IP, productize it, and transfer it to manufacturing. Silicon constitutes a significant fraction of the total solar cell cost, resulting in an industry-wide drive to lower silicon usage. Solexel's disruptive Solar cell structure got around these challenges and promised superior light trapping, efficiency and mechanical strength, despite being significantly thinner than commercially available cells. Solexel's successful participation in this incubator project became evident as the company is now moving into commercial production and position itself to be competitive for the next Technology Pathway Partnerships (TPP) funding opportunity.

  20. Alterations at chromosome 17 loci in peripheral nerve sheath tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lothe, R.A.; Slettan, A.; Saeter, G. [Norwegian Radium Hospital, Oslo (Norway)] [and others

    1995-01-01

    Little is known about the molecular genetic changes in malignant peripheral nerve sheath tumors (MPNST). Inactivation of the TP53 gene in l7p has been reported in a few tumors. The MPNST is one of the manifestations of neurofibromatosis 1 (NF1), suggesting that the NF1 gene in 17q might be important. We present a study of 15 neurofibromas and MPNST from nine individuals. Seven patients had NF1 and six of these developed MPNST. Genetic alterations at nine polymorphic loci on chromosome 17 were examined. Allelic imbalance was detected only in the malignant tumors from NF1 patients (4/6). Complete loss of heterozygosity of 17q loci was found in three of these tumors, all including loci within the NF1 gene. Two of the malignant tumors also showed deletions on 17p. No mutations were detected within exon 5-8 of the TP53 in any of the MPNST, and none of them were TP53 protein-positive using immunostaining with mono- and polyclonal antibodies against TP53. The numbers of chromosome 17 present in each tumor were evaluated by use of fluorescence in situ hybridization (FISH) on interphase nuclei with a centromere-specific probe. A deviation from the disomic status of chromosome 17 was observed in two of the MPNST from NF1 patients. These results support the hypothesis of inactivation of both NF1 gene alleles during development of MPNST in patients with NF1. In contrast to other reports, we did not find evidence for a homozygous mutated condition of the TP53 gene in the same tumors. Finally, FISH analysis was in accordance with the DNA analysis in the deduction of the numbers of chromosome 17 in these tumors. 29 refs., 3 figs., 2 tabs.

  1. New Y chromosomes and early stages of sex chromosome differentiation: sex determination in Megaselia

    Indian Academy of Sciences (India)

    Walther Traut

    2010-09-01

    The phorid fly Megaselia scalaris is a laboratory model for the turnover and early differentiation of sex chromosomes. Isolates from the field have an XY sex-determining mechanism with chromosome pair 2 acting as X and Y chromosomes. The sex chromosomes are homomorphic but display early signs of sex chromosome differentiation: a low level of molecular differences between X and Y. The male-determining function $(M)$, maps to the distal part of the Y chromosome’s short arm. In laboratory cultures, new Y chromosomes with no signs of a molecular differentiation arise at a low rate, probably by transposition of to these chromosomes. Downstream of the primary signal, the homologue of the Drosophila doublesex (dsx) is part of the sex-determining pathway while Sex-lethal (Sxl), though structurally conserved, is not.

  2. Novel gene acquisition on carnivore Y chromosomes.

    Directory of Open Access Journals (Sweden)

    William J Murphy

    2006-03-01

    Full Text Available Despite its importance in harboring genes critical for spermatogenesis and male-specific functions, the Y chromosome has been largely excluded as a priority in recent mammalian genome sequencing projects. Only the human and chimpanzee Y chromosomes have been well characterized at the sequence level. This is primarily due to the presumed low overall gene content and highly repetitive nature of the Y chromosome and the ensuing difficulties using a shotgun sequence approach for assembly. Here we used direct cDNA selection to isolate and evaluate the extent of novel Y chromosome gene acquisition in the genome of the domestic cat, a species from a different mammalian superorder than human, chimpanzee, and mouse (currently being sequenced. We discovered four novel Y chromosome genes that do not have functional copies in the finished human male-specific region of the Y or on other mammalian Y chromosomes explored thus far. Two genes are derived from putative autosomal progenitors, and the other two have X chromosome homologs from different evolutionary strata. All four genes were shown to be multicopy and expressed predominantly or exclusively in testes, suggesting that their duplication and specialization for testis function were selected for because they enhance spermatogenesis. Two of these genes have testis-expressed, Y-borne copies in the dog genome as well. The absence of the four newly described genes on other characterized mammalian Y chromosomes demonstrates the gene novelty on this chromosome between mammalian orders, suggesting it harbors many lineage-specific genes that may go undetected by traditional comparative genomic approaches. Specific plans to identify the male-specific genes encoded in the Y chromosome of mammals should be a priority.

  3. A molecularly defined duplication set for the X chromosome of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Venken, Koen J. T.; Popodi, Ellen; Holtzman, Stacy L.; Schulze, Karen L.; Park, Soo; Carlson, Joseph W.; Hoskins, Roger A.; Bellen, Hugo J.; Kaufman, Thomas C.

    2010-07-22

    We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using C31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.

  4. The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.

    Science.gov (United States)

    Huang, Chun-Jie; Yuan, Yi-Feng; Wu, Di; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Huo, Li-Jun

    2017-03-01

    Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.

  5. The two Cis-acting sites, parS1 and oriC1, contribute to the longitudinal organisation of Vibrio cholerae chromosome I.

    Directory of Open Access Journals (Sweden)

    Ariane David

    2014-07-01

    Full Text Available The segregation of bacterial chromosomes follows a precise choreography of spatial organisation. It is initiated by the bipolar migration of the sister copies of the replication origin (ori. Most bacterial chromosomes contain a partition system (Par with parS sites in close proximity to ori that contribute to the active mobilisation of the ori region towards the old pole. This is thought to result in a longitudinal chromosomal arrangement within the cell. In this study, we followed the duplication frequency and the cellular position of 19 Vibrio cholerae genome loci as a function of cell length. The genome of V. cholerae is divided between two chromosomes, chromosome I and II, which both contain a Par system. The ori region of chromosome I (oriI is tethered to the old pole, whereas the ori region of chromosome II is found at midcell. Nevertheless, we found that both chromosomes adopted a longitudinal organisation. Chromosome I extended over the entire cell while chromosome II extended over the younger cell half. We further demonstrate that displacing parS sites away from the oriI region rotates the bulk of chromosome I. The only exception was the region where replication terminates, which still localised to the septum. However, the longitudinal arrangement of chromosome I persisted in Par mutants and, as was reported earlier, the ori region still localised towards the old pole. Finally, we show that the Par-independent longitudinal organisation and oriI polarity were perturbed by the introduction of a second origin. Taken together, these results suggest that the Par system is the major contributor to the longitudinal organisation of chromosome I but that the replication program also influences the arrangement of bacterial chromosomes.

  6. The two Cis-acting sites, parS1 and oriC1, contribute to the longitudinal organisation of Vibrio cholerae chromosome I.

    Science.gov (United States)

    David, Ariane; Demarre, Gaëlle; Muresan, Leila; Paly, Evelyne; Barre, François-Xavier; Possoz, Christophe

    2014-07-01

    The segregation of bacterial chromosomes follows a precise choreography of spatial organisation. It is initiated by the bipolar migration of the sister copies of the replication origin (ori). Most bacterial chromosomes contain a partition system (Par) with parS sites in close proximity to ori that contribute to the active mobilisation of the ori region towards the old pole. This is thought to result in a longitudinal chromosomal arrangement within the cell. In this study, we followed the duplication frequency and the cellular position of 19 Vibrio cholerae genome loci as a function of cell length. The genome of V. cholerae is divided between two chromosomes, chromosome I and II, which both contain a Par system. The ori region of chromosome I (oriI) is tethered to the old pole, whereas the ori region of chromosome II is found at midcell. Nevertheless, we found that both chromosomes adopted a longitudinal organisation. Chromosome I extended over the entire cell while chromosome II extended over the younger cell half. We further demonstrate that displacing parS sites away from the oriI region rotates the bulk of chromosome I. The only exception was the region where replication terminates, which still localised to the septum. However, the longitudinal arrangement of chromosome I persisted in Par mutants and, as was reported earlier, the ori region still localised towards the old pole. Finally, we show that the Par-independent longitudinal organisation and oriI polarity were perturbed by the introduction of a second origin. Taken together, these results suggest that the Par system is the major contributor to the longitudinal organisation of chromosome I but that the replication program also influences the arrangement of bacterial chromosomes.

  7. Abnormalities of chromosome 17 in myelodysplastic syndromes: Incidence and biological significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2004-01-01

    Full Text Available Cytogenetic analysis has proven to be a mandatory part of the diagnosis of myelodysplastic syndromes (MDS as well as a major indicator for predicting clinical course and outcome. Aside from the 5q-syndrome, no specific clinico-cytogenetic entity has been reported. To determine the incidence and clinical significance of acquired abnormalities of chromosome 17 in adult primary MDS, we reviewed the cytogenetic features of 271 patients detected at our institution during a 10-year period. Clonal cytogenetic abnormalities were identified in 109 cases. Among them, abnormalities of chromosome 17 were identified in 13 patients (11.9%. Five patients had „single" defects, while in eight patients abnormalities of chromosome 17 were associated with other chromosomal rearrangements („complex" defects. After chromosomes 5,7,8 and 1, abnormalities of chromosome 17 were the most frequent chromosomal rearrangements in our patients with MDS. Following „single" defects of chromosome 17 were identified: del(17(pl2 in two cases, and i(17(q10, del(17(q21;q23 and del(17(ql2;q22 in one case each. Two patients with del(17p, one with RAEB-t and the other one with CMML, had an aggressive course of the disease with accelerated leukemic transformation and short survival. Patient with i(17q had RARS subtype and died soon after diagnosis, while other two cases with interstitial deletions of the long arm of chromosome 17 had RAEB subtype and stable, no progressive course of the disease. Among „complex" karyotypes with abnormalities of chromosome 17 we identified der(l 7 in four, monosomy 17 in two, and del(17p and i(17q in one case each. Most of these patients transformed to acute leukemia and had very short survival. The results of this study suggest that abnormalities of chromosome 17 are frequent finding in MDS. Loss of genetic material in 17p, both in „single" and „complex" defects, seems to be closely related to poor prognosis of MDS patients.

  8. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Li, Yilong; Schwab, Claire; Ryan, Sarra L; Papaemmanuil, Elli; Robinson, Hazel M; Jacobs, Patricia; Moorman, Anthony V; Dyer, Sara; Borrow, Julian; Griffiths, Mike; Heerema, Nyla A; Carroll, Andrew J; Talley, Polly; Bown, Nick; Telford, Nick; Ross, Fiona M; Gaunt, Lorraine; McNally, Richard J Q; Young, Bryan D; Sinclair, Paul; Rand, Vikki; Teixeira, Manuel R; Joseph, Olivia; Robinson, Ben; Maddison, Mark; Dastugue, Nicole; Vandenberghe, Peter; Haferlach, Claudia; Stephens, Philip J; Cheng, Jiqiu; Van Loo, Peter; Stratton, Michael R; Campbell, Peter J; Harrison, Christine J

    2014-04-03

    Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.

  9. [Progress in eyeglass optics].

    Science.gov (United States)

    Köppen, W

    1995-08-01

    In this article product developments for ophthalmic lenses are discussed: new materials, designs and coatings. High-index plastic substrates allow to offer corrections which are simultaneously light and thin and for the first time there are high performant plastic photochromic lenses. Head and eye movements with latest generation's progressives are very similar to natural vision behaviour. Special aspheric designs have been developed for comfortable vision for near and intermediate distances. Finally there are new coatings which protect the high quality surfaces of plastic lenses distinctly longer than before.

  10. Cloning, structure, and chromosome localization of the mouse glutaryl-CoA dehydrogenase gene

    Energy Technology Data Exchange (ETDEWEB)

    Koeller, D.M.; DiGiulio, A.; Frerman, F.E. [Univ. of Colorado Health Sciences Center, Denver, CO (United States)] [and others

    1995-08-10

    Glutaryl-CoA dehydrogenase (GCDH) is a nuclear-encoded, mitochondrial matrix enzyme. In humans, deficiency of GCDH leads to glutaric acidemia type I, and inherited disorder of amino acid metabolism characterized by a progressive neurodegenerative disease. In this report we describe the cloning and structure of the mouse GCDH (Gcdh) gene and cDNA and its chromosomal localization. The mouse Gcdh cDNA is 1.75 kb long and contains and open reading frame of 438 amino acids. The amino acid sequences of mouse, human, and pig GCDH are highly conserved. The mouse Gcdh gene contains 11 exons and spans 7 kb of genomic DNA. Gcdh was mapped by backcross analysis to mouse chromosome 8 within a region that is homologous to a region of human chromosome 19, where the human gene was previously mapped. 14 refs., 3 figs.

  11. Binding of Multiple Rap1 Proteins Stimulates Chromosome Breakage Induction during DNA Replication.

    Directory of Open Access Journals (Sweden)

    Greicy H Goto

    2015-08-01

    Full Text Available Telomeres, the ends of linear eukaryotic chromosomes, have a specialized chromatin structure that provides a stable chromosomal terminus. In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length. Here we show that binding of multiple Rap1 proteins stimulates DNA double-stranded break (DSB induction at both telomeric and non-telomeric regions. Consistent with the role of DSB induction, Rap1 stimulates nearby recombination events in a dosage-dependent manner. Rap1 recruits Rif1 and Rif2 to telomeres, but neither Rif1 nor Rif2 is required for DSB induction. Rap1-mediated DSB induction involves replication fork progression but inactivation of checkpoint kinase Mec1 does not affect DSB induction. Rap1 tethering shortens artificially elongated telomeres in parallel with telomerase inhibition, and this telomere shortening does not require homologous recombination. These results suggest that Rap1 contributes to telomere homeostasis by promoting chromosome breakage.

  12. Developmental regulation of X-chromosome inactivation.

    Science.gov (United States)

    Payer, Bernhard

    2016-08-01

    With the emergence of sex-determination by sex chromosomes, which differ in composition and number between males and females, appeared the need to equalize X-chromosomal gene dosage between the sexes. Mammals have devised the strategy of X-chromosome inactivation (XCI), in which one of the two X-chromosomes is rendered transcriptionally silent in females. In the mouse, the best-studied model organism with respect to XCI, this inactivation process occurs in different forms, imprinted and random, interspersed by periods of X-chromosome reactivation (XCR), which is needed to switch between the different modes of XCI. In this review, I describe the recent advances with respect to the developmental control of XCI and XCR and in particular their link to differentiation and pluripotency. Furthermore, I review the mechanisms, which influence the timing and choice, with which one of the two X-chromosomes is chosen for inactivation during random XCI. This has an impact on how females are mosaics with regard to which X-chromosome is active in different cells, which has implications on the severity of diseases caused by X-linked mutations.

  13. Algorithms for reconstruction of chromosomal structures.

    Science.gov (United States)

    Lyubetsky, Vassily; Gershgorin, Roman; Seliverstov, Alexander; Gorbunov, Konstantin

    2016-01-19

    One of the main aims of phylogenomics is the reconstruction of objects defined in the leaves along the whole phylogenetic tree to minimize the specified functional, which may also include the phylogenetic tree generation. Such objects can include nucleotide and amino acid sequences, chromosomal structures, etc. The structures can have any set of linear and circular chromosomes, variable gene composition and include any number of paralogs, as well as any weights of individual evolutionary operations to transform a chromosome structure. Many heuristic algorithms were proposed for this purpose, but there are just a few exact algorithms with low (linear, cubic or similar) polynomial computational complexity among them to our knowledge. The algorithms naturally start from the calculation of both the distance between two structures and the shortest sequence of operations transforming one structure into another. Such calculation per se is an NP-hard problem. A general model of chromosomal structure rearrangements is considered. Exact algorithms with almost linear or cubic polynomial complexities have been developed to solve the problems for the case of any chromosomal structure but with certain limitations on operation weights. The computer programs are tested on biological data for the problem of mitochondrial or plastid chromosomal structure reconstruction. To our knowledge, no computer programs are available for this model. Exactness of the proposed algorithms and such low polynomial complexities were proved. The reconstructed evolutionary trees of mitochondrial and plastid chromosomal structures as well as the ancestral states of the structures appear to be reasonable.

  14. Engineered human dicentric chromosomes show centromere plasticity.

    Science.gov (United States)

    Higgins, Anne W; Gustashaw, Karen M; Willard, Huntington F

    2005-01-01

    The centromere is essential for the faithful distribution of a cell's genetic material to subsequent generations. Despite intense scrutiny, the precise genetic and epigenetic basis for centromere function is still unknown. Here, we have used engineered dicentric human chromosomes to investigate mammalian centromere structure and function. We describe three classes of dicentric chromosomes isolated in different cell lines: functionally monocentric chromosomes, in which one of the two genetically identical centromeres is consistently inactivated; functionally dicentric chromosomes, in which both centromeres are consistently active; and dicentric chromosomes heterogeneous with respect to centromere activity. A study of serial single cell clones from heterogeneous cell lines revealed that while centromere activity is usually clonal, the centromere state (i.e. functionally monocentric or dicentric) in some lines can switch within a growing population of cells. Because pulsed field gel analysis indicated that the DNA at the centromeres of these chromosomes did not change detectably, this switching of the centromere state is most likely due to epigenetic changes. Inactivation of one of the two active centromeres in a functionally dicentric chromosome was observed in a percentage of cells after treatment with Trichostatin A, an inhibitor of histone deacetylation. This study provides evidence that the activity of human centromeres, while largely stable, can be subject to dynamic change, most likely due to epigenetic modification.

  15. [Y chromosome structural abnormalities and Turner's syndrome].

    Science.gov (United States)

    Ravel, C; Siffroi, J-P

    2009-06-01

    Although specifically male, the human Y chromosome may be observed in female karyotypes, mostly in women with Turner syndrome stigmata. In women with isolated gonadal dysgenesis but otherwise normal stature, the testis determining factor or SRY gene may have been removed from the Y chromosome or may be mutated. In other women with Turner syndrome, the karyotype is usually abnormal and shows a frequent 45,X/46,XY mosaicism. In these cases, the phenotype depends on the ratio between Y positive and 45,X cell lines in the body. When in mosaicism, Y chromosomes are likely to carry structural abnormalities which explain mitotic instability, such as the existence of two centromeres. Dicentric Y isochromosomes for the short arm (idic[Yp]) or ring Y chromosomes (r[Y]) are the most frequent abnormal Y chromosomes found in infertile patients and in Turner syndrome in mosaic with 45,X cells. Although monocentric, deleted Y chromosomes for the long arm and those carrying microdeletions in the AZF region are also instable and are frequently associated with a 45,X cell line. Management of infertile patients carrying such abnormal Y chromosomes must take into account the risk and the consequences of a mosaicism in the offspring.

  16. Chromosome I duplications in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    McKim, K.S.; Rose, A.M. (Univ. of British Columbia, Vancouver (Canada))

    1990-01-01

    We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left half of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.

  17. Development of a two-parameter slit-scan flow cytometer for screening of normal and aberrant chromosomes: application to a karyotype of Sus scrofa domestica (pig)

    Science.gov (United States)

    Hausmann, Michael; Doelle, Juergen; Arnold, Armin; Stepanow, Boris; Wickert, Burkhard; Boscher, Jeannine; Popescu, Paul C.; Cremer, Christoph

    1992-07-01

    Laser fluorescence activated slit-scan flow cytometry offers an approach to a fast, quantitative characterization of chromosomes due to morphological features. It can be applied for screening of chromosomal abnormalities. We give a preliminary report on the development of the Heidelberg slit-scan flow cytometer. Time-resolved measurement of the fluorescence intensity along the chromosome axis can be registered simultaneously for two parameters when the chromosome axis can be registered simultaneously for two parameters when the chromosome passes perpendicularly through a narrowly focused laser beam combined by a detection slit in the image plane. So far automated data analysis has been performed off-line on a PC. In its final performance, the Heidelberg slit-scan flow cytometer will achieve on-line data analysis that allows an electro-acoustical sorting of chromosomes of interest. Interest is high in the agriculture field to study chromosome aberrations that influence the size of litters in pig (Sus scrofa domestica) breeding. Slit-scan measurements have been performed to characterize chromosomes of pigs; we present results for chromosome 1 and a translocation chromosome 6/15.

  18. Analysis of chromosome conservation in Lemur catta studied by chromosome paints and BAC/PAC probes.

    Science.gov (United States)

    Cardone, Maria Francesca; Ventura, Mario; Tempesta, Sergio; Rocchi, Mariano; Archidiacono, Nicoletta

    2002-12-01

    A panel of human chromosome painting probes and bacterial and P1 artificial chromosome (BAC/PAC) clones were used in fluorescence in situ hybridization (FISH) experiments to investigate the chromosome conservation of the ring-tailed lemur (Lemur catta, LCA) with respect to human. Whole chromosome paints specific for human chromosomes 7, 9, 11, 13, 14, 17, 18, 20, 21, and X were found to identify a single chromosome or an uninterrupted chromosomal region in LCA. A large set of partial chromosome paints and BAC/PAC probes were then used to refine the characterization of the rearrangements differentiating the two karyotypes. The results were also used to reconstruct the ancestral Lemuridae karyotype. Lemur catta, indeed, can be used as an outgroup, allowing symplesiomorphic (ancestral) rearrangements to be distinguished from apomorphic (derived) rearrangements in lemurs. Some LCA chromosomes are difficult to distinguish morphologically. The 'anchorage' of most LCA chromosomes to specific probes will contribute to the standardization of the karyotype of this species.

  19. Large-scale reconstruction of 3D structures of human chromosomes from chromosomal contact data.

    Science.gov (United States)

    Trieu, Tuan; Cheng, Jianlin

    2014-04-01

    Chromosomes are not positioned randomly within a nucleus, but instead, they adopt preferred spatial conformations to facilitate necessary long-range gene-gene interactions and regulations. Thus, obtaining the 3D shape of chromosomes of a genome is critical for understanding how the genome folds, functions and how its genes interact and are regulated. Here, we describe a method to reconstruct preferred 3D structures of individual chromosomes of the human genome from chromosomal contact data generated by the Hi-C chromosome conformation capturing technique. A novel parameterized objective function was designed for modeling chromosome structures, which was optimized by a gradient descent method to generate chromosomal structural models that could satisfy as many intra-chromosomal contacts as possible. We applied the objective function and the corresponding optimization method to two Hi-C chromosomal data sets of both a healthy and a cancerous human B-cell to construct 3D models of individual chromosomes at resolutions of 1 MB and 200 KB, respectively. The parameters used with the method were calibrated according to an independent fluorescence in situ hybridization experimental data. The structural models generated by our method could satisfy a high percentage of contacts (pairs of loci in interaction) and non-contacts (pairs of loci not in interaction) and were compatible with the known two-compartment organization of human chromatin structures. Furthermore, structural models generated at different resolutions and from randomly permuted data sets were consistent.

  20. Chromosomal abnormalities and Y chromosome microdeletions in infertile men from Morocco.

    Science.gov (United States)

    Naasse, Yassine; Charoute, Hicham; El Houate, Brahim; Elbekkay, Chadli; Razoki, Lunda; Malki, Abderrahim; Barakat, Abdelhamid; Rouba, Hassan

    2015-09-18

    Male infertility is responsible for 50% of infertile couples. Thirty percent of male infertility is due to cytogenetic and genetic abnormalities. In Arab and North African populations, several studies have shown the association of these chromosomal abnormalities with male infertility. Our objective is to evaluate the frequency of chromosomal abnormalities and Y chromosome microdeletions in infertile men from Morocco. A total of 573 Moroccan infertile men (444 azoospermic and 129 oligozoospermic men) referred for cytogenetic analysis to the Department of Cytogenetics of the Pasteur Institute of Morocco, were screened for the presence of chromosomal abnormalities and Y chromosome microdeletions. Chromosomal abnormalities accounted for approximately 10.5% (60/573). Fifty six cases among them have sex chromosome abnormalities (93.34%), including Klinefelter's syndrome in 41 patients (68.34%). Autosomal chromosome abnormalities (6.66%) were observed in 4 patients. Chromosomal abnormalities were more prevalent in azoospermic men (13.06%) than in oligospermic men (1.55%). Y microdeletions were detected in 16 of 85 patients (AZFc: 14.12%, AZFbc: 4.70%), most of them where azoospermic men with no chromosomal abnormality. These results highlighted the need for efficient molecular genetic testing in male infertility diagnosis. In addition, a genetic screening should be performed in infertile men before starting assisted reproductive treatments.