WorldWideScience

Sample records for chromosomal translocations involving

  1. Chromosome segregation analysis in human embryos obtained from couples involving male carriers of reciprocal or Robertsonian translocation.

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz

    Full Text Available The objective of this study was to investigate the frequency and type of chromosome segregation patterns in cleavage stage embryos obtained from male carriers of Robertsonian (ROB and reciprocal (REC translocations undergoing preimplantation genetic diagnosis (PGD at our reproductive center. We used FISH to analyze chromosome segregation in 308 day 3 cleavage stage embryos obtained from 26 patients. The percentage of embryos consistent with normal or balanced segregation (55.1% vs. 27.1% and clinical pregnancy (62.5% vs. 19.2% rates were higher in ROB than the REC translocation carriers. Involvement of non-acrocentric chromosome(s or terminal breakpoint(s in reciprocal translocations was associated with an increase in the percent of embryos consistent with adjacent 1 but with a decrease in 3∶1 segregation. Similar results were obtained in the analysis of nontransferred embryos donated for research. 3∶1 segregation was the most frequent segregation type in both day 3 (31% and spare (35% embryos obtained from carriers of t(11;22(q23;q11, the only non-random REC with the same breakpoint reported in a large number of unrelated families mainly identified by the birth of a child with derivative chromosome 22. These results suggest that chromosome segregation patterns in day 3 and nontransferred embryos obtained from male translocation carriers vary with the type of translocation and involvement of acrocentric chromosome(s or terminal breakpoint(s. These results should be helpful in estimating reproductive success in translocation carriers undergoing PGD.

  2. BCR translocation to derivative chromosome 2, a new case of chronic myeloid leukemia with complex variant translocation and Philadelphia chromosome

    International Nuclear Information System (INIS)

    Al-Achkar, W.; Wafa, A.; Al-Medani, S.

    2011-01-01

    The well-known typical fusion gene BCR/ABL can be observed in connection with a complex translocation event in only 5-8% of cases with chronic myeloid leukemia (CML). Herein we report an exceptional CML case with complex chromosomal aberrations not observed before, translocated BCR to the derivative chromosome 2 [der(2)], additional to involving a four chromosomes translocation implying chromosomal regions such as 1p32 and 2q21 besides 9q34 and 22q11.2. Which were characterized by molecular cytogenetics. (author)

  3. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites

    Directory of Open Access Journals (Sweden)

    Pierce Levi CT

    2009-01-01

    Full Text Available Abstract Background Gene rearrangements such as chromosomal translocations have been shown to contribute to cancer development. Human chromosomal fragile sites are regions of the genome especially prone to breakage, and have been implicated in various chromosome abnormalities found in cancer. However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations. Results Using up-to-date databases containing all cancer-specific recurrent translocations, we have examined 444 unique pairs of genes involved in these translocations to determine the correlation of translocation breakpoints and fragile sites in the gene pairs. We found that over half (52% of translocation breakpoints in at least one gene of these gene pairs are mapped to fragile sites. Among these, we examined the DNA sequences within and flanking three randomly selected pairs of translocation-prone genes, and found that they exhibit characteristic features of fragile DNA, with frequent AT-rich flexibility islands and the potential of forming highly stable secondary structures. Conclusion Our study is the first to examine gene pairs involved in all recurrent chromosomal translocations observed in tumor cells, and to correlate the location of more than half of breakpoints to positions of known fragile sites. These results provide strong evidence to support a causative role for fragile sites in the generation of cancer-specific chromosomal rearrangements.

  4. A rare balanced nonrobertsonian translocation involving acrocentric chromosomes: Chromosome abnormality of t(13;15(p11.2;q22.1

    Directory of Open Access Journals (Sweden)

    Dalvi Rupa

    2016-01-01

    Full Text Available BACKGROUND: Balanced non-robertsonian translocation (RT, involving acrocentric chromosomes, is a rare event and only a few cases are reported. Most of the RTs are balanced involving acrocentric chromosomes with the breakpoints (q10;q10. MATERIALS AND METHODS: Chromosome analysis was performed as per standard procedure – Giemsa-trypsin banding with 500 band resolution was analyzed for chromosome identification. RESULTS: In the present study, we report a rare balanced non-RTs involving chromosomes 13 and 15 with cytogenetic finding of 46, XX, t(13;15(p11.2;q22.1. CONCLUSION: To the best of our knowledge, this is the first such report of an unusual non-RT of t(13:15 with (p11.2;q22.1 break points.

  5. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...

  6. Label Free Chromosome Translocation Detection with Silicon nanowires

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Andersen, Karsten Brandt; Frøhling, Kasper Bayer

    HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method is a Fluore......HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method...

  7. Noninvolvement of the X chromosome in radiation-induced chromosome translocations in the human lymphoblastoid cell line TK6

    International Nuclear Information System (INIS)

    Jordan, R.; Schwartz, J.L.

    1994-01-01

    Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by 60 Co γ rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized autosome chromosome 7. When corrected for DNA content, acentric fragments were induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases in chromosomal interchanges involving chromosome 7 were noted, and the frequencies of balanced translocations and dicentrics produced were approximately equal. Chromosome interchanges involving the X chromosome were rare and showed no apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive to the induction of chromosome breaks, the X chromosome is much less likely to interact with autosomes than chromosome 7. The noninvolvement of the X chromosome in translocations with autosomes may reflect a more peripheral and separate location for the X chromosome in the mammalian nucleus. 20 refs., 2 figs., 1 tab

  8. Frequency and distribution analysis of chromosomal translocations induced by x-ray in human lymphocytes

    International Nuclear Information System (INIS)

    Lopez Hidalgo, Juana Ines

    2000-01-01

    The characteristic of ionizing radiation suggests that induced chromosomal damage in the form of translocations would appear to be randomly distributed. However, the outcome of tests performed in vitro and in vivo (irradiated individuals) are contradictories. The most translocation-related chromosomes, as far as some studies reveal on one hand, appear to be less involved in accordance with others. These data, together with those related to molecular mechanisms involved in translocations production suggest that in G 0 -irradiated cells, the frequency and distribution of this kind of chromosomal rearrangement, does not take place at random. They seem to be affected by in-nucleus chromosome distribution, by each chromosome's DNA length and functional features, by the efficiency of DNA repair mechanisms, and by inter individual differences. The objective of this study was to establish the frequency pattern of each human chromosome involved in radio-induced translocations, as well as to analyze the importance the chromosome length, the activity of DNA polymerase- dependant repair mechanisms, and inter individual differences within the scope of such distribution. To achieve the goals, peripheral blood lymphocytes from healthy donors were irradiated in presence and absence of 2'-3' dideoxithimidine (ddThd), a Β - DNA polymerase inhibitor, which takes part in the base repair mechanism (B E R). The results showed that: The presence of ddThd during the irradiation increase the basal frequency of radioinduced translocations in 60 %. This result suggests that ddThd repair synthesis inhibition can be in itself a valid methodology for radiation-induced bases damage assessment, damage which if not BER-repaired may result in translocation-leading double strand breaks. A statistically significant correlation between translocation frequency and chromosome length, in terms of percentage of genome, has been noticed both in (basal) irradiation and in irradiation with ddThd inhibitor

  9. Importance of No. 21 chromosome in translocation t(8:21) in acute myelocytic leukemia (AML) to the genesis of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, T; Minamihisamatsu, M

    1986-05-01

    The results are reported of the chromosome analysis of 17 cases of acute myelocytic leukemia (AML), mostly belonging to M2 of the FAB classification, especially on the translocation t(8:21) and its variant translocations. The presence of two cases with simple variant translocation not involving No. 8 chromosome seems to suggest that No. 21 chromosome is more important to the genesis of AML than the No. 8 chromosome. This assumption appears to be supported by findings on cases with complex translocation: In two cases with complex translocation, the portion translocated from No. 21 chromosome onto No. 8 was firmly maintained in the specific site (q21) on No. 8 whereas the portion translocated from No. 8 chromosome onto No. 21 was involved in further translocation with another chromosome, onto which it was re-translocated. The results of the present cytogenetic study indicate that the analysis of variant translocations in various specific chromosome translocations in leukemia and other malignant disorders is very useful to elucidate the problem as to whether the genesis of such disorders lies in either one or both of the pair of chromosomes involved in the specific translocations of the respective diseases.

  10. Complex Variant t(9;22 Chromosome Translocations in Five Cases of Chronic Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Valencia

    2009-01-01

    Full Text Available The Philadelphia (Ph1 chromosome arising from the reciprocal t(9;22 translocation is found in more than 90% of chronic myeloid leukemia (CML patients and results in the formation of the chimeric fusion gene BCR-ABL. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11. We report five CML cases carrying variant Ph translocations involving both chromosomes 9 and 22 as well as chromosomes 3, 5, 7, 8, or 10. G-banding showed a reciprocal three-way translocation involving 3q21, 5q31, 7q32, 8q24, and 10q22 bands. BCR-ABL fusion signal on der(22 was found in all of the cases by FISH.

  11. Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenic forms of Burkitt lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Neri, A.; Barriga, F.; Knowles, D.M.; Magrath, I.T.; Dalla-Favera, R.

    1988-04-01

    The authors show that endemic (eBL), sporadic (sBL), and acquired immunodeficiency syndrome-associated (AIDS-BL) forms of Burkitt lymphoma (BL) carrying t(8; 14) chromosomal translocations display different breakpoints within the immunoglobulin heavy-chain locus (IGH) on chromosome 14. In sBL (7 out of 11) and AIDS-BL (5 out of 6), the breakpoints occurred within or near the IGH ..mu.. switch (S/sub mu/) region on chromosome 14 and within the c-myc locus (MYC) on chromosome 8. In most eBL (13 out of 16) the breakpoints were mapped within or 5' to the IGH joining J/sub H/ region on chromosome 14 and outside the MYC locus on chromosome 8. Cloning and sequencing of the (8; 14) chromosomal junctions from two eBL cell lines and one eBL biopsy sample show that the recombination do not involve IGH-specific recombination signals on chromosome 14 or homologous sequences on chromosome 8, suggesting that these events are not likely to be mediated by the same mechanisms or enzymes as in IGH rearrangements. In general, these data have implications for the timing of occurrence of chromosomal translocations during B-cell differentiation in different BL types.

  12. CHROMOSOMAL SUBLOCALIZATION OF THE 2 13 TRANSLOCATION BREAKPOINT IN ALVEOLAR RHABDOMYOSARCOMA

    NARCIS (Netherlands)

    SHAPIRO, DN; VALENTINE, MB; SUBLETT, JE; SINCLAIR, AE; TEREBA, AM; SCHEFFER, H; BUYS, CHCM; LOOK, AT

    A characteristic balanced reciprocal chromosomal translocation [t(2;13)(q35;q14)] has been identified in more than 50% of alveolar rhabdomyosarcomas. As the first step in characterization of the genes involved in this translocation, we constructed somatic cell hybrids that retained either the

  13. Frequencies of X-ray and fast neutron induced chromosome translocations in human peripheral blood lymphocytes as detected by in situ hybridization using chromosome specific DNA libraries

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Darroudi, F.; Vermeulen, S.; Wiegant, J.

    1992-01-01

    DNA libraries of six human chromosomes were used to detect translocations in human lymphocytes induced by different doses of X-rays and fast neutrons. Results show that with X-rays, one can detect about 1.5 to 2.0 fold more translocations in comparison to dicentrics, whereas following fast neutron irradiation, the difference between these two classes of aberrations are significantly different at high doses. In addition, triple fluorescent in situ hybridization technique was used to study the frequencies of radiation-induced translocations involving a specific chromosome. Chromosome number 1 was found to be involved in translocations more frequently than chromosomes number 2, 3, 4, 8 and X. (author). 10 refs., 1 fig., 2 tabs

  14. Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. I. Results obtained after hybridization of human cells carrying reciprocal translocations involving chromosome 1.

    Science.gov (United States)

    Jongsma, A P; Burgerhout, W G

    1977-01-01

    Regional localization studies of genes coding for human PGD, PPH1, PGM1, UGPP, GuK1, Pep-C, and FH, which have been assigned to chromosome 1, were performed with man-Chinese hamster somatic cell hybrids, Informative hybrids that retained fragments of the human chromosome 1 were produced by fusion of hamster cells with human cells carrying reciprocal translocations involving chromosome 1. Analysis of the hybrids that retained one of the translocation chromosomes or de novo rearrangements involving the human 1 revealed the following gene positions: PGD and PPH1 in 1pter leads to 1p32, PGM1 in 1p32 leads to 1p22, UGPP and GuK1 in 1q21 leads to 1q42, FH in 1qter leads to 1q42, and Pep-C probably in 1q42.

  15. Recombinase, chromosomal translocations and lymphoid neoplasia: targeting mistakes and repair failures.

    Science.gov (United States)

    Marculescu, Rodrig; Vanura, Katrina; Montpellier, Bertrand; Roulland, Sandrine; Le, Trang; Navarro, Jean-Marc; Jäger, Ulrich; McBlane, Fraser; Nadel, Bertrand

    2006-09-08

    A large number of lymphoid malignancies is characterized by specific chromosomal translocations, which are closely linked to the initial steps of pathogenesis. The hallmark of these translocations is the ectopic activation of a silent proto-oncogene through its relocation at the vicinity of an active regulatory element. Due to the unique feature of lymphoid cells to somatically rearrange and mutate receptor genes, and to the corresponding strong activity of the immune enhancers/promoters at that stage of cell development, B- and T-cell differentiation pathways represent propitious targets for chromosomal translocations and oncogene activation. Recent progress in the understanding of the V(D)J recombination process has allowed a more accurate definition of the translocation mechanisms involved, and has revealed that V(D)J-mediated translocations result both from targeting mistakes of the recombinase, and from illegitimate repair of the V(D)J recombination intermediates. Surprisingly, V(D)J-mediated translocations turn out to be restricted to two specific sub-types of lymphoid malignancies, T-cell acute lymphoblastic leukemias, and a restricted set of mature B-cell Non-Hodgkin's lymphomas.

  16. Chromosomal Translocations: Chicken or Egg? | Center for Cancer Research

    Science.gov (United States)

    Many tumor cells have abnormal chromosomes. Some of these abnormalities are caused by chromosomal translocations, which occur when two chromosomes break and incorrectly rejoin, resulting in an exchange of genetic material. Translocations can activate oncogenes, silence tumor suppressor genes, or result in the creation of completely new fusion gene products. While there is

  17. A strategy for generation and balancing of autosome: Y chromosome translocations.

    Science.gov (United States)

    Joshi, Sonal S; Cheong, Han; Meller, Victoria H

    2014-01-01

    We describe a method for generation and maintenance of translocations that move large autosomal segments onto the Y chromosome. Using this strategy we produced ( 2;Y) translocations that relocate between 1.5 and 4.8 Mb of the 2nd chromosome.. All translocations were easily balanced over a male-specific lethal 1 (msl-1) mutant chromosome. Both halves of the translocation carry visible markers, as well as P-element ends that enable molecular confirmation. Halves of these translocations can be separated to produce offspring with duplications and with lethal second chromosome deficiencies . Such large deficiencies are otherwise tedious to generate and maintain.

  18. Preliminary analysis of numerical chromosome abnormalities in reciprocal and Robertsonian translocation preimplantation genetic diagnosis cases with 24-chromosomal analysis with an aCGH/SNP microarray.

    Science.gov (United States)

    Xie, Yanxin; Xu, Yanwen; Wang, Jing; Miao, Benyu; Zeng, Yanhong; Ding, Chenhui; Gao, Jun; Zhou, Canquan

    2018-01-01

    The aim of this study was to determine whether an interchromosomal effect (ICE) occurred in embryos obtained from reciprocal translocation (rcp) and Robertsonian translocation (RT) carriers who were following a preimplantation genetic diagnosis (PGD) with whole chromosome screening with an aCGH and SNP microarray. We also analyzed the chromosomal numerical abnormalities in embryos with aneuploidy in parental chromosomes that were not involved with a translocation and balanced in involved parental translocation chromosomes. This retrospective study included 832 embryos obtained from rcp carriers and 382 embryos from RT carriers that were biopsied in 139 PGD cycles. The control group involved embryos obtained from age-matched patient karyotypes who were undergoing preimplantation genetic screening (PGS) with non-translocation, and 579 embryos were analyzed in the control group. A single blastomere at the cleavage stage or trophectoderm from a blastocyst was biopsied, and 24-chromosomal analysis with an aCGH/SNP microarray was conducted using the PGD/PGS protocols. Statistical analyses were implemented on the incidences of cumulative aneuploidy rates between the translocation carriers and the control group. Reliable results were obtained from 138 couples, among whom only one patient was a balanced rcp or RT translocation carrier, undergoing PGD testing in our center from January 2012 to June 2014. For day 3 embryos, the aneuploidy rates were 50.7% for rcp carriers and 49.1% for RT carriers, compared with the control group, with 44.8% at a maternal age < 36 years. When the maternal age was ≥ 36 years, the aneuploidy rates were increased to 61.1% for rcp carriers, 56.7% for RT carriers, and 60.3% for the control group. There were no significant differences. In day 5 embryos, the aneuploidy rates were 24.5% for rcp carriers and 34.9% for RT carriers, compared with the control group with 53.6% at a maternal age < 36 years. When the maternal age was ≥ 36

  19. Meiotic chromosomal translocations in male mice induced by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Savkovic, N.; Pecevski; Vuksanovic, L.; Radivojevic, D.; Alavantic, D.

    1983-01-01

    The dose-response curve for reciprocal translocations induced by acute exposure of spermatogonial stem cells to X-rays in treated mice and their F-1 sons was examined. Male mice were totally irradiated with doses of 1Gy;5x1Gy and 5Gy. The obtained results show that frequency of the chromosomal translocations in directly treated animals is dose dependent. The percentage of animals irradiated with 1Gy which had the chromosomal translocations was 60, while this percentage in animals irradiated with single and fractionated dose of 5Gy was 100. The frequency of chromosomal translocations varies from 1.5% to 8.0%. Multivalent configurations in F-1 males were observed after exposure to 5Gy only. The incidence of F-1 translocated males was 17.5%.

  20. Use of chromosome translocations for measuring prior environment exposures in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J. D.

    1997-05-01

    Recent advances in cytogenetic methodology are beginning to have a major impact upon our ability to provide assessments of environmental exposure in humans. The advent of fluorescent-based techniques for `painting` whole chromosomes has made the analysis of chromosome translocations rapid, specific, sensitive and routine. Chromosome painting has been used to address a wide variety of scientific questions, resulting in an increased understanding of the biological consequences of adverse environmental exposure. This paper describes the use of chromosome translocations as a biological marker of exposure and effect in humans. The relevance of translocations is discussed, as are the advantages and disadvantages of painting compared to classical cytogenetic methods for translocation evaluation. The factors to consider in the use of translocations as a retrospective indicator of exposure are then described. Several theoretical parameters that are important to the use of translocations are provided, and the paper concludes with a vision for the future of cytogenetic methodology.

  1. A paternally transmitted complex chromosomal rearrangement (CCR) involving chromosomes 2, 6, and 18 includes eight breakpoints and five insertional translocations (ITs) through three generations.

    Science.gov (United States)

    Gruchy, Nicolas; Barreau, Morgane; Kessler, Ketty; Gourdier, Dominique; Leporrier, Nathalie

    2010-01-01

    Complex chromosomal rearrangements (CCRs) are uncommon and mainly occur de novo. We report here on a familial CCR involving chromosomes 2, 6, and 18. The propositus is a boy first referred because of growth delays, hypotonia, and facial anomalies, suggestive of deletion 18q syndrome. However, a cytogenetic family study disclosed a balanced CCR in three generations, which was detailed by FISH using BAC clones, and consisted of eight breakpoints with five insertional translocations (ITs). The propositus had a cryptic 18q deletion and a 6p duplication. Paternal transmission of this CCR was observed through three generations without meiotic recombination. Our investigation allowed us to provide porosities counseling and management of prenatal diagnosis for propositus cousin who carries this particular CCR.

  2. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  3. Sex Chromosome Translocations in the Evolution of Reproductive Isolation

    Science.gov (United States)

    Tracey, Martin L.

    1972-01-01

    Haldane's rule states that in organisms with differentiated sex chromosomes, hybrid sterility or inviability is generally expressed more frequently in the heterogametic sex. This observation has been variously explained as due to either genic or chromosomal imbalance. The fixation probabilities and mean times to fixation of sex-chromosome translocations of the type necessary to explain Haldane's rule on the basis of chromosomal imbalance have been estimated in small populations of Drosophila melanogaster. The fixation probability of an X chromosome carrying the long arm of the Y(X·YL) is approximately 30% greater than expected under the assumption of no selection. No fitness differences associated with the attached YL segment were detected. The fixation probability of a deficient Y chromosome is 300% greater than expected when the X chromosome contains the deleted portion of the Y. It is suggested that sex-chromosome translocations may play a role in the establishment of reproductive isolation. PMID:4630586

  4. Chromosomal translocation in a mongoloid male child and his normal mother

    Directory of Open Access Journals (Sweden)

    Willy Beçak

    1963-09-01

    Full Text Available The presence of a translocation 21/13-15 is related in 46 chromosomes, karyotypes of a mongoloid male child (Down's syndrome. The abnormal chromosome was transmitted by the mother of the patient. The possible deficiency of translocated chromosome 21 and the possible origin of the anomaly in the family was discussed and the presence of a markedly large Y chromosome in the karyotypes of the patient as in those of his father was also noted.

  5. 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.

  6. Comparative Genomics of Interreplichore Translocations in Bacteria: A Measure of Chromosome Topology?

    Directory of Open Access Journals (Sweden)

    Supriya Khedkar

    2016-06-01

    Full Text Available Genomes evolve not only in base sequence but also in terms of their architecture, defined by gene organization and chromosome topology. Whereas genome sequence data inform us about the changes in base sequences for a large variety of organisms, the study of chromosome topology is restricted to a few model organisms studied using microscopy and chromosome conformation capture techniques. Here, we exploit whole genome sequence data to study the link between gene organization and chromosome topology in bacteria. Using comparative genomics across ∼250 pairs of closely related bacteria we show that: (a many organisms show a high degree of interreplichore translocations throughout the chromosome and not limited to the inversion-prone terminus (ter or the origin of replication (oriC; (b translocation maps may reflect chromosome topologies; and (c symmetric interreplichore translocations do not disrupt the distance of a gene from oriC or affect gene expression states or strand biases in gene densities. In summary, we suggest that translocation maps might be a first line in defining a gross chromosome topology given a pair of closely related genome sequences.

  7. Comparative Genomics of Interreplichore Translocations in Bacteria: A Measure of Chromosome Topology?

    Science.gov (United States)

    Khedkar, Supriya; Seshasayee, Aswin Sai Narain

    2016-06-01

    Genomes evolve not only in base sequence but also in terms of their architecture, defined by gene organization and chromosome topology. Whereas genome sequence data inform us about the changes in base sequences for a large variety of organisms, the study of chromosome topology is restricted to a few model organisms studied using microscopy and chromosome conformation capture techniques. Here, we exploit whole genome sequence data to study the link between gene organization and chromosome topology in bacteria. Using comparative genomics across ∼250 pairs of closely related bacteria we show that: (a) many organisms show a high degree of interreplichore translocations throughout the chromosome and not limited to the inversion-prone terminus (ter) or the origin of replication (oriC); (b) translocation maps may reflect chromosome topologies; and (c) symmetric interreplichore translocations do not disrupt the distance of a gene from oriC or affect gene expression states or strand biases in gene densities. In summary, we suggest that translocation maps might be a first line in defining a gross chromosome topology given a pair of closely related genome sequences. Copyright © 2016 Khedkar and Seshasayee.

  8. Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.

    Science.gov (United States)

    Wafa, Abdulsamad; As'sad, Manar; Liehr, Thomas; Aljapawe, Abdulmunim; Al Achkar, Walid

    2017-04-07

    The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20. Moreover, the translocation t(1;19) correlates with known clinical high risk factors, such as elevated white blood cell count, high serum lactate dehydrogenase levels, and central nervous system involvement; early reports indicated that patients with translocation t(1;19) had a poor outcome under standard treatment. We report the case of a 15-year-old Syrian boy with pre-B cell acute lymphoblastic leukemia with abnormal karyotype with a der(19)t(1;19)(q21.1;p13.3) and two yet unreported chromosomal aberrations: an interstitial deletion 6q12 to 6q26 and a der(13)t(1;13)(q21.1;p13). According to the literature, cases who are translocation t(1;19)-positive have a significantly higher incidence of central nervous system relapse than patients with acute lymphoblastic leukemia without the translocation. Of interest, central nervous system involvement was also seen in our patient. To the best of our knowledge, this is the first case of childhood pre-B cell acute lymphoblastic leukemia with an unbalanced translocation t(1;19) with two additional chromosomal aberrations, del(6)(q12q26) and t(1;13)(q21.3;p13), which seem to be recurrent and could influence clinical outcome. Also the present case confirms the impact of the translocation t(1;19) on central nervous system relapse, which should be studied for underlying mechanisms in future.

  9. Occurence of translocations between irradiated and intact chromosomes of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Myasnyankina, E.N.; Abeleva, Eh.A.; Generalova, M.V.

    1980-01-01

    Two translocations between irradiated father and intact mother autosomes are obtained in Drosophila melanogaster. Five out of 283 regular translocations (between the second and the third chromosomes of an irradiated male) are accompanied by a recombination over the second or the third chromosomes. Nine flies out of twenty considered to be recombinants, could originate due to mutations. The data obtained prove that intact female autosomes can take part in the exchange with homologic (recombinations) and heterologic (translocations) irradiated male autosomes

  10. Experimental observation of G banding verifying X-ray workers' chromosome translocation detected by FISH

    International Nuclear Information System (INIS)

    Sun Yuanming; Li Jin; Wang Qin; Tang Weisheng; Wang Zhiquan

    2002-01-01

    Objective: FISH is the most effective way of detecting chromosome aberration and many factors affect its accuracy. G-banding is used to verify the results of early X-ray workers' chromosome translocation examined by FISH. Methods: The chromosome translocations of early X-ray workers have been analysed by FISH (fluorescence in situ hybridization) and G-banding, yields of translocation treated with statistics. Results: The chromosome aberrations frequencies by tow methods are closely related. Conclusion: FISH is a feasible way to analyse chromosome aberrations of X-ray workers and reconstruct dose

  11. Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders?

    Science.gov (United States)

    Rego, Eduardo M; Pandolfi, Pier Paolo

    2002-08-01

    Chromosomal translocations are frequently involved in the pathogenesis of leukemias, lymphomas and sarcomas. They can lead to aberrant expression of oncogenes or the generation of chimeric proteins. Classically, one of the products is thought to be oncogenic. For example, in acute promyelocytic leukaemia (APL), reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) gene lead to the formation of two fusion genes: X-RARalpha and RARalpha-X (where X is the alternative RARalpha fusion partner: PML, PLZF, NPM, NuMA and STAT 5b). The X-RARalpha fusion protein is indeed oncogenic. However, recent data indicate that the RARalpha-X product is also critical in determining the biological features of this leukemia. Here, we review the current knowledge on the role of reciprocal products in cancer pathogenesis, and highlight how their expression might impact on the biology of their respective tumour types.

  12. Translocations of chromosome end-segments and facultative heterochromatin promote meiotic ring formation in evening primroses.

    Science.gov (United States)

    Golczyk, Hieronim; Massouh, Amid; Greiner, Stephan

    2014-03-01

    Due to reciprocal chromosomal translocations, many species of Oenothera (evening primrose) form permanent multichromosomal meiotic rings. However, regular bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends, which makes homologous recombination virtually undetectable. Genetic diversity is achieved by changing linkage relations of chromosomes in rings and bivalents via hybridization and reciprocal translocations. Although the structural prerequisite for this system is enigmatic, whole-arm translocations are widely assumed to be the mechanistic driving force. We demonstrate that this prerequisite is genome compartmentation into two epigenetically defined chromatin fractions. The first one facultatively condenses in cycling cells into chromocenters negative both for histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in differentiating cells. The second fraction is euchromatin confined to distal chromosome segments, positive for histone H3 lysine 4 dimethylation and for histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical telomeres but capped with constitutive heterochromatin. This genomic organization promotes translocation breakpoints between the two chromatin fractions, thus facilitating exchanges of end-segments. We challenge the whole-arm translocation hypothesis by demonstrating why reciprocal translocations of chromosomal end-segments should strongly promote meiotic rings and evolution toward permanent translocation heterozygosity. Reshuffled end-segments, each possessing a major crossover hot spot, can furthermore explain meiotic compatibility between genomes with different translocation histories.

  13. Transfer of Hessian fly resistance from rye to wheat via radiation-induced terminal and intercalary chromosomal translocations

    International Nuclear Information System (INIS)

    Friebe, B.; Hatchett, J.H.; Gill, B.S.; Mukai, Y.; Sebesta, E.E.

    1991-01-01

    A new Hessian fly (Mayetiola destructor) resistance gene derived from 'Balbo' rye and its transfer to hexaploid wheat via radiation-induced terminal and intercalary chromosomal translocations are described. Crosses between resistant 'Balbo' rye and susceptible 'Suwon 92' wheat and between the F1 amphidiploids and susceptible 'TAM 106' and 'Amigo' wheats produced resistant BC2F3 lines that were identified by C-banding analysis as being 6RL telocentric addition lines. Comparative chromosomal analyses and resistance tests revealed that the resistance gene is located on the 6RL telocentric chromosome. X-irradiated pollen of 6RL addition plants was used to fertilize plants of susceptible wheats 'TAM 106,' 'TAM 101,' and 'Vona.' After several generations of selection for resistance, new sublines were obtained that were homogeneous for resistance. Thirteen of these lines were analyzed by C-banding, and three different wheat-6RL chromosomal translocations (T) were identified. Wheat chromosomes involved in the translocations were 6B, 4B, and 4A. Almost the complete 6RL arm is present in T6BS · 6BL-6RL. Only the distal half of 6RL is present in T4BS · 4BL-6RL, which locates the resistance gene in the distal half of 6RL. Only a very small segment (ca 1.0 μm) of the distal region of 6RL is present in an intercalary translocation (Ti) Ti4AS · 4AL-6RL-4AL. The 6RL segment is inserted in the intercalary region between the centromere of chromosome 4A and the large proximal C-band of 4AL. The break-points of the translocations are outside the region of the centromere, indicating that they were induced by the X-ray treatment. All three translocations are cytologically stable and can be used directly in wheat breeding programs

  14. Chromosomal Translocations in Black Flies (Diptera: Simuliidae-Facilitators of Adaptive Radiation?

    Directory of Open Access Journals (Sweden)

    Peter H Adler

    Full Text Available A macrogenomic investigation of a Holarctic clade of black flies-the Simulium cholodkovskii lineage-provided a platform to explore the implications of a unique, synapomorphic whole-arm interchange in the evolution of black flies. Nearly 60 structural rearrangements were discovered in the polytene complement of the lineage, including 15 common to all 138 analyzed individuals, relative to the central sequence for the entire subgenus Simulium. Three species were represented, of which two Palearctic entities (Simulium cholodkovskii and S. decimatum were sympatric; an absence of hybrids confirmed their reproductive isolation. A third (Nearctic entity had nonhomologous sex chromosomes, relative to the other species, and is considered a separate species, for which the name Simulium nigricoxum is revalidated. A cytophylogeny is inferred and indicates that the two Palearctic taxa are sister species and these, in turn, are the sister group of the Nearctic species. The rise of the S. cholodkovskii lineage encompassed complex chromosomal and genomic restructuring phenomena associated with speciation in black flies, viz. expression of one and the same rearrangement as polymorphic, fixed, or sex linked in different species; taxon-specific differentiation of sex chromosomes; and reciprocal translocation of chromosome arms. The translocation is hypothesized to have occurred early in male spermatogonia, with the translocated chromosomal complement being transmitted to the X- and Y-bearing sperm during spermatogenesis, resulting in alternate disjunction of viable F1 translocation heterozygotes and the eventual formation of more viable and selectable F2 translocation homozygous progeny. Of 11 or 12 independently derived whole-arm interchanges known in the family Simuliidae, at least six are associated with subsequent speciation events, suggesting a facilitating role of translocations in adaptive radiations. The findings are discussed in the context of potential

  15. Follow-up of translocations and dicentrics by chromosome painting (Fish) after accidental exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Lindhom, C.; Salomaa, S.; Tekkel, M.; Veidebaum, T.

    1997-01-01

    Chromosome painting was applied to follow the frequencies of translocations and dicentrics in blood lymphocytes from eight persons involved in a radiation accident in Estonia, 1994. Complete translocation frequencies remained relatively constant during the first year of study, whereas the rate of complete dicentrics declined rapidly in patients exposed to 1 Gy or more. The high proportion of incomplete translocations observed right after the accident declined during the first year after the exposure, approaching the level of incomplete dicentrics. (authors)

  16. Balanced Chromosomal Translocation of Chromosomes 6 and 7: A Rare Male Factor of Spontaneous Abortions

    Directory of Open Access Journals (Sweden)

    Sefa Resim

    2013-06-01

    Full Text Available Background: Carriers of structural chromosomal rearrangements such as Robertsonian or reciprocal translocations have an increased risk of spontaneous abortion and producing offspring with genetic abnormalities. Case Report: We report a man with balanced chromosomal translocations located at 6p22, and 7q22. His wife has a history of four spontaneous abortions. Conclusion: Couples with a history of abortions should be investigated cytogenetically, after other causes of miscarriages are excluded. The possibility of spontaneous abortions can be reduced with preimplantation genetic diagnosis (PGD before embryo transfer.

  17. Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression.

    Science.gov (United States)

    Karlsson, Asa; Deb-Basu, Debabrita; Cherry, Athena; Turner, Stephanie; Ford, James; Felsher, Dean W

    2003-08-19

    DNA repair mechanisms are essential for the maintenance of genomic integrity. Disruption of gene products responsible for DNA repair can result in chromosomal damage. Improperly repaired chromosomal damage can result in the loss of chromosomes or the generation of chromosomal deletions or translocations, which can lead to tumorigenesis. The MYC protooncogene is a transcription factor whose overexpression is frequently associated with human neoplasia. MYC has not been previously implicated in a role in DNA repair. Here we report that the overexpression of MYC disrupts the repair of double-strand DNA breaks, resulting in a several-magnitude increase in chromosomal breaks and translocations. We found that MYC inhibited the repair of gamma irradiation DNA breaks in normal human cells and blocked the repair of a single double-strand break engineered to occur in an immortal cell line. By spectral karyotypic analysis, we found that MYC even within one cell division cycle resulted in a several-magnitude increase in the frequency of chromosomal breaks and translocations in normal human cells. Hence, MYC overexpression may be a previously undescribed example of a dominant mutator that may fuel tumorigenesis by inducing chromosomal damage.

  18. Chromosome translocations in chinese medical X-ray workers analyzed by fluorescence in situ hybridization

    International Nuclear Information System (INIS)

    Sun Yuanming; Li Jin; Wang Qin; Tang Weisheng; Wang Zhiquan

    2002-01-01

    Objective: To study long-term radiation effect in occupational workers exposed to low dose X-rays using the method of fluorescence in situ hybridization (FISH). Method: Chromosome translocations of 25 medical X-ray workers were analyzed by FISH with chromosome No. 4 and No. 7 probes according to PAINT (The Protocol for Aberration Identification and Nomenclature Terminology) system. Results: The frequency of genome translocation in X-ray workers was (13.14 ± 1.23)/1000 cells. The rate of complete and incomplete translocation was 1:1.7. According to the calendar year of entry before/after the year of 1965 as the border, the data showed that the incomplete translocation of the after 1965 group was obviously higher than those of the controls (P < 0.01 and P < 0.05, respectively). Conclusion: The chromosome translocation in early Chinese medical X-ray workers is mainly the incomplete one, the frequency of translocation does not dependent on chromosomal DNA content, and incomplete and complete ones increase along with prolongation of working years in their position

  19. TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription.

    Science.gov (United States)

    Gómez-Herreros, Fernando; Zagnoli-Vieira, Guido; Ntai, Ioanna; Martínez-Macías, María Isabel; Anderson, Rhona M; Herrero-Ruíz, Andrés; Caldecott, Keith W

    2017-08-10

    DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation 'hotspot', MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.DNA double-strand breaks (DSBs) induced by topoisomerase II (TOP2) are rejoined by TDP2-dependent non-homologous end-joining (NHEJ) but whether this promotes or suppresses translocations is not clear. Here the authors show that TDP2 suppresses chromosome translocations from DSBs introduced during gene transcription.

  20. High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA

    Directory of Open Access Journals (Sweden)

    Benjamin Powers

    2015-01-01

    Full Text Available Acute promyelocytic leukemia (APL is classically characterized by chromosomal translocation (15;17, resulting in the PML-RARA fusion protein leading to disease. Here, we present a case of a 50-year-old man who presented with signs and symptoms of acute leukemia with concern for APL. Therapy was immediately initiated with all-trans retinoic acid. The morphology of his leukemic blasts was consistent with the hypogranular variant of APL. Subsequent FISH and cytogenetic analysis revealed a unique translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. Molecular testing demonstrated PML/RARA fusion transcripts. Treatment with conventional chemotherapy was added and he went into a complete remission. Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given. The patient remains on maintenance therapy and remains in remission. This is the first such report of a 5-way chromosomal translocation leading to APL. Similar to APL with chromosomal translocations other than classical t(15;17 which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission.

  1. Occupational exposure to pesticides and occurrence of the chromosomal translocation t(14;18 among farmers in Jordan

    Directory of Open Access Journals (Sweden)

    Bara’a M. Qaqish

    Full Text Available Background: An increased incidence of non-Hodgkin’s lymphoma (NHL has been reported in farmers and other occupational groups working with pesticides. In these individuals, an increased prevalence of the chromosomal translocation t(14;18(q32;q21, one of the most common chromosomal abnormalities in NHL, has been detected in peripheral blood lymphocytes. This translocation juxtaposes the antiapoptotic BCL2 protein to the immunoglobulin heavy chain gene locus (IGH leading to overexpression of BCL2. This causes an increase in cell survival, paving the way for malignant transformation. Aim of the study: The present study aimed to evaluate the association between the occurrence of the chromosomal translocation t(14;18 and occupational exposure to pesticides among a group of Jordanian farmers. Methods: A total of 192 male subjects including 96 agricultural workers and 96 control subjects participated in this study. BCL2-IGH t(14;18 fusions were detected by a nested polymerase chain reaction (PCR assay targeting the major breakpoint region (MBR. Results: We found that occupational exposure to pesticides in open-field farming and insecticide used on animals increased the frequency of the chromosomal translocation t(14;18. Farmers occupationally exposed to pesticides and insecticide were 13.5 times more likely to harbor t(14;18. 63.5% (61 of 96 of farmers compared to 11.5% (11 of 96 of controls carried the translocation (odds ratio: 13.5; 95% confidence interval (CI = 6.3–28.6. We ruled out the influence of possible confounding factors such as age, duration of sun exposure, alcohol intake, smoking, and use of personal protective equipment. Conclusion: Our results indicate that pesticides increased the frequency of chromosomal translocation in the 14q32 region. Accordingly, the presented data agrees with previous suggestions from the literature that pesticides might be involved in the development of NHL through the t(14;18 pathway. Keywords

  2. The chromosomal risk in sperm from heterozygous Robertsonian translocation carriers is related to the sperm count and the translocation type.

    Science.gov (United States)

    Ferfouri, Fatma; Selva, Jacqueline; Boitrelle, Florence; Gomes, Denise Molina; Torre, Antoine; Albert, Martine; Bailly, Marc; Clement, Patrice; Vialard, François

    2011-12-01

    To study the chromosomal risk in sperm from Robertsonian translocation (RobT) carriers as a function of the sperm count and translocation type. Prospective study. Departments of reproductive biology, cytogenetics, gynecology, and obstetrics. A total of 29 RobT patients (8 normozoospermic and 21 oligozoospermic) and 20 46,XY patients (10 normozoospermic and 10 oligozoospermic). Sperm fluorescence in situ hybridization with probes for translocation malsegregation and chromosome 13, 18, 21, X, and Y probes for studying the interchromosomal effect (ICE). Translocation malsegregation and ICE aneuploidy rates. In RobT carriers, the sperm translocation malsegregation rate was significantly lower in normozoospermic patients (9.7%) than in oligozoospermic patients (18.0%). Considering only oligozoospermic patients, sperm malsegregation rates were significantly lower for rob(14;21) than for rob(13;14) (11.4% vs. 18.9%). In turn, the rates were significantly lower for rob(13;14) than for rare RobTs (18.9% vs. 25.3%). In sperm from normozoospermic RobT, an ICE was suggested by higher chromosome 13 and 21 aneuploidy rates than in control sperm. Conversely, chromosome 13 and 21 sperm aneuploidy rates were lower in oligozoospermic RobT patients than in oligozoospermic 46,XY patients, but higher than in control subjects. Both translocation type and sperm count influence the RobT malsegregation risk. Of the chromosomes analyzed (13, 18, 21, X, and Y), only chromosomes 13 and 21 were found to be associated with an ICE. Relative to the RobT effect, idiopathic alterations in spermatogenesis in 46,XY patients appear to be more harmful for meiosis. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Chromosome 2 short arm translocations revealed by M-FISH analysis of neuroblastoma cell lines.

    Science.gov (United States)

    Van Roy, N; Van Limbergen, H; Vandesompele, J; Van Gele, M; Poppe, B; Laureys, G; De Paepe, A; Speleman, F

    2000-12-01

    M-FISH analysis was performed on 18 neuroblastoma cell lines, which were previously studied with cytogenetic, standard FISH and CGH data. One of the most striking findings of this study was the detection of chromosome 2 short arm rearrangements in 61% of the investigated cell lines. These rearrangements resulted from translocations with various partner chromosomes. All translocations, except one were unbalanced, leading to the consistent gain of chromosome segment 2pter-p22. A cryptic balanced translocation t(2;4) was observed with a breakpoint located in the vicinity of MYCN in cell line NBL-S. Combination of M-FISH results together with cytogenetic, standard FISH and CGH data yielded the most comprehensive description of chromosome 2 short arm rearrangements, leading to a consistent gain of chromosome 2 short arm material. Copyright 2000 Wiley-Liss, Inc.

  4. Translocations of Chromosome End-Segments and Facultative Heterochromatin Promote Meiotic Ring Formation in Evening Primroses[W][OPEN

    Science.gov (United States)

    Golczyk, Hieronim; Massouh, Amid; Greiner, Stephan

    2014-01-01

    Due to reciprocal chromosomal translocations, many species of Oenothera (evening primrose) form permanent multichromosomal meiotic rings. However, regular bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends, which makes homologous recombination virtually undetectable. Genetic diversity is achieved by changing linkage relations of chromosomes in rings and bivalents via hybridization and reciprocal translocations. Although the structural prerequisite for this system is enigmatic, whole-arm translocations are widely assumed to be the mechanistic driving force. We demonstrate that this prerequisite is genome compartmentation into two epigenetically defined chromatin fractions. The first one facultatively condenses in cycling cells into chromocenters negative both for histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in differentiating cells. The second fraction is euchromatin confined to distal chromosome segments, positive for histone H3 lysine 4 dimethylation and for histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical telomeres but capped with constitutive heterochromatin. This genomic organization promotes translocation breakpoints between the two chromatin fractions, thus facilitating exchanges of end-segments. We challenge the whole-arm translocation hypothesis by demonstrating why reciprocal translocations of chromosomal end-segments should strongly promote meiotic rings and evolution toward permanent translocation heterozygosity. Reshuffled end-segments, each possessing a major crossover hot spot, can furthermore explain meiotic compatibility between genomes with different translocation histories. PMID:24681616

  5. Detection of reciprocal chromosome translocations as an indicator of organism exposure to ionizing radiation by FISH-WCP method

    International Nuclear Information System (INIS)

    Holeckova, B.; Sivikova, K.; Dianovsky, J.; Piesova, E.; Lakatosova, M.

    2006-01-01

    Chromosome translocations are considered to be the gold standard for assessing ionizing radiation exposure. Because translocations are inherently more stable through cell division than dicentrics, translocations have become the aberration of choice for evaluating many types of exposure. Fluorescence in situ hybridization with whole chromosome painting probes (FISH-WCP) has been shown to be a rapid method of detecting chromosomal rearrangements, and appears to be especially useful for analysis of induced translocations. The present paper shortly describes FISH-WCP method for detection of reciprocal translocations as indicators of exposure to ionizing radiation. (authors)

  6. Radiation induced wheat-rye chromosomal translocations in triticale. Optimizing the dose using fluorescence in situ hybridization

    International Nuclear Information System (INIS)

    Ahmad, F.; Comeau, A.; Chen, Q.; Collin, J.; St-Pierre, C.A.

    2000-01-01

    Fluorescent in situ hybridization (FISH) was utilized to monitor the level of ionizing radiation ( 60 Co source) in their ability to cause intra- and intergeneric chromosomal aberrations in triticale seeds. Seeds were irradiated with 0, 20, 50, 100, 200, 300, 400, 500 and 1000 Gy doses. The root growth of irradiated seeds was greatly inhibited at 200 Gy and above. Various types of aberrations including wheat-rye, wheat-wheat, rye-rye, wheat-rye-wheat, rye-wheat-rye translocations and acentric fragments with or without translocations were observed. There was a consistent increase in proportion of aberrations per cell with an increase in radiation dose. It was concluded that for an optimal level of chromosomal translocation and least number of acentric fragments, a 20 Gy dose was quite sufficient for inducing a desirable level of wheat-rye chromosomal translocations. The excellent efficiency and importance of utilizing FISH in such studies of alien-introgression via chromosomal translocations are discussed. (author)

  7. Radiation induced wheat-rye chromosomal translocations in triticale. Optimizing the dose using fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, F. [Brandon Univ., Manitoba (Canada); Comeau, A.; Chen, Q.; Collin, J.; St-Pierre, C.A.

    2000-03-01

    Fluorescent in situ hybridization (FISH) was utilized to monitor the level of ionizing radiation ({sup 60}Co source) in their ability to cause intra- and intergeneric chromosomal aberrations in triticale seeds. Seeds were irradiated with 0, 20, 50, 100, 200, 300, 400, 500 and 1000 Gy doses. The root growth of irradiated seeds was greatly inhibited at 200 Gy and above. Various types of aberrations including wheat-rye, wheat-wheat, rye-rye, wheat-rye-wheat, rye-wheat-rye translocations and acentric fragments with or without translocations were observed. There was a consistent increase in proportion of aberrations per cell with an increase in radiation dose. It was concluded that for an optimal level of chromosomal translocation and least number of acentric fragments, a 20 Gy dose was quite sufficient for inducing a desirable level of wheat-rye chromosomal translocations. The excellent efficiency and importance of utilizing FISH in such studies of alien-introgression via chromosomal translocations are discussed. (author)

  8. Cloning of the gene encoding the δ subunit of the human T-cell receptor reveals its physical organization within the α-subunit locus and its involvement in chromosome translocations in T-cell malignancy

    International Nuclear Information System (INIS)

    Isobe, M.; Russo, G.; Haluska, F.G.; Croce, C.M.

    1988-01-01

    By taking advantage of chromosomal walking techniques, the authors have obtained clones that encompass the T-cell receptor (TCR) δ-chain gene. They analyzed clones spanning the entire J α region extending 115 kilobases 5' of the TCR α-chain constant region and have shown that the TCR δ-chain gene is located over 80 kilobases 5' of C α . TCR δ-chain gene is rearranged in the γ/δ-expressing T-cell line Peer and is deleted in α/β-expressing T-cell lines. Sequence analysis of portions of this genomic region demonstrates its identity with previously described cDNA clones corresponding to the C δ and J δ segments. Furthermore, they have analyzed a t(8;14)-(q24;q11) chromosome translocation from a T-cell leukemia and have shown that the J δ segment is rearranged in cells deriving from this tumor and probably directly involved in the translocation. Thus, the newly clones TCR δ chain is implicated in the genesis of chromosome translocations in T-cell malignancies carrying cytogenetic abnormalities of band 14q11

  9. Development of a biological dosimeter for translocation scoring based on two-color fluorescence in situ hybridization of chromosome subsets

    Energy Technology Data Exchange (ETDEWEB)

    Popp, S; Cremer, T [Heidelberg Univ. (Germany). Inst. of Human Genetics and Anthropology

    1992-03-01

    Recently fluorescence in situ hybridization protocols have been developed which allow the paining of individual chromosomes using DNA-libraries from sorted human chromosomes. This approach has the particular advantage that radiation induced chromosome translocations can be easily detected, if chromosomes of distinctly different colors take part in the translocation event. To enhance the sensitivity of this approach two metaphase chromosome subsets A and B (A: chromosome 1, 2, 4, 8, 16; B: 3, 5, 9, 10, 13) were simultaneously painted in green and red color. Counterstaining of the chromosomes with DAPI resulted in a third subset which exhibited blue fluorescence only. Green-red, green-blue and red-blue translocation chromosomes could be easily detected after irradiation of lymphocyte cultures with {sup 137}Cs-{gamma}-rays. Analyses of painted chromosomes can be combined with conventional GTG-banding analyses. This new biological dosimeter should become useful to monitor both long term effects of single irradiation events and the cumulative effects of multiple or chronic irradiation exposure. In contrast to translocation scoring based on the analysis of banded chromosomes, this new approach has the particular advantage that a rapid, automated scoring of translocations can now be envisaged. (author).

  10. Primary vitreoretinal dysplasia resembling Norrie's disease in a female: association with X autosome chromosomal translocation.

    OpenAIRE

    Ohba, N.; Yamashita, T.

    1986-01-01

    A female infant with the typical clinical and histopathological features of vitreoretinal dysplasia is described. She had an apparently balanced reciprocal chromosomal translocation 46XX,t(X;10) with the X chromosome breakpoint being on the short arm. Since the parents' karyotypes were normal, it is most plausible that a de novo chromosomal translocation disrupted the vitreoretinal dysplasia gene itself. The severe clinical symptoms of this heterozygous female patient were explained by non-ra...

  11. Use of FISH-translocations analyses for retrospective biological dosimetry: How stable are stable chromosome aberrations?

    International Nuclear Information System (INIS)

    Darroudi, F.

    2000-01-01

    Chromosome aberrations, in particular dicentrics, in peripheral blood lymphocytes are used to estimate the absorbed dose immediately following a radiation accident. However, difficulties for dose estimation arise with old exposures, due to a decline of cells containing unstable dicentric aberrations. The fluorescence in situ hybridisation (FISH) technique employing chromosome specific DNA libraries to 'paint' individual human chromosomes has opened new perspectives for rapid and reliable detection of stable chromosome aberrations such as translocations. The inherent stability of translocations over cell generations has enabled them to be used as a biodosemeter. However, due to the limited life of circulating T-lymphocytes, a level of uncertainty exists on the long-term persistence of stable translocations. The objectives of the present work are to present the current state of knowledge on the stability of translocations detected by FISH. The following aspects have been considered; (1) experience so far of retrospective biological dosimetry in humans following accidental and occupational over-exposure, (2) animal studies using mice and monkeys, (3) the influence of subsequent cell divisions on the yield and persistence of translocations following in vitro irradiation of human lymphocytes, and (4) the needs for further work to standardise and validate the use of FISH as a biological dosemeter, and to investigate the influence of various parameters such as radiation quality, dose rate and the discrimination of sub-types of translocations on persistence. (author)

  12. Centrifugally driven microfluidic disc for detection of chromosomal translocations

    DEFF Research Database (Denmark)

    Brøgger, Anna Line; Kwasny, Dorota; Bosco, Filippo G.

    2012-01-01

    and prognosis of patients. In this work we demonstrate a novel, centrifugally-driven microfluidic system for controlled manipulation of oligonucleotides and subsequent detection of chromosomal translocations. The device is fabricated in the form of a disc with capillary burst microvalves employed to control...

  13. Nuchal translucency thickness and outcome in chromosome translocation diagnosed in the first trimester.

    Science.gov (United States)

    Sepulveda, W; Be, C; Youlton, R; Carstens, E; Reyes, M

    2001-09-01

    In order to determine the significance of nuchal translucency thickness on the subsequent natural history of first-trimester fetuses with a chromosome translocation, seven consecutive cases diagnosed between 11 and 13 weeks of gestation were reviewed. Nuchal translucency measurements were successfully obtained before chorionic villus sampling (CVS) in all cases. Three fetuses had an unbalanced translocation and all were associated with increased nuchal translucency and multiple anomalies at the detailed second-trimester scan. There were no survivors in this group. The remaining four fetuses had a balanced translocation; all had normal nuchal translucency thickness and no structural anomalies were detected in the second trimester. Three of these fetuses were born at > or =35 weeks of gestation and were phenotypically normal. However, an unexpected single fetal demise occurred in a dichorionic twin pregnancy at 28 weeks of gestation. It is concluded that nuchal translucency measurements provide important prognostic information on pregnancy outcome in first-trimester fetuses with a chromosome translocation. In parents with a known balanced translocation, the detection of increased nuchal translucency at 11-14 weeks of gestation is associated with unbalanced translocations, structural anomalies and poor pregnancy outcome. Copyright 2001 John Wiley & Sons, Ltd.

  14. Breeding few-seed/seedless watermelon via chromosome reciprocal translocation induced by gamma-ray

    International Nuclear Information System (INIS)

    Ming, W.; Xingping, Z.; Xian, Z.; Kechi, N.; Shuai, Z.; Juenlian, Z.

    1988-01-01

    The development of autotriploid watermelon was a great advance in the field of watermelon breeding. However, some disadvantages still existed with this type of seedless watermelon. Partial sterility may be induced in diploid watermelon via chromosome reciprocal translocation. We used gamma-rays to irradiate the seeds of homozygous translocation strains with one translocation ring composed of 4 chromosomes (symbol (4) ). Watermelon strains were 'Asahi Yamato', 'Mioyaka', and 'Fumin' saent to us by H. Kihara in 1977. In order to further induce multiple reciprocal translocations for developing new few-seed/seedless watermelon strains, the seeds of the above 3 strains were sown for further selfing in 1978. The seeds of each selfed fruit were grown as a single plant line in 1979 for evaluation of their characters. In addition, some crosses between common diploid watermelon cultivars and translocations were carried out to test the seed setting rate of the heterozygous translocation strains. Some of the crosses were 'Sugar Baby' x 'Asahi Yamato AT-1' and 'Akakotama' x Asahi Yamato AT-2'. The plump seed setting rate of the F1 of these crosses were ca. 50%

  15. Evolution of the Banana Genome (Musa acuminata) Is Impacted by Large Chromosomal Translocations.

    Science.gov (United States)

    Martin, Guillaume; Carreel, Françoise; Coriton, Olivier; Hervouet, Catherine; Cardi, Céline; Derouault, Paco; Roques, Danièle; Salmon, Frédéric; Rouard, Mathieu; Sardos, Julie; Labadie, Karine; Baurens, Franc-Christophe; D'Hont, Angélique

    2017-09-01

    Most banana cultivars are triploid seedless parthenocarpic clones derived from hybridization between Musa acuminata subspecies and sometimes M. balbisiana. M. acuminata subspecies were suggested to differ by a few large chromosomal rearrangements based on chromosome pairing configurations in intersubspecies hybrids. We searched for large chromosomal rearrangements in a seedy M. acuminata ssp. malaccensis banana accession through mate-pair sequencing, BAC-FISH, targeted PCR and marker (DArTseq) segregation in its progeny. We identified a heterozygous reciprocal translocation involving two distal 3 and 10 Mb segments from chromosomes 01 and 04, respectively, and showed that it generated high segregation distortion, reduced recombination and linkage between chromosomes 01 and 04 in its progeny. The two chromosome structures were found to be mutually exclusive in gametes and the rearranged structure was preferentially transmitted to the progeny. The rearranged chromosome structure was frequently found in triploid cultivars but present only in wild malaccensis ssp. accessions, thus suggesting that this rearrangement occurred in M. acuminata ssp. malaccensis. We propose a mechanism for the spread of this rearrangement in Musa diversity and suggest that this rearrangement could have played a role in the emergence of triploid cultivars. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. Fungal genome and mating system transitions facilitated by chromosomal translocations involving intercentromeric recombination.

    Directory of Open Access Journals (Sweden)

    Sheng Sun

    2017-08-01

    rearrangements mediated by intercentromeric recombination have occurred during descent of the 2 lineages from their common ancestor. Taken together, our findings support a model in which the evolution of the bipolar mating system was initiated by an ectopic recombination event mediated by similar repetitive centromeric DNA elements shared between chromosomes. This translocation brought the P/R and HD loci onto the same chromosome, and further chromosomal rearrangements then resulted in the 2 MAT loci becoming physically linked and eventually fusing to form the single contiguous MAT locus that is now extant in the pathogenic Cryptococcus species.

  17. Identification of 2nd chromosome region translocated onto the W chromosome by RFLP with EST-cDNA clones in the Gensei-kouken strains of the mulberry silkworm, Bombyx mori L

    Directory of Open Access Journals (Sweden)

    Sivaramakurup Sreekumar

    2010-01-01

    Full Text Available In silkworms, sex-limited strains are either obtained spontaneously or induced by X-rays or gamma rays. When a fragment of an autosome carrying a dominant allele of those genes responsible for certain characters is translocated onto a W chromosome, the female of the successive generations will express these phenotypic characters and sex discrimination can be facilitated. Gensei-kouken strains are sex-limited strains of silkworms developed by irradiating the pupae with gamma rays, by which a portion of the second chromosome is translocated onto the W chromosome. In these improved strains, the females are yellow-blooded and spin yellow cocoons. By using the EST-cDNA clones mapped on the Z chromosome, we identified the sex according to the polymorphic banding pattern or intensity of the signals. Furthermore, by using the clones on the second chromosome, the region of the second chromosome translocated onto the W chromosome was also defined. In both the A95 and A 96 strains selected for the present study, only the mid-portion of the second chromosome was translocated. The differences in length of the fragments translocated in these strains are discussed.

  18. International study of factors affecting human chromosome translocations

    Czech Academy of Sciences Publication Activity Database

    Sigurdson, A.J.; Ha, M.; Hauptmann, M.; Bhatti, P.; Šrám, Radim; Beskid, Olena; Tawn, E.J.; Whitehouse, C.A.; Lindholm, C.; Nakano, M.; Kodama, Y.; Nakamura, N.; Vorobtsova, I.; Oestreicher, U.; Stephan, G.; Yong, L.C.; Bauchinger, M.; Schmid, E.; Chung, H.W.; Darroudi, F.; Roy, L.; Voisin, P.; Barquinero, J.F.; Livingston, G.; Blakey, D.; Hayata, I.; Zhang, W.; Wang, Ch.; Benett, L.M.; Littlefield, L.G.; Edwards, A.A.; Kleinerman, R.A.; Tucker, J.D.

    2008-01-01

    Roč. 652, č. 2 (2008), s. 112-121 ISSN 1383-5718 R&D Projects: GA MŽP SL/5/160/05; GA MŽP SI/340/2/00; GA MŽP SL/740/5/03 Institutional research plan: CEZ:AV0Z50390512 Keywords : Chromosome translocations * FISH * Background frequency Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.363, year: 2008

  19. Tyrosine kinase chromosomal translocations mediate distinct and overlapping gene regulation events

    International Nuclear Information System (INIS)

    Kim, Hani; Gillis, Lisa C; Jarvis, Jordan D; Yang, Stuart; Huang, Kai; Der, Sandy; Barber, Dwayne L

    2011-01-01

    Leukemia is a heterogeneous disease commonly associated with recurrent chromosomal translocations that involve tyrosine kinases including BCR-ABL, TEL-PDGFRB and TEL-JAK2. Most studies on the activated tyrosine kinases have focused on proximal signaling events, but little is known about gene transcription regulated by these fusions. Oligonucleotide microarray was performed to compare mRNA changes attributable to BCR-ABL, TEL-PDGFRB and TEL-JAK2 after 1 week of activation of each fusion in Ba/F3 cell lines. Imatinib was used to control the activation of BCR-ABL and TEL-PDGFRB, and TEL-JAK2-mediated gene expression was examined 1 week after Ba/F3-TEL-JAK2 cells were switched to factor-independent conditions. Microarray analysis revealed between 800 to 2000 genes induced or suppressed by two-fold or greater by each tyrosine kinase, with a subset of these genes commonly induced or suppressed among the three fusions. Validation by Quantitative PCR confirmed that eight genes (Dok2, Mrvi1, Isg20, Id1, gp49b, Cxcl10, Scinderin, and collagen Vα1(Col5a1)) displayed an overlapping regulation among the three tested fusion proteins. Stat1 and Gbp1 were induced uniquely by TEL-PDGFRB. Our results suggest that BCR-ABL, TEL-PDGFRB and TEL-JAK2 regulate distinct and overlapping gene transcription profiles. Many of the genes identified are known to be involved in processes associated with leukemogenesis, including cell migration, proliferation and differentiation. This study offers the basis for further work that could lead to an understanding of the specificity of diseases caused by these three chromosomal translocations

  20. Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.

    Science.gov (United States)

    Sun, Jiying; Shi, Lin; Kinomura, Aiko; Fukuto, Atsuhiko; Horikoshi, Yasunori; Oma, Yukako; Harata, Masahiko; Ikura, Masae; Ikura, Tsuyoshi; Kanaar, Roland; Tashiro, Satoshi

    2018-05-08

    Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities. © 2018, Sun et al.

  1. Dose-response curve for translocation frequency with single pair of painted chromosome. A comparison with dicentric and micronuclei frequency

    Energy Technology Data Exchange (ETDEWEB)

    Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K

    2000-07-01

    A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (autho000.

  2. Dose-response curve for translocation frequency with single pair of painted chromosome. A comparison with dicentric and micronuclei frequency

    International Nuclear Information System (INIS)

    Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K.

    2000-01-01

    A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (author)

  3. Amplification of chromosomal translocation junctions from paraffin-embedded tissues of follicular lymphoma patients

    International Nuclear Information System (INIS)

    Nambiar, Mridula; Raghavan, Sathees C; Choudhary, Bibha; Rao, Clementina R

    2008-01-01

    Follicular lymphoma is associated with the t(14;18) translocation, which is one of the most common chromosomal translocations in cancer. Generally, tissues from such patients are preserved as formalin-fixed and paraffin-embedded samples. Most of the time, retrieving the molecular information from such samples is hampered due to quality of preservation, extraction procedures and reaction conditions. In the present study, we isolate the chromosomal DNA from the paraffin-embedded nodal tissues of lymphoma patients and use a highly sensitive nested PCR approach to detect t(14;18) translocation. Our studies show that despite the sheared DNA obtained, appropriate modification of PCR reaction conditions can help in obtaining the desired amplifications. The DNA extraction protocol from paraffin-embedded nodal tissues and modifications in the PCR conditions are discussed. This study would contribute to the successful use of archival tissue samples in obtaining valuable information for cancer research

  4. Amplification of chromosomal translocation junctions from paraffin-embedded tissues of follicular lymphoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Nambiar, Mridula; Raghavan, Sathees C [Department of Biochemistry, Indian Institute of Science, Bangalore-560 012 (India); Choudhary, Bibha [Manipal Institute of Regenerative Medicine, Manipal University, Bangalore-560 071 (India); Rao, Clementina R [Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore-560 029 (India)], E-mail: sathees@biochem.iisc.ernet.in

    2008-09-01

    Follicular lymphoma is associated with the t(14;18) translocation, which is one of the most common chromosomal translocations in cancer. Generally, tissues from such patients are preserved as formalin-fixed and paraffin-embedded samples. Most of the time, retrieving the molecular information from such samples is hampered due to quality of preservation, extraction procedures and reaction conditions. In the present study, we isolate the chromosomal DNA from the paraffin-embedded nodal tissues of lymphoma patients and use a highly sensitive nested PCR approach to detect t(14;18) translocation. Our studies show that despite the sheared DNA obtained, appropriate modification of PCR reaction conditions can help in obtaining the desired amplifications. The DNA extraction protocol from paraffin-embedded nodal tissues and modifications in the PCR conditions are discussed. This study would contribute to the successful use of archival tissue samples in obtaining valuable information for cancer research.

  5. Increased frequency of chromosome translocations in airline pilots with long-term flying experience.

    Science.gov (United States)

    Yong, L C; Sigurdson, A J; Ward, E M; Waters, M A; Whelan, E A; Petersen, M R; Bhatti, P; Ramsey, M J; Ron, E; Tucker, J D

    2009-01-01

    Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience. We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromosome painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying. There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33). Our data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.

  6. Chromosome translocations measured by fluorescence in-situ hybridization: A promising biomarker

    International Nuclear Information System (INIS)

    Lucas, J.N.; Straume, T.

    1995-10-01

    A biomarker for exposure and risk assessment would be most useful if it employs an endpoint that is highly quantitative, is stable with time, and is relevant to human risk. Recent advances in chromosome staining using fluorescence in situ hybridization (FISH) facilitate fast and reliable measurement of reciprocal translocations, a kind of DNA damage linked to both prior exposure and risk. In contrast to other biomarkers available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time post exposure, has a rather small inter-individual variability, and can be measured accurately at the low levels. Here, the authors discuss results from their studies demonstrating that chromosome painting can be used to reconstruct radiation dose for workers exposed within the dose limits, for individuals exposed a long time ago, and even for those who have been diagnosed with leukemia but not yet undergone therapy

  7. A Balanced Chromosomal Translocation Disrupting ARHGEF9 Is Associated With Epilepsy, Anxiety, Aggression, and Mental Retardation

    OpenAIRE

    Kalscheuer, Vera M.; Musante, Luciana; Fang, Cheng; Hoffmann, Kirsten; Fuchs, Celine; Carta, Eloisa; Deas, Emma; Venkateswarlu, Kanamarlapudi; Menzel, Corinna; Ullmann, Reinhard; Tommerup, Niels; Dalprà, Leda; Tzschach, Andreas; Selicorni, Angelo; Lüscher, Bernhard

    2009-01-01

    Clustering of inhibitory γ-aminobutyric acidA (GABAA) and glycine receptors at synapses is thought to involve key interactions between the receptors, a “scaffolding” protein known as gephyrin and the RhoGEF collybistin. We report the identification of a balanced chromosomal translocation in a female patient presenting with a disturbed sleep-wake cycle, late-onset epileptic seizures, increased anxiety, aggressive behavior, and mental retardation, but not hyperekplexia. Fine mapping of the brea...

  8. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    NARCIS (Netherlands)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. It is generally accepted that, when no chromosomal rearrangements are involved, man

  9. Genetic markers, translocations and sexing genes on chromosome 2 of Ceratitis capitata

    International Nuclear Information System (INIS)

    Cladera, J.L.

    1997-01-01

    A review is presented of results obtained in a search for genetic markers, translocations and selectable genes obtained at the Instituto de Genetica, Castelar, Argentina, with special reference to chromosome 2 linked mutations and genes useful for developing self-sexing strains in Ceratitis capitata. (author)

  10. A somatic origin of homologous Robertsonian translocations and isochromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A. (Univ. of Zurich (Switzerland)); Basaran, S.; Yueksel-Apak, M. (Univ. of Istanbul (Turkey)); Neri, G. (Universita Cattolica, Rome (Italy)); Serville, F. (Hopital d' Enfants Pellegrin, Bordeaux (France)); Balicek, P.; Haluza, R. (Univ. Hospital of Hradeck Kralove, Hradec Kralove (Czech Republic)); Farah, L.M.S. (Escuola Paulista de Medicina, Sao Paulo (Brazil)) (and others)

    1994-02-01

    One t(14q 14q), three t(15q 15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange. 75 refs., 1 fig., 4 tabs.

  11. Anhidrotic ectodermal dysplasia gene region cloned in yeast artificial chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Kere, J. [Washington Univ. School of Medicine, St. Louis, MO (United States)]|[Univ. of Helsinki (Finland); Grzeschik, K.H. [Univ. of Marburg (Germany); Limon, J. [Medical Academy, Gdansk (Poland); Gremaud, M.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); De La Chapelle, A. [Univ. of Helsinki (Finland)

    1993-05-01

    Anhidrotic ectodermal dysplasia (EDA), an X-chromosomal recessive disorder, is expressed in a few females with chromosomal translocations involving bands Xq12-q13. Using available DNA markers from the region and somatic cell hybrids the authors mapped the X-chromosomal breakpoints in two such translocations. The breakpoints were further mapped within a yeast artificial chromosome contig constructed by chromosome walking techniques. Genomic DNA markers that map between the two translocation breakpoints were recovered representing putative portions of the EDA gene. 32 refs., 3 figs., 1 tab.

  12. Familial cryptic translocation in Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Weyerts, L.K.; Wiley, J.E.; Loud, K.M. [ECU School of Medicine, Greenville, NC (United States)] [and others

    1994-09-01

    The majority of patients with Angelman syndrome have been shown to have a cytogenetic or molecular deletion on the maternally derived chromosome 15. We report on a case of Angelman syndrome in which this deletion occurs as an unbalanced cryptic translocation involving chromosomes 14 and 15. The proband was diagnosed clinically as having Angelman syndrome. Multiple cytogenetic studies were done without detecting any deletion. When DNA probes (Oncor) specific for the Prader Willi/Angelman locus became available, the patient was restudied and found to be deleted for {open_quotes}region A{close_quotes} (D15S11) but not for {open_quotes}region B{close_quotes} (GABRB3). No other abnormality was detected. The proband`s mother was then studied. The chromosome 15 marker probe and D15S11 were detected on different chromosomes. Using alpha-satellite probes, a cryptic 14;15 translocation was uncovered. This balanced translocation was also found to be carried by the sister of the proband. This case, along with a case presented at the 1993 ASHG meeting, illustrates the need for using acrocentric probes when studying Angelman syndrome patients. The proband was studied using additional probes specific for this region and found to be deleted for SNRPN but not for D15S10. The breakpoint of the translocation in this patient delineates the smallest deletion of the Angelman syndrome region reported to date and therefore may represent the specific gene involved.

  13. Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients

    Directory of Open Access Journals (Sweden)

    Dilhan Kuru

    2011-09-01

    Full Text Available Objective: The Philadelphia (Ph chromosome, consisting of the t(9;22(q34;q11 translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML. Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.Materials and Methods: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. Results: Variant Ph translocations in the 6 patients were as follows: t(7;22(p22;q11, t(9;22;15(q34;q11;q22, t(15;22(p11;q11, t(1;9;22;3(q24;q34;q11;q21, t(12;22(p13;q11, and t(4;8;9;22(q11;q13;q34;q11.Conclusion: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3(q24;q34;q11;q21 apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22(q11;q13;q34;q11 full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients.

  14. Homologous alpha satellite sequences on human acrocentric chromosomes with selectivity for chromosomes 13, 14, and 21: implications for recombination between nonhomologues and Robertsonian translocations

    Energy Technology Data Exchange (ETDEWEB)

    Choo, K H; Vissel, B; Brown, R; Filby, R G; Earle, E

    1988-02-25

    The authors report a new subfamily of alpha satellite DNA (pTRA-2) which is found on all the human acrocentric chromosomes. The alphoid nature of the cloned DNA was established by partial sequencing. Southern analysis of restriction enzyme-digested DNA fragments from mouse/human hybrid cells containing only human chromosome 21 showed that the predominant higher-order repeating unit for pTRA-2 is a 3.9 kb structure. Analysis of a consensus in situ hybridization profile derived from 13 normal individuals revealed the localization of 73% of all centromeric autoradiographic grains over the five acrocentric chromosomes, with the following distribution: 20.4%, 21.5%, 17.1%, 7.3% and 6.5% on chromosomes 13, 14, 21, 15 and 22 respectively. An average of 1.4% of grains was found on the centromere of each of the remaining 19 nonacrocentric chromosomes. These results indicate the presence of a common subfamily of alpha satellite DNA on the five acrocentric chromosomes and suggest an evolutionary process consistent with recombination exchange of sequences between the nonhomologues. The results further suggests that such exchanges are more selective for chromosomes 13, 14 and 21 than for chromosomes 15 and 22. The possible role of centromeric alpha satellite DNA in the aetiology of 13q14q and 14q21q Robertsonian translocation involving the common and nonrandom association of chromosomes 13 and 14, and 14 and 21 is discussed.

  15. Chondromyxoid fibroma of rib with a novel chromosomal translocation: a report of four additional cases at unusual sites

    Directory of Open Access Journals (Sweden)

    Parwani Anil V

    2007-11-01

    Full Text Available Abstract Background Chondromyxoid fibromas (CMFs are rare benign chondroid/myxoid matrix-producing tumors that occur in metaphyses of long tubular bones, and very rarely in small bones of hands and feet. Flat bone involvement is even more uncommon. Prior cytogenetic analyses have identified complex abnormalities involving chromosome 6 in the majority of cases. Methods A search for CMF over an 8-year period (1999–2006 from the surgical pathology files of our institution yielded 16 cases. Four cases occurred in relatively unusual regions, three from the small bones of distal extremities and one from the rib. The rib lesion wassubmitted forroutinecytogenetic analysis. Results Radiographic studies revealed that all four lesions were well-defined expansile radiolucent lesions which expanded the bony cortices with lobulated margins, sclerotic rim, septation, and no calcification. Morphologically, all four lesions showed typical features of CMF and had low proliferative index with Ki-67. Cytogenetic analysis on the rib lesion revealed a novel chromosomal translocation, t(1;5(p13;p13. None of the four patients had a recurrence after a mean duration of follow-up of 24 months. Conclusion CMF originating in unusual locations should be distinguished from chondrosarcomas, especially on small biopsies, and should be included in the differential diagnosis. As previously noted in the literature, the cells can be positive for actin but unlike conventional chondroid neoplasms can be negative for S-100. To our knowledge, this is the first report describing a novel chromosomal translocation, t(1;5(p13;p13 in CMF.

  16. First Birth after Sperm Selection through Discontinuous Gradient Centrifugation and Artificial Insemination from a Chromosomal Translocation Carrier

    Directory of Open Access Journals (Sweden)

    Alexandre Rouen

    2014-01-01

    Full Text Available Introduction. Balanced chromosomal carriers, though usually healthy, are confronted with recurrent spontaneous abortions and malformations in the offspring. Those are related to the transmission of an abnormal, chromosomally unbalanced genotype. We evidenced that the proportion of unbalanced spermatozoa can be significantly decreased through a sperm preparation process called discontinuous gradient centrifugation (DGC. We therefore started offering intrauterine inseminations with this procedure to couples with a male translocation carriers. Case Presentation. We report the case of a 37-year-old man carrying a t(3;10(q25;p13 reciprocal translocation. He and his partner had had trouble conceiving for ten years and had four spontaneous abortions. DGC in this patient decreased the proportion of unbalanced spermatozoa from 63.6% to 52.3%. They were therefore offered intrauterine insemination with DGC, which eventually led to the birth of a healthy female child carrying the paternal translocation. Conclusion. We showed that translocation carriers could be offered intrauterine inseminations with DGC. Before this, the only two options were natural conception with prenatal diagnosis and termination of chromosomally unbalanced fetuses or preimplantation genetic diagnosis, which is a much heavier and costly procedure. We are currently offering this option through a multicentric program in France, and this is the first birth originating from it.

  17. A disseminated alveolar rhabdomyosarcoma in a 9-year-old boy disclosed by chromosomal translocation (2;13) (q35;q14)

    Science.gov (United States)

    Brichard, B; Ninane, J; Gosseye, S; Verellen-Dumoulin, C; Vermylen, C; Rodhain, J; Cornu, G

    1991-01-01

    A 9-year-old boy presented with a small subcutaneous tumor of the trunk and diffuse bone marrow involvement. The first histological diagnosis given was undifferentiated malignancy possibly of neural crest origin and chemotherapy was started immediately using vincristine, cyclophosphamide, cisplatin, and teniposide (OPEC). Complete response was achieved after four courses of chemotherapy. Histological slides were then reviewed and the final diagnosis of alveolar rhabdomyosarcoma (RMS) was retained. Moreover, chromosome analysis of malignant cells in the bone marrow revealed a translocation involving chromosomes 2 and 13:t(2;13) (q35;q14). This specific karyotype finding has been recently reported in a few cases and could be specific for alveolar RMS. The patient had a relapse 7 months after diagnosis and died 4 months later.

  18. X-ray induction of autosomal translocations in spermatozoa of Drosophila melanogaster and maternal effects of X.Y-chromosomes

    International Nuclear Information System (INIS)

    Leigh, B.

    1979-01-01

    Wild-type ORK Drosophila melanogaster males were given an exposure of 3000 R X-radiation. Mature sperm were then sampled by mating to X.Y/X.Y, X.Y/X, or X/X females that carried markers on the second and third chromosomes for the detection of induced autosomal translocations. Two pairs of maternal stocks were used and heterozygous X.Y/X females were obtained by making both reciprocal crosses. The highest frequencies of induced translocations were obtained with X/X females. In one series these frequencies are higher than those obtained with either X.Y/X or X.Y/X.Y females. In the other series a uniform frequency of translocations was obtained with all types of female, except for one of the two types of heterozygous female, which gave lower frequencies. The experiments have provided data which show that the addition of Y-chromosomes to the maternal genome does not have a specific effect on the recovery of induced paternal autosomal translocations. Maternal Y-chromosomes increased the proportions of fertile F 1 males, this effect being consistent in direction but varying in degree. (Auth.)

  19. Interchanges in popcorn (Zea mays L. involving the nucleolus organizer chromosome

    Directory of Open Access Journals (Sweden)

    Maria Suely Pagliarini

    2006-01-01

    Full Text Available The analysis of microsporogenesis in endogamous plants of popcorn (S5 to S7 showed several and distinctinterchanges which involve the nucleolus organizer (chromosome 6. The detection of cells with interchanges was facilitatedby the presence of two nucleoli of different sizes in contrast to normal ones with a single big nucleolus. Interchange points donot always seem to be at the same place. Whereas in several situations the interchange point clearly involved more than twochromosome pairs, a simple terminal translocation seemed to occur in others. During diplotene, a cross-shaped configurationconnected with the nucleoli was observed in some meiocytes. Some heteromorphic bivalents were found during diakinesis,after which meiosis progressed normally to the end and gave rise to apparently normal tetrads with one normal nucleolus ineach microspore. Tests of pollen viability in fixed pollen grains showed 100% stainability in normal and in affected plants.This is the first report on chromosome interchanges in popcorn.

  20. Cloning of the chromosome translocation breakpoint junction of the t(14;19) in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    McKeithan, T.W.; Rowley, J.D.; Shows, T.B.; Diaz, M.O.

    1987-01-01

    The authors' laboratory has reported that t(14;19)(q32;q13.1) is a recurring translocation in the neoplastic cells of patients with chronic lymphocytic leukemia. In the present study, they have analyzed the leukemic cells from one such patient with probes from the immunoglobulin heavy-chain locus, which is present on band q32 of chromosome 14. Using a probe for the α constant-region gene segments, they detected a rearranged band by Southern blot analysis. This rearranged band was cloned and mapped. A subclone free of repetitive sequences was shown to be from chromosome 19 by analysis of human-mouse somatic cell hybrids, confirming that the rearranged band contains the translocation breakpoint junction. This probe may be used to identify a gene on chromosome 19 adjacent to the breakpoint that can contribute to the malignant development of B lymphocytes

  1. The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia.

    Science.gov (United States)

    Zerrouki, Rachid; Benhassine, Traki; Bensaada, Mustapha; Lauzon, Patricia; Trabzi, Anissa

    2016-03-01

    Many subtypes of acute lymphoblastic leukemia (ALL) are associated with specific chromosomal rearrangements. The complex translocation t(9;14;14), a variant of the translocation (14;14)(q11;q32), is a rare but recurrent chromosomal abnormality involving the immunoglobulin heavy-chain (IGH) and CCAAT enhancer-binding protein (CEBPE) genes in B-lineage ALL (B-ALL) and may represent a new B-ALL subgroup. We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH) with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9)(p21),t(14;14)(q11;q32). FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC) probes showed a complex t(9;14;14) associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) and paired box gene 5 (PAX5) at 9p21-13 and duplication of the fusion gene IGH-CEBPE.

  2. Molecular cytogenetic identification of a novel wheat-Agropyron elongatum chromosome translocation line with powdery mildew resistance.

    Science.gov (United States)

    Li, Xiaojun; Jiang, Xiaoling; Chen, Xiangdong; Song, Jie; Ren, Cuicui; Xiao, Yajuan; Gao, Xiaohui; Ru, Zhengang

    2017-01-01

    Agropyron elongatum (Host.) Neviski (synonym, Thinopyrum ponticum Podp., 2n = 70) has been used extensively as a valuable source for wheat breeding. Numerous chromosome fragments containing valuable genes have been successfully translocated into wheat from A. elongatum. However, reports on the transfer of powdery mildew resistance from A. elongatum to wheat are rare. In this study, a novel wheat-A. elongatum translocation line, 11-20-1, developed and selected from the progenies of a sequential cross between wheat varieties (Lankaoaizaoba, Keyu 818 and BainongAK 58) and A. elongatum, was evaluated for disease resistance and characterized using molecular cytogenetic methods. Cytological observations indicated that 11-20-1 had 42 chromosomes and formed 21 bivalents at meiotic metaphase I. Genomic in situ hybridization analysis using whole genomic DNA from A. elongatum as a probe showed that the short arms of a pair of wheat chromosomes were replaced by a pair of A. elongatum chromosome arms. Fluorescence in situ hybridization, using wheat D chromosome specific sequence pAs1 as a probe, suggested that the replaced chromosome arms of 11-20-1 were 5DS. This was further confirmed by wheat SSR markers specific for 5DS. EST-SSR and EST-STS multiple loci markers confirmed that the introduced A. elongatum chromosome arms belonged to homoeologous group 5. Therefore, it was deduced that 11-20-1 was a wheat-A. elongatum T5DL∙5AgS translocation line. Both resistance observation and molecular marker analyses using two specific markers (BE443538 and CD452608) of A. elongatum in a F2 population from a cross between line 11-20-1 and a susceptible cultivar Yannong 19 verified that the A. elongatum chromosomes were responsible for the powdery mildew resistance. This work suggests that 11-20-1 likely contains a novel resistance gene against powdery mildew. We expect this line to be useful for the genetic improvement of wheat.

  3. Pregnancy outcomes following 24-chromosome preimplantation genetic diagnosis in couples with balanced reciprocal or Robertsonian translocations.

    Science.gov (United States)

    Idowu, Dennis; Merrion, Katrina; Wemmer, Nina; Mash, Janine Gessner; Pettersen, Barbara; Kijacic, Dusan; Lathi, Ruth B

    2015-04-01

    To report live birth rates (LBR) and total aneuploidy rates in a series of patients with balanced translocations who pursued in vitro fertilization (IVF)-preimplantation genetic diagnosis (PGD) cycles. Retrospective cohort analysis. Genetic testing reference laboratory. Seventy-four couples who underwent IVF-PGD due to a parental translocation. IVF cycles and embryo biopsies were performed by referring clinics. Biopsy samples were sent to a single reference lab for PGD for the translocation plus 24-chromosome aneuploidy screening with the use of a single-nucleotide polymorphism (SNP) microarray. LBR per biopsy cycle, aneuploidy rate, embryo transfer (ET) rate, miscarriage rate. The LBR per IVF biopsy cycle was 38%. LBR for patients reaching ET was 52%. Clinical miscarriage rate was 10%. Despite a mean age of 33.8 years and mean of 7 embryos biopsied, there was a 30% chance for no chromosomally normal embryos. Maternal age >35 years, day 3 biopsy, and having fewer than five embryos available for biopsy increased the risk of no ET. IVF-PGD for translocation and aneuploidy screening had good clinical outcomes. Patients carrying a balanced translocation who are considering IVF-PGD should be aware of the high risk of no ET, particularly in women ≥35 years old. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Partial deletions of the W chromosome due to reciprocal translocation in the silkworm Bombyx mori.

    Science.gov (United States)

    Abe, H; Seki, M; Ohbayashi, F; Tanaka, N; Yamashita, J; Fujii, T; Yokoyama, T; Takahashi, M; Banno, Y; Sahara, K; Yoshido, A; Ihara, J; Yasukochi, Y; Mita, K; Ajimura, M; Suzuki, M G; Oshiki, T; Shimada, T

    2005-08-01

    In the silkworm, Bombyx mori (female, ZW; male, ZZ), femaleness is determined by the presence of a single W chromosome, irrespective of the number of autosomes or Z chromosomes. The W chromosome is devoid of functional genes, except the putative female-determining gene (Fem). However, there are strains in which chromosomal fragments containing autosomal markers have been translocated on to W. In this study, we analysed the W chromosomal regions of the Zebra-W strain (T(W;3)Ze chromosome) and the Black-egg-W strain (T(W;10)+(w-2) chromosome) at the molecular level. Initially, we undertook a project to identify W-specific RAPD markers, in addition to the three already established W-specific RAPD markers (W-Kabuki, W-Samurai and W-Kamikaze). Following the screening of 3648 arbitrary 10-mer primers, we obtained nine W-specific RAPD marker sequences (W-Bonsai, W-Mikan, W-Musashi, W-Rikishi, W-Sakura, W-Sasuke, W-Yukemuri-L, W-Yukemuri-S and BMC1-Kabuki), almost all of which contained the border regions of retrotransposons, namely portions of nested retrotransposons. We confirmed the presence of eleven out of twelve W-specific RAPD markers in the normal W chromosomes of twenty-five silkworm strains maintained in Japan. These results indicate that the W chromosomes of the strains in Japan are almost identical in type. The Zebra-W strain (T(W;3)Ze chromosome) lacked the W-Samurai and W-Mikan RAPD markers and the Black-egg-W strain (T(W;10)+(w-2) chromosome) lacked the W-Mikan RAPD marker. These results strongly indicate that the regions containing the W-Samurai and W-Mikan RAPD markers or the W-Mikan RAPD marker were deleted in the T(W;3)Ze and T(W;10)+(w-2) chromosomes, respectively, due to reciprocal translocation between the W chromosome and the autosome. This deletion apparently does not affect the expression of Fem; therefore, this deleted region of the W chromosome does not contain the putative Fem gene.

  5. Application of conventional chromosomal aberration and fluorescence in-situ hybridisation translocation in the assessment of occupationally derived irradiation

    International Nuclear Information System (INIS)

    Samavat, H.; Seaward, M. R. D.; Gonzales, D. H.; Azizian, Gh.

    2004-01-01

    Background: Most of our current understanding of the biological effects of exposure to ionising radiation is based on conventional cytogenetic techniques, which enable our to determine the relationship between chromosomal aberration and dose received by radiation workers. However, conventional techniques have numerous limitations and chromosomal aberrations can be easily missed. Since fluorescence in situ hybridisation plays an important role in detecting chromosomal changes, this method was used to reassess data derived from previous studies employing conventional techniques. Materials and Methods: Two groups of radiographers were the subject of a study on conventional chromosomal aberration and fluorescence in situ hybridisation for translocation. The first group was chosen following an accidental contamination incident in a nuclear medicine department. The second group was composed of six radiographers working in an x-ray department with a previous record of overdose as recorded by film-badges; these workers had been the subjects of a previous chromosomal study. Coded blood samples from 11 radiographers and 11 controls were analysed for chromosomal aberration and by fluorescence in-situ hybridisation for translocation. 200 metaphases from the peripheral blood lymphocytes per subject were analysed to investigate possible frequencies of chromosome and chromatid type aberration and 2000 metaphases per subject were scored in fluorescence in-situ hybridisation method. Results: There was no significant difference between the radiographers and the control groups in conventional analysis; also there was no significant difference at the 95 % level of confidence in fluorescence in-situ hybridisation analysis. There was no correlation between levels of translocation and total lifetime doses from occupational ( according film-badge and TLD) and/or background irradiation. Conclusion: The overall conclusion is that the frequency of chromosomal damage in both groups of

  6. Tourette syndrome in a pedigree with a 7;18 translocation: Identification of a YAC spanning the translocation breakpoint at 18q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Boghosian-Sell, L.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Comings, D.E. [City of Hope Medical Center, Duarte, CA (United States)

    1996-11-01

    Tourette syndrome is a neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics. Associated pathologies include attention deficit disorder and obsessive-compulsive disorder (OCD). Extensive linkage analysis based on an autosomal dominant mode of transmission with reduced penetrance has failed to show linkage with polymorphic markers, suggesting either locus heterogeneity or a polygenic origin for Tourette syndrome. An individual diagnosed with Tourette syndrome has been described carrying a constitutional chromosome translocation. Other family members carrying the translocation exhibit features seen in Tourette syndrome including motor tics, vocal tics, and OCD. Since the disruption of specific genes by a chromosomal rearrangement can elicit a particular phenotype, we have undertaken the physical mapping of the 7;18 translocation such that genes mapping at the site of the breakpoint can be identified and evaluated for a possible involvement in Tourette syndrome. Using somatic cell hybrids retaining either the der(7) or the der(18), a more precise localization of the breakpoints on chromosomes 7 and 18 have been determined. Furthermore, physical mapping has identified two YAC clones that span the translocation breakpoint on chromosome 18 as determined by FISH. These YAC clones will be useful for the eventual identification of genes that map to chromosomes 7 and 18 at the site of the translocation. 41 refs., 3 figs., 1 tab.

  7. The complex translocation (9;14;14 involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Rachid Zerrouki

    2016-03-01

    Full Text Available Abstract Many subtypes of acute lymphoblastic leukemia (ALL are associated with specific chromosomal rearrangements. The complex translocation t(9;14;14, a variant of the translocation (14;14(q11;q32, is a rare but recurrent chromosomal abnormality involving the immunoglobulin heavy-chain (IGH and CCAAT enhancer-binding protein (CEBPE genes in B-lineage ALL (B-ALL and may represent a new B-ALL subgroup. We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9(p21,t(14;14(q11;q32. FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC probes showed a complex t(9;14;14 associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A and paired box gene 5 (PAX5 at 9p21-13 and duplication of the fusion gene IGH-CEBPE.

  8. High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots.

    Science.gov (United States)

    Yong, Lee C; Petersen, Martin R

    2011-02-01

    Experimental studies suggest that B vitamins such as niacin, folate, riboflavin, vitamin B6 and vitamin B12 may protect against DNA damage induced by ionising radiation (IR). However, to date, data from IR-exposed human populations are not available. We examined the intakes of these B vitamins and their food sources in relation to the frequency of chromosome translocations as a biomarker of cumulative DNA damage, in eighty-two male airline pilots. Dietary intakes were estimated by using a self-administered semi-quantitative FFQ. Translocations in peripheral blood lymphocytes were scored by using fluorescence in situ hybridisation whole-chromosome painting. Negative binomial regression was used to estimate rate ratios and 95 % CI, adjusted for age and occupational and lifestyle factors. We observed a significant inverse association between translocation frequency and dietary intake of niacin (P = 0·02): adjusted rate ratio for subjects in the highest tertile compared with the lowest tertile was 0·58 (95 % CI 0·40, 0·83). Translocation frequency was not associated with total niacin intake from food and supplements as well as dietary or total intake of folate, riboflavin or vitamin B6 or B12. However, the adjusted rate ratios were significant for subjects with ≥ median compared with food or a diet high in whole grains but low in red and processed meat may protect against cumulative DNA damage in IR-exposed persons.

  9. Analysis of chromosome translocation in the residents of Namie Town after the accident of Fukushima Daiichi Nuclear Power Plant

    International Nuclear Information System (INIS)

    Yoshida, Mitsuaki A.; Nakata, Akifumi; Miura, Tomisato; Nishimura, Miya; Takamagi, Shizuka; Kasai, Kosuke; Konno, Norio; Yoshida, Ryoko; Sekine, Shunji

    2014-01-01

    The dose estimation by behavior survey of the residents carried out by Fukushima Prefecture after the accident reported that there are no residents who were exposed by over 1 mSv radiation. However, a lot of the parents are worrying about the health condition of their children in future. Our Hirosaki University accepted the request of the local government of this Namie-Town in Fukushima which wants to know whether children were exposed by radiological substances or not and started the inspection about the contamination and exposure level and dose estimation at an accident using chromosomal translocation analysis for 855 out of 3700 children whose age was under 18 years old at the time of accident. In order to estimate radiation dose using chromosome aberration in the accidents, there are four kinds of cytogenetic method; dicentric assay, a translocation assay, the PCC-ring assay and micronucleus test. A dicentric assay is used for the dose estimation in acute and external exposure cases, the chromosomal translocation method for dose assessment in chronic and old exposure and the PCC method for high dose exposure, respectively. In the case of the residents in Namie-Town, since about one year and ten months had already passed after the accident when implementation of this inspection was determined, the chromosomal translocation method was applied for the dose estimation of the initial exposure level. The main purpose of this translocation analysis using their own cells is to take away affairs of the residents including parents and children and also to reduce the uneasiness which is not wiped away by the health check due to a behavioral survey. In this inspection, after the contents and process of this analysis were explained in the Tsushima, Namie-Town temporarily constructed clinic, 3∼4 ml of whole 5 blood were taken from each children whose parents agreed with this analysis. The lymphocytic cells are isolated from the whole blood using CPT (Cell Preparation Tube

  10. High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots.

    Science.gov (United States)

    Yong, Lee C; Petersen, Martin R; Sigurdson, Alice J; Sampson, Laura A; Ward, Elizabeth M

    2009-11-01

    Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, beta-carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food (P food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for > or =median compared with or =median compared with food: 0.27 (0.14, 0.55). High combined intakes of vitamins C and E, beta-carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food, or a diet high in their food sources, may protect against cumulative DNA damage in IR-exposed persons.

  11. Chromosome translocation in residents of the high background radiation areas in southern China

    International Nuclear Information System (INIS)

    Hayata, Isamu; Minamihisamatsu, Masako; Wang Chunyan; Wei Zhang; Chen Deqing; Morishima, Hiroshige; Yuan Yongling; Wei Luxin; Sugahara, Tsutomu

    2000-01-01

    We performed a cytogenetical study using chromosome painting analysis on 9 residents of the naturally high background radiation areas (HBRA) and 8 residents of the control areas in southern China. The estimated dose (air kerma) of each resident measured by an electric pocket dosimeter showed 2.20-4.23 mGy/year in HBRA and 0.56-0.70 mGy/year in the control areas. A total of 14,096 cells (1,566 cells/case) in the former and 17,522 cells (2,190 cells/case) in the latter were analyzed. Children, both in HBRA and in the control areas, had translocations at low frequencies. The frequency of translocations among elder individuals varied widely and it was not possible to detect dose effect although it was detected in dicentrics. The effect of radiation on the induction of chromosome aberrations, which have a statistically potential risk of causing malignant or congenital diseases, seems to be less significant than those of metabolic factors and/or mutagenic agents (excluding radiation) even in HBRA in China. (author)

  12. Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered

    International Nuclear Information System (INIS)

    Finver, S.N.; Nishikura, K.; Finger, L.R.; Haluska, F.G.; Finan, J.; Nowell, P.C.; Croce, C.M.

    1988-01-01

    The authors cloned the translocation-associated and homologous normal MYC alleles from SKW-3, a leukemia T-cell line with the t(8; 14)(q24; q11) translocation, and determined the sequence of the MYC oncogene first exon and flanking 5' putative regulatory regions. S1 nuclease protection experiments utilizing a MYC first exon probe demonstrated transcriptional deregulation of the MYC gene associated with the T-cell receptor α locus on the 8q + chromosome of SKW-3 cells. Nucleotide sequence analysis of the translocation-associated (8q +) MYC allele identified a single base substitution within the upstream flanking region; the homologous nontranslocated allele contained an additional substitution and a two-base deletion. None of the deletions or substitutions localized to putative 5' regulatory regions. The MYC first exon sequence was germ line in both alleles. These results demonstrate that alterations within the putative 5' MYC regulatory regions are not necessarily involved in MYC deregulation in T-cell leukemias, and they show that juxtaposition of the T-cell receptor α locus to a germ-line MYC oncogene results in MYC deregulation

  13. Anterior pituitary failure (panhypopituitarism) with balanced chromosome translocation 46,XY,t(11;22)(q24;q13).

    Science.gov (United States)

    Yang, C Y; Chou, C W; Chen, S Y; Cheng, H M

    2001-04-01

    Hypopituitarism is the clinical syndrome that results from failure of the anterior pituitary gland to produce its hormones. Hypopituitarism can result from: (1) intrinsic or primary pituitary disease; (2) intrinsic hypothalamic or secondary pituitary disease; or (3) extrinsic extrasellar or parasellar disease. The etiologies of primary hypopituitarism are miscellaneous. The dominant clinical picture of hypopituitarism in the adult is that of hypogonadism. Reports have associated hypopituitarism with anti-pituitary-antibodies, hereditary syndrome and chromosome defects, but hypopituitarism has rarely been associated with balanced chromosome translocation (11;22)(q24;q13). Here, we describe a case of anterior pituitary failure with balanced chromosome translocation. A 19-year-old Chinese teenager presented with failure of pubertal development and sexual infantilism. On examination, the patient had the classic appearance of hypogonadism. Endocrine studies and three combined pituitary function tests revealed panhypopituitarism. A chromosomal study revealed 46,XY,t(11;22)(q24;q13), a balanced translocation between 11q24 and 22q13. Chest films showed delayed fusion of bilateral humeral head epiphyses and bilateral acromions. Scrotal sonography revealed testes were small bilaterally. Magnetic resonance imaging (MRI) of the sella revealed pituitary dwarfism. The patient received 19 months replacement therapy, including steroids (prednisolone 5 mg each day), L-thyroxine (Eltroxin 100 ug each day), and testosterone enanthate 250 mg every two weeks. His height increased 4 cm with secondary sexual characteristics developed, and muscle power increased.

  14. Inactivation of the P16INK4/MTS1 gene by a chromosome translocation t(9;14)(p21-22;q11) in an acute lymphoblastic leukemia of B-cell type.

    Science.gov (United States)

    Duro, D; Bernard, O; Della Valle, V; Leblanc, T; Berger, R; Larsen, C J

    1996-02-15

    We have reported previously a preliminary study of a t(9;14)(p21-22; q11) in B-cell acute lymphoblastic leukemia. This translocation had rearranged the TCRA/D locus on chromosome band 14q11 and the locus encoding the tumor suppressor gene P16INK4/MTS1 (P16) on band 9p21 (D. Duro et al., Oncogene, 11: 21-29, 1995). In the present report, the breakpoints were precisely localized on each chromosome partner. On the 14q- derivative, the sequence derived from chromosome 9 was interrupted at 1.0 kb upstream of the first exon of P16, close to a consensus recombination heptamer, CACTGTG. In addition, the chromosome 14 breakpoint was localized at the end of the TCRD2 (delta 2) segment, and 22 residues with unknown origin were present at the translocation junction. On the 9p+ derivative, chromosome 9 sequences were in continuity with those displaced onto chromosome 14, and the 14q11 breakpoint was located within TCRJA29 segment. These features are consistent with aberrant activity of the TCR gene recombinase complex. Although all three coding exons of P16 were displaced onto the chromosome 14q-derivative, no P16 transcript was detected in the leukemic cells. Because the region spanning the P16 exon 1 was not inactivated by methylation and because the other P16 allele was deleted, the implication is that the chromosome breakpoint was likely to disrupt regulatory elements involved in the normal expression of the gene. As a whole, then, our results show that translocations affecting band 9p21 can participate to the inactivation of P16, thus justifying a systematic survey of translocations of the 9p21 band in acute lymphoblastic leukemia.

  15. Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature.

    Science.gov (United States)

    Arn, P H; Younie, L; Russo, S; Zackowski, J L; Mankinen, C; Estabrooks, L

    1995-07-03

    We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious.

  16. Chromosomal instability mediated by non-B DNA: cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans.

    Science.gov (United States)

    Inagaki, Hidehito; Ohye, Tamae; Kogo, Hiroshi; Kato, Takema; Bolor, Hasbaira; Taniguchi, Mariko; Shaikh, Tamim H; Emanuel, Beverly S; Kurahashi, Hiroki

    2009-02-01

    Chromosomal aberrations have been thought to be random events. However, recent findings introduce a new paradigm in which certain DNA segments have the potential to adopt unusual conformations that lead to genomic instability and nonrandom chromosomal rearrangement. One of the best-studied examples is the palindromic AT-rich repeat (PATRR), which induces recurrent constitutional translocations in humans. Here, we established a plasmid-based model that promotes frequent intermolecular rearrangements between two PATRRs in HEK293 cells. In this model system, the proportion of PATRR plasmid that extrudes a cruciform structure correlates to the levels of rearrangement. Our data suggest that PATRR-mediated translocations are attributable to unusual DNA conformations that confer a common pathway for chromosomal rearrangements in humans.

  17. Molecular cytogenetics: A novel approach for measuring chromosome translocations in individuals years after exposure to low levels of ionizing radiation

    International Nuclear Information System (INIS)

    Lucas, J.N.; Straume, T.

    1992-04-01

    Chromosome painting was developed in our laboratory to facilitate rapid and accurate detection of chromosome translocations in human cells. Chromosome painting is the selective staining of one or more chromosomes by fluorescence in situ hybridization (FISH) using whole chromosome probes. This method permits essentially uniform hybridization and staining along the entire lengths of targeted chromosomes. Staining all other chromosomes a different color makes interchromosomal exchange aberrations readily apparent as bicolored chromosomes. Here we present a brief discussion of this methodology and recent results from studies in our laboratory

  18. Incidental detection of congenital Robertsonian translocation at diagnosis of Philadelphia chromosome-positive acute lymphocytic leukemia.

    Science.gov (United States)

    Yamaguchi, Tsukasa; Igarashi, Aiko; Kawamura, Machiko; Ozasa, Yuka; Yoshida, Masayuki; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2015-05-01

    A man in his early forties who had undergone 3 years of unsuccessful treatment for infertility due to oligospermia and asthenospermia developed fever and bone pain in December 20XX. He was subsequently diagnosed with acute lymphocytic leukemia. Conventional cytogenetic analysis revealed Robertsonian translocation (RT) with der(13;14)(q10;q10) in addition to the Philadelphia (Ph) chromosome. Dasatinib and prednisolone induced complete remission (CR) with disappearance of the Ph chromosome. However, RT persisted despite achieving CR. We speculate that RT is possibly congenital in our present case and might also have been responsible for the aforementioned infertility. Hematologists should be aware of the possibility that congenital chromosomal disorders might be found incidentally through diagnostic chromosome analysis for leukemia.

  19. Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Arn, P.H.; Younie, L.; Russo, S. [Nemours Children`s Clinic, Jacksonville, FL (United States)] [and others

    1995-07-03

    We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious. 23 refs., 2 figs., 1 tab.

  20. Structural variations of chromosome 1 R from rye cultivar Jingzhouheimai induced by irradiation

    International Nuclear Information System (INIS)

    Wang Conglei; Zhuang Lifang; Qi Zengjun

    2012-01-01

    Irradiated with 60 Co γ-rays (12 Gy), the pollen of wheat landrace Huixianhong-Secale cereal cv. Jingzhouheimai DA1R was pollinated to the emasculated spikes of Huixianhong. Analyzed with genomic in situ hybridization GISH using gDNA of rye cv. Jingzhouheimai as a probe, four plants with reciprocal translocation, four plants with large segmental translocation and one plant with distal segmental translocation, one plant with one telocentric chromosome were identified from 33 M 1 seeds. The results showed that the translocation frequency was 30.30% and of the total 11 breakage-fusion events, 1 involved centric regions and 10 involved interstitial regions. The experiment showed that pollen irradiation was an effective method to induce wheat alien chromosomal structural variations which could effectively by used in deletion mapping, chromosomal location of important agronomic genes and development of small segmental translocations with target genes. (authors)

  1. High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots1234

    Science.gov (United States)

    Petersen, Martin R; Sigurdson, Alice J; Sampson, Laura A; Ward, Elizabeth M

    2009-01-01

    Background: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food (P food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for ≥median compared with food: 0.27 (0.14, 0.55). Conclusion: High combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food, or a diet high in their food sources, may protect against cumulative DNA damage in IR-exposed persons. PMID:19793852

  2. A Balanced Chromosomal Translocation Disrupting ARHGEF9 Is Associated With Epilepsy, Anxiety, Aggression, and Mental Retardation

    Science.gov (United States)

    Kalscheuer, Vera M.; Musante, Luciana; Fang, Cheng; Hoffmann, Kirsten; Fuchs, Celine; Carta, Eloisa; Deas, Emma; Venkateswarlu, Kanamarlapudi; Menzel, Corinna; Ullmann, Reinhard; Tommerup, Niels; Dalprà, Leda; Tzschach, Andreas; Selicorni, Angelo; Lüscher, Bernhard; Ropers, Hans-Hilger; Harvey, Kirsten; Harvey, Robert J.

    2013-01-01

    Clustering of inhibitory γ-aminobutyric acidA (GABAA) and glycine receptors at synapses is thought to involve key interactions between the receptors, a “scaffolding” protein known as gephyrin and the RhoGEF collybistin. We report the identification of a balanced chromosomal translocation in a female patient presenting with a disturbed sleep-wake cycle, late-onset epileptic seizures, increased anxiety, aggressive behavior, and mental retardation, but not hyperekplexia. Fine mapping of the breakpoint indicates disruption of the collybistin gene (ARHGEF9) on chromosome Xq11, while the other breakpoint lies in a region of 18q11 that lacks any known or predicted genes. We show that defective collybistin transcripts are synthesized and exons 7–10 are replaced by cryptic exons from chromosomes X and 18. These mRNAs no longer encode the pleckstrin homology (PH) domain of collybistin, which we now show binds phosphatidylinositol-3-phosphate (PI3P/ PtdIns-3-P), a phosphoinositide with an emerging role in membrane trafficking and signal transduction, rather than phosphatidylinositol 3,4,5-trisphosphate (PIP3/PtdIns-3,4,5-P) as previously suggested in the “membrane activation model” of gephyrin clustering. Consistent with this finding, expression of truncated collybistin proteins in cultured neurons interferes with synaptic localization of endogenous gephyrin and GABAA receptors. These results suggest that collybistin has a key role in membrane trafficking of gephyrin and selected GABAA receptor subtypes involved in epilepsy, anxiety, aggression, insomnia, and learning and memory. PMID:18615734

  3. Monitoring translocations by M-FISH and three-color FISH painting techniques. A study of two radiotherapy patients

    International Nuclear Information System (INIS)

    Pouzoulet, F.; Roch-Lefevre, S.; Giraudet, AL.

    2007-01-01

    To compare translocation rate using either M-FISH or FISH-3 in two patients treated for head and neck cancer, with a view to retrospective dosimetry. Translocation analysis was performed on peripheral blood lymphocyte cultures from blood samples taken at different times during the radiotherapy (0 Gy, 12 Gy and 50 Gy) and a few months after the end of the treatment (follow-up). Estimated translocation yield varied according to the FISH technique used. At 50 Gy and follow-up points, the translocation yields were higher with FISH-3 than with M-FISH. This difference can be attributed to three events. First, an increase in complex aberrations was observed for 50 Gy and follow-up points compared with 0 Gy and 12 Gy points. Second, at the end of treatment for patient A, involvement of chromosomes 2, 4, 12 in translocations was less than expected according to the Lucas formula. Third, a clone bearing a translocation involving a FISH-3 painted chromosome was detected. More translocations were detected with M-FISH than with FISH-3, and so M-FISH is expected to improve the accuracy of chromosome aberration analyses in some situations. (author)

  4. Radiation induced reciprocal translocations and inversions in anopheles albimanus

    International Nuclear Information System (INIS)

    Kaiser, P.E.; Seawright, J.A.; Benedict, M.Q.; Narang, S.

    1982-01-01

    Reciprocal translocations and inversions were induced in Anopheles albimanus Wiedemann by irradiation of males with X rays. A total of 1669 sperm were assayed, and 175 new aberrations were identified as follows: 102 reciprocal translocations (67 autosomal and 35 sex-linked), 45 pericentric inversions, and 28 paracentric inversions. Eleven of the translocations were nearly whole-arm interchanges, and these were selected for the construction of 'capture systems' for compound chromosomes. Two double-heterozygous translocation strains and four homozygous translocation strains were established. Anopheles albimanus females were irradiated, and a pseudolinkage scheme involving mutant markers was employed to identify reciprocal translocations. The irradiation of females was very inefficient; only one translocation was recovered from 1080 ova tested

  5. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation

    International Nuclear Information System (INIS)

    Rowley, J.D.

    1991-06-01

    This document lists the major accomplishments funded by DOE in the period of January 1989 through June 1991. Specific topics covered include: studies of chromosome translocations in patients with Acute Myeloid Leukemia (AML) de novo; correlation of karyotype and therapeutic response; the relationship of specific chromosomal abnormalities to a patient's occupational history; definition of regions on chromosome 5 involved in leukemogenesis; the influence of pervious chemotherapy on leukemogenesis; identification of genes at or near breakpoints involved in leukemia and lymphoma; identification of the critical rearrangement in the 9;11 translocation; molecular analysis of translocations involving 11q23; identification of other genes (like RAS) involved in leukemogenesis; development of fluorescence in situ hybridization as a cytogenetic tool; and examination of an unequivocal case of radiation induced preleukemia. 26 refs., 8 figs., 6 tabs

  6. Most Uv-Induced Reciprocal Translocations in SORDARIA MACROSPORA Occur in or near Centromere Regions.

    Science.gov (United States)

    Leblon, G; Zickler, D; Lebilcot, S

    1986-02-01

    In fungi, translocations can be identified and classified by the patterns of ascospore abortion in asci from crosses of rearrangement x normal sequence. Previous studies of UV-induced rearrangements in Sordaria macrospora revealed that a major class (called type III) appeared to be reciprocal translocations that were anomalous in producing an unexpected class of asci with four aborted ascospores in bbbbaaaa linear sequence (b = black; a = abortive). The present study shows that the anomalous type III rearrangements are, in fact, reciprocal translocations having both breakpoints within or adjacent to centromeres and that bbbbaaaa asci result from 3:1 disjunction from the translocation quadrivalent.-Electron microscopic observations of synaptonemal complexes enable centromeres to be visualized. Lengths of synaptonemal complexes lateral elements in translocation quadrivalents accurately reflect chromosome arm lengths, enabling breakpoints to be located reliably in centromere regions. All genetic data are consistent with the behavior expected of translocations with breakpoints at centromeres.-Two-thirds of the UV-induced reciprocal translocations are of this type. Certain centromere regions are involved preferentially. Among 73 type-III translocations, there were but 13 of the 21 possible chromosome combinations and 20 of the 42 possible combinations of chromosome arms.

  7. Jumping translocations in hematological malignancies: a cytogenetic study of five cases.

    Science.gov (United States)

    Manola, Kalliopi N; Georgakakos, Vasileios N; Stavropoulou, Chryssa; Spyridonidis, Alexandros; Angelopoulou, Maria K; Vlachadami, Ioanna; Katsigiannis, Andreas; Roussou, Paraskevi; Pantelias, Gabriel E; Sambani, Constantina

    2008-12-01

    Jumping translocations (JT) are rare cytogenetic aberrations in hematological malignancies that include unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to two or more different recipient chromosomes in different cell lines. We report five cases associated with different hematologic disorders and JT to contribute to the investigation of the origin, pathogenesis, and clinical significance of JT. These cases involve JT of 1q in a case of acute myeloblastic leukemia (AML)-M1, a case of Burkitt lymphoma, and a case of BCR/ABL-positive acute lymphoblastic leukemia, as well as a JT of 13q in a case of AML-M5, and a JT of 11q segment in a case of undifferentiated leukemia. To our knowledge, with regard to hematologic malignancies, this study presents the first case of JT associated with AML-M1, the first case of JT involving 13q as a donor chromosome, and the first report of JT involving a segment of 11q containing two copies of the MLL gene, jumping on to two recipient chromosomes in each cell line and resulting in six copies of the MLL gene. Our investigation suggests that JT may not contribute to the pathogenesis but rather to the progression of the disease, and it demonstrates that chromosome band 1q10 as a breakpoint of the donor chromosome 1q is also implicated in AML, not only in multiple myeloma as it has been known until now.

  8. Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Erikson, J.; Griffin, C.A.; Ar-Rushdi, A.

    1986-01-01

    In chronic myelogenous leukemias (CML) with the t(9;22)(q34;q11) chromosome translocation the breakpoints on chromosome 22 occur within a 5.8-kilobase segment of DNA referred to as breakpoint cluster region (bcr). The same cytogenetically indinstinguishable translocation occurs in approximately 10% of patients with acute lymphocytic leukemias (ALL). In this study the authors have investigated the chromosome breakpoints in several cases of ALL carrying the t(9;22) translocation. In three of five cases of ALL they found that the bcr region was not involved in the chromosome rearrangement and that the 22q11 chromosome breakpoints were proximal (5') to the bcr region at band 22q11. In addition, they observed normal size bcr and c-alb transcripts in an ALL cell line carrying the t(9;22) translocation. They conclude, therefore, that if c-alb is inappropriately expressed in ALL cells without bcr rearrangements, the genetic mechanism of activation must be different from that reported for CML

  9. Variants forms of Philadelphia translocation in two patients with chronic myeloid leukemia

    International Nuclear Information System (INIS)

    Valent, A.; Zamecnikova, A.; Krizan, P.; Karlic, H.; Nowotny, H.

    1996-01-01

    During a 4-year period (December 1990-December 1994), among other diagnoses hundred cases of chronic myeloid leukemia (CML) were analyzed in our departments. We focused our attention on two cases with a variant form of Philadelphia translocation. Cytogenetic and molecular genetic studies were performed to resolve the status of BCR and ABL in the bone marrow or peripheral blood cells of the two CML patients with complex translocations involving chromosomes, 3, 9, 22 and 9, 12, 22 respectively. In the first case the presence of Ph chromosome was detected cytogenetically, BCR-ABL translocation was detected by Southern hybridization. In the second phase, only the PCR method showed BCR-ABL rearrangement. The second case, with a random variant form of Ph translocation, could be detected using different methods of clinical molecular genetics. (author)

  10. Persistence of radiation-induced chromosome aberrations in a long-term cell culture.

    Science.gov (United States)

    Duran, Assumpta; Barquinero, Joan Francesc; Caballín, María Rosa; Ribas, Montserrat; Barrios, Leonardo

    2009-04-01

    The aim of the present study was to evaluate the persistence of chromosome aberrations induced by X rays. FISH painting and mFISH techniques were applied to long-term cultures of irradiated cells. With painting, at 2 Gy the frequency of apparently simple translocations remained almost invariable during all the culture, whereas at 4 Gy a rapid decline was observed between the first and the second samples, followed by a slight decrease until the end of the culture. Apparently simple dicentrics and complex aberrations disappeared after the first sample at 2 and 4 Gy. By mFISH, at 2 Gy the frequency of complete plus one-way translocations remained invariable between the first and last sample, but at 4 Gy a 60% decline was observed. True incomplete simple translocations disappeared at 2 and 4 Gy, indicating that incompleteness could be a factor to consider when the persistence of translocations is analyzed. The analysis by mFISH showed that the frequency of complex aberrations and their complexity increased with dose and tended to disappear in the last sample. Our results indicate that the influence of dose on the decrease in the frequency of simple translocations with time postirradiation cannot be fully explained by the disappearance of true incomplete translocations and complex aberrations. The chromosome involvement was random for radiation-induced exchange aberrations and non-random for total aberrations. Chromosome 7 showed the highest deviations from expected, being less and more involved than expected in the first and last samples, respectively. Some preferential chromosome-chromosome associations were observed, including a coincidence with a cluster from radiogenic chromosome aberrations described in other studies.

  11. 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

  12. Instability of isochromosome 4p in a child with pure trisomy 4p syndrome features and entire 4q-arm translocation.

    Science.gov (United States)

    Pota, Pruthvi; Grammatopoulou, Vasiliki; Torti, Erin; Braddock, Stephen; Batanian, Jacqueline R

    2014-01-01

    Constitutional chromosome instability so far has mainly been associated with ring formation. In addition, isochromosome formation involving the short arm with translocation of the entire long arm is rarely observed. This type of rearrangement has been reported for chromosomes 4, 5, 7, 9, 10, 12, and 20. Here, we present the third patient having an isochromosome 4p with 4q translocation, but showing for the first time chromosome instability detected by FISH following chromosome microarray analysis.

  13. Analysis of 1;17 translocation breakpoints in neuroblastoma: implications for mapping of neuroblastoma genes

    NARCIS (Netherlands)

    van Roy, N.; Laureys, G.; van Gele, M.; Opdenakker, G.; Miura, R.; van der Drift, P.; Chan, A.; Versteeg, R.; Speleman, F.

    1997-01-01

    Deletions and translocations resulting in loss of distal 1p-material are known to occur frequently in advanced neuroblastomas. Fluorescence in situ hybridisation (FISH) showed that 17q was most frequently involved in chromosome 1p translocations. A review of the literature shows that 10 of 27 cell

  14. Experience with FISH-detected translocations as an indicator in retrospective dose reconstructions

    International Nuclear Information System (INIS)

    Pressl, S.; Romm, H.; Ganguly, B.B.; Stephan, G.

    2000-01-01

    The prerequisite for the use of translocations as an indicator in retrospective dose reconstructions, is knowledge of the background level, persistence, and the availability of dose response curves for the conversion of translocation frequencies into doses. The results obtained in these areas are summarised. Cells with complete painted chromosome material are evaluated. Those showing any aberrations which involve painted material are stored in a computerised system, and described in detail. The simultaneous painting of whole chromosomes and centromeres has proved to provide a better level of discrimination between translocations and dicentrics. Following irradiation, direct proportionality was observed between DNA content covered by the painted chromosomes (11-19%) and the translocation frequency. The background level of translocations was determined in 42 healthy subjects, aged between 21 and 73 years of age. The statistical analyses of the data revealed no influence from sex and smoking habits on the translocation frequency. A clear increase in translocation yield was, however, observed for age. For the whole genome the frequency is at a level of 3 to 11 per 1000 cells, for all types of translocations. In a radiation accident victim (Estonia) the frequency of translocations was determined over a post-exposure time of four years. For two-way translocations, the half-time was calculated to be 7.0 years, and that for one-way translocations 5.2 years. On the basis of our control data and our dose response curve, the lowest detectable radiation dose is about 0.3 Gy in subjects under 40 years of age, and about 0.5 Gy for those older than 40 years of age. (author)

  15. A feasible strategy of preimplantation genetic diagnosis for carriers with chromosomal translocation: Using blastocyst biopsy and array comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Chu-Chun Huang

    2013-09-01

    Conclusion: Our study demonstrates an effective PGD strategy with promising outcomes. Blastocyst biopsy can retrieve more genetic material and may provide more reliable results, and aCGH offers not only detection of chromosomal translocation but also more comprehensive analysis of 24 chromosomes than traditional FISH. More cases are needed to verify our results and this strategy might be considered in general clinical practice.

  16. Further studies on the possible relationship between radiation-induced reciprocal translocations and intrinsic radiosensitivity of human tumor cells

    International Nuclear Information System (INIS)

    Virsik-Peuckert, P.; Rave-Fraenk, M.; Schmidberger, H.

    1996-01-01

    Background and purpose. The aim of the present study was to estimate yields of radiation-induced translocations in surviving cells of several human tumor cell lines and in normal diploid human fibroblasts, and to compare these yields with corresponding intrinsic radiosensitivities determined by standard colony-formation assay. Material and methods. The yields of radiation-induced reciprocal translocations were investigated by fluorescence in situ hybridization. Chromosomes no. 1 and no. 4 were 'painted' with fluorescent hybridization probes for whole chromosomes. Translocation yields and cell survival were determined for different doses up to 6 Gy of 200 kV X-rays. Results. We observed a higher frequency of reciprocal translocations in the radiosensitive cells MCF-7 and MDA-MB-436 than in the radioresistant cells CaSki, WiDr, A549 and normal skin fibroblasts. For primary squamous cell carcinoma cells, ZMK-1, an intermediate radiosensitivity and an intermediate translocation yield were observed. The dose-dependence of translocation yields involving chromosomes no. 1 or no. 4 varied in different cell lines: it was linear or linear with a plateau at higher doses. Conclusions. A comparison of the data obtained with chromosomes no. 1 and no. 4 in the investigated cell types, indicates that intrinsic radiosensitivity of different tumor cells observed at the survival level, is correlated with different translocation yields, respectively. This correlation was observed for all cell types investigated, independent of the number of copies of the painted chromosome per cell or the radiation dose. However, for low doses (under 1 Gy), the yields of translocations determined for the individual chromosomes seem to be too low for a discrimination between radioresistant or radiosensitive cells

  17. Development and identification of a wheat-Roegneria kamoji translocation line T7A/1Rk no.1

    International Nuclear Information System (INIS)

    Bie Tongde; Feng Yigao; Chen Peidu; Xu Chuanmei

    2009-01-01

    Pollen of Triticum aestivum-Roegneria kamoji del1Rk No.1L disomic addition line, treated with 10 Gy 6 0C o γ-rays, was pollinated to T · aestivum cv. Chinese Spring. A reciprocal chromosomal translocation line involving wheat 7A and R.kamoji 1Rk No.1 was identified in M 2 generation using the techniques including C-banding, GISH, sequential C-banding/45S rDNA-FISH, and sequential GISH/45S rDNA-FISH. A 45S rDNA locus and its corresponding red band in GISH pattern were observed specific to the short arm of 1Rk No.1 and could be used as a marker of 1Rk No.1 chromosome. Analyses of chromosome constitution of M 2 population and test-crosses showed that the reciprocal translocation chromosomes were co-segregated in offspring, and the transmitting ratios were both higher through female gametes than through male ones. The results of scab resistance identification in 2004, 2005 and 2006 showed that the translocation line conveyed scab resistance that varied in different years in different district. The experiment also showed that pollen irradiation was an effective method to induce wheat-alien chromosome translocations. (authors)

  18. Extra skeletal Soft Tissue Ewing?s Sarcoma with Variant Translocation of Chromosome t (4; 22) (q35; q12)-A Case Report

    OpenAIRE

    Nagaraj, Prashanth; H, Srinivas C; Rao, Raghavendra; Manohar, Sandesh

    2013-01-01

    Introduction: Ewing’s sarcomas is a rare primitive neuroectodermal tumour (PNET) which has an annual incidence of 2.9 /million population in USA 1Jeffery Toretsky et al (2008) They are very uncommon in African and Asian population .lt is commonly associated with reciprocal translocation between chromosome 11 and 12 t (11:12) or less frequently the t(21 ;22)(q22;ql 2) translocation. It is highly aggressive tumor which is PAS- and CD99 (MIC2)-positive relatively few variant translocations have ...

  19. Diagnostic radiation and chromosome aberrations

    International Nuclear Information System (INIS)

    Patil, S.R.; Hecht, F.; Lubs, H.A.; Kimberling, W.; Brown, J.; Gerald, P.S.; Summitt, R.L.

    1977-01-01

    Some evidence is presented suggesting that diagnostic X-rays may be important in the origin of a new chromosomal abnormality other than Down syndrome. Chromosome analyses have been carried out on 4342 children, seven or eight years old. Maternal diagnostic irradiation in the year before conception and up to third lunar month of the index pregnancy was recorded, before the chromosome study began, together with a large amount of family and clinical data. Information on X-ray exposure was supplied by the mothers, s o radiation dosage could not be estimated. 21 children (including a pair of twins and a pair of siblings) born to 19 mothers had chromosomal aberrations. The mothers of six children with inherited translocations, rearrangements and XYY karyotypes were excluded, and 3 (23%) of the remaining 13 mothers had received abdominal and pelvic X-ray exposures. In the whole sample, however, only 6% of the mothers had diagnostic irradiation. Two of these mothers, aged sixteen and twenty, gave birth to a child each with de-novo autosomal translocations, and the third mother, aged thirty-two, had a child with a complex mosaicism involving one X chromosome. Although the sample size of the mothers with chromosomally abnormal children is small, the results are significant. (U.K.)

  20. Diagnostic radiation and chromosome aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Patil, S R; Hecht, F [Dept. of Pediatrics, Child Development and Rehabilitation Center, Univ. of Oregon Health Sciences Center, Portland, Oregon (USA); Lubs, H A; Kimberling, W; Brown, J; Gerald, P S; Summitt, R L

    1977-01-15

    Some evidence is presented suggesting that diagnostic X-rays may be important in the origin of a new chromosomal abnormality other than Down syndrome. Chromosome analyses have been carried out on 4342 children, seven or eight years old. Maternal diagnostic irradiation in the year before conception and up to third lunar month of the index pregnancy was recorded, before the chromosome study began, together with a large amount of family and clinical data. Information on X-ray exposure was supplied by the mothers, so radiation dosage could not be estimated. 21 children (including a pair of twins and a pair of siblings) born to 19 mothers had chromosomal aberrations. The mothers of six children with inherited translocations, rearrangements and XYY karyotypes were excluded, and 3 (23%) of the remaining 13 mothers had received abdominal and pelvic X-ray exposures. In the whole sample, however, only 6% of the mothers had diagnostic irradiation. Two of these mothers, aged sixteen and twenty, gave birth to a child each with de-novo autosomal translocations, and the third mother, aged thirty-two, had a child with a complex mosaicism involving one X chromosome. Although the sample size of the mothers with chromosomally abnormal children is small, the results are significant.

  1. Genetic analysis of γ-ray induced W-translocation strain on Bombyx nori

    International Nuclear Information System (INIS)

    Onuma, Akio; Murakami, Akio

    1976-01-01

    In the process of analyzing a γ-ray induced mutant of Bombyx nori oo cyte, new type translocation strains of W chromosomes and No.5 chromosomes were detected. The constitution of their translocated chromosomes was assumed to be Z/(W-V) + sup(pe)-V + sup(oc)/v. Owing to such chromosome constitution, it was considered that non-disjunction was induced at meiosis, and Z/(W-V) + sup(pe)/V, Z/(W-V) + sup(pe), V/V were produced besides Z/(W-V) + sup(pe)-V + sup(oc)/V in the female chromosomes (gene) of the next progeny, while V/V and Z/Z, V + sup(oc)/V were produced besides Z/Z, V/V in male. Death of some male eggs in this translocation strain was also observed. No dissociated individual of translocated chromosomes was segregated in the next progeny of the female moth with Z/(W-V) + sup(pe), V/V chromosome constitution and the marker stock male moth, while a few dissociated individuals appeared in the next progeny of Z/(W-V) + sup(pe)-V + sup(oc)/V female moth group. This fact seemed to be resulted from the complicated translocated chromosome constitution of the translocation strain. (Kobatake, H.)

  2. Preimplantation genetic diagnosis outcomes and meiotic segregation analysis of robertsonian translocation carriers.

    Science.gov (United States)

    Ko, Duck Sung; Cho, Jae Won; Lee, Hyoung-Song; Kim, Jin Yeong; Kang, Inn Soo; Yang, Kwang Moon; Lim, Chun Kyu

    2013-04-01

    To investigate the meiotic segregation patterns of cleavage-stage embryos from robertsonian translocation carriers and aneuploidy of chromosome 18 according to meiotic segregation patterns. Retrospective study. Infertility center and laboratory of reproductive biology and infertility. Sixty-two couples with robertsonian translocation carriers. One blastomere was biopsied from embryos and diagnosed with the use of fluorescence in situ hybridization (FISH). Translocation chromosomes were analyzed with the use of locus-specific and subtelomeric FISH probes. Aneuploidy of chromosome 18 was assessed simultaneously with translocation chromosomes. Preimplantation genetic diagnosis (PGD) outcomes, meiotic segregation patterns of robertsonian translocation, and aneuploidy of chromosome 18 depending on meiotic segregation patterns. Two hundred seventy embryos of 332 transferrable embryos were transferred in 113 cycles, and 27 healthy babies were born. The alternate segregation was significantly higher in male carriers than in female carriers (43.9% vs. 29.9%, respectively), and adjacent segregation was higher in female carriers than in male carriers (44.7% vs. 38.7%, respectively). Aneuploidy of chromosome 18 was significantly increased in 3:0-segregated or chaotic embryos. Forty-seven alternate embryos were excluded from embryo replacement owing to aneuploidy of chromosome 18. In carriers of robertsonian translocation, meiotic segregation showed differences between men and women. Frequent meiotic errors caused by premature predivision or nondisjunction and less stringent checkpoint in women might cause such differences between sexes. Aneuploidy of chromosome 18 might be influenced by meiotic segregation of translocation chromosomes. Factors that cause malsegregation, such as 3:0 or chaotic segregation, seem to play a role in aneuploidy of chromosome 18. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Missense Mutations Allow a Sequence-Blind Mutant of SpoIIIE to Successfully Translocate Chromosomes during Sporulation.

    Science.gov (United States)

    Bose, Baundauna; Reed, Sydney E; Besprozvannaya, Marina; Burton, Briana M

    2016-01-01

    SpoIIIE directionally pumps DNA across membranes during Bacillus subtilis sporulation and vegetative growth. The sequence-reading domain (γ domain) is required for directional DNA transport, and its deletion severely impairs sporulation. We selected suppressors of the spoIIIEΔγ sporulation defect. Unexpectedly, many suppressors were intragenic missense mutants, and some restore sporulation to near-wild-type levels. The mutant proteins are likely not more abundant, faster at translocating DNA, or sequence-sensitive, and rescue does not involve the SpoIIIE homolog SftA. Some mutants behave differently when co-expressed with spoIIIEΔγ, consistent with the idea that some, but not all, variants may form mixed oligomers. In full-length spoIIIE, these mutations do not affect sporulation, and yet the corresponding residues are rarely found in other SpoIIIE/FtsK family members. The suppressors do not rescue chromosome translocation defects during vegetative growth, indicating that the role of the γ domain cannot be fully replaced by these mutations. We present two models consistent with our findings: that the suppressors commit to transport in one arbitrarily-determined direction or delay spore development. It is surprising that missense mutations somehow rescue loss of an entire domain with a complex function, and this raises new questions about the mechanism by which SpoIIIE pumps DNA and the roles SpoIIIE plays in vivo.

  4. Missense Mutations Allow a Sequence-Blind Mutant of SpoIIIE to Successfully Translocate Chromosomes during Sporulation.

    Directory of Open Access Journals (Sweden)

    Baundauna Bose

    Full Text Available SpoIIIE directionally pumps DNA across membranes during Bacillus subtilis sporulation and vegetative growth. The sequence-reading domain (γ domain is required for directional DNA transport, and its deletion severely impairs sporulation. We selected suppressors of the spoIIIEΔγ sporulation defect. Unexpectedly, many suppressors were intragenic missense mutants, and some restore sporulation to near-wild-type levels. The mutant proteins are likely not more abundant, faster at translocating DNA, or sequence-sensitive, and rescue does not involve the SpoIIIE homolog SftA. Some mutants behave differently when co-expressed with spoIIIEΔγ, consistent with the idea that some, but not all, variants may form mixed oligomers. In full-length spoIIIE, these mutations do not affect sporulation, and yet the corresponding residues are rarely found in other SpoIIIE/FtsK family members. The suppressors do not rescue chromosome translocation defects during vegetative growth, indicating that the role of the γ domain cannot be fully replaced by these mutations. We present two models consistent with our findings: that the suppressors commit to transport in one arbitrarily-determined direction or delay spore development. It is surprising that missense mutations somehow rescue loss of an entire domain with a complex function, and this raises new questions about the mechanism by which SpoIIIE pumps DNA and the roles SpoIIIE plays in vivo.

  5. Unique mosaicism of structural chromosomal rearrangement: is chromosome 18 preferentially involved?

    NARCIS (Netherlands)

    Pater, J.M. de; Smeets, D.F.C.M.; Scheres, J.M.J.C.

    2003-01-01

    The mentally normal mother of a 4-year-old boy with del(18)(q21.3) syndrome was tested cytogenetically to study the possibility of an inherited structural rearrangement of chromosome 18. She was found to carry an unusual mosaicism involving chromosomes 18 and 21. Two unbalanced cell lines were seen

  6. Measurement of background translocation frequencies in individuals with clones

    Energy Technology Data Exchange (ETDEWEB)

    Wade, Marcelle J. [California State Univ. (CalState), Hayward, CA (United States)

    1996-08-01

    In the leukemia case the unseparated B and T lymphocytes had a high translocation frequency even after 0.0014, respectively. After purging all clones from the data, the translocation frequencies for Bio 8 and Bio 23 were 0.00750.0014 and 0.0073 metaphases were scored for chromosomal aberrations,, specifically reciprocal translocations, using fluorescence in situ hybridization (FISH). Metaphase spreads were used from two healthy, unexposed individuals (not exposed to radiation, chemotherapy or radiotherapy) and one early B- precursor acute lymphocytic leukemia (ALL) patient (metaphase spreads from both separated T lymphocytes and unseparated B and T lymphocytes were scored). All three individuals had an abnormally high translocation frequency. The high translocation frequencies resulted from clonal expansion of specific translocated chromosomes. I show in this thesis that by purging (discounting or removing) clones from the data of unexposed individuals, one can obtain true background translocation frequencies. In two cases, Bio 8 and Bio 23, the measured translocation frequency for chromosomes 1, 2 and 4 was 0.0124 purging all of the clones from the data. This high translocation frequency may be due to a low frequency of some clones and may not be recognized. The separated T lymphocytes had a higher translocation frequency than expected.

  7. XY pair associates with the synaptonemal complex of autosomal male-sterile translocations in pachytene spermatocytes of the mouse (Mus musculus).

    Science.gov (United States)

    Forejt, J; Gregorová, S; Goetz, P

    1981-01-01

    Analysis of the chromosome behaviour at pachytene has been performed by means of the silver staining technique visualizing the synaptonemal complexes (SCs) in male mice heterozygous for the male-sterile translocations T(5;12)31Hm T(16;17)43H and T(7;19)145H, respectively. the T(9;17)138Ca male heterozygotes and T43H/T43H homozygous males were used as fertile controls. The sterile mice displayed a high frequency (about 60%) of pachytene spermatocytes with autosomal translocation configuration located in close vicinity of the XY pair. The dense round body (XAB), normally located near the X-chromosome axis in fertile males, exhibited abnormal affinity to translocation configuration in the sterile translocation heterozygotes. The incomplete synapsis of autosomes involved in translocation configuration was observed in more than 70% of the pachytene spermatocytes with the male-sterile translocations but less than 20% of the cells from T138Ca fertile male.s. A hypothesis relating the spermatogenic arrest of carriers of male-sterile rearrangements to the presumed interference with X chromosome inactivation in male meiosis is discussed.

  8. A recurrent translocation is mediated by homologous recombination between HERV-H elements

    Directory of Open Access Journals (Sweden)

    Hermetz Karen E

    2012-01-01

    Full Text Available Abstract Background Chromosome rearrangements are caused by many mutational mechanisms; of these, recurrent rearrangements can be particularly informative for teasing apart DNA sequence-specific factors. Some recurrent translocations are mediated by homologous recombination between large blocks of segmental duplications on different chromosomes. Here we describe a recurrent unbalanced translocation casued by recombination between shorter homologous regions on chromosomes 4 and 18 in two unrelated children with intellectual disability. Results Array CGH resolved the breakpoints of the 6.97-Megabase (Mb loss of 18q and the 7.30-Mb gain of 4q. Sequencing across the translocation breakpoints revealed that both translocations occurred between 92%-identical human endogenous retrovirus (HERV elements in the same orientation on chromosomes 4 and 18. In addition, we find sequence variation in the chromosome 4 HERV that makes one allele more like the chromosome 18 HERV. Conclusions Homologous recombination between HERVs on the same chromosome is known to cause chromosome deletions, but this is the first report of interchromosomal HERV-HERV recombination leading to a translocation. It is possible that normal sequence variation in substrates of non-allelic homologous recombination (NAHR affects the alignment of recombining segments and influences the propensity to chromosome rearrangement.

  9. Effects of caffeine upon material repair systems involved in the rejoining of x-ray-induced chromosome breaks in the paternal genome of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Osgood, C.J.

    1977-01-01

    Experiments were carried out in which ring-X/B/sup s/Yy + males were x-irradiated and mated with females which had been fed on either 1.0% caffeine in 10% sucrose, 0.2% caffeine in 10% sucrose, or on 10% sucrose alone. F1 progeny were scored for dominant lethals and sex chromosome losses, while in the F2 generation the frequency of translocations was monitored. In line with previous reports it was found that at a concentration of 0.2% caffeine the frequencies of dominant lethals and sex chromosome losses were increased while the frequency of translocations was depressed. At the higher concentration of 1.0% caffeine the frequencies of dominant lethals and sex chromosome losses were depressed. With respect to translocations, while the formation of translocations between autosomes was enhanced in the presence of 1.0% caffeine, the frequency of translocations between the Y and the autosomes was depressed relative to sucrose controls. The proposal is made that at high effective concentrations, caffeine promotes the rejoining of breaks induced in sperm, supported by evidence of an enhancement in the frequency of autosomal translocations in the 1.0% caffeine series and consistent with the depression in the frequencies of dominant lethals and sex chromosome losses in the 1.0% series as compared to sucrose controls

  10. Efficient induction of Wheat-agropyron cristatum 6P translocation lines and GISH detection.

    Directory of Open Access Journals (Sweden)

    Liqiang Song

    Full Text Available The narrow genetic background restricts wheat yield and quality improvement. The wild relatives of wheat are the huge gene pools for wheat improvement and can broaden its genetic basis. Production of wheat-alien translocation lines can transfer alien genes to wheat. So it is important to develop an efficient method to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome carries many potential genes beneficial to disease resistance, stress tolerance and high yield. Chromosome 6P possesses the desirable genes exhibiting good agronomic traits, such as high grain number per spike, powdery mildew resistance and stress tolerance. In this study, the wheat-A. cristatum disomic addition was used as bridge material to produce wheat-A. cristatum translocation lines induced by (60Co-γirradiation. The results of genomic in situ hybridization showed that 216 plants contained alien chromosome translocation among 571 self-pollinated progenies. The frequency of translocation was 37.83%, much higher than previous reports. Moreover, various alien translocation types were identified. The analysis of M2 showed that 62.5% of intergeneric translocation lines grew normally without losing the translocated chromosomes. The paper reported a high efficient technical method for inducing alien translocation between wheat and Agropyroncristatum. Additionally, these translocation lines will be valuable for not only basic research on genetic balance, interaction and expression of different chromosome segments of wheat and alien species, but also wheat breeding programs to utilize superior agronomic traits and good compensation effect from alien chromosomes.

  11. G-banding analysis of radiation-induced chromosome damage in lymphocytes of Hiroshima atomic-bomb survivors

    International Nuclear Information System (INIS)

    Ohtaki, Kazuo; Nakashima, Eiji.

    1994-06-01

    This report describes the G-banding analysis of somatic chromosomes in lymphocytes from 63 atomic-bomb survivors in Hiroshima to determine the type and frequency of radiation-induced chromosome aberrations. Summary findings are as follows: (1) The cells with stable-type chromosome aberrations (Cs cells) predominated among the aberrant cells and showed a dose-dependent increase. All stable chromosome aberrations were classified into 9 types: reciprocal translocations (t), translocations of complex type (t-cx), insertions (ins), complex exchanges (e-cx), peri- and paracentric inversions (inv-peri, inv-para), terminal and interstitial deletions (del-ter, del-int), and unidentified rearrangements. Aberration frequencies increased with increasing dose for all aberration categories. Among the chromosome aberrations classified, reciprocal translocations predominated in all dose ranges. The frequencies of complex aberrations were low at the low-dose level but increased sharply as dose increased. (2) The linear model was fitted to test the dose-response relationship for Cs-cell frequencies. With a constant neutron relative biological effectiveness of 10, an estimated linear slope of 15.2%/Sv was obtained for Dosimetry System 1986 bone-marrow dose with an intercept of 2.9% at dose 0. The present observation confirmed a wide variability of Cs-cell frequencies among individual survivors in every dose category.(3) Statistical analysis of data on 3370 break sites showed good correlations between relative DNA content and the distribution of chromosome breaks involved in translocations, although the involvement of chromosome 1 is significantly higher, for as-yet-unknown reasons. (J.P.N.)

  12. Preimplantation genetic haplotyping a new application for diagnosis of translocation carrier's embryos- preliminary observations of two robertsonian translocation carrier families.

    Science.gov (United States)

    Shamash, Jana; Rienstein, Shlomit; Wolf-Reznik, Haike; Pras, Elon; Dekel, Michal; Litmanovitch, Talia; Brengauz, Masha; Goldman, Boleslav; Yonath, Hagith; Dor, Jehoshua; Levron, Jacob; Aviram-Goldring, Ayala

    2011-01-01

    Preimplantation genetic diagnosis using fluorescence in-situ hybridization (PGD-FISH) is currently the most common reproductive solution for translocation carriers. However, this technique usually does not differentiate between embryos carrying the balanced form of the translocation and those carrying the homologous normal chromosomes. We developed a new application of preimplantation genetic haplotyping (PGH) that can identify and distinguish between all forms of the translocation status in cleavage stage embryos prior to implantation. Polymorphic markers were used to identify and differentiate between the alleles that carry the translocation and those that are the normal homologous chromosomes. Embryos from two families of robertsonian translocation carriers were successfully analyzed using polymorphic markers haplotyping. Our preliminary results indicate that the PGH is capable of distinguishing between normal, balanced and unbalanced translocation carrier embryos. This method will improve PGD and will enable translocation carriers to avoid transmission of the translocation and the associated medical complications to offspring.

  13. Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity.

    Directory of Open Access Journals (Sweden)

    Heather C Whalley

    Full Text Available Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1 is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11 (q42.1;q14.3.Within the original pedigree, we examined the effects of the t(1;11 translocation on white matter integrity, measured by fractional anisotropy (FA. This included family members with (n = 7 and without (n = 13 the translocation, along with a clinical control sample of patients with psychosis (n = 34, and a group of healthy controls (n = 33.We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity.We demonstrate that the t(1;11 translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis.

  14. Production and identification of wheat - Agropyron cristatum (1.4P) alien translocation lines.

    Science.gov (United States)

    Liu, Wei-Hua; Luan, Yang; Wang, Jing-Chang; Wang, Xiao-Guang; Su, Jun-Ji; Zhang, Jin-Peng; Yang, Xin-Ming; Gao, Ai-Nong; Li, Li-Hui

    2010-06-01

    The P genome of Agropyron Gaertn., a wild relative of wheat, contains an abundance of desirable genes that can be utilized as genetic resources to improve wheat. In this study, wheat - Aegilops cylindrica Host gametocidal chromosome 2C addition lines were crossed with wheat - Agropyron cristatum (L.) Gaertn. disomic addition line accession II-21 with alien recombinant chromosome (1.4)P. We successfully induced wheat - A. cristatum alien chromosomal translocations for the first time. The frequency of translocation in the progeny was 3.75%, which was detected by molecular markers and genomic in situ hybridization (GISH). The translocation chromosomes were identified by dual-color GISH /fluorescence in situ hybridization (FISH). The P genomic DNA was used as probe to detect the (1.4)P chromosome fragment, and pHvG39, pAs1, or pSc119.2 repeated sequences were used as probes to identify wheat translocated chromosomes. The results showed that six types of translocations were identified in the three wheat - A. cristatum alien translocation lines, including the whole arm or terminal portion of a (1.4)P chromosome. The (1.4)P chromosome fragments were translocated to wheat chromosomes 1B, 2B, 5B, and 3D. The breakpoints were located at the centromeres of 1B and 2B, the pericentric locations of 5BS, and the terminals of 5BL and 3DS. In addition, we obtained 12 addition-deletion lines that contained alien A. cristatum chromosome (1.4)P in wheat background. All of these wheat - A. cristatum alien translocation lines and addition-deletion lines would be valuable for identifying A. cristatum chromosome (1.4)P-related genes and providing genetic resources and new germplasm accessions for the genetic improvement of wheat. The specific molecular markers of A. cristatum (1.4)P chromosome have been developed and used to track the (1.4)P chromatin.

  15. Radiation-induced chromosome breakages in bread wheat (Triticum aestivum L.)

    International Nuclear Information System (INIS)

    Larik, A.S.

    1975-01-01

    Meiosis and pollen fertility were studied in the M 2 generation in four varieties of hexaploid wheat. Meiosis was characterized by the formation of interchange configurations, such as rings and chains of four chromosomes in several cells. Chromosomal aberrations showed linear relationship with gamma irradiation; 45 kR dose induced the highest chromosomal abnormalities. Most multivalents were interchange rings of four chromosomes. Translocations involving two pairs of homologous or nonhomologous chromosomes seemed to be higher in frequency than those involving more than two pairs of chromosomes. Anaphase abnormalities, such as laggards, bridges and fragments and unequal segregation of chromosomes, were frequently observed. Pollen fertility was considerably reduced in the M 2 plants arising form the treatments of higher doses of gamma rays because of the induced chromosome interchanges. (author)

  16. Molecular and cytogenetic characterization of the 5DS-5BS chromosome translocation conditioning soft kernel texture in durum wheat

    Science.gov (United States)

    Cultivar ‘Soft Svevo’, a new non-GMO soft durum cultivar with soft kernel texture, was developed through a 5DS(5BS) chromosomal translocation from event. cv. Chinese Spring, and subsequently used to create new soft durum germplasm. The development of Soft Svevo featured the Ph1b-mediated homoeologou...

  17. The clinical impact of chromosomal rearrangements with breakpoints upstream of the SOX9 gene: two novel de novo balanced translocations associated with acampomelic campomelic dysplasia.

    Science.gov (United States)

    Fonseca, Ana Carolina S; Bonaldi, Adriano; Bertola, Débora R; Kim, Chong A; Otto, Paulo A; Vianna-Morgante, Angela M

    2013-05-07

    The association of balanced rearrangements with breakpoints near SOX9 [SRY (sex determining region Y)-box 9] with skeletal abnormalities has been ascribed to the presumptive altering of SOX9 expression by the direct disruption of regulatory elements, their separation from SOX9 or the effect of juxtaposed sequences. We report on two sporadic apparently balanced translocations, t(7;17)(p13;q24) and t(17;20)(q24.3;q11.2), whose carriers have skeletal abnormalities that led to the diagnosis of acampomelic campomelic dysplasia (ACD; MIM 114290). No pathogenic chromosomal imbalances were detected by a-CGH. The chromosome 17 breakpoints were mapped, respectively, 917-855 kb and 601-585 kb upstream of the SOX9 gene. A distal cluster of balanced rearrangements breakpoints on chromosome 17 associated with SOX9-related skeletal disorders has been mapped to a segment 932-789 kb upstream of SOX9. In this cluster, the breakpoint of the herein described t(17;20) is the most telomeric to SOX9, thus allowing the redefining of the telomeric boundary of the distal breakpoint cluster region related to skeletal disorders to 601-585 kb upstream of SOX9. Although both patients have skeletal abnormalities, the t(7;17) carrier presents with relatively mild clinical features, whereas the t(17;20) was detected in a boy with severe broncheomalacia, depending on mechanical ventilation. Balanced and unbalanced rearrangements associated with disorders of sex determination led to the mapping of a regulatory region of SOX9 function on testicular differentiation to a 517-595 kb interval upstream of SOX9, in addition to TESCO (Testis-specific enhancer of SOX9 core). As the carrier of t(17;20) has an XY sex-chromosome constitution and normal male development for his age, the segment of chromosome 17 distal to the translocation breakpoint should contain the regulatory elements for normal testis development. These two novel translocations illustrate the clinical variability in carriers of balanced

  18. Preimplantation diagnosis of repeated miscarriage due to chromosomal translocations using metaphase chromosomes of a blastomere biopsied from 4- to 6-cell-stage embryos.

    Science.gov (United States)

    Tanaka, Atsushi; Nagayoshi, Motoi; Awata, Shoichiro; Mawatari, Yoshifumi; Tanaka, Izumi; Kusunoki, Hiroshi

    2004-01-01

    To evaluate the safety and accuracy of karyotyping the blastomere chromosomes at metaphase in the natural cell cycle for preimplantation diagnosis. A pilot study. A private infertility clinic and a university laboratory. Eleven patients undergoing IVF and preimplantation diagnosis. Intact human embryos at the 4- to 6-cell stage and human-mouse heterokaryons were cultured and checked hourly for disappearance of the nuclear envelope. After it disappeared, the metaphase chromosomes were analyzed by fluorescence in situ hybridization. Percentage of analyzable metaphase plates and safety and accuracy of the method. The success rate of electrofusion to form human-mouse heterokaryons was 87.1% (27/31), and analyzable chromosomes were obtained from 77.4% (24/31) of the heterokaryons. On the other hand, disappearance of the nuclear envelope occurred in 89.5% (17/19) of the human embryos and it began earlier than that in the heterokaryons. Analyzable chromosomes were obtained and their translocation sites were identified in all blastomeres biopsied from the 17 embryos. After the biopsy, 67.0% of the embryos could develop to the blastocyst stage. The natural cell cycle method reported herein requires frequent observation, but it is safe, with no artificial effects on the chromosomes and without loss of or damage to blastomeres, which occurred with the electrofusion method. Using the natural cell cycle method, we could perform preimplantation diagnosis with nearly 100% accuracy.

  19. Meiotic events in Oenothera - a non-standard pattern of chromosome behaviour.

    Science.gov (United States)

    Golczyk, Hieronim; Musiał, Krystyna; Rauwolf, Uwe; Meurer, Jörg; Herrmann, Reinhold G; Greiner, Stephan

    2008-11-01

    The genus Oenothera shows an intriguing extent of permanent translocation heterozygosity. Reciprocal translocations of chromosome arms in species or populations result in various kinds of chromosome multivalents in diakinesis. Early meiotic events conditioning such chromosome behaviour are poorly understood. We found a surprising uniformity of the leptotene-diplotene period, regardless of the chromosome configuration at diakinesis (ring of 14, 7 bivalents, mixture of bivalents and multivalents). It appears that the earliest chromosome interactions at Oenothera meiosis are untypical, since they involve pericentromeric regions. During early leptotene, proximal chromosome parts cluster and form a highly polarized Rabl configuration. Telomeres associated in pairs were seen at zygotene. The high degree of polarization of meiotic nuclei continues for an exceptionally long period, i.e., during zygotene-pachytene into the diplotene contraction stage. The Rabl-polarized meiotic architecture and clustering of pericentromeres suggest a high complexity of karyotypes, not only in structural heterozygotes but also in bivalent-forming homozygous species.

  20. WARBURG EFFECT AND TRANSLOCATION-INDUCED GENOMIC INSTABILITY: TWO YEAST MODELS FOR CANCER CELLS

    Directory of Open Access Journals (Sweden)

    Valentina eTosato

    2013-01-01

    Full Text Available Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression i the activity of pyruvate kinase (PK, which recapitulates metabolic features of cancer cells, including the Warburg effect, and ii Bridge-Induced chromosome Translocation (BIT mimicking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect, and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, pyruvate kinase, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and posttranslational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants (translocants, between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the Bridge-Induced Translocation system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast.

  1. Chronic myeloid leukemia with variation of translocation at (Ph) [ins (22;9) (q11;q21q34)]: a case report.

    Science.gov (United States)

    Wang, Zhiqiong; Zen, Wen; Meng, Fankai; Xin, Xing; Luo, Li; Sun, Hanying; Zhou, Jianfeng; Huang, Lifang

    2015-01-01

    Chronic myeloid leukemia (CML) is most frequently observed in middle-aged individuals. In most patients, normal marrow cells are replaced by cells with an abnormal G-group chromosome, the Philadelphia (Ph) chromosome. The Ph chromosome that is characterized by the translocation (9;22) (q34;q11) is noted in 90-95% of patients diagnosed with CML. Studies have also shown that CML can be associated with various other cytogenetic abnormalities, with 5-10% of these cases showing complex translocation involving another chromosome in addition to the Ph chromosome. Here, we report the case of a Ph(+) CML patient with an inserted karyotype who presented clinically in the chronic phase but with atypical features. This case highlights the significance of cytogenetic abnormalities on the prognosis in CML.

  2. Analysis of the Ceratitis capitata y chromosome using in situ hybridization to mitotic chromosomes

    International Nuclear Information System (INIS)

    Willhoeft, U.; Franz, G.

    1998-01-01

    In Ceratitis capitata the Y chromosome is responsible for sex-determination. We used fluorescence in situ hybridization (FISH) for cytogenetic analysis of mitotic chromosomes. FISH with the wild-type strain EgyptII and two repetitive DNA probes enabled us to differentiate between the short and the long arm of the Y chromosome and gives a much better resolution than C-banding of mitotic chromosomes. We identified the Y-chromosomal breakpoints in Y-autosome translocations using FISH. Even more complex rearrangements i.e. deletions and insertions in some translocation strains were detected by this method. A strategy for mapping the primary sex determination factor in Ceratitis capitata by FISH is presented. (author)

  3. Factors that determine the in vivo dose-response relationship for stable chromosome aberrations in A-bomb survivors

    International Nuclear Information System (INIS)

    Awa, A.A.; Nakano, Mimako; Ohtaki, Kazuo; Kodama, Yoshiaki; Lucas, J.; Gray, J.

    1992-01-01

    An overview is given of the dose-response relationship for stable chromosome aberrations (i.e., translocations and inversions) in the peripheral blood lymphocytes of A-bomb survivors in Hiroshima. Special emphasis is placed on (i) the overdispersion of survivor cases with either unexpectedly high or low aberration frequencies relative to the estimated DS86 kerma values assigned to individual survivors, termed 'cytogenetic outliers', and (ii) the correlation of chromosome aberration frequencies with other biological endpoints, such as acute radiation symptoms (severe epilation). A new molecular biological technique, known as fluorescence in situ hybridization (FISH) with composite, whole-chromosome probes to paint differentially the target chromosomes, has facilitated rapid, efficient, and extensive scoring of translocation-type chromosome aberrations in which the target chromosomes are involved. Using this methodology, the observed findings on translocation frequencies in A-bomb survivors have shown that the frequency of stable chromosome aberrations, which have persisted for years without change in frequency in irradiated persons, is indeed useful as an indicator for biological dosimetry. (author)

  4. High-performance analysis of single interphase cells with custom DNA probes spanning translocation break points

    Science.gov (United States)

    Weier, Heinz-Ulli G.; Munne, S.; Lersch, Robert A.; Marquez, C.; Wu, J.; Pedersen, Roger A.; Fung, Jingly

    1999-06-01

    The chromatin organization of interphase cell nuclei, albeit an object of intense investigation, is only poorly understood. In the past, this has hampered the cytogenetic analysis of tissues derived from specimens where only few cells were actively proliferating or a significant number of metaphase cells could be obtained by induction of growth. Typical examples of such hard to analyze cell systems are solid tumors, germ cells and, to a certain extent, fetal cells such as amniocytes, blastomeres or cytotrophoblasts. Balanced reciprocal translocations that do not disrupt essential genes and thus do not led to disease symptoms exit in less than one percent of the general population. Since the presence of translocations interferes with homologue pairing in meiosis, many of these individuals experience problems in their reproduction, such as reduced fertility, infertility or a history of spontaneous abortions. The majority of translocation carriers enrolled in our in vitro fertilization (IVF) programs carry simple translocations involving only two autosomes. While most translocations are relatively easy to spot in metaphase cells, the majority of cells biopsied from embryos produced by IVF are in interphase and thus unsuitable for analysis by chromosome banding or FISH-painting. We therefore set out to analyze single interphase cells for presence or absence of specific translocations. Our assay, based on fluorescence in situ hybridization (FISH) of breakpoint-spanning DNA probes, detects translocations in interphase by visual microscopic inspection of hybridization domains. Probes are prepared so that they span a breakpoint and cover several hundred kb of DNA adjacent to the breakpoint. On normal chromosomes, such probes label a contiguous stretch of DNA and produce a single hybridization domain per chromosome in interphase cells. The translocation disrupts the hybridization domain and the resulting two fragments appear as physically separated hybridization domains in

  5. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  6. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

  7. Cloning of the anhidrotic ectodermal dysplasia gene: Identification of cDNAs associated with CpG islands mapped near translocation breakpoint in two female patients

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, A.K.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); Kere, J. [Univ. of Helsinki (Finland)] [and others

    1994-09-01

    The gene for the X chromosomal developmental disorder anhidrotic ectodermal dysplasia (EDA) has been mapped to Xq12-q13 by linkage analysis and is expressed in a few females with chromosomal translocations involving band Xq12-q13. A yeast artificial chromosome (YAC) contig (2.0 Mb) spanning two translocation breakpoints has been assembled by sequence-tagged site (STS)-based chromosomal walking. The two translocation breakpoints (X:autosome translocations from the affected female patients) have been mapped less than 60 kb apart within a YAC contig. Unique probes and intragenic STSs (mapped between the two translocations) have been developed and a somatic cell hybrid carrying the translocated X chromosome from the AK patient has been analyzed by isolating unique probes that span the breakpoint. Several STSs made from intragenic sequences have been found to be conserved in mouse, hamster and monkey, but we have detected no mRNAs in a number of tissues tested. However, a probe and STS developed from the DNA spanning the AK breakpoint is conserved in mouse, hamster and monkey, and we have detected expressed sequences in skin cells and cDNA libraries. In addition, unique sequences have been obtained from two CpG islands in the region that maps proximal to the breakpoints. cDNAs containing these sequences are being studied as candidates for the gene affected in the etiology of EDA.

  8. Chromosome painting in biological dosimetry: Semi-automatic system to score stable chromosome aberrations

    International Nuclear Information System (INIS)

    Garcia-Sagredo, J.M.; Vallcorba, I.; Sanchez-Hombre, M.C.; Ferro, M.T.; San Roman Cos-Gayon, C.; Santos, A.; Malpica, N.; Ortiz, C.

    1997-01-01

    From the beginning of the description of the procedure of chromosome painting by fluorescence in situ hybridization (FISH), it was thought its possible application to score induced chromosomal aberrations in radiation exposition. With chromosome painting it is possible to detect changes between chromosomes that has been validated in radiation exposition. Translocation scoring by FISH, contrarily to the unstable dicentrics, mainly detect stable chromosome aberrations that do not disappear, it allows the capability of quantify delayed acute expositions or chronic cumulative expositions. The large number of cells that have to be analyzed for high accuracy, specially when dealing with low radiation doses, makes it almost imperative to use an automatic analysis system. After validate translocation scoring by FISH in our, we have evaluated the ability and sensitivity to detect chromosomal aberrations by chromosome using different paint probes used, showing that any combination of paint probes can be used to score induced chromosomal aberrations. Our group has developed a FISH analysis that is currently being adapted for translocation scoring analysis. It includes systematic error correction and internal control probes. The performance tests carried out show that 9,000 cells can be analyzed in 10 hr. using a Sparc 4/370. Although with a faster computer, a higher throughput is expected, for large population screening or very low radiation doses, this performance still has to be improved. (author)

  9. Chromosome aberrations in human lymphocytes for investigation of individual radiosensitivity

    International Nuclear Information System (INIS)

    Zitzelsberger, H.; Bauchinger, M.

    2000-01-01

    Stable translocations and insertions which are not selected against during cell proliferation can be reliably scored by use of fluorescence in situ hybridisation (FISH) which allows painting of selected chromosomes along their entire length. This temporal persistence makes them particulary valuable for quantifying post human radiation exposures ('biodosimetry'). A disadvantage of this approach is that for routine use only a partial genome analysis can be performed which is mostly based on triple combinations of DNA probes for particular chromosomes. Translocation frequencies from partial genome analysis are often scaled-up to equal the full genome. Basic assumptions for such scaling are, that double strand breaks leading to translocations must be distributed randomly throughout the genome and no preferential interaction between particular pairs of chromosomes occurs. Thus, the probability of a particular chromosome being involved in an exchange is proportional to its DNA content. However, this is not always supported by experimental findings and may thus indicate a differential radiosensitivity of particular chromosomes. Translocation measurements in peripheral blood of different healthy donors irradiated in vitro with the same dose revealed also some evidence for the existence of interindividual differences in radiosensitivity. Similar findings have been already demonstrated after therapeutic irradiation of tumour patients. Consequences thereof may result for long-term retrospective biodosimetry. In order to provide reliable estimates of an individual's exposure to ionising radiation, the extent, distribution and dose-dependence of the observed variability has to be carefully examined in larger groups of persons and larger sets of calibration data. (orig.) [de

  10. Retrospective dosimetry using chromosome painting

    International Nuclear Information System (INIS)

    Nasazzi, N.B.; Giorgio, M.D.; Taja, M.R.

    2000-01-01

    Chromosome aberration frequency measured in peripheral lymphocytes of persons exposed to ionizing radiation has been used since 1960s for dose assessment. Suspected overexposure is usually evaluated by the frequency of dicentrics and centric rings using an appropriate in vitro calibration curve. However, these chromosome aberrations are unstable with time after exposure and dose reconstruction may encounter uncertainties when the time between the exposure and the analysis is considerable or even unknown. It appears that translocations persist with time after exposure and may be used as an indication of acute past overexposures. Moreover, they appear to accumulate the cytogenetical information, which correlates with the dose received under fractionated, chronic or even occupational exposure conditions. Translocations may be detected using G-banding, which allows to score the total amount of radiation induced translocations but it is a time consuming method, or by Chromosome Painting, a method base on the Fluorescence in situ Hybridization (FISH) technique, painting only some chromosome pairs with specific whole chromosome probes and then extrapolating the observed translocation frequencies to the full genome. The latter method allows a faster aberration scoring than G-banding and appears to be the most promissory tool for biodosimetry, particularly when it is necessary to assess low doses and consequently to score a large number of metaphases, e.g. radiation workers exposed within dose limits. As with the unstable chromosome aberration, it is necessary an in vitro calibration curve based on the frequency of stable chromosome aberrations to assess doses. Our laboratory performed calibration curves for Co 60 γ-rays based on the frequencies of unstable (dicentrics and centric rings detected by conventional Giemsa staining) and stable chromosome aberrations (translocations and inversions, detected by G-banding). In order to minimize the interlaboratory variability, we

  11. Karyotype evolution in Rhinolophus bats (Rhinolophidae, Chiroptera) illuminated by cross-species chromosome painting and G-banding comparison.

    Science.gov (United States)

    Mao, Xiuguang; Nie, Wenhui; Wang, Jinhuan; Su, Weiting; Ao, Lei; Feng, Qing; Wang, Yingxiang; Volleth, Marianne; Yang, Fengtang

    2007-01-01

    Rhinolophus (Rhinolophidae) is the second most speciose genus in Chiroptera and has extensively diversified diploid chromosome numbers (from 2n = 28 to 62). In spite of many attempts to explore the karyotypic evolution of this genus, most studies have been based on conventional Giemsa staining rather than G-banding. Here we have made a whole set of chromosome-specific painting probes from flow-sorted chromosomes of Aselliscus stoliczkanus (Hipposideridae). These probes have been utilized to establish the first genome-wide homology maps among six Rhinolophus species with four different diploid chromosome numbers (2n = 36, 44, 58, and 62) and three species from other families: Rousettus leschenaulti (2n = 36, Pteropodidae), Hipposideros larvatus (2n = 32, Hipposideridae), and Myotis altarium (2n = 44, Vespertilionidae) by fluorescence in situ hybridization. To facilitate integration with published maps, human paints were also hybridized to A. stoliczkanus chromosomes. Our painting results substantiate the wide occurrence of whole-chromosome arm conservation in Rhinolophus bats and suggest that Robertsonian translocations of different combinations account for their karyotype differences. Parsimony analysis using chromosomal characters has provided some new insights into the Rhinolophus ancestral karyotype and phylogenetic relationships among these Rhinolophus species so far studied. In addition to Robertsonian translocations, our results suggest that whole-arm (reciprocal) translocations involving multiple non-homologous chromosomes as well could have been involved in the karyotypic evolution within Rhinolophus, in particular those bats with low and medium diploid numbers.

  12. Structural rearrangements of chromosomes in the domestic chicken: experimental production by X-irradiation of spermatozoa

    International Nuclear Information System (INIS)

    Wooster, W.E.; Fechheimer, N.S.; Jaap, R.G.

    1977-01-01

    In order to produce chicks heterozygous for structural aberrations of chromosomes, 67 hens were inseminated with semen that had been exposed to 1200 R of X-rays. A sample of 204 chicks was hatched and survived. Among these, 18 (8.9%) contained rearrangements comprising 19 translocations and one pericentric inversion. All 10 males and eight females heterozygous for rearrangements were fertile and transmitted these rearrangements to approximately half their hatched progeny. Each of the major chromosomes of the chicken karyotype, except number 6, was involved in one or more of the translocations. The pericentric inversion was of a segment of chromosome number 2. (author)

  13. Translocation heterozygosity in southern African species of Viscum

    Directory of Open Access Journals (Sweden)

    D. Wiens

    1980-11-01

    Full Text Available Sex-associated and floating translocation complexes are characteristic of dioecious species of  Viscum,  but are virtually absent in monoecious species. The majority of dioecious species has fixed sex-associated translocation complexes with the male being the heterozygous sex. The sex-associated multivalent is usually O4 (ring-of-four or O6 , rarely O8 . Dioecious species without sex-associated translocations are much less common. Most of the dioecious species are also polymorphic for floating translocations, producing one or more additional multivalents ranging from O4 to O12. Floating translocations may be more frequent in species that do not have sex-associated translocations. Supernumerary chromosomes are also present in several species. Sex ratios are at unity in most dioecious species, but female-biased ratios may occur in some species. The high correlation between dioecy and translocation heterozygosity suggests that translocations are primarily associated with the origin and establishment of dioecy. Any róle in the maintenance of biased sex ratios through meiotic drive is probably secondary. Sex-associated translocations may serve to stabilize dioecy by bringing the sex factors into close linkage. Subsequent structural rearrangements within a sex-associated translocation complex may bring the sex factors together in one chromosome pair, releasing floating translocations. The high frequencies of floating translocation heterozygosity in some species indicate that such heterozygosity also has adaptive value.

  14. Chromosomal geometry in the interface from the frequency of the radiation induced chromosome aberrations

    International Nuclear Information System (INIS)

    Nasazzi, N.; Otero, D.; Di Giorgio, M.

    1996-01-01

    Ionizing radiation induces DNA double-strand breaks (DSBs) and their interaction and illegitimate recombination produces chromosomal aberrations. Stable chromosomal aberrations comprise inter-chromosomal events (translocations) and intra-chromosomal events (inversions). When DSBs induction and interaction is done at random, and the proximity effects are neglected, the expected relation between translocations and inversions is F=86, based on chromosome arm length. The number of translocations and inversions is analyzed by using G-banding in 16 lymphocytes cultures from blood samples acutely irradiated with γ-rays (dose range: 0,5 Gy - 3 Gy). The result obtained was: F=13,5, significantly smaller than F=86. Literature data show similar small F values, but strongly spread. The excess of inversions could be explained by a 'proximity effect', it means that more proximate DSBs have more interaction probability. Therefore, it is possible to postulate a special chromosome arrangement during irradiation and the subsequent interval. We propose a model where individual chromosomes show spherical confinement with some degree of overlapping and DSBs induction proportional to cross section. A DSBs interaction probability function with cut-off length= 1μ is assumed. According to our results, the confinement volume is ≅ 6.4% of the nuclear volume. Nevertheless, we presume that large spread in F data could be due to temporal variation in overlapping and spatial chromosomal confinement. (authors). 14 refs

  15. Chromosome painting analysis of X-ray-induced aberrations in human lymphocytes in vitro

    International Nuclear Information System (INIS)

    Matsuoka, A.; Hayashi, M.; Yamazaki, N.; Sofuni, T.

    1994-01-01

    Chromosomal rearrangements in human lymphocytes induced by X-rays (0, 0.5, 1.0 and 2.0 Gray) were analyzed using chromosome painting. DNA probes for human chromosomes 1, 3 or 4 alone, and a combination of 1 and 4, were used for analysis. The frequency of cells with rearrangements, i.e. reciprocal translocations, dicentrics, insertions, tricentrics and fragments, involving chromosome 4 increased with dose in both 48 and 72 h cultures. The number of translocations per cell also increased with dose at 48 and 72 h. Dicentrics increased with dose in 48 h but not in 72 h cultures. The estimated genomic frequency of aberrations per cell was comparable with results in banded cells. No difference was shown on the detection efficiency of chromosome rearrangements among the various DNA probes used. Since this technique does not necessarily require well-spread metaphases for analysis, it is possible to increase the number of analyzable metaphases compared with the banding technique. Chromosome painting is a simpler, more objective and practical method for detecting chromosome rearrangements than conventional banding analyses. (Author)

  16. Detection of Chromosome X;18 Breakpoints and Translocation of the Xq22.3;18q23 Regions Resulting in Variable Fertility Phenotypes

    Directory of Open Access Journals (Sweden)

    Attila Szvetko

    2012-01-01

    Full Text Available We describe a familial pattern of gonosomal-autosomal translocation between the X and 18 chromosomes, balanced and unbalanced forms, in male and female siblings. The proposita was consulted for hypergonadotropic hypogonadism. Karyotype analysis revealed a balanced 46, X, t(X;18(q22.3;q23 genotype. The sister of the proband presented with oligomenorrhea with irregular menses and possesses an unbalanced form of the translocation 46, X, der(X, t(X;18(q22.3;q23. The brother of the proband was investigated and was found to possess the balanced form of the same translocation, resulting in disrupted spermatogenesis. Maternal investigation revealed the progenitor karyotype 46, X, t(X;18(q22.3;q23. Maternal inheritance and various genomic events contributed to the resultant genotypes. Primary infertility was initially diagnosed in all progeny; however, the male individual recently fathered twins. We briefly review the mechanisms associated with X;18 translocations and describe a pattern of inheritance, where breakpoints and translocation of the Xq22.3;18q23 regions have resulted in variable fertility.

  17. Evaluating changes in stable chromosomal translocation frequency in patients receiving radioimmunotherapy

    International Nuclear Information System (INIS)

    Wong, Jeffrey Y.C.; Wang Jianyi; Liu An; Odom-Maryon, Tamara; Shively, John E.; Raubitschek, Andrew A.; Williams, Lawrence E.

    2000-01-01

    Purpose: The lack of any consistent correlation between radioimmunotherapy (RIT) dose and observed hematologic toxicity has made it difficult to validate RIT radiation dose estimates to marrow. Stable chromosomal translocations (SCT) which result after radiation exposure may be a biologic parameter that more closely correlates with RIT radiation dose. Increases in the frequency of SCT are observed after radiation exposure and are highly correlated with absorbed radiation dose. SCT are cumulative after multiple radiation doses and conserved through an extended number of cell divisions. The purpose of this study was to evaluate whether increases in SCT frequency were detectable in peripheral lymphocytes after RIT and whether the magnitude of these increases correlated with estimated radiation dose to marrow and whole body. Methods and Materials: Patients entered in a Phase I dose escalation therapy trial each received 1-3 intravenous cycles of the radiolabeled anti-carcinoembryonic antigen (CEA) monoclonal antibody, 90 Y-chimeric T84.66. Five mCi of 111 In-chimeric T84.66 was co-administered for imaging and biodistribution purposes. Blood samples were collected immediately prior to the start of therapy and 5-6 weeks after each therapy cycle. Peripheral lymphocytes were harvested after 72 hours of phytohemagglutinin stimulation and metaphase spreads prepared. Spreads were then stained by fluorescence in situ hybridization (FISH) using commercially available chromosome paint probes to chromosomes 3 and 4. Approximately 1000 spreads were evaluated for each chromosome sample. Red marrow radiation doses were estimated using the AAPM algorithm and blood clearance curves. Results: Eighteen patients were studied, each receiving at least one cycle of therapy ranging from 5-22 mCi/m 2 . Three patients received 2 cycles and two patients received 3 cycles of therapy. Cumulative estimated marrow doses ranged from 9.2 to 310 cGy. Increases in SCT frequencies were observed after

  18. A high incidence of meiotic silencing of unsynapsed chromatin is not associated with substantial pachytene loss in heterozygous male mice carrying multiple simple robertsonian translocations.

    Directory of Open Access Journals (Sweden)

    Marcia Manterola

    2009-08-01

    Full Text Available Meiosis is a complex type of cell division that involves homologous chromosome pairing, synapsis, recombination, and segregation. When any of these processes is altered, cellular checkpoints arrest meiosis progression and induce cell elimination. Meiotic impairment is particularly frequent in organisms bearing chromosomal translocations. When chromosomal translocations appear in heterozygosis, the chromosomes involved may not correctly complete synapsis, recombination, and/or segregation, thus promoting the activation of checkpoints that lead to the death of the meiocytes. In mammals and other organisms, the unsynapsed chromosomal regions are subject to a process called meiotic silencing of unsynapsed chromatin (MSUC. Different degrees of asynapsis could contribute to disturb the normal loading of MSUC proteins, interfering with autosome and sex chromosome gene expression and triggering a massive pachytene cell death. We report that in mice that are heterozygous for eight multiple simple Robertsonian translocations, most pachytene spermatocytes bear trivalents with unsynapsed regions that incorporate, in a stage-dependent manner, proteins involved in MSUC (e.g., gammaH2AX, ATR, ubiquitinated-H2A, SUMO-1, and XMR. These spermatocytes have a correct MSUC response and are not eliminated during pachytene and most of them proceed into diplotene. However, we found a high incidence of apoptotic spermatocytes at the metaphase stage. These results suggest that in Robertsonian heterozygous mice synapsis defects on most pachytene cells do not trigger a prophase-I checkpoint. Instead, meiotic impairment seems to mainly rely on the action of a checkpoint acting at the metaphase stage. We propose that a low stringency of the pachytene checkpoint could help to increase the chances that spermatocytes with synaptic defects will complete meiotic divisions and differentiate into viable gametes. This scenario, despite a reduction of fertility, allows the spreading

  19. Frequencies of chromosome aberration on radiation workers

    International Nuclear Information System (INIS)

    Yanti Lusiyanti; Zubaidah Alatas

    2016-01-01

    Radiation exposure of the body can cause damage to the genetic material in cells (cytogenetic) in the form of changes in the structure or chromosomal aberrations in peripheral blood lymphocytes. Chromosomal aberrations can be unstable as dicentric and ring chromosomes, and is stable as translocation. Dicentric chromosome is the gold standard biomarker due to radiation exposure, and chromosome translocation is a biomarker for retrospective biodosimetry. The aim of this studi is to conduct examination of chromosomal aberrations in the radiation worker to determine the potential damage of cell that may arise due to occupational radiation exposure. The examination have been carried out on blood samples from 55 radiation workers in the range of 5-30 year of service. Chromosome aberration frequency measurement starts with blood sampling, culturing, harvesting, slide preparations, and lymphocyte chromosome staining with Giemsa and painting with Fluorescence In Situ Hybridization (FISH) technique. The results showed that chromosomal translocations are not found in blood samples radiation workers and dicentric chromosomes found only on 2 blood samples of radiation workers with a frequency of 0.001/cell. The frequency of chromosomal aberrations in the blood cells such workers within normal limits and this means that the workers have been implemented a radiation safety aspects very well. (author)

  20. 40 CFR 798.5955 - Heritable translocation test in drosophila melanogaster.

    Science.gov (United States)

    2010-07-01

    ... drosophila melanogaster. 798.5955 Section 798.5955 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....5955 Heritable translocation test in drosophila melanogaster. (a) Purpose. The heritable translocation test in Drosophila measures the induction of chromosomal translocations in germ cells of insects...

  1. Abnormalities of chromosome No. 1: significance in malignant transformation

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J D

    1978-01-01

    Studies of human hematologic malignancies have provided sufficient data not only for the identification of nonrandom abnormalities of whole chromosomes, but also for determination of the specific chromosome regions involved. In clonal aberrations leading to an excess of chromosome No. 1, or a partial excess of No. 1, trisomy for bands 1q25 to 1q32 was noted in the myeloid cells obtained from every one of 35 patients who had various disorders, such as acute leukemia, polycythemia vera, or myelofibrosis. Similar chromosome changes were a consistent finding in various solid tumors as well. This rearrangement was not the result of a particularly fragile site in that region of the chromosome, since the break points in reciprocal translocations that involve No. 1 occurred almost exclusively in the short arm. The nonrandom chromosome changes found in neoplastic cells can now be correlated with the gene loci on these chromosomes or chromosome segments as an attempt is made to identify specific genes that might be related to malignancy.

  2. Exceptional Complex Chromosomal Rearrangements in Three Generations

    Directory of Open Access Journals (Sweden)

    Hannie Kartapradja

    2015-01-01

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

  3. Familial X/Y Translocation Encompassing ARSE in Two Moroccan Siblings with Sensorineural Deafness.

    Science.gov (United States)

    Amasdl, Saadia; Smaili, Wiam; Natiq, Abdelhafid; Hassani, Amale; Sbiti, Aziza; Agadr, Aomar; Sanlaville, Damien; Sefiani, Abdelaziz

    2017-01-01

    Unbalanced translocations involving X and Y chromosomes are rare and associated with a contiguous gene syndrome. The clinical phenotype is heterogeneous including mainly short stature, chondrodysplasia punctata, ichthyosis, hypogonadism, and intellectual disability. Here, we report 2 brothers with peculiar gestalt, short stature, and hearing loss, who harbor an X/Y translocation. Physical examination, brainstem acoustic potential evaluation, bone age, hormonal assessment, and X-ray investigations were performed. Because of their dysmorphic features, karyotyping, FISH, and aCGH were carried out. The probands had short stature, hypertelorism, midface hypoplasia, sensorineural hearing loss, normal intelligence as well as slight radial and ulnar bowing with brachytelephalangy. R-banding identified a derivative X chromosome with an abnormally expanded short arm. The mother was detected as a carrier of the same aberrant X chromosome. aCGH disclosed a 3.1-Mb distal deletion of chromosome region Xp22.33pter. This interval encompasses several genes, especially the short stature homeobox (SHOX) and arylsulfatase (ARSE) genes. The final karyotype of the probands was: 46,Y,der(X),t(X;Y)(p22;q12).ish der(X)(DXYS129-,DXYS153-)mat.arr[hg19] Xp22.33(61091_2689408)×1mat,Xp22.33(2701273_3258404)×0mat,Yq11.222q12 (21412851_59310245)×2. Herein, we describe a Moroccan family with a maternally inherited X/Y translocation and discuss the genotype-phenotype correlations according to the deleted genes. © 2017 S. Karger AG, Basel.

  4. A Rare De novo Complex Chromosomal Rearrangement (CCR) Involving Four Chromosomes in An Oligo-asthenosperm Infertile Man.

    Science.gov (United States)

    Asia, Saba; Vaziri Nasab, Hamed; Sabbaghian, Marjan; Kalantari, Hamid; Zari Moradi, Shabnam; Gourabi, Hamid; Mohseni Meybodi, Anahita

    2014-01-01

    Complex chromosomal rearrangements (CCRs) are rare events involving more than two chromosomes and over two breakpoints. They are usually associated with infertility or sub fertility in male carriers. Here we report a novel case of a CCR in a 30-year-old oligoasthenosperm man with a history of varicocelectomy, normal testes size and normal endocrinology profile referred for chromosome analysis to the Genetics unit of Royan Reproductive Biomedicine Research Center. Chromosomal analysis was performed using peripheral blood lymphocyte cultures and analyzed by GTG banding. Additional tests such as C-banding and multicolor fluorescence in situ hybridization (FISH) procedure for each of the involved chromosomes were performed to determine the patterns of the segregations. Y chromosome microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction. To identify the history and origin of this CCR, all the family members were analyzed. No micro deletion in Y chromosome was detected. The same de novo reciprocal exchange was also found in his monozygous twin brother. The other siblings and parents were normal. CCRs are associated with male infertility as a result of spermatogenic disruption due to complex meiotic configurations and the production of chromosomally abnormal sperms. These chromosomal rearrangements might have an influence on decreasing the number of sperms.

  5. Translocation 1;7 in dyshematopoiesis: possibly induced with a nonrandom geographic distribution

    International Nuclear Information System (INIS)

    Scheres, J.M.; Hustinx, T.W.; Holdrinet, R.S.; Geraedts, J.P.; Hagemeijer, A.; van der Blij-Philipsen, M.

    1984-01-01

    Eight patients with various hematologic disorders had an identical chromosomal aberration in their bone marrow or unstimulated peripheral blood, a translocation t(1;7) interpreted as t(1;7)(p11;p11). The translocation chromosome replaced one normal chromosome number7; therefore, the karyotype of the abnormal cells was trisomic for 1q and monosomic for 7q. Including four cases from the literature, a total of 12 patients (4 women, 8 men) with this translocation are known at the moment. The translocation does not seem to be associated with a specific disorder, but almost all patients had a preleukemic syndrome during some stage of their disease. It is very remarkable that 11 of the 12 patients lived in the Netherlands, and 7 patients had a history of iatrogenic exposure to alkylating agents or irradiation; one patient was a radiation worker and another one had a history of toxic exposure to chloramphenicol. It is suggested, therefore, that the t(1;7) is a possibly induced chromosomal aberration with a clearly nonrandom geographic distribution

  6. Structural rearrangements of chromosome 15 satellites resulting in Prader-Willi syndrome suggest a complex mechanism for uniparental disomy

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fijel, S.; Gunter, K.; Olson, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1994-09-01

    We report two cases of PWS in which there was abnormal meiosis I segregation of chromosome 15 following a rare translocation event between the heteromorphic satellite regions of chromosomes 14 and 15 and an apparent meiotic recombination in the unstable region of 15q11.2. PWS and normal appearing chromosomes in case one prompted a chromosome 15 origin analysis. PCR analysis indicated maternal isodisomy for the long arm of chromosome. However, only one chromosome 15 had short arm heteromorphisms consistent with either paternal or maternal inheritance. VNTR DNA analysis and heteromorphism data suggest that a maternal de novo translocation between chromosome 14 and 15 occurred prior to meiosis I. This was followed by recombination between D15Z1 and D15S11 and subsequent meiosis I nondisjunction. Proband and maternal karyotype display a distamycin A-DAPI positive region on the chromosome 14 homolog involved in the translocation. Fluorescent in situ hybridization (FISH) analyses of ONCOR probes D15S11, SNRPN, D15S11 and GABRB 3 were normal, consistent with the molecular data. Case two received a Robertsonian translocation t(14;15)(p13;p13) of maternal origin. Chromosome analysis revealed a meiosis I error producing UPD. FISH analysis of the proband and parents showed normal hybridization of ONCOR probes D15Z1, D15S11, SNRPN, D15S10 and GABRB3. In both cases the PWS probands received a structurally altered chromosome 15 that had rearranged with chromosome 14 prior to meiosis. If proper meiotic segregation is dependent on the resolution of chiasmata and/or the binding to chromosome-specific spindle fibers, then it may be possible that rearrangements of pericentric or unstable regions of the genome disrupt normal disjunction and lead to uniparental disomy.

  7. Warburg effect and translocation-induced genomic instability: two yeast models for cancer cells

    International Nuclear Information System (INIS)

    Tosato, Valentina; Grüning, Nana-Maria; Breitenbach, Michael; Arnak, Remigiusz; Ralser, Markus; Bruschi, Carlo V.

    2013-01-01

    Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression (i) the activity of pyruvate kinase (PK), which recapitulates metabolic features of cancer cells, including the Warburg effect, and (ii) chromosome bridge-induced translocation (BIT) mimiking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect), and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, PK, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and post-translational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants (“translocants”), between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the BIT system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast.

  8. Warburg effect and translocation-induced genomic instability: two yeast models for cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tosato, Valentina [International Centre for Genetic Engineering and Biotechnology, Trieste (Italy); Grüning, Nana-Maria [Cambridge System Biology Center, Department of Biochemistry, University of Cambridge, Cambridge (United Kingdom); Breitenbach, Michael [Division of Genetics, Department of Cell Biology, University of Salzburg, Salzburg (Austria); Arnak, Remigiusz [International Centre for Genetic Engineering and Biotechnology, Trieste (Italy); Ralser, Markus [Cambridge System Biology Center, Department of Biochemistry, University of Cambridge, Cambridge (United Kingdom); Bruschi, Carlo V., E-mail: bruschi@icgeb.org [International Centre for Genetic Engineering and Biotechnology, Trieste (Italy)

    2013-01-18

    Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression (i) the activity of pyruvate kinase (PK), which recapitulates metabolic features of cancer cells, including the Warburg effect, and (ii) chromosome bridge-induced translocation (BIT) mimiking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect), and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, PK, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and post-translational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants (“translocants”), between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the BIT system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast.

  9. A leukemic double-hit follicular lymphoma associated with a complex variant translocation, t(8;14;18)(q24;q32;q21), involving BCL2, MYC, and IGH.

    Science.gov (United States)

    Minakata, Daisuke; Sato, Kazuya; Ikeda, Takashi; Toda, Yumiko; Ito, Shoko; Mashima, Kiyomi; Umino, Kento; Nakano, Hirofumi; Yamasaki, Ryoko; Morita, Kaoru; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Oh, Iekuni; Fujiwara, Shin-Ichiro; Ohmine, Ken; Kawata, Hirotoshi; Muroi, Kazuo; Miura, Ikuo; Kanda, Yoshinobu

    2018-01-01

    Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes. Based on a combination of fluorescence in situ hybridization (FISH), using BCL2, MYC and IGH, and spectral karyotyping (SKY), the karyotype was interpreted as being the result of a multistep mechanism in which the precursor B-cell gained t(14;18) in the bone marrow and acquired a translocation between der(14)t(14;18) and chromosome 8 in the germinal center, resulting in t(8;14;18). The pathological diagnosis was consistently FL, not only at presentation but even after a second relapse. The patient responded well to standard chemotherapies but relapsed after a short remission. This patient is a unique case of leukemic DH-FL with t(8;14;18) that remained in FL even at a second relapse. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Human chromosome-specific changes in a human-hamster hybrid cell line (AL) assessed by fluorescent in situ hybridization (fish)

    International Nuclear Information System (INIS)

    Geard, Charles R.; Jenkins, Gloria

    1995-01-01

    Purpose: To quantitatively assess all gamma-ray induced chromosomal changes confined to one human chromosome using fluorescence microscopy and in situ hybridization with a fluorescently labeled human chromosome specific nucleic acid probe. Methods and Materials: Synchronized human-hamster hybrid cells containing human chromosome 11 were obtained by a modified mitotic shake-off procedure. G1 phase cells (> 95%) were irradiated with 137 Cs gamma rays (0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, and 10.0 Gy) at a dose rate of 1.1 Gy/min and mitotic cells collected 16-20 h later; chromosomal spreads were prepared, denatured, and hybridized with a fluorescein-tagged nucleic acid probe against total human DNA. Chromosomes were examined by fluorescence microscopy and all categories of change involving the human chromosome 11 as target, recorded. Results: Overall, of the 3104 human-hamster hybrid cells examined, 82.1% were euploid, of which 88.6% contained one copy of human chromosome 11, 6.2% contained two copies, and 5.2% contained 0 copies. This is compatible with mitotic nondisjunction in a small fraction of cells. Of the remaining 17.9% of cells, 85.2% were tetraploid cells with two copies of human chromosome 11. For all aberrations involving human chromosome 11 there was a linear relationship between yield and absorbed dose of 0.1 aberrations per chromosome per Gy. The yield of dicentrics, translocations, and terminal deletions that involve one lesion on the human chromosome was linear, while the yield of interstitial deletions that arise from two interacting lesions on the human chromosome was curvilinear. The frequencies of dicentrics and translocations were about equal, while there was a high (40-60%) incidence of incomplete exchanges between human and hamster chromosomes. Conclusions: Fluorescent in situ hybridization (FISH) procedures allow for the efficient detection of a broad range of induced changes in target chromosomes. Symmetrical exchanges induced in G1

  11. Constitutional abnormalities of chromosome 21 predispose to iAMP21-acute lymphoblastic leukaemia.

    Science.gov (United States)

    Harrison, Christine J; Schwab, Claire

    2016-03-01

    In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ∼2,700 increased risk of developing ALL with iAMP21 (intrachromosomal amplification of chromosome 21). In these patients, chromosome 15 as well as chromosome 21 is involved in the formation of iAMP21, referred to here as der(21)(15;21). Individuals with constitutional ring chromosomes involving chromosome 21, r(21)c, are also predisposed to iAMP21-ALL, involving the same series of mutational processes as seen in sporadic- and der(21)(15;21)-iAMP21 ALL. Evidence is accumulating that the dicentric nature of the Robertsonian and ring chromosome is the initiating factor in the formation of the complex iAMP21 structure. Unravelling these intriguing predispositions to iAMP21-ALL may provide insight into how other complex rearrangements arise in cancer. Copyright © 2016. Published by Elsevier Masson SAS.

  12. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

    Science.gov (United States)

    Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

    1996-01-01

    Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

  13. De novo unbalanced translocations in Prader-Willi and Angelman syndrome might be the reciprocal product of inv dup(15s.

    Directory of Open Access Journals (Sweden)

    Elena Rossi

    Full Text Available The 15q11-q13 region is characterized by high instability, caused by the presence of several paralogous segmental duplications. Although most mechanisms dealing with cryptic deletions and amplifications have been at least partly characterized, little is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations, including a jumping one, having most of 15q transposed to the end of another chromosome, whereas the der(15(pter->q11-q13 was missing. Imbalances were associated either with Prader-Willi or Angelman syndrome. Array-CGH demonstrated the absence of any copy number changes in the recipient chromosome in three cases, while one carried a cryptic terminal deletion and another a large terminal deletion, already diagnosed by classical cytogenetics. We cloned the breakpoint junctions in two cases, whereas cloning was impaired by complex regional genomic architecture and mosaicism in the others. Our results strongly indicate that some of our translocations originated through a prezygotic/postzygotic two-hit mechanism starting with the formation of an acentric 15qter->q1::q1->qter representing the reciprocal product of the inv dup(15 supernumerary marker chromosome. An embryo with such an acentric chromosome plus a normal chromosome 15 inherited from the other parent could survive only if partial trisomy 15 rescue would occur through elimination of part of the acentric chromosome, stabilization of the remaining portion with telomere capture, and formation of a derivative chromosome. All these events likely do not happen concurrently in a single cell but are rather the result of successive stabilization attempts occurring in different cells of which only the fittest will finally survive. Accordingly, jumping translocations might represent successful rescue attempts in different cells rather than transfer of the same 15q portion to different chromosomes. We also hypothesize that

  14. De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome.

    Science.gov (United States)

    Sagar, Angela; Pinto, Dalila; Najjar, Fedra; Guter, Stephen J; Macmillan, Carol; Cook, Edwin H

    2017-06-01

    Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. (2011) Neuron 70: 863-885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. (2010) Pediatrics 125: e727-735]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al. (2002) Circulation 102: 432-437]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al. (1997) Journal of Medical Genetics 34: 719-728]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al. (2008) The American Journal of Human Genetics 82: 477-488] . There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al. (1997)]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1→ter; 23.1→ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints. © 2017 Wiley Periodicals, Inc.

  15. Radiation induced chromosome aberrations and interphase DNA geometry

    International Nuclear Information System (INIS)

    Nasazzi, N.; Di Giorgio, M.; Otero, D.

    1995-01-01

    Ionizing radiation induces DNA double strand breaks (DSBs) and their interaction and illegitimate recombination produces chromosome aberrations. Stable chromosome aberrations comprise inter-chromosomal events (translocations) and intra-chromosomal events (inversions). Assuming DSBs induction and interaction is completely random and neglecting proximity effects, the expected ratio of translocations to inversions is F=86, based on chromosome arm lengths. We analyzed the number of translocations and inversions using G-banding, in 16 lymphocyte cultures from blood samples acutely irradiated with γ-rays (dose range: 0.5Gy-3Gy). Our results give F=13.5, significantly smaller than F=86. Literature data show similar small F values but strongly spread. The excess of inversions could be explained by a 'proximity effect', it means that more proximate DSBs have an extra probability of interaction. Therefore, it is possible to postulate a special chromosome arrangement during irradiation and the subsequent interval. We propose a model where individual chromosomes show spherical confinement with some degree of overlapping and DSBs induction proportional to cross section. We assume a DSBs interaction probability function with cut-off length = 1 μ. We propose that large spread in F data could be due to temporal variation in overlapping and spatial chromosome confinement. (author). 14 refs

  16. New insights into sex chromosome evolution in anole lizards (Reptilia, Dactyloidae).

    Science.gov (United States)

    Giovannotti, M; Trifonov, V A; Paoletti, A; Kichigin, I G; O'Brien, P C M; Kasai, F; Giovagnoli, G; Ng, B L; Ruggeri, P; Cerioni, P Nisi; Splendiani, A; Pereira, J C; Olmo, E; Rens, W; Caputo Barucchi, V; Ferguson-Smith, M A

    2017-03-01

    Anoles are a clade of iguanian lizards that underwent an extensive radiation between 125 and 65 million years ago. Their karyotypes show wide variation in diploid number spanning from 26 (Anolis evermanni) to 44 (A. insolitus). This chromosomal variation involves their sex chromosomes, ranging from simple systems (XX/XY), with heterochromosomes represented by either micro- or macrochromosomes, to multiple systems (X 1 X 1 X 2 X 2 /X 1 X 2 Y). Here, for the first time, the homology relationships of sex chromosomes have been investigated in nine anole lizards at the whole chromosome level. Cross-species chromosome painting using sex chromosome paints from A. carolinensis, Ctenonotus pogus and Norops sagrei and gene mapping of X-linked genes demonstrated that the anole ancestral sex chromosome system constituted by microchromosomes is retained in all the species with the ancestral karyotype (2n = 36, 12 macro- and 24 microchromosomes). On the contrary, species with a derived karyotype, namely those belonging to genera Ctenonotus and Norops, show a series of rearrangements (fusions/fissions) involving autosomes/microchromosomes that led to the formation of their current sex chromosome systems. These results demonstrate that different autosomes were involved in translocations with sex chromosomes in closely related lineages of anole lizards and that several sequential microautosome/sex chromosome fusions lead to a remarkable increase in size of Norops sagrei sex chromosomes.

  17. Sequence analysis of the breakpoint regions of an X;5 translocation in a female with Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Bakel, I. van; Holt, S.; Craig, I. [Univ. of Oxford (United Kingdom)] [and others

    1995-08-01

    X;autosome translocations in females with Duchenne muscular dystrophy (DMD) provide an opportunity to study the mechanisms responsible for chromosomal rearrangements that occur in the germ line. We describe here a detailed molecular analysis of the translocation breakpoints of an X;autosome reciprocal translocation, t(X;5) (p21;q31.1), in a female with DMD. Cosmid clones that contained the X-chromosome breakpoint region were identified, and subclones that hybridized to the translocation junction fragment in restriction digests of the patient`s DNA were isolated and sequenced. Primers designed from the X-chromosomal sequence were used to obtain the junction fragments on the der(X) and the der(5) by inverse PCR. The resultant clones were also cloned and sequenced, and this information used to isolate the chromosome 5 breakpoint region. Comparison of the DNA sequences of the junction fragments with those of the breakpoint regions on chromosomes X and 5 revealed that the translocation arose by nonhomologous recombination with an imprecise reciprocal exchange. Four and six base pairs of unknown origin are inserted at the exchange points of the der(X) and der(5), respectively, and three nucleotides are deleted from the X-chromosome sequence. Two features were found that may have played a role in the generation of the translocation. These were (1) a repeat motif with an internal homopyrimidine stretch 10 bp upstream from the X-chromosome breakpoint and (2) a 9-bp sequence of 78% homology located near the breakpoints on chromosomes 5 and X. 32 refs., 4 figs., 2 tabs.

  18. [Molecular and cytogenetic characterization of six 46, XX males due to translocations between the short arms of X and Y chromosomes].

    Science.gov (United States)

    Xing, Ya; Ji, Xing; Xiao, Bing; Jiang, Wen-ting; Hu, Qin; Hu, Juan; Cao, Ying; Tao, Jiong

    2012-08-01

    To characterize molecular and cytogenetic abnormalities in six 46, XX males, and to investigate the clinical manifestations and underlying mechanisms in such patients. Clinical data of six XX male patients were collected. Karyotyping, multiple polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) were utilized to detect and locate the sex determining region (SRY) gene. PCR and FISH showed that all patients were SRY-positive XX males. All patients have their SRY gene located at the tip of derivative X chromosomes, which have resulted from translocation between short arms of X and Y chromosomes. High resolution karyotyping at 550-750 band level has revealed that the translocation breakpoints were at Xp22.33 and Yp11.2 in three patients. In the remaining patients, the breakpoints were either at Xp22.32 and Yp11.31 or Xp22.31 and Yp11.2. The breakpoints at Xp22.32, Xp22.31 and Yp11.31 were rarely reported. Genotype-phenotype correlation analysis indicated that the clinical manifestations were age-specific. Four adult patients have come to clinical attention due to infertility, with typical features including azoospermia and testis dysgenesis, whereas poorly developed secondary sexual characteristics and short stature were main complaints of adolescence patients, and short stature was the sole symptom in a child patient. Combined karyotyping, PCR and FISH are important for the analysis of XX males. Particularly, high resolution karyotyping is valuable for the refinement of chromosome breakpoints and detailed analysis of genotype-phenotype correlation.

  19. Structural differences in reciprocal translocations. Potential for a model of risk in Rcp.

    Science.gov (United States)

    Daniel, A

    1979-10-01

    Interchange segment sizes and the sizes of chromosome imbalance arising from the different modes of meiotic segregation were measured in a selected sample of 20 reciprocal translocations (Rep). The Rep were selected by two modes of ascertainment: (I) neonates with an unbalanced form of the translocation, and (II) couples with recurrent spontaneous abortions without evidence of full-term translocation aneuploid offspring. The measurements (% of haploid autosomal length: %HAL) were plotted as the observed or potential chromosomal imbalance with monosomy (abscissa) and trisomy (ordinate). It was found that (a) the interchange segments were larger in the spontaneous abortion Rcp, (b) that all of the imbalances observed in full-term neonates plotted close to the origin and to the left of the line joining 4% trisomy to 2% monosomy, and (c) the imbalances observed in the neonates in each individual Rcp were of the smallest size possible arising by any segregation mode. It was concluded that a major factor in the survival to term of aneuploid conceptuses is the size (proportion of genome) of the chromosome abnormality, irrespective of the origin of the chromosome regions. These results are discussed in relation to their use as a model to evaluate the risk of abnormal offspring in the progeny of translocation heterozygotes (the Chromosome Imbalance Size-Viability Model).

  20. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    a duplication (Dp) of the translocated segment and four inviable (white, W) ascospores with .... of this work, namely, the definition of breakpoint junction sequences of 12 ..... then our results would place supercontig 10.9 in distal. LG VIR. A third ...

  1. Towards a cumulative biological dosimeter based on chromosome painting and digital image analysis

    International Nuclear Information System (INIS)

    Popp, S.; Cremer, C.; Remm, B.; Hausmann, M.; Cremer, T.; Luehrs, H.; Kaick, G. van

    1990-01-01

    An approach for a long-term (cumulative) biological dosimeter is described, based on the idea that stem cells with irradiation-induced reciprocal translocations and their progeny would neither lose nor gain genetic material and thus should retain the same proliferative potential as non-irradiated cells. Rapid detection of chromosome translocations has become possible in irradiated human lymphocytes by a newly developed fluorescent in situ hybridization method called 'chromosome painting'. We have used this approach to score chromosome aberrations, including translocation events, in over 8000 chromosomes painted in lymphocytes from two patients exposed to an X-ray contrast medium containing Th-232 and from two age-matched control persons. The percentage of both the total fraction of aberrant painted chromosomes and of translocations was found significantly higher in exposed patients. A program was developed which can automatically determine the number of normal and aberrant painted chromosomes and classify evaluated cells as 'normal' or 'aberrant' within 1 to 2 seconds. (orig.) [de

  2. Chromosomal rearrangement interferes with meiotic X chromosome inactivation

    Czech Academy of Sciences Publication Activity Database

    Homolka, David; Ivánek, Robert; Čapková, Jana; Jansa, Petr; Forejt, Jiří

    2007-01-01

    Roč. 17, č. 10 (2007), s. 1431-1437 ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA301/06/1334; GA ČR GA301/07/1383 Grant - others:Howard Hughes Medical Institute(US) HHMI 55000306 Institutional research plan: CEZ:AV0Z50520514 Keywords : chromosomal translocations * meiotic X chromosome inactivation * spermatogenesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.224, year: 2007

  3. [Identification of the genetic sex chromosomes in the monogenic blowfly Chrysomya rufifacies (Calliphoridae, Diptera)].

    Science.gov (United States)

    Ullerich, F H

    1975-01-01

    Previous investigations have shown the sex determination in the monogenic blowfly Chrysomya rufifacies to be controlled by a cytologically not discernible homogametry-heterogamety mechanism in the female. Female-producing (thelygenic) females are assumed to be heterozygous for a dominant female sex realizer (F') with sex-predetermining properties, while male-producing (arrhenogenic) females as well as males are supposed to be homozygous for the recessive allele (f). In order to identify the genetic sex chromosomes of C. rufifacies among its five pairs of long euchromatic chromosomes (nos. 1-5) plus one pair of small heterochromatic ones (no. 6), all chromosomes were marked by reciprocal translocations induced by X-ray treatment of adult males. The inheritance of thirteen different heteroxygous translocations has been analyzed. All of the translocations (eleven) between two of the four longer chromosomes did not show sex-linked inheritance, thus demonstrating the autosomal character of the chromosomes nos 1, 2, 3 and 4. The same is true for the translocation T6 (2/6). Therefore the small heterochromatic chromosome no. 6, corresponding to the morphlogically differentiated six chromosomes within the amphogenic calliphorid species, remains without sex determining function in the monogenic fly. This could be confirmed by the analysis of monosomic (monosomy-6) and trisomic (trisomy-6) individuals, which resulted from meiotic non-disfunction in T6/+ translocation heterozygotes. Contrary to these translocations, the heteroxygous 5/2 translocation (T14) exhibited sex-linked inheritance: There was but a very low frequency (0,76 per cent) of recombinants resulting from crossing-over between F'/f and the translocation breakage point in theylgenic F1 T14/+females. The sex-linked inheritance of T14 was confirmed by the progeny of a thelygenic F1 T14/+ female crossed to a homozygous T14/T14 translocation male.Among the offspring of that F1 T14/+ female, which had received the

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

    International Nuclear Information System (INIS)

    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

  5. Roles of the Y chromosome genes in human cancers

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2015-06-01

    Full Text Available Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

  6. 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...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... 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...

  7. TA3 - Dosimetry and instrumentation supply of the M-Fish technique to the Fish-3 painting technique for analysing translocations: A radiotherapy-treated patient study

    International Nuclear Information System (INIS)

    Pouzoulet, F.; Roch-Lefevre, S.; Giraudet, A.L.; Vaurijoux, A.; Voisin, P.A.; Buard, V.; Delbos, M.; Voisin, Ph.; Roy, L.; Bourhis, J.

    2006-01-01

    Purpose: Currently, the chromosome translocation study is the best method to estimate the dose of an old radiation exposure. Fluorescent In Situ Hybridization (F.I.S.H.) technique allows an easy detection of this kind of aberrations. However, as only a few number of chromosomes is usually painted, some bias could skew the result. To evaluate the advantage of using full genome staining (M-F.I.S.H. technique) compared with three chromosomes labelling (F.I.S.H.-3 painting), we compared translocation yields in radiotherapy treated patients. Methods: Chromosome aberration analyses were performed on peripheral blood lymphocyte cultures of two patients treated for a throat cancer by radiotherapy. Blood samples were obtained, before, along the treatment and six or four months later. For each sample, a dicentrics analysis was performed together with translocation analysis either with F.I.S.H.-3 painting or M-F.I.S.H.. Results: By confronting results from the F.I.S.H.-3 painting technique and the M-F.I.S.H. technique, significant differences were revealed. The translocations yield seemed to be stable with the F.I.S.H.-3 painting technique whereas it is not the case with the M-F.I.S.H. technique. This difference in results was explained by the bias induced by F.I.S.H.-3 Painting technique in the visualisation of complex aberrations. Furthermore, we found the presence of a clone bearing a translocation involving a painted chromosome. Conclusions: According to the potential bias of F.I.S.H.-3 painting on translocations study, the M-F.I.S.H. technique should provide more precise and reproducible results. Because of its more difficult implement, it seems hardly applicable to retrospective dosimetry instead of F.I.S.H.-3 painting technique. (authors)

  8. TA3 - Dosimetry and instrumentation supply of the M-Fish technique to the Fish-3 painting technique for analysing translocations: A radiotherapy-treated patient study

    Energy Technology Data Exchange (ETDEWEB)

    Pouzoulet, F.; Roch-Lefevre, S.; Giraudet, A.L.; Vaurijoux, A.; Voisin, P.A.; Buard, V.; Delbos, M.; Voisin, Ph.; Roy, L. [Institut de Radioprotection et de Surete Nucleaire, Lab. de Dosimetrie Biologique, 92 - Fontenay aux Roses (France); Bourhis, J. [Laboratoire UPRES EA 27-10, Radiosensibilite des Tumeurs et Tissus sains, PR1, 94 - Villejuif (France)

    2006-07-01

    Purpose: Currently, the chromosome translocation study is the best method to estimate the dose of an old radiation exposure. Fluorescent In Situ Hybridization (F.I.S.H.) technique allows an easy detection of this kind of aberrations. However, as only a few number of chromosomes is usually painted, some bias could skew the result. To evaluate the advantage of using full genome staining (M-F.I.S.H. technique) compared with three chromosomes labelling (F.I.S.H.-3 painting), we compared translocation yields in radiotherapy treated patients. Methods: Chromosome aberration analyses were performed on peripheral blood lymphocyte cultures of two patients treated for a throat cancer by radiotherapy. Blood samples were obtained, before, along the treatment and six or four months later. For each sample, a dicentrics analysis was performed together with translocation analysis either with F.I.S.H.-3 painting or M-F.I.S.H.. Results: By confronting results from the F.I.S.H.-3 painting technique and the M-F.I.S.H. technique, significant differences were revealed. The translocations yield seemed to be stable with the F.I.S.H.-3 painting technique whereas it is not the case with the M-F.I.S.H. technique. This difference in results was explained by the bias induced by F.I.S.H.-3 Painting technique in the visualisation of complex aberrations. Furthermore, we found the presence of a clone bearing a translocation involving a painted chromosome. Conclusions: According to the potential bias of F.I.S.H.-3 painting on translocations study, the M-F.I.S.H. technique should provide more precise and reproducible results. Because of its more difficult implement, it seems hardly applicable to retrospective dosimetry instead of F.I.S.H.-3 painting technique. (authors)

  9. Detection of three common translocation breakpoints in non-Hodgkin's lymphomas by fluorescence in situ hybridization on routine paraffin-embedded tissue sections

    NARCIS (Netherlands)

    Haralambieva, E; Kleiverda, K; Mason, DY; Schuuring, E; Kluin, PM

    2002-01-01

    Non-random chromosomal translocations are specifically involved in the pathogenesis of many non-Hodgkin's lymphomas and have clinical implications as diagnostic and/or prognostic markers. Their detection is often impaired by technical problems, including the distribution of the breakpoints over

  10. Infertile spermatozoa in a human carrier of robertsonian translocation 14;22.

    Science.gov (United States)

    Baccetti, Baccio; Capitani, Serena; Collodel, Giulia; Estenoz, Mariela; Gambera, Laura; Piomboni, Paola

    2002-11-01

    To present the ultrastructural, functional, and chromosomal analyses of spermatozoa from an infertile man with normal phenotype and chromosomal translocation 14;22. Case report. Regional Reference Center for Male Infertility in Siena, Italy. A 36-year-old man with primary infertility for 3 years and his parents. Family history and lymphocytic karyotypes, physical and hormonal assays, and semen analysis. Morphological sperm evaluation was performed by light, fluorescent, and electron microscopy; chromosomal constitution was examined by the fluorescence in situ hybridization (FISH) technique. The penetration ability of spermatozoa was checked by the hamster test. The spermatozoa of the patient showed unusual ultrastructural defects. The nuclei were large, spheroidal, and generally uncondensed; the acrosomes were frequently absent or reduced; and the axonemes were often devoid of dynein arms or central singlet tubules. These characteristics are related to immaturity. The lymphocytic karyotype revealed a robertsonian translocation 14;22 in the sterile patient and his mother. FISH sperm analysis demonstrated a high frequency of diploidy for the chromosome 18,XY. The hamster penetration test gave negative results. The unusual structural sperm immaturity is associated with the translocation 14;22. This chromosomal anomaly may therefore negatively influence the spermatogenesis; an interchromosomal effect on meiosis segregation is also suggested.

  11. Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

    2010-08-19

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding

  12. Production of reciprocal translocation lines and genetical analysis of tetravalent behavior in barley

    Energy Technology Data Exchange (ETDEWEB)

    Makino, Tokuhiko

    1988-03-01

    The seeds of a barley cultivar, Chikurinibaraki No.1 and of an early mutant line, Ea 52, derived from it were exposed to the external irradiation of gamma ray and thermal neutrons, and to the internal irradiation with the alpha ray from the nuclear reaction B-10 (n, alpha) Li-7 generated by the thermal neutron irradiation of B-10 imbibed seeds. The reciprocal translocation induced by these irradiation was detected and bred in the pedigrees of irradiated materials by the selection in terms of the partial sterility of seeds. The examination of seed fertility and chromosome pairing at the MI of meiosis of the F/sub 1/ hybrid between the selected lines and the original cultivar was also used. Consequently, 50 homozygous lines of reciprocal translocation were confirmed. The tester lines for translocated chromosomes were established by the cytological examination of the chromosome pairing in the hybrids between each two of the tester lines. The investigation of the inheritance of translocation heterozygotes showed that most of the newly obtained lines differently behaved from the expectation on the genetical basis of reciprocal translocation. (Kako, I.).

  13. Production of reciprocal translocation lines and genetical analysis of tetravalent behavior in barley

    International Nuclear Information System (INIS)

    Makino, Tokuhiko

    1988-01-01

    The seeds of a barley cultivar, Chikurinibaraki No.1 and of an early mutant line, Ea 52, derived from it were exposed to the external irradiation of gamma ray and thermal neutrons, and to the internal irradiation with the alpha ray from the nuclear reaction B-10 (n, alpha) Li-7 generated by the thermal neutron irradiation of B-10 imbibed seeds. The reciprocal translocation induced by these irradiation was detected and bred in the pedigrees of irradiated materials by the selection in terms of the partial sterility of seeds. The examination of seed fertility and chromosome pairing at the MI of meiosis of the F 1 hybrid between the selected lines and the original cultivar was also used. Consequently, 50 homozygous lines of reciprocal translocation were confirmed. The tester lines for translocated chromosomes were established by the cytological examination of the chromosome pairing in the hybrids between each two of the tester lines. The investigation of the inheritance of translocation heterozygotes showed that most of the newly obtained lines differently behaved from the expectation on the genetical basis of reciprocal translocation. (Kako, I.)

  14. Chromatid Painting for Chromosomal Inversion Detection, Phase II

    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...

  15. Chromatid Painting for Chromosomal Inversion Detection, Phase I

    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...

  16. Impact of personal and environmental factors on the rate of chromosome aberrations named translocations - Part 1: age, gender, smoking, alcohol; Impact des facteurs individuels et environnementaux sur le taux d'aberrations chromosomiques de type translocations - Partie 1: age, sexe, tabac, alcool

    Energy Technology Data Exchange (ETDEWEB)

    Gregoire, E.; Gruel, G.; Martin, C.; Roch-Lefevre, S.; Vaurijoux, A.; Voisin, P.; Roy, L. [IRSN, Laboratoire de Dosimetrie Biologique, 92 - Fontenay-aux-Roses (France)

    2010-04-15

    The assessment of exposure to ionizing radiation, carried out long time after exposure, is currently performed by scoring of translocations, a specific type of chromosomal aberrations. The translocations rate observed in peripheral blood lymphocytes of exposed subjects is compared to that observed in a control population. However, the translocation specificity towards radiation exposure is not clearly identified. To avoid any hasty conclusion, it is necessary to identify all the factors likely to induce translocation. To our knowledge, no study has thus far examined the effects of all these different factors on translocation rates. A review of the literature thus allowed us to assess the impact of host factors and lifestyle on the production of translocations. This study confirms that age appears to be the factor having the greatest impact on the rate of translocations, especially over 60 years. To date, the factor 'age' is already considered in estimating the impact of radiation on the rate of translocation for all age groups. However, the study also shows that this rate varies significantly when the patient is exposed simultaneously and significantly towards many lifestyle agents. A precise threshold translocation rate should thus be established as a function of known behavioral exposures, below which it is impossible to conclude that radiological exposure has occurred. The effects of chemicals on the translocation rate after occupational exposure will be the subject of a second part. (authors)

  17. Delayed manifestation and transmission bias of de novo chromosome mutations. Their relevance for radiation health effect

    International Nuclear Information System (INIS)

    Sasaki, Masao S.

    2006-01-01

    The origin and transmission of de novo chromosome mutations were reviewed on the basis of our chromosome studies in retinoblastoma patients and male infertility. In a series of 264 sporadic retinoblastoma families, gross chromosome rearrangements involving the RB1 locus were identified in 23 cases (8.7%), of which 16 were non-mosaic and 7 were mosaic mutations. The newly formed chromosome mutations, whether they were non-mosaic or mosaic, had a strong bias towards paternally derived chromosome, indicating that they shared a common mechanism where a pre-mutational event or instability is carried over to zygote by sperm and manifested as gross chromosome mutation at the early stages of development. The de novo chromosome mutations are preferentially transmitted through female carriers. This transmission bias is consistent with the finding of higher frequencies of translocation carriers in infertile men (7.69% versus 0.27% in general populations) in whom meiotic progression is severely suppressed, possibly through activation of meiotic checkpoints. Such a meiotic surveillance mechanism may minimize the spreading of newly-arisen chromosome mutations in populations. A quantitative model of meiotic surveillance mechanism is proposed and successfully applied to the published data on ''humped'' dose-response curves for radiation-induced spermatogonial reciprocal translocations in several mammalian species. (author)

  18. Duplication of C7orf58, WNT16 and FAM3C in an obese female with a t(7;22)(q32.1;q11.2) chromosomal translocation and clinical features resembling Coffin-Siris Syndrome.

    Science.gov (United States)

    Zhu, Jun; Qiu, Jun; Magrane, Gregg; Abedalthagafi, Malak; Zanko, Andrea; Golabi, Mahin; Chehab, Farid F

    2012-01-01

    We characterized the t(7;22)(q32;q11.2) chromosomal translocation in an obese female with coarse features, short stature, developmental delay and a hypoplastic fifth digit. While these clinical features suggest Coffin-Siris Syndrome (CSS), we excluded a CSS diagnosis by exome sequencing based on the absence of deleterious mutations in six chromatin-remodeling genes recently shown to cause CSS. Thus, molecular characterization of her translocation could delineate genes that underlie other syndromes resembling CSS. Comparative genomic hybridization microarrays revealed on chromosome 7 the duplication of a 434,682 bp region that included the tail end of an uncharacterized gene termed C7orf58 (also called CPED1) and spanned the entire WNT16 and FAM3C genes. Because the translocation breakpoint on chromosome 22 did not disrupt any apparent gene, her disorder was deemed to result from the rearrangement on chromosome 7. Mapping of yeast and bacterial artificial chromosome clones by fluorescent in situ hybridization on chromosome spreads from this patient showed that the duplicated region and all three genes within it were located on both derivative chromosomes 7 and 22. Furthermore, DNA sequencing of exons and splice junctional regions from C7orf58, WNT16 and FAM3C revealed the presence of potential splice site and promoter mutations, thereby augmenting the detrimental effect of the duplicated genes. Hence, dysregulation and/or disruptions of C7orf58, WNT16 and FAM3C underlie the phenotype of this patient, serve as candidate genes for other individuals with similar clinical features and could provide insights into the physiological role of the novel gene C7orf58.

  19. Duplication of C7orf58, WNT16 and FAM3C in an obese female with a t(7;22(q32.1;q11.2 chromosomal translocation and clinical features resembling Coffin-Siris Syndrome.

    Directory of Open Access Journals (Sweden)

    Jun Zhu

    Full Text Available We characterized the t(7;22(q32;q11.2 chromosomal translocation in an obese female with coarse features, short stature, developmental delay and a hypoplastic fifth digit. While these clinical features suggest Coffin-Siris Syndrome (CSS, we excluded a CSS diagnosis by exome sequencing based on the absence of deleterious mutations in six chromatin-remodeling genes recently shown to cause CSS. Thus, molecular characterization of her translocation could delineate genes that underlie other syndromes resembling CSS. Comparative genomic hybridization microarrays revealed on chromosome 7 the duplication of a 434,682 bp region that included the tail end of an uncharacterized gene termed C7orf58 (also called CPED1 and spanned the entire WNT16 and FAM3C genes. Because the translocation breakpoint on chromosome 22 did not disrupt any apparent gene, her disorder was deemed to result from the rearrangement on chromosome 7. Mapping of yeast and bacterial artificial chromosome clones by fluorescent in situ hybridization on chromosome spreads from this patient showed that the duplicated region and all three genes within it were located on both derivative chromosomes 7 and 22. Furthermore, DNA sequencing of exons and splice junctional regions from C7orf58, WNT16 and FAM3C revealed the presence of potential splice site and promoter mutations, thereby augmenting the detrimental effect of the duplicated genes. Hence, dysregulation and/or disruptions of C7orf58, WNT16 and FAM3C underlie the phenotype of this patient, serve as candidate genes for other individuals with similar clinical features and could provide insights into the physiological role of the novel gene C7orf58.

  20. Rapid Simultaneous Amplification and Detection of the MBR/JH Chromosomal Translocation by Fluorescence Melting Curve Analysis

    Science.gov (United States)

    Bohling, Sandra D.; King, Thomas C.; Wittwer, Carl T.; Elenitoba-Johnson, Kojo S. J.

    1999-01-01

    Polymerase chain reaction (PCR) amplification and product analysis for the detection of chromosomal translocations, such as the t(14;18), has traditionally been a two-step process. PCR product detection has generally entailed gel electrophoresis and/or hybridization or sequencing for confirmation of assay specificity. Using a microvolume fluorimeter integrated with a thermal cycler and a PCR-compatible double-stranded DNA (dsDNA) binding fluorescent dye (SYBR Green I), we investigated the feasibility of simultaneous thermal amplification and detection of MBR/JH translocation products by fluorescence melting curve analysis. We analyzed DNA from 30 cases of lymphoproliferative disorders comprising 19 cases of previously documented MBR/JH-positive follicle center lymphoma and 11 reactive lymphadenopathies. The samples were coded and analyzed blindly for the presence of MBR/JH translocations by fluorescence melting curve analysis. We also performed dilutional assays using the MBR/JH-positive cell line SUDHL-6. Multiplex PCR for MBR/JH and β-globin was used to simultaneously assess sample adequacy. All (100%) of the 19 cases previously determined to be MBR/JH positive by conventional PCR analysis showed a characteristic sharp decrease in fluorescence at ∼90°C by melting curve analysis after amplification. Fluorescence melting peaks obtained by plotting the negative derivative of fluorescence over temperature (−dF/dT) versus temperature (T) showed melting temperatures (Tm) at 88.85 ± 1.15°C. In addition, multiplex assays using both MBR/JH and β-globin primers yielded easily distinguishable fluorescence melting peaks at ∼90°C and 81.2°C, respectively. Dilutional assays revealed that fluorescence melting curve analysis was more sensitive than conventional PCR and agarose gel electrophoresis with ultraviolet transillumination by as much as 100-fold. Simultaneous amplification and fluorescence melting curve analysis is a simple, reliable, and sensitive method

  1. Cerebellar and brainstem hypoplasia in a child with a partial monosomy for the short arm of chromosome 5 and partial trisomy for the short arm of chromosome 10

    NARCIS (Netherlands)

    Arts, W F M; Hofstee, Y; Drejer, G F; Beverstock, G C; Oosterwijk, J C

    A child with hypoplasia of the cerebellum and brainstem in association with an unbalanced translocation, resulting in a partial deletion of the short arm of chromosome 5 and a partial trisomy of the short arm of chromosome 10, is described. A balanced translocation was present in his mother and

  2. Meiotic Recombination Analyses in Pigs Carrying Different Balanced Structural Chromosomal Rearrangements.

    Directory of Open Access Journals (Sweden)

    Nicolas Mary

    Full Text Available Correct pairing, synapsis and recombination between homologous chromosomes are essential for normal meiosis. All these events are strongly regulated, and our knowledge of the mechanisms involved in this regulation is increasing rapidly. Chromosomal rearrangements are known to disturb these processes. In the present paper, synapsis and recombination (number and distribution of MLH1 foci were studied in three boars (Sus scrofa domestica carrying different chromosomal rearrangements. One (T34he was heterozygote for the t(3;4(p1.3;q1.5 reciprocal translocation, one (T34ho was homozygote for that translocation, while the third (T34Inv was heterozygote for both the translocation and a pericentric inversion inv(4(p1.4;q2.3. All three boars were normal for synapsis and sperm production. This particular situation allowed us to rigorously study the impact of rearrangements on recombination. Overall, the rearrangements induced only minor modifications of the number of MLH1 foci (per spermatocyte or per chromosome and of the length of synaptonemal complexes for chromosomes 3 and 4. The distribution of MLH1 foci in T34he was comparable to that of the controls. Conversely, the distributions of MLH1 foci on chromosome 4 were strongly modified in boar T34Inv (lack of crossover in the heterosynaptic region of the quadrivalent, and crossover displaced to the chromosome extremities, and also in boar T34ho (two recombination peaks on the q-arms compared with one of higher magnitude in the controls. Analyses of boars T34he and T34Inv showed that the interference was propagated through the breakpoints. A different result was obtained for boar T34ho, in which the breakpoints (transition between SSC3 and SSC4 chromatin on the bivalents seemed to alter the transmission of the interference signal. Our results suggest that the number of crossovers and crossover interference could be regulated by partially different mechanisms.

  3. MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility.

    Science.gov (United States)

    Röpke, Albrecht; Tüttelmann, Frank

    2017-11-01

    Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo- or a-zoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistent with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the male-associated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased copy number variation (CNV) burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: (1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). (2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. (3) CNVs affecting the X chromosome. (4) Point mutations disrupting X-chromosomal genes. All these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years. © 2017 European Society of Endocrinology.

  4. Slit scan flow cytometry of isolated chromosomes following fluorescence hybridization: an approach of online screening for specific chromosomes and chromosome translocations

    NARCIS (Netherlands)

    Hausmann, M.; Dudin, G.; Aten, J. A.; Heilig, R.; Diaz, E.; Cremer, C.

    1991-01-01

    The recently developed methods of non radioactive in situ hybridization of chromosomes offer new aspects for chromosome analysis. Fluorescent labelling of hybridized chromosomes or chromosomal subregions allows to facilitate considerably the detection of specific chromosomal abnormalities. For many

  5. Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.

    Science.gov (United States)

    Polgar, Doris; Leisser, Christina; Maier, Susanne; Strasser, Stephan; Rüger, Beate; Dettke, Markus; Khorchide, Maya; Simonitsch, Ingrid; Cerni, Christa; Krupitza, Georg

    2005-02-15

    The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.

  6. Partial trisomy 9p derivatived from a maternal reciprocal translocation 9;15. Case reports.

    Directory of Open Access Journals (Sweden)

    Elodia Torres

    2015-12-01

    Full Text Available Objectives: to highlight the importance of performing karyotype in children with congenital malformations in order to have a confirmatory diagnosis, in parents to exclude the possibility of being carriers of chromosomal abnormalities and perform the genetic counseling. Clinical cases description: Female patient with 3 years and 2 months old to whom karyotype was performed by global neurodevelopmental delay and microcephaly, and her mother with 34 years old without any clinical manifestations, to both patients, lymphocyte culture and chromosomal analysis with a High Resolution Banding techniques GTG and C were performed. The mother’s karyotype was 46,XX,t(9;15(q10;q10(p10;p10,add14p. The father’s karyotype was normal, 46,XY, and the girl’s karyotype resulted in a pure Trisomy 9p:  47,XX,+del(9(q11. Discussion: This chromosomal rearrangement in mother included a nonhomologous reciprocal translocation between the long arms of pair chromosomes 9 and 15 and between the short arms of the same chromosomes, additional to it, an unknown origin material was also observed in short arm from one chromosome of the 14 pair. In meiosis of this type of rearrangement, the father’s normal homologous chromosomes are paired with the mother’s translocated chromosomes and as a result of 3:1 segregation a gamete with one chromosome else was originated that after fertilization resulted in an unbalanced translocation confirming the pure trisomy in the patient.

  7. Can Characteristics of Reciprocal Translocations Predict the Chance of Transferable Embryos in PGD Cycles?

    Directory of Open Access Journals (Sweden)

    Elsbeth Dul

    2014-04-01

    Full Text Available Translocation carriers have an increased risk of miscarriage or the birth of a child with congenital anomalies. Preimplantation genetic diagnosis (PGD is performed in translocation carriers to select for balanced embryos and, thus, increase the chance of an ongoing pregnancy. However, a common experience is that reciprocal translocation carriers produce a high percentage of unbalanced embryos, which cannot be transferred. Therefore, the pregnancy rates in PGD in this patient group are low. In a cohort of 85 reciprocal translocation carriers undergoing PGD we have searched for cytogenetic characteristics of the translocations that can predict the percentage of balanced embryos. Using shape algorithms, the most likely segregation mode per translocation was determined. Shape algorithm, breakpoint location, and relative chromosome segment sizes proved not to be independent predictors of the percentage of balanced embryos. The ratio of the relative sizes of the translocated segments of both translocation chromosomes can give some insight into the chance of transferable embryos: Very asymmetrical translocations have a higher risk of unbalanced products (p = 0.048. Counseling of the couples on the pros and cons of all their reproductive options remains very important.

  8. No evidence for a paternal interchromosomal effect from analysis of the origin of nondisjunction in Down syndrome patients with concomitant familial chromosome rearrangements.

    OpenAIRE

    Schinzel, A A; Adelsberger, P A; Binkert, F; Basaran, S; Antonarakis, S E

    1992-01-01

    The parental origin of the extra chromosome 21 was determined with DNA polymorphisms in seven families in whom the proband and one of the parents carried an additional chromosome rearrangement (balanced translocation or pericentric inversion) not involving chromosome 21. The balanced rearrangement was inherited from the mother in two families and from the father in five families, whereas the additional chromosome 21 was derived from the mother in all seven families. These findings are not in ...

  9. Chromosomal mechanisms in murine radiation acute myeloid leukemogenesis

    International Nuclear Information System (INIS)

    Bouffler, S.D.; Breckon, G.; Cox, R.

    1996-01-01

    Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-radiation events in bone marrow cells in vivo and karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2; 11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal tranlocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis. (Author)

  10. Genotype/phenotype analysis in a male patient with partial trisomy 4p and monosomy 20q due to maternal reciprocal translocation (4;20): A case report.

    Science.gov (United States)

    Wu, Dong; Zhang, Hui; Hou, Qiaofang; Wang, Hongdan; Wang, Tao; Liao, Shixiu

    2017-11-01

    Translocations are the most frequent structural aberration in the human genome. Carriers of balanced chromosome rearrangement exhibit an increased risk of abortion and/or a chromosomally‑unbalanced child. The present study reported a clinical and cytogenetic analysis of a child who exhibited typical trisomy 4p and monosomy 20q features, including intellectual disability, delayed speech, tall stature, seizures and facial dysmorphism. The karyotype of the proband exhibited 46, XY, add(20) (q13.3). The karyotype of the mother indicated a balanced translocation karyotype: 46, XX, t(4;20) (p15.2;q13.1). The array‑based comparative genomic hybridization (aCGH) analysis identified partial trisomy of the short arm of chromosome 4 and partial monosomy of distal 20q in the proband due to maternal balanced reciprocal translocation 4;20. The analysis of genotype/phenotype correlation demonstrated that fibroblast growth factor receptor 3 and msh homeobox 1 may be the important genes for 4p duplication, and that potassium voltage‑gated channel subfamily Q member 2, myelin transcription factor 1 and cholinergic receptor nicotinic α4 subunit may be the important genes for 20q deletion. To the best of our knowledge, the present study was the first to report an unbalanced translocation involving chromosomes 4p and 20q. The present study additionally demonstrated that aCGH analysis is able to reliably detect unbalanced submicroscopic chromosomal aberrations.

  11. Genome sequencing and transcriptome analysis of Trichoderma reesei QM9978 strain reveals a distal chromosome translocation to be responsible for loss of vib1 expression and loss of cellulase induction.

    Science.gov (United States)

    Ivanova, Christa; Ramoni, Jonas; Aouam, Thiziri; Frischmann, Alexa; Seiboth, Bernhard; Baker, Scott E; Le Crom, Stéphane; Lemoine, Sophie; Margeot, Antoine; Bidard, Frédérique

    2017-01-01

    The hydrolysis of biomass to simple sugars used for the production of biofuels in biorefineries requires the action of cellulolytic enzyme mixtures. During the last 50 years, the ascomycete Trichoderma reesei , the main source of industrial cellulase and hemicellulase cocktails, has been subjected to several rounds of classical mutagenesis with the aim to obtain higher production levels. During these random genetic events, strains unable to produce cellulases were generated. Here, whole genome sequencing and transcriptomic analyses of the cellulase-negative strain QM9978 were used for the identification of mutations underlying this cellulase-negative phenotype. Sequence comparison of the cellulase-negative strain QM9978 to the reference strain QM6a identified a total of 43 mutations, of which 33 were located either close to or in coding regions. From those, we identified 23 single-nucleotide variants, nine InDels, and one translocation. The translocation occurred between chromosomes V and VII, is located upstream of the putative transcription factor vib1 , and abolishes its expression in QM9978 as detected during the transcriptomic analyses. Ectopic expression of vib1 under the control of its native promoter as well as overexpression of vib1 under the control of a strong constitutive promoter restored cellulase expression in QM9978, thus confirming that the translocation event is the reason for the cellulase-negative phenotype. Gene deletion of vib1 in the moderate producer strain QM9414 and in the high producer strain Rut-C30 reduced cellulase expression in both cases. Overexpression of vib1 in QM9414 and Rut-C30 had no effect on cellulase production, most likely because vib1 is already expressed at an optimal level under normal conditions. We were able to establish a link between a chromosomal translocation in QM9978 and the cellulase-negative phenotype of the strain. We identified the transcription factor vib1 as a key regulator of cellulases in T. reesei whose

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

    International Nuclear Information System (INIS)

    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

  13. 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.

  14. Chromosome aberrations of bone marrow cells in heavily exposed atomic bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Kamada, Nanao; Kuramoto, Atsushi; Ohkita, Takeshi

    1986-01-01

    Seven hundred and ten bone marrow cells from 13 A-bomb survivors, who were heavily exposed to atomic radiation, were examined using chromosome banding method. An average frequency of chromosome aberrations was 17 %. The most common structural abnormality was translocation (47 %), followed by complex aberrations involving three or more chromosomes (32 %). These abnormalities were frequently seen in A-bomb survivors exposed to estimated doses of 3.5 - 4.0 Gy. Eighty two percent of the structural aberrations were stable. Diploid cells were seen in 0.4 % and tetraploid cells were seen in 0.7 %. The frequency of breakpoint sites was high in chromosomes 1 and 17; while it was low in chromosomes 3, 6, 9, and 11. Abnormal clones were seen in one of the 13 survivors. Chromosome aberrations common to the bone marrow cells and peripheral lymphocytes were not seen in the same individual. (Namekawa, K.)

  15. Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes.

    Directory of Open Access Journals (Sweden)

    Kaitlin M Stimpson

    2010-08-01

    Full Text Available Genome rearrangement often produces chromosomes with two centromeres (dicentrics that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extra-chromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.

  16. Automatic aberration scoring using whole chromosome F.I.S.H

    International Nuclear Information System (INIS)

    Piper, J.; Bayley, R.; Boyle, S.; Fantes, J.A.; Green, D.K.; Gordon, J.; Hill, W.; Ji, L.; Malloy, P.; Perry, P.; Rutovitz, D.; Stark, M.; Whale, D.

    1993-01-01

    A radiation-induced rearrangement involving a painted and a non-painted chromosome will usually result in two partly-painted chromosomes, typically either a dicentric chromosome and associated fragment, or a reciprocal translocation pair. A consequence of such a rearrangement is that the number of painted image regions in the metaphase is increased by one, and their size distribution is altered. More complex rearrangements are uncommon, particularly at low doses. A high proportion of damaged cells can therefore be registered simply by detecting when the distribution of painted components differs from the expected number and size. A system has been constructed to pre-screen for damaged cells. It comprises automatic fluorescence metaphase finding followed by relocation and digitization of probe and counterstain channels at high resolution. Fully automatic segmentation in counterstain discriminates chromosomes from interphase nuclei and determines whether a metaphase is approximately diploid. The painted regions are segmented and their relative sizes estimated. Rules are applied which reduce the false positives due to artifacts such as overlapped painted chromosomes. More than 70% of cells with radiation damage involving painted and unpainted chromosomes were detected in a preliminary experiment using a small data set, with a low false positive rate. Results from a larger experiment in progress are presented

  17. Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia.

    Science.gov (United States)

    Coignet, L J; Lima, C S; Min, T; Streubel, B; Swansbury, J; Telford, N; Swanton, S; Bowen, A; Nagai, M; Catovsky, D; Fonatsch, C; Dyer, M J

    1999-07-01

    Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.

  18. A cohort of balanced reciprocal translocations associated with dyslexia: identification of two putative candidate genes at DYX1

    DEFF Research Database (Denmark)

    Buonincontri, Roberta; Bache, Iben; Silahtaroglu, Asli

    2011-01-01

    Dyslexia is one of the most common neurodevelopmental disorders where likely many genes are involved in the pathogenesis. So far six candidate dyslexia genes have been proposed, and two of these were identified by rare chromosomal translocations in affected individuals. By systematic re......-examination of all translocation carriers in Denmark, we have identified 16 different translocations associated with dyslexia. In four families, where the translocation co-segregated with the phenotype, one of the breakpoints concurred (at the cytogenetic level) with either a known dyslexia linkage region--at 15q21...... (DYX1), 2p13 (DYX3) and 1p36 (DYX8)--or an unpublished linkage region at 19q13. As a first exploitation of this unique cohort, we identify three novel candidate dyslexia genes, ZNF280D and TCF12 at 15q21, and PDE7B at 6q23.3, by molecular mapping of the familial translocation with the 15q21 breakpoint....

  19. 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.

  20. MODY-like diabetes associated with an apparently balanced translocation: possible involvement of MPP7 gene and cell polarity in the pathogenesis of diabetes

    Directory of Open Access Journals (Sweden)

    Bartov Guy

    2009-02-01

    Full Text Available Abstract Background Characterization of disease-associated balanced translocations has led to the discovery of genes responsible for many disorders, including syndromes that include various forms of diabetes mellitus. We studied a man with unexplained maturity onset diabetes of the young (MODY-like diabetes and an apparently balanced translocation [46,XY,t(7;10(q22;p12] and sought to identify a novel diabetes locus by characterizing the translocation breakpoints. Results Mutations in coding exons and splice sites of known MODY genes were first ruled out by PCR amplification and DNA sequencing. Fluorescent in situ hybridization (FISH studies demonstrated that the translocation did not disrupt two known diabetes-related genes on 10p12. The translocation breakpoints were further mapped to high resolution using FISH and somatic cell hybrids and the junctions PCR-amplified and sequenced. The translocation did not disrupt any annotated transcription unit. However, the chromosome 10 breakpoint was 220 kilobases 5' to the Membrane Protein, Palmitoylated 7 (MPP7 gene, which encodes a protein required for proper cell polarity. This biological function is shared by HNF4A, a known MODY gene. Databases show MPP7 is highly expressed in mouse pancreas and is expressed in human islets. The translocation did not appear to alter lymphoblastoid expression of MPP7 or other genes near the breakpoints. Conclusion The balanced translocation and MODY-like diabetes in the proband could be coincidental. Alternatively, the translocation may cause islet cell dysfunction by altering MPP7 expression in a subtle or tissue-specific fashion. The potential roles of MPP7 mutations in diabetes and perturbed islet cell polarity in insulin secretion warrant further study.

  1. Persistence of X-ray-induced chromosomal rearrangements in long-term cultures of human diploid fibroblasts

    International Nuclear Information System (INIS)

    Kano, Y.; Little, J.B.

    1984-01-01

    As part of a long-term study of mechanisms of human cell neoplastic transformation, the authors have examined the change in the frequencies of X-ray-induced chromosome rearrangements in density-inhibited human foreskin fibroblasts as a function of subculture time. In nonproliferating cells, the frequency of chromosomal aberrations declined within 24 to 48 hr but still remained at a relatively high level up to 43 days after irradiation. Aberrations disappeared rapidly, however, when the cells were allowed to proliferate, indicating that these lesions are lethal to dividing cells. The frequency of induced translocations, as determined by analysis of G-banded karyotypes, was dose dependent and remained stable up to 20 mean population doublings after irradiation. When subculture of density-inhibited cultures was delayed for 4 hr after irradiation (confluent holding), the frequency of chromosomal aberrations in the first mitosis declined, whereas the translocation frequencies at later passage were elevated as compared with cells subcultured immediately. This correlates with the reported increase in the frequency of transformation under similar conditions. These findings support the hypothesis that chromosomal rearrangements induced by DNA damage may be involved in the initiation of cancer

  2. Use of radiation to transfer alien chromosome segments to wheat

    International Nuclear Information System (INIS)

    Sears, E.R.

    1993-01-01

    Ionizing radiation can accomplish the transfer of genetic information from species so distantly related to wheat (Triticum aestivum L. em Thell.) that their chromosomes pair very little, if at all, with those of wheat, even in the absence of the homoeologous-pairing suppressor Ph1. In a successful transfer, the alien segment must almost always replace a homoeologous wheat segment, but radiation induces translocations largely at random; therefore automatic selection in favor of desirable translocations must be provided if the size of the project is to be kept within reasonable limits. Pollen selection will occur if seeds or plants monosomic for both an alien chromosome and one of its wheat homoeologues are irradiated. Making the plants also deficient for Ph1 may increase the number of suitable transfers. High-frequency occurrence of the desired alien character in M2 head-rows from plants grown from irradiated seed can identify favorable transfers with little cytological work. Irradiation of plants shortly before meiosis, using them to pollinate ditelosomics or double ditelosomics for the wheat arm or chromosome concerned, and cytologically examining offspring which have the alien character can not only identify the desirable transfers, but also reveal the lengths of the alien segments involved

  3. Fetal chromosome analysis

    DEFF Research Database (Denmark)

    Philip, J; Tabor, A; 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...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... 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...

  4. [Molecular genetics in chronic myeloid leukemia with variant Ph translocation].

    Science.gov (United States)

    Wu, Wei; Li, Jian-yong; Zhu, Yu; Qiu, Hai-rong; Pan, Jin-lan; Xu, Wei; Chen, Li-juan; Shen, Yun-feng; Xue, Yong-quan

    2007-08-01

    To explore the value of fluorescence in situ hybridization (FISH) and multiplex fluorescence in situ hybridization (M-FISH) techniques in the detection of genetic changes in chronic myeloid leukemia (CML) with variant Philadelphia translocation (vPh). Cytogenetic preparations from 10 CML patients with vPh confirmed by R banding were assayed with dual color dual fusion FISH technique. If only one fusion signal was detected in interphase cells, metaphase cells were observed to determine if there were derivative chromosome 9[der (9)] deletions. Meanwhile, the same cytogenetic preparations were assayed with M-FISH technique. Of the 10 CML patients with vPh, 5 were detected with der (9) deletions by FISH technique. M-FISH technique revealed that besides the chromosome 22, chromosomes 1, 3, 5, 6, 8, 10, 11 and 17 were also involved in the vPh. M-FISH technique also detected the abnormalities which were not found with conventional cytogenetics (CC), including two never reported abnormalities. The combination of CC, FISH and M-FISH technique could refine the genetic diagnosis of CML with vPh.

  5. Live birth from a patient with a three-way balanced translocation t(5 ...

    African Journals Online (AJOL)

    Objectives: Array comparative genomic hybridisation (array-CGH) was used to screen embryos for chromosome imbalances. Methods: Embryo biopsy, preimplantation genetic diagnosis using a 24sure+ kit to detect translocations in embryos. Results: Of 10 embryos tested, 2 were found to have an unbalanced translocation, ...

  6. Location of a High-Lysine Gene and the DDT-Resistance Gene on Barley Chromosome 7

    DEFF Research Database (Denmark)

    Jensen, J.

    1979-01-01

    mutants, nos 1508.18, and 19. Linkage studies with translocations locate the Lys3 locus in the centromere region ofchromosome 7. A linkage study involving the loci lys3 and ddt (resistance to DDT) together with the marker locifi (fragile stem), s(short rachilla hairs), and r (smooth awn) show...... that the order of the five loci on chromosome 7 from the long to the short chromosome arm is Y, s,fi, lys3, ddt. The distance from locus I to locus ddt is about 100 centimorgans....

  7. MicroRNA-125b-1 and BLID upregulation resulting from a novel IGH translocation in childhood B-Cell precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Tassano, Elisa; Acquila, Maura; Tavella, Elisa; Micalizzi, Concetta; Panarello, Claudio; Morerio, Cristina

    2010-08-01

    Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus are common abnormalities in mature B-cell neoplasms. Recent findings have also revealed their significant role in B-cell precursor acute lymphoblastic leukemia. As a rule, IGH translocations generate transcriptional activation of the oncogene localized in the proximity of the breakpoint. In this study, we describe a pediatric case of B-cell precursor acute lymphoblastic leukemia showing microRNA-125b-1 (MIR125B1) and BLID gene overexpression, resulting from a novel t(11;14)(q24.1;q32) translocation involving IGH. This is the first report describing the upregulation of a microRNA due to its juxtaposition to protein-coding gene regulatory elements and the overexpression of two neighboring genes as a consequence of transcriptional enhancers localized in the vicinity of the IGH gene.

  8. Uniparental isodisomy of chromosome 14 in two cases: An abnormal child and a normal adult

    Energy Technology Data Exchange (ETDEWEB)

    Papenhausen, P.R.; Mueller, O.T.; Sutcliffe, M.; Diamond, T.M.; Kousseff, B.G. [Univ. of South Florida College of Medicine, Tampa, FL (United States); Johnson, V.P. [Univ. of South Dakota, Sioux Falls, SD (United States)

    1995-11-20

    Uniparental disomy (UPD) of a number of different chromosomes has been found in association with abnormal phenotypes. A growing body of evidence for an imprinting effect involving chromosome 14 has been accumulating. We report on a case of paternal UPD of chromosome 14 studied in late gestation due to polyhydramnios and a ventral wall hernia. A prenatal karyotype documented a balanced Robertsonian 14:14 translocation. The baby was born prematurely with hairy forehead, retrognathia, mild puckering of the lips and finger contractures. Hypotonia has persisted since birth and at age one year, a tracheostomy for laryngomalacia and gastrostomy for feeding remain necessary. Absence of maternal VNTR polymorphisms and homozygosity of paternal polymorphisms using chromosome 14 specific probes at D14S22 and D14S13 loci indicated paternal uniparental isodisomy (pUPID). Parental chromosomes were normal. We also report on a case of maternal LTPD in a normal patient with a balanced Robertsonian 14:14 translocation and a history of multiple miscarriages. Five previous reports of chromosome 14 UPD suggest that an adverse developmental effect may be more severe whenever the UPD is paternal in origin. This is the second reported patient with paternal UPD and the fifth reported with maternal UPD, and only few phenotypic similarities are apparent. Examination of these chromosome 14 UPD cases of maternal and paternal origin suggests that there are syndromic imprinting effects. 30 refs., 3 figs.

  9. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    Science.gov (United States)

    Baruffi, Marcelo Razera; de Souza, Deise Helena; Bicudo da Silva, Rosana Aparecida; Ramos, Ester Silveira; Moretti-Ferreira, Danilo

    2012-01-01

    Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process. PMID:23074688

  10. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    Directory of Open Access Journals (Sweden)

    Marcelo Razera Baruffi

    2012-01-01

    Full Text Available Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19(p21.2;q13.4. Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY. Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.

  11. Involvement of TR3/Nur77 translocation to the endoplasmic reticulum in ER stress-induced apoptosis

    International Nuclear Information System (INIS)

    Liang Bin; Song Xuhong; Liu Gefei; Li Rui; Xie Jianping; Xiao Lifeng; Du Mudan; Zhang Qiaoxia; Xu Xiaoyuan; Gan Xueqiong; Huang Dongyang

    2007-01-01

    Nuclear orphan receptor TR3/Nur77/NGFI-B is a novel apoptotic effector protein that initiates apoptosis largely by translocating from the nucleus to the mitochondria, causing the release of cytochrome c. However, it is possible that TR3 translocates to other organelles. The present study was designed to determine the intracellular localization of TR3 following CD437-induced nucleocytoplasmic translocation and the mechanisms involved in TR3-induced apoptosis. In human neuroblastoma SK-N-SH cells and human esophageal squamous carcinoma EC109 and EC9706 cells, 5 μM CD437 induced translocation of TR3 to the endoplasmic reticulum (ER). This distribution was confirmed by immunofluorescence analysis, subcellular fractionation analysis and coimmunoprecipitation analysis. The translocated TR3 interacted with ER-targeting Bcl-2; initiated an early release of Ca 2+ from ER; resulted in ER stress and induced apoptosis through ER-specific caspase-4 activation, together with induction of mitochondrial stress and subsequent activation of caspase-9. Our results identified a novel distribution of TR3 in the ER and defined two parallel mitochondrial- and ER-based pathways that ultimately result in apoptotic cell death

  12. Application of DNA RFLP procedures in interspecific gene transfer: The Lr19 translocation of wheat

    International Nuclear Information System (INIS)

    Prins, R.; Marais, G.F.; Marais, A.S.; Pretorius, Z.A.; Janse, B.J.H.

    1998-01-01

    Twenty-nine lines with deletions in the Lr19 ('Indis') translocated chromosome segment were used to physically map Thinopyrum Restriction Fragment Length Polymorphism (RFLP) loci as well as the Sr25 and Sdl loci. The relative distances between marker loci on the translocation were then calculated. The information was then used as an aid to characterize several recombined forms of the translocation. The data confirmed the reported homoeology between the Lr19 segment and chromosome arm 7DL of wheat. Also, it seems that the Lr19 translocation in 'Indis' is very similar to the Lr19 segment in the T4 source and that the former may not derive from Thinopyrum distichum. Near-isogenic lines of the recombined segments were derived and used to study their expression of leaf rust resistance. It became evident that only one potentially useful recombinant was obtained in an earlier attempt to induce allosyndetic pairing between the Lr19 translocation and 7DL of wheat. (author)

  13. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

    DEFF Research Database (Denmark)

    Leucci, E; Cocco, M; Onnis, A

    2008-01-01

    at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

  14. The effects of exposure to different clastogens on the pattern of chromosomal aberrations detected by FISH whole chromosome painting in occupationally exposed individuals

    International Nuclear Information System (INIS)

    Beskid, O.; Dusek, Z.; Solansky, I.; Sram, R.J.

    2006-01-01

    The pattern of chromosomal aberrations (CA) was studied by fluorescence in situ hybridization (FISH) technique (whole chromosomes 1 and 4 painting) in workers occupationally exposed to any of the four following conditions: acrylonitrile (ACN), ethyl benzene (EB), carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), and irradiation in nuclear power plants (NPP), respectively. Decrease in the relative frequency of translocations was observed in EB group, and an increase in reciprocal translocations in ACN and NPP-exposed groups. An increase in a relative number of insertions was registered under all four conditions (significant at ACN, EB, c-PAHs, quasisignificant at NPP-exposed groups). Significant differences in the percentage of lymphocytes with aberrations on chromosome 1 (58.8 ± 32.7%, versus 73.8 ± 33.6% in the controls, P G /100) increased with age (P G /100 (P < 0.05), but did not affect the pattern of chromosomal aberrations. Our results seem to indicate that different carcinogens may induce a different pattern of chromosomal aberrations

  15. Meiotic chromosome behaviours in M1 generation of bread wheat irradiated by gamma-rays

    International Nuclear Information System (INIS)

    Watanabe, Y.; Takato, S.

    1982-01-01

    Growing plants of bread wheat (Triticum aestivum L. 2 n=6x=42, AABBDD) were subjected to acute or chronic irradiation by gamma-rays from 60Co and meiotic chromosome behaviours of PMCS in M 1 generation were cytologically compared. Both acute and chronic irradiations produced different types of chromosomal aberrations at the meiotic stages. Among them, translocation type was the most frequent, followed by univalent type. A mixed type, i. e. translocation accompanying one or more univalents was often detected. Even normal type which lacked translocation and univalent included laggards and briclges without exception. Other meiotic abnormalities such as deletion, iso-chromosome and micronuclei were observed frequently in both treatments. Dose dependency of translocation frequency was not recognized in this experiment. In chronic irradiation, different chromosome numbers and meiotic behaviours were found not only among florets of a spike but also among anthers of a floret. A number of plants with aneuploid-like grass types occurred at a high frequency in M 1 , especially with low exposure

  16. Chromosome aberrations and oncogene alterations in atomic bomb related leukemias - different mechanisms from de novo leukemias

    International Nuclear Information System (INIS)

    Tanaka, K.; Tanaka, H.; Kamada, N.

    2003-01-01

    It is well known that leukemia occurred more frequently among atomic bomb survivors. In 132 atomic bomb related ( AB- related) leukemia patients during 1978-1999, 33 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients had their exposure doses of more than 1Gy (DS86). Chromosome aberrations of the 33 patients were compared with those from 588 de novo AML/MDS patients who had been bone before August 1945 as control. No FAB M3 patient was observed in the exposed group. Most AB-related AML preceded a long term of MDS stage. Twenty seven of the 33 patients showed complex types of chromosome aberrations with more than three chromosomes involving chromosomes 5,7 and 11. The number of chromosomes abnormality per cell in the AB-related leukemia was 3.78 while 0.92 in de novo leukemia. Only one of the 33 patients had normal karyotype, while 44.1% in de novo leukemia patients. Translocations of chromosome 11 at 11q13 to 11q23 and deletion/ loss of chromosome 20 were frequently observed in AB-related leukemia. No leukemia-type specific translocations such as t(8;21),t(15;17) and 11q23 were found in the 33 AB-related leukemia patients. Furthermore, molecular analyses using FISH and PCR-SSCP revealed the presence of breakpoint located outside of MLL gene in the patients with translocations at 11q22-23 and DNA base derangements of RUNT domain of AML1(CBF β 2)gene with AML/MDS patients without t(8;21) and with a high dose of exposure. These results suggest that AB-related leukemia derives from an exposed pluripotent hematopoietic stem cell which has been preserved for a long time in the bone marrow, expressing high genetic instability such as microsatellite instability. On the other hand, de novo leukemia develops from a committed hematopoietic stem cell and shows simple and leukemia-type specific chromosome aberrations. These findings are important for understanding mechanisms for radiation-induced leukemia

  17. Visualizing how cancer chromosome abnormalities form in living cells

    Science.gov (United States)

    For the first time, scientists have directly observed events that lead to the formation of a chromosome abnormality that is often found in cancer cells. The abnormality, called a translocation, occurs when part of a chromosome breaks off and becomes attac

  18. Prenatal diagnosis of a fetus with a cryptic translocation 4p;18p and Wolf-Hirschhorn syndrome (WHS).

    Science.gov (United States)

    Kohlschmidt, N; Zielinski, J; Brude, E; Schäfer, D; Olert, J; Hallermann, C; Coerdt, W; Arnemann, J

    2000-02-01

    Wolf-Hirschhorn Syndrome (WHS) is caused by distal deletion of the short arm of chromosome 4 and is characterized by growth deficiency, mental retardation, a distinctive, 'greek-helmet' facial appearance, microcephaly, ear lobe anomalies, and sacral dimples. We report a family with a balanced chromosomal translocation 4;18(p15.32;p11.21) in the father and an unbalanced translocation resulting in partial monosomy 4 and partial trisomy 18 in one living boy and a prenatally diagnosed male fetus. Both showed abnormalities consistent with WHS and had in addition aplasia of one umbilical artery. Karyotyping of another stillborn fetus revealed a supernumerary derivative chromosome der(18)t(4;18)(p15.32;p11.21) of paternal origin and two normal chromosomes 4. The umbilical cord had three normal vessels. A third stillborn fetus with the same balanced translocation as the father had a single umbilical artery and hygroma colli. Copyright 2000 John Wiley & Sons, Ltd.

  19. Effect of gamma irradiation on sex chromatin body appearance and the sex chromosome aberrations in the potato tuber moth, phthorimaea operculella (Lepidoptera: Gelechiidae)

    International Nuclear Information System (INIS)

    Makee, H.

    2007-01-01

    Genetic sexing technique based on the construction of a Balanced Lethal Strain (BLS) has been proposed for Phthorimaea operculella (Zeller). The isolation of female with T(W. Z) translocation is a fundamental step to develop such strain. Gamma irradiation was used to induce the requested translocations. The availability of sex-linked morphological marker is required to facilitate the detection of such mutations. Since a visible sex-linked marker has not been found in P. operculella, therefore main aim of our study was to determine the possibility of using sex heterochromatin body as a marker to identify the required translocated females. The appearance of sex heterochromatin body and the analysis of sex chromosomes in F1 females of irradiated P. operculella females were investigated. The percentage of abnormality in sex heterochromatin body in highly polyploid Malpighian tubule nuclei was increased by increasing the applied dose. Based on the appearance of this body, 3 mutant lines were isolated: elongated, small, fragmented lines. W chromosome was easily distinguished from Z chromosome when the analysis of pachytene sex chromosome bivalents of P. operculella females was carried out. The aberrations involved W chromosome directly influenced the appearance of sex heterochromatin body in highly polyploid somatic cells of the isolated mutant lines. The results showed that sex heterochromatin could be used as sex determination and cytogenetic marker in P. operculella. (Author)

  20. Effect of gamma irradiation on sex chromatin body appearance and the sex chromosome aberrations in the potato tuber moth, phthorimaea operculella (Lepidoptera: Gelechiidae)

    International Nuclear Information System (INIS)

    Makee, H.

    2006-05-01

    Genetic sexing technique based on the construction of a Balanced Lethal Strain (BLS) has been proposed for Phthorimaea operculella (Zeller). The isolation of female with T(W; Z) translocation is a fundamental step to develop such strain. Gamma irradiation was used to induce the requested translocations. The availability of sex-linked morphological marker is required to facilitate the detection of such mutations. Since a visible sex-linked marker has not been found in P. operculella, therefore main aim of our study was to determine the possibility of using sex heterochromatin body as a marker to identify the required translocated females. The appearance of sex heterochromatin body and the analysis of sex chromosomes in F1 females of irradiated P. operculella females were investigated. The percentage of abnormality in sex heterochromatin body in highly polyploid Malpighian tubule nuclei was increased by increasing the applied dose. Based on the appearance of this body, 3 mutant lines were isolated: elongated, small, fragmented lines. W chromosome was easily distinguished from Z chromosome when the analysis of pachytene sex chromosome bivalents of P. operculella females was carried out. The aberrations involved W chromosome directly influenced the appearance of sex heterochromatin body in highly polyploid somatic cells of the isolated mutant lines. The results showed that sex heterochromatin could be used as sex determination and cytogenetic marker in P. operculella. (Author)

  1. Chromosome analysis of nuclear power plant workers using fluorescence in situ hybridization and Giemsa assay

    International Nuclear Information System (INIS)

    Hristova, Rositsa; Hadjidekova, Valeria; Grigorova, Mira; Nikolova, Teodora; Bulanova, Minka; Popova, Ljubomira; Staynova, Albena; Benova, Donka

    2013-01-01

    The aim of this study was to evaluate the genotoxic effects of ionizing radiation in vivo in exposed Bulgarian nuclear power plant workers by using classical cytogenetic and molecular cytogenetic analyses of peripheral lymphocytes. Chromosome analysis using fluorescence in situ hybrydization (FISH) and Giemsa techniques was undertaken on 63 workers and 45 administrative staff controls from the Bulgarian Nuclear Power Plant. Using the Giemsa method, the frequencies of cells studied with chromosome aberrations, dicentrics plus rings and chromosome fragments in the radiation workers were significantly higher compared with the control group (P=0.044, P=0.014, and P=0.033, respectively). A significant association between frequencies of dicentrics plus rings and accumulated doses was registered (P<0.01). In the present study, a FISH cocktail of whole chromosome paints for chromosomes 1, 4 and 11 was used. A significant association between frequency of translocations and accumulated doses was also observed (P<0.001). Within the control group, a correlation was found between age and the spontaneous frequency of translocations. No correlation was found between smoking status and frequency of translocations. When compared with the control group, workers with accumulated doses up to 100 mSv showed no increase in genome translocation frequency, whereas workers with accumulated doses from 101 to 200 mSv showed a statistically significant doubling of genome translocation frequency (P=0.009). Thus, in cases of chronic exposure and for purposes of retrospective dosimetry, the genome frequency of translocations is a more useful marker for evaluation of genotoxic effects than dicentric frequency. (author)

  2. Delayed chromosomal instability caused by large deletion

    International Nuclear Information System (INIS)

    Ojima, M.; Suzuki, K.; Kodama, S.; Watanabe, M.

    2003-01-01

    Full text: There is accumulating evidence that genomic instability, manifested by the expression of delayed phenotypes, is induced by X-irradiation but not by ultraviolet (UV) light. It is well known that ionizing radiation, such as X-rays, induces DNA double strand breaks, but UV-light mainly causes base damage like pyrimidine dimers and (6-4) photoproducts. Although the mechanism of radiation-induced genomic instability has not been thoroughly explained, it is suggested that DNA double strand breaks contribute the induction of genomic instability. We examined here whether X-ray induced gene deletion at the hprt locus induces delayed instability in chromosome X. SV40-immortalized normal human fibroblasts, GM638, were irradiated with X-rays (3, 6 Gy), and the hprt mutants were isolated in the presence of 6-thioguanine (6-TG). A 2-fold and a 60-fold increase in mutation frequency were found by 3 Gy and 6 Gy irradiation, respectively. The molecular structure of the hprt mutations was determined by multiplex polymerase chain reaction of nine exons. Approximately 60% of 3 Gy mutants lost a part or the entire hprt gene, and the other mutants showed point mutations like spontaneous mutants. All 6 Gy mutants show total gene deletion. The chromosomes of the hprt mutants were analyzed by Whole Human Chromosome X Paint FISH or Xq telomere FISH. None of the point or partial gene deletion mutants showed aberrations of X-chromosome, however total gene deletion mutants induced translocations and dicentrics involving chromosome X. These results suggest that large deletion caused by DNA double strand breaks destabilizes chromosome structure, which may be involved in an induction of radiation-induced genomic instability

  3. Cross-species chromosome painting in bats from Madagascar: the contribution of Myzopodidae to revealing ancestral syntenies in Chiroptera.

    Science.gov (United States)

    Richards, Leigh R; Rambau, Ramugondo V; Lamb, Jennifer M; Taylor, Peter J; Yang, Fengtang; Schoeman, M Corrie; Goodman, Steven M

    2010-09-01

    The chiropteran fauna of Madagascar comprises eight of the 19 recognized families of bats, including the endemic Myzopodidae. While recent systematic studies of Malagasy bats have contributed to our understanding of the morphological and genetic diversity of the island's fauna, little is known about their cytosystematics. Here we investigate karyotypic relationships among four species, representing four families of Chiroptera endemic to the Malagasy region using cross-species chromosome painting with painting probes of Myotis myotis: Myzopodidae (Myzopoda aurita, 2n = 26), Molossidae (Mormopterus jugularis, 2n = 48), Miniopteridae (Miniopterus griveaudi, 2n = 46), and Vespertilionidae (Myotis goudoti, 2n = 44). This study represents the first time a member of the family Myzopodidae has been investigated using chromosome painting. Painting probes of M. myotis were used to delimit 29, 24, 23, and 22 homologous chromosomal segments in the genomes of M. aurita, M. jugularis, M. griveaudi, and M. goudoti, respectively. Comparison of GTG-banded homologous chromosomes/chromosomal segments among the four species revealed the genome of M. aurita has been structured through 14 fusions of chromosomes and chromosomal segments of M. myotis chromosomes leading to a karyotype consisting solely of bi-armed chromosomes. In addition, chromosome painting revealed a novel X-autosome translocation in M. aurita. Comparison of our results with published chromosome maps provided further evidence for karyotypic conservatism within the genera Mormopterus, Miniopterus, and Myotis. Mapping of chromosomal rearrangements onto a molecular consensus phylogeny revealed ancestral syntenies shared between Myzopoda and other bat species of the infraorders Pteropodiformes and Vespertilioniformes. Our study provides further evidence for the involvement of Robertsonian (Rb) translocations and fusions/fissions in chromosomal evolution within Chiroptera.

  4. SEARCHING FOR ELECTRICAL PROPERTIES, PHENOMENA AND MECHANISMS IN THE CONSTRUCTION AND FUNCTION OF CHROMOSOMES

    Directory of Open Access Journals (Sweden)

    Ivan Kanev

    2013-03-01

    Full Text Available Our studies reveal previously unidentified electrical properties of chromosomes: (1 chromosomes are amazingly similar in construction and function to electrical transformers; (2 chromosomes possess in their construction and function, components similar to those of electric generators, conductors, condensers, switches, and other components of electrical circuits; (3 chromosomes demonstrate in nano-scale level electromagnetic interactions, resonance, fusion and other phenomena similar to those described by equations in classical physics. These electrical properties and phenomena provide a possible explanation for unclear and poorly understood mechanisms in clinical genetics including: (a electrically based mechanisms responsible for breaks, translocations, fusions, and other chromosomal abnormalities associated with cancer, intellectual disability, infertility, pregnancy loss, Down syndrome, and other genetic disorders; (b electrically based mechanisms involved in crossing over, non-disjunction and other events during meiosis and mitosis; (c mechanisms demonstrating heterochromatin to be electrically active and genetically important.

  5. Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12).

    Science.gov (United States)

    Machida, Junichiro; Félix, Têmis M; Murray, Jeffrey C; Yoshiura, Koh-ichiro; Tanemura, Mitsuyo; Kamamoto, Munefumi; Shimozato, Kazuo; Sonta, Shin-ichi; Ono, Takao

    2009-09-01

    Identification of the breakpoints of disease-associated chromosome rearrangements can provide informative clues to a positional cloning approach for genes responsible for inherited diseases. Recently, we found a three-generation Japanese family segregating balanced chromosome translocation t(9;17)(q32;q12). One of the subjects had cleft lip and palate. We examined whether regions near the breakpoint could be associated with cleft lip and/or palate. We determined the breakpoints involved in the translocation by fluorescence in situ hybridization analysis and subsequent long-range polymerase chain reaction. In order to study the role of these disrupted regions in nonsyndromic cleft lip and/or palate, we performed mutation analysis and a haplotype-based transmission disequilibrium test using tagging single-nucleotide polymorphisms in the flanking regions of the breakpoints in white and Filipino nonsyndromic cleft lip and/or palate populations. Sequence analysis demonstrated that two genes, SLC31A1 (solute carrier family 31 member 1) on chromosome 9 and CCL2 (chemokine ligand 2) on chromosome 17, were rearranged with the breaks occurring within their introns. It is interesting that SLC31A1 lies closed to BSPRY (B-box and SPRY domain), which is a candidate for involvement with cleft lip and/or palate. Some of the variants in BSPRY and CCL2 showed significant p values in the cleft lip and/or palate population compared with the control population. There was also statistically significant evidence of transmission distortion for haplotypes on both chromosomes 9 and 17. The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.

  6. Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. II. Results obtained after induction of breaks in chromosome 1 by X-irradiation.

    Science.gov (United States)

    Burgerhout, W G; Smit, S L; Jongsma, A P

    1977-01-01

    The position of genes coding for PGD, PPH1, UGPP, GuK1, PGM1, Pep-C, and FH on human chromosome 1 was investigated by analysis of karyotype and enzyme phenotypes in man-Chinese hamster somatic cell hybrids carrying aberrations involving chromosome 1. Suitable hybrid cell lines were obtained by X-irradiation of hybrid cells carrying an intact chromosome 1 and by fusion of human cells from a clonal population carrying a translocation involving chromosome 1 with Chinese hamster cells. The latter human cell population had been isolated following X-irradiation of primary Lesch-Nyhan fibroblasts. In addition, products of de novo chromosome breakage in the investigated hybrid lines were utilized. By integrating the results of these analyses with earlier findings in our laboratory, the following positions of genes are deduced: PGD and PPH1 in 1p36 leads to 1p34; PGM1 in 1p32; UGPP in 1q21 leads to 1q23; GuK1 in 1q31 leads to 1q42; Pep-C in 1q42; and FH in 1qter leads to 1q42.

  7. Localization of the cellular retinoic acid binding protein (CRABP) gene relative to the acute promyelocytic leukemia-associated breakpoint on human chromosome 15

    NARCIS (Netherlands)

    A.H.M. Geurts van Kessel (Ad); H. de Leeuw (H.); E.J. Dekker (Erik Jan); J.M. Rijks (Jolianne); N. Spurr (N.); A.M. Ledbetter (Andrew M.); E. Kootwijk (E.); M.J. Vaessen (Marie-Josée)

    1991-01-01

    textabstractA human genomic fragment comprising the cellular retinoic acid binding protein (CRABP) gene was isolated. By using a panel of somatic cell hybrids, this gene could be assigned to human chromosome 15. Subsequently, a possible involvement of the CRABP gene in translocation (15;17)

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

    DEFF Research Database (Denmark)

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

    1992-01-01

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

  9. Flow cytogenetics: progress toward chromosomal aberration detection

    International Nuclear Information System (INIS)

    Carrano, A.V.; Gray, J.W.; Van Dilla, M.A.

    1977-01-01

    Using clonal derivatives of the Chinese hamster M3-1 cell line, we demonstrate the potential of flow systems to karyotype homogeneous aberrations (aberrations which are identical and present in every cell) and to detect heterogeneous aberrations (aberrations which occur randomly in a population and are not identical in every cell). Flow cytometry (FCM) of ethidium bromide stained isolated chromosomes from clone 650A of the M3-1 cells distinguishes nine chromosome types from the fourteen present in the actual karyotype. X-irradiation of this parent 650A clone produced two sub-clones with an altered flow karyotype, that is, their FCM distributions were characterized by the addition of new peaks and alterations in area under existing peaks. From the relative DNA content and area for each peak, as determined by computer analysis, we predicted that each clone had undergone a reciprocal translocation involving chromosomes from two peaks. This prediction was confirmed by Giemsa-banding the metaphase cells. Heterogeneous aberrations are reflected in the flow karyotype as an increase in background, that is, an increase in area underlying the chromosome peaks. This increase is dose dependent but, as yet, the sample variability has been too large for quantitative analysis. Flow sorting of the valleys between chromosome peaks produces enriched fractions of aberrant chromosomes for visual analysis. These approaches are potentially applicable to the analysis of chromsomal aberrations induced by environmental contaminants

  10. Molecular cytogenetic characterization of a new wheat-rye 4R chromosome translocation line resistant to powdery mildew.

    Science.gov (United States)

    An, Diaoguo; Zheng, Qi; Zhou, Yilin; Ma, Pengtao; Lv, Zhenling; Li, Lihui; Li, Bin; Luo, Qiaoling; Xu, Hongxing; Xu, Yunfeng

    2013-07-01

    Rye is an important and valuable gene resource for wheat improvement. However, due to extensive growing of cultivars with disease resistance genes from short arm of rye chromosome 1R and coevolution of pathogen virulence and host resistance, these cultivars successively lost resistance to pathogens. Identification and deployment of new resistance gene sources in rye are, therefore, of especial importance and urgency. A new wheat-rye line, designated as WR41-1, was produced through distant hybridization and chromosome engineering protocols between common wheat cultivar Xiaoyan 6 and rye cultivar German White. It was proved to be a new wheat-rye T4BL·4RL and T7AS·4RS translocation line using sequential genomic in situ hybridization (GISH), multicolor fluorescence in situ hybridization (mc-FISH), and expressed sequence tag-simple sequence repeat (EST-SSR) marker analysis. WR41-1 showed high levels of resistance to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) pathogens prevalent in China at the adult growth stage and 13 of 23 Bgt isolates tested at the seedling stage. According to its resistant pattern to 23 different Bgt isolates, WR41-1 may possess new gene(s) for resistance to powdery mildew, which differed from previously identified and known powdery mildew genes from rye (Pm7, Pm8, Pm17, and Pm20). In addition, WR41-1 was cytologically stable, had a desirable fertility, and is expected to be useful in wheat improvement.

  11. Bridge-Induced Translocation between NUP145 and TOP2 Yeast Genes Models the Genetic Fusion between the Human Orthologs Associated With Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Valentina Tosato

    2017-09-01

    Full Text Available In mammalian organisms liquid tumors such as acute myeloid leukemia (AML are related to spontaneous chromosomal translocations ensuing in gene fusions. We previously developed a system named bridge-induced translocation (BIT that allows linking together two different chromosomes exploiting the strong endogenous homologous recombination system of the yeast Saccharomyces cerevisiae. The BIT system generates a heterogeneous population of cells with different aneuploidies and severe aberrant phenotypes reminiscent of a cancerogenic transformation. In this work, thanks to a complex pop-out methodology of the marker used for the selection of translocants, we succeeded by BIT technology to precisely reproduce in yeast the peculiar chromosome translocation that has been associated with AML, characterized by the fusion between the human genes NUP98 and TOP2B. To shed light on the origin of the DNA fragility within NUP98, an extensive analysis of the curvature, bending, thermostability, and B-Z transition aptitude of the breakpoint region of NUP98 and of its yeast ortholog NUP145 has been performed. On this basis, a DNA cassette carrying homologous tails to the two genes was amplified by PCR and allowed the targeted fusion between NUP145 and TOP2, leading to reproduce the chimeric transcript in a diploid strain of S. cerevisiae. The resulting translocated yeast obtained through BIT appears characterized by abnormal spherical bodies of nearly 500 nm of diameter, absence of external membrane and defined cytoplasmic localization. Since Nup98 is a well-known regulator of the post-transcriptional modification of P53 target genes, and P53 mutations are occasionally reported in AML, this translocant yeast strain can be used as a model to test the constitutive expression of human P53. Although the abnormal phenotype of the translocant yeast was never rescued by its expression, an exogenous P53 was recognized to confer increased vitality to the translocants, in

  12. Genetic mechanisms leading to primary amenorrhea in balanced X-autosome translocations.

    Science.gov (United States)

    Moysés-Oliveira, Mariana; Guilherme, Roberta Dos Santos; Dantas, Anelisa Gollo; Ueta, Renata; Perez, Ana Beatriz; Haidar, Mauro; Canonaco, Rosane; Meloni, Vera Ayres; Kosyakova, Nadezda; Liehr, Thomas; Carvalheira, Gianna Maria; Melaragno, Maria Isabel

    2015-05-01

    To map the X-chromosome and autosome breakpoints in women with balanced X-autosome translocations and primary amenorrhea, searching candidate genomic loci for female infertility. Retrospective and case-control study. University-based research laboratory. Three women with balanced X-autosome translocation and primary amenorrhea. Conventional cytogenetic methods, genomic array, array painting, fluorescence in situ hybridization, and quantitative reverse transcription-polymerase chain reaction. Karyotype, copy number variation, breakpoint mapping, and gene expression levels. All patients presented with breakpoints in the Xq13q21 region. In two patients, the X-chromosome breakpoint disrupted coding sequences (KIAA2022 and ZDHHC15 genes). Although both gene disruptions caused absence of transcription in peripheral blood, there is no evidence that supports the involvement of these genes with ovarian function. The ZDHHC15 gene belongs to a conserved syntenic region that encompasses the FGF16 gene, which plays a role in female germ line development. The break in the FGF16 syntenic block may have disrupted the interaction between the FGF16 promoter and its cis-regulatory element. In the third patient, although both breakpoints are intergenic, a gene that plays a role in the DAX1 pathway (FHL2 gene) flanks distally the autosome breakpoint. The FHL2 gene may be subject to position effect due to the attachment of an autosome segment in Xq21 region. The etiology of primary amenorrhea in balanced X-autosome translocation patients may underlie more complex mechanisms than interruption of specific X-linked candidate genes, such as position effect. The fine mapping of the rearrangement breakpoints may be a tool for identifying genetic pathogenic mechanisms for primary amenorrhea. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Preimplantation genetic diagnosis by fluorescence in situ hybridization of reciprocal and Robertsonian translocations.

    Science.gov (United States)

    Chen, Chun-Kai; Wu, Dennis; Yu, Hsing-Tse; Lin, Chieh-Yu; Wang, Mei-Li; Yeh, Hsin-Yi; Huang, Hong-Yuan; Wang, Hsin-Shin; Soong, Yung-Kuei; Lee, Chyi-Long

    2014-03-01

    The presence of reciprocal and Robertsonian chromosomal rearrangement is often related to recurrent miscarriage. Using preimplantation genetic diagnosis, the abortion rate can be decreased. Cases treated at our center were reviewed. A retrospective analysis for either Robertsonian or reciprocal translocations was performed on all completed cycles of preimplantation genetic diagnosis at our center since the first reported case in 2004 until the end of 2010. Day 3 embryo biopsies were carried out, and the biopsied cell was checked by fluorescent in situ hybridization using relevant informative probes. Embryos with a normal or balanced translocation karyotype were transferred on Day 4. Thirty-eight preimplantation genetic diagnosis cycles involving 17 couples were completed. A total of 450 (82.6%) of the total oocytes were MII oocytes, and 158 (60.0%) of the two-pronuclei embryos were biopsied. In 41.4% of the fluorescent in situ hybridization analyses, the results were either normal or balanced. Embryos were transferred back after 21 cycles. Three babies were born from Robertsonian translocation carriers and another two from reciprocal translocation carriers. The miscarriage rate was 0%. Among the reciprocal translocation group, the live delivery rate was 8.3% per ovum pick-up cycle and 18.2% per embryo transfer cycle. Among the Robertsonian translocation group, the live delivery rate was 14.3% per ovum pick-up cycle and 20.0% per embryo transfer cycle. There is a trend whereby the outcome for Robertsonian translocation group carriers is better than that for reciprocal translocation group carriers. Aneuploidy screening may possibly be added in order to improve the outcome, especially for individuals with an advanced maternal age. The emergence of an array-based technology should help improve this type of analysis. Copyright © 2014. Published by Elsevier B.V.

  14. Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication.

    Science.gov (United States)

    Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E; Ventura, Mario

    2008-01-01

    Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Human bacterial artificial chromosome/p1 artificial chromosome probes spanning the length of chromosome 17 were used in FISH experiments on great apes, Old World monkeys and New World monkeys to study the evolutionary history of this chromosome. We observed that the macaque marker order represents the ancestral organization. Human, chimpanzee and gorilla homologous chromosomes differ by a paracentric inversion that occurred specifically in the Homo sapiens/Pan troglodytes/Gorilla gorilla ancestor. Detailed analyses of the paracentric inversion revealed that the breakpoints mapped to two regions syntenic to human 17q12/21 and 17q23, both rich in segmental duplications. Sequence analyses of the human and macaque organization suggest that the duplication events occurred in the catarrhine ancestor with the duplication blocks continuing to duplicate or undergo gene conversion during evolution of the hominoid lineage. We propose that the presence of these duplicons has mediated the inversion in the H. sapiens/P. troglodytes/G. gorilla ancestor. Recently, the same duplication blocks have been shown to be polymorphic in the human population and to be involved in triggering microdeletion and duplication in human. These results further support a model where genomic architecture has a direct role in both rearrangement involved in karyotype evolution and genomic instability in human.

  15. Ring Chromosome 17 Not Involving the Miller-Dieker Region: A Case with Drug-Resistant Epilepsy.

    Science.gov (United States)

    Coppola, Antonietta; Morrogh, Deborah; Farrell, Fiona; Balestrini, Simona; Hernandez-Hernandez, Laura; Krithika, S; Sander, Josemir W; Waters, Jonathan J; Sisodiya, Sanjay M

    2017-12-01

    Chromosomal abnormalities are often identified in people with neurodevelopmental disorders including intellectual disability, autism, and epilepsy. Ring chromosomes, which usually involve gene copy number loss, are formed by fusion of subtelomeric or telomeric chromosomal regions. Some ring chromosomes, including ring 14, 17, and 20, are strongly associated with seizure disorders. We report an individual with a ring chromosome 17, r(17)(p13.3q25.3), with a terminal 17q25.3 deletion and no short arm copy number loss, and with a phenotype characterized by intellectual disability and drug-resistant epilepsy, including a propensity for nonconvulsive status epilepticus.

  16. SMC Progressively Aligns Chromosomal Arms in Caulobacter crescentus but Is Antagonized by Convergent Transcription

    Directory of Open Access Journals (Sweden)

    Ngat T. Tran

    2017-08-01

    Full Text Available The structural maintenance of chromosomes (SMC complex plays an important role in chromosome organization and segregation in most living organisms. In Caulobacter crescentus, SMC is required to align the left and the right arms of the chromosome that run in parallel down the long axis of the cell. However, the mechanism of SMC-mediated alignment of chromosomal arms remains elusive. Here, using genome-wide methods and microscopy of single cells, we show that Caulobacter SMC is recruited to the centromeric parS site and that SMC-mediated arm alignment depends on the chromosome-partitioning protein ParB. We provide evidence that SMC likely tethers the parS-proximal regions of the chromosomal arms together, promoting arm alignment. Furthermore, we show that highly transcribed genes near parS that are oriented against SMC translocation disrupt arm alignment, suggesting that head-on transcription interferes with SMC translocation. Our results demonstrate a tight interdependence of bacterial chromosome organization and global patterns of transcription.

  17. Clinical outcomes for couples containing a reciprocal chromosome translocation carrier without preimplantation genetic diagnosis.

    Science.gov (United States)

    Yin, Biao; Zhu, Yuanchang; Wu, Tonghua; Shen, Shuqiu; Zeng, Yong; Liang, Desheng

    2017-03-01

    To evaluate the pregnancy outcomes of couples containing a carrier of a reciprocal chromosome translocation (RCT) after assisted reproductive technology without preimplantation genetic diagnosis. A retrospective study was performed using data for couples with an RCT carrier and control couples with a normal karyotype (1:4 ratio) who underwent assisted reproductive technology cycles at a Chinese fertility center in 2010-2011. The embryos were fertilized via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Only the first pick-up cycles were used for analysis. Clinical variables were compared. Compared with the control group (n=164), the RCT group (n=41) had a marginally lower clinical pregnancy rate (46.3% [19/41] vs 54.3% [89/164]), implantation rate (21.7% [23/106] vs 26.9% [118/438]), multiple-gestation pregnancy rate (21.1% [4/19] vs 32.6% [29/89]), and delivery rate (36.6% [15/41] vs 47.6% [78/164]), whereas the spontaneous abortion rate was slightly higher (21.1% [4/19] vs 12.4% [11/89]). However, none of these differences were significant. The clinical outcomes for RCT carriers were acceptable after IVF/ICSI without performing preimplantation genetic diagnosis, indicating that this approach might comprise a feasible alternative fertility treatment for RCT carriers. © 2016 International Federation of Gynecology and Obstetrics.

  18. Identification of copy number variations and translocations in cancer cells from Hi-C data.

    Science.gov (United States)

    Chakraborty, Abhijit; Ay, Ferhat

    2017-10-18

    Eukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions and outcomes including changes in epigenetic landscape and in gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities (e.g., copy number variations (CNVs) and translocations) altering their genomes both at the sequence level and at the level of 3D organization. High-throughput chromosome conformation capture techniques (e.g., Hi-C), which are originally developed for decoding the 3D structure of the chromatin, provide a great opportunity to simultaneously identify the locations of genomic rearrangements and to investigate the 3D genome organization in cancer cells. Even though Hi-C data has been used for validating known rearrangements, computational methods that can distinguish rearrangement signals from the inherent biases of Hi-C data and from the actual 3D conformation of chromatin, and can precisely detect rearrangement locations de novo have been missing. In this work, we characterize how intra and inter-chromosomal Hi-C contacts are distributed for normal and rearranged chromosomes to devise a new set of algorithms (i) to identify genomic segments that correspond to CNV regions such as amplifications and deletions (HiCnv), (Nurtdinov et al.) to call inter-chromosomal translocations and their boundaries (HiCtrans) from Hi-C experiments, and (iii) to simulate Hi-C data from genomes with desired rearrangements and abnormalities (AveSim) in order to select optimal parameters for and to benchmark the accuracy of our methods. Our results on 10 different cancer cell lines with Hi-C data show that we identify a total number of 105 amplifications and 45 deletions together with 90 translocations, whereas we identify virtually no such events for two karyotypically normal cell lines. Our CNV predictions correlate very well with whole genome sequencing (WGS) data among chromosomes

  19. Mapping of novel powdery mildew resistance gene(s) from Agropyron cristatum chromosome 2P.

    Science.gov (United States)

    Li, Huanhuan; Jiang, Bo; Wang, Jingchang; Lu, Yuqing; Zhang, Jinpeng; Pan, Cuili; Yang, Xinming; Li, Xiuquan; Liu, Weihua; Li, Lihui

    2017-01-01

    A physical map of Agropyron cristatum 2P chromosome was constructed for the first time and the novel powdery mildew resistance gene(s) from chromosome 2P was(were) also mapped. Agropyron cristatum (L.) Gaertn. (2n = 28, PPPP), a wild relative of common wheat, is highly resistant to powdery mildew. Previous studies showed that wheat-A. cristatum 2P disomic addition line II-9-3 displayed high resistance to powdery mildew, and the resistance was attributable to A. cristatum chromosome 2P. To utilize and physically map the powdery mildew resistance gene(s), 15 wheat-A. cristatum 2P translocation lines and three A. cristatum 2P deletion lines with different chromosomal segment sizes, obtained from II-9-3 using 60 Co-γ ray irradiation, were characterized using cytogenetic and molecular marker analysis. A. cristatum 2P chromosomal segments in the translocations were translocated to different wheat chromosomes, including 1A, 4A, 5A, 6A, 7A, 1B, 2B, 3B, 7B, 3D, 4D, and 6D. A physical map of the 2P chromosome was constructed with 82 STS markers, consisting of nine bins with 34 markers on 2PS and eight bins with 48 markers on 2PL. The BC 1 F 2 populations of seven wheat-A. cristatum 2P translocation lines (2PT-3, 2PT-4, 2PT-5, 2PT-6, 2PT-8, 2PT-9, and 2PT-10) were developed by self-pollination, tested with powdery mildew and genotyped with 2P-specific STS markers. From these results, the gene(s) conferring powdery mildew resistance was(were) located on 2PL bin FL 0.66-0.86 and 19 2P-specific markers were identified in this bin. Moreover, two new powdery mildew-resistant translocation lines (2PT-4 and 2PT-5) with small 2PL chromosome segments were obtained. The newly developed wheat lines with powdery mildew resistance and the closely linked molecular markers will be valuable for wheat disease breeding in the future.

  20. Fine mapping of the human renal oncocytoma-associated translocation (5;11)(q35;q13) breakpoint

    NARCIS (Netherlands)

    Sinke, RJ; Dijkhuizen, T; Janssen, B; Weghuis, DO; Merkx, G; vandenBerg, E; Schuuring, E; Meloni, AM; deJong, B; vanKessel, AG

    1997-01-01

    Recent cytogenetic analysis of a series of human renal oncocytomas revealed the presence of a recurring chromosomal translocation (5;11)(q35;q13) as sole anomaly in a subset of the tumors. The molecular characterization of this translocation was initiated using two primary t(5;11)-positive renal

  1. The Genetics of a Probable Insertional Translocation in SORDARIA BREVICOLLIS.

    Science.gov (United States)

    Bond, D J

    1979-05-01

    A chromosome rearrangement has been isolated and characterized in Sordaria brevicollis. Crosses to spore color mutants on each of the seven linkage groups have enabled the breakpoints to be mapped. The simplest hypothesis to account for the results is that a piece of linkage group VI has been translocated to linkage group V and inserted 2.7 map units from its centromere. Previous reports of markers on this linkage group with centromere distances greater than 2.7 units make it unlikely that the translocation is quasiterminal.

  2. Effects of hormone treatment on chromosomal radiosensitivity of somatic and germ cells of Snell's dwarf mice

    International Nuclear Information System (INIS)

    Buul, P.P.W. van; Buul-Offers, S.C. van

    1988-01-01

    The X-ray induction of micronuclei and structural chromosomal aberrations was studied in bone-marrow cells of normal and dwarf mice in combination with thyroxin and/or prolactin treatment or otherwise. Hormone treatment clearly increased micronuclei induction but not chromosome breakage, suggesting that indirect effects were involved. Since no clear differences in the timing of the final stage of erythropoiesis could be found, it is likely that the indirect effects are mediated via the formation-differentiation kinetics of erythroblasts. The induction of reciprocal translocations by X-rays in stem cell spermatogonia of dwarf mice was lower than in normals and treatment with prolactin, growth hormone and/or thyroxin, did not influence the chromosomal radiosensitivity of spermatogonial cells. 19 refs.; 1 figure; 4 tabs

  3. Chromosome identification by new molecular markers and genomic in situ hybridization in the Triticum-Secale-Thinopyrum trigeneric hybrids.

    Science.gov (United States)

    Dai, Yi; Duan, Yamei; Chi, Dawn; Liu, Huiping; Huang, Shuai; Cao, Wenguang; Gao, Yong; Fedak, George; Chen, Jianmin

    2017-08-01

    It is very important to use chromosome-specific markers for identifying alien chromosomes in advanced generations of distant hybridization. The chromosome-specific markers of rye and Thinopyrum elongatum, as well as genomic in situ hybridization, were used to identify the alien chromosomes in eight lines that were derived from the crossing between Triticum trititrigia (AABBEE) and triticale (AABBRR). The results showed that four lines contained all rye chromosomes but no Th. elongatum chromosomes. The line RE36-1 contained all of the rye chromosomes except for chromosome 2R. The lines RE33-2 and RE62-1 contained all rye chromosomes and 1E and 5E translocated chromosome, respectively. The line RE24-4 contained 12 rye chromosomes plus a 7E chromosome or 12 rye chromosomes plus one R-E translocated chromosome. Chromosome identification in the above lines was consistent using chromosome-specific markers and genomic in situ hybridization. These chromosome-specific markers provide useful tools for detecting alien chromosomes in trigeneric hybrids, and these lines could be utilized as valuable germplasm in wheat improvement.

  4. Alternative Lengthening of Telomeres: Recurrent Cytogenetic Aberrations and Chromosome Stability under Extreme Telomere Dysfunction

    Directory of Open Access Journals (Sweden)

    Despoina Sakellariou

    2013-11-01

    Full Text Available Human tumors using the alternative lengthening of telomeres (ALT exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines.We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted.We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth.

  5. Molecular Mechanisms and Diagnosis of Chromosome 22q11.2 Rearrangements

    Science.gov (United States)

    Emanuel, Beverly S.

    2008-01-01

    Several recurrent, constitutional genomic disorders are present on chromosome 22q. These include the translocations and deletions associated with DiGeorge and velocardiofacial syndrome and the translocations that give rise to the recurrent t(11;22) supernumerary der(22) syndrome (Emanuel syndrome). The rearrangement breakpoints on 22q cluster…

  6. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    International Nuclear Information System (INIS)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. As an exogeneous factor of possible influence, the meiotic effects of two types of radiation (fission neutrons and X-rays) administered at relatively low doses 2 and 3 hours before prometaphase-metaphase II (probably during metaphase-anaphase I), were determined in Rb4Bnr/+-males. (Auth.)

  7. An X-linked Myh11-CreERT2 mouse line resulting from Y to X chromosome-translocation of the Cre allele.

    Science.gov (United States)

    Liao, Mingmei; Zhou, Junmei; Wang, Fen; Ali, Yasmin H; Chan, Kelvin L; Zou, Fei; Offermanns, Stefan; Jiang, Zhisheng; Jiang, Zhihua

    2017-09-01

    The Myh11-CreER T2 mouse line (Cre + ) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/Y Cre+ ), which excluded its application in female mice. Our group established a Cre + colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X-linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/X Cre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/Y Cre+ mice. This mosaicism, however, diminished in homozygous X Cre+ /X Cre+ mice. In a model of aortic aneurysm induced by a SMC-specific Tgfbr1 deletion, the homozygous X Cre+ /X Cre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/X Cre+ Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X-inactivation. The homozygous X Cre+ /X Cre+ mice produce uniform Cre activity in arterial SMCs. © 2017 Wiley Periodicals, Inc.

  8. A multiple translocation event in a patient with hexadactyly, facial dysmorphism, mental retardation and behaviour disorder characterised comprehensively by molecular cytogenetics. Case report and review of the literature.

    Science.gov (United States)

    Seidel, Jörg; Heller, Anita; Senger, Gabriele; Starke, Heike; Chudoba, Ilse; Kelbova, Christina; Tönnies, Holger; Neitzel, Heidemarie; Haase, Claudia; Beensen, Volkmar; Zintl, Felix; Claussen, Uwe; Liehr, Thomas

    2003-09-01

    We report a 13-year-old female patient with multiple congenital abnormalities (microcephaly, facial dysmorphism, anteverted dysplastic ears and postaxial hexadactyly), mental retardation, and adipose-gigantism. Ultrasonography revealed no signs of a heart defect or renal abnormalities. She showed no speech development and suffered from a behavioural disorder. CNS abnormalities were excluded by cerebral MRI. Initial cytogenetic studies by Giemsa banding revealed an aberrant karyotype involving three chromosomes, t(2;4;11). By high resolution banding and multicolour fluoresence in-situ hybridisation (M-FISH, MCB), chromosome 1 was also found to be involved in the complex chromosomal aberrations, confirming the karyotype 46,XX,t(2;11;4).ish t(1;4;2;11)(q43;q21.1;p12-p13.1;p14.1). To the best of our knowledge no patient has been previously described with such a complex translocation involving 4 chromosomes. This case demonstrates that conventional chromosome banding techniques such as Giemsa banding are not always sufficient to characterise complex chromosomal abnormalities. Only by the additional utilisation of molecular cytogenetic techniques could the complexity of the present chromosomal rearrangements and the origin of the involved chromosomal material be detected. Further molecular genetic studies will be performed to clarify the chromosomal breakpoints potentially responsible for the observed clinical symptoms. This report demonstrates that multicolour-fluorescence in-situ hybridisation studies should be performed in patients with congenital abnormalities and suspected aberrant karyotypes in addition to conventional Giemsa banding.

  9. Chromosome Studies in Patients with Polycythaemia Vera after Treatment with {sup 32}P

    Energy Technology Data Exchange (ETDEWEB)

    Millard, Rosemary E.; Kay, H. E.M.; Lawler, S. D. [Royal Marsden Hospital, London (United Kingdom)

    1969-11-15

    The chromosomes of bone-marrow cells and blood lymphocytes of forty-six patients with polycythaemia vera were analysed to trace the sequence of events leading to the development of bone-marrow failure or 'leukaemia'. All except one of the patients had received radiophosphorus ({sup 32}P). It might be expected that the yield of chromosomal aberrations of the two-break type (translocations etc.) from the low dose-rate beta radiation of {sup 32}P would be small. However, 'unstable' types of abnormality (dicentrics, fragments) and stable types (translocations, inversions, deletions) were observed in 6-25% of the blood lymphocytes; there was no evidence of clones of abnormal cells. In the majority of patients the bone marrow was predominantly normal diploid; occasional sporadic cells with 'stable' chromosomal abnormalities were seen in two-thirds of the cases, but 'unstable' aberrations were rare. In seven cases there were clones of cells characterised by deletions or translocations. All these chromosomal changes are probably radiation-induced. Clones of cells with a similar abnormality, an apparent deletion of one of the F-group chromosomes, were observed in the bone marrow in ten patients. Eight of these had received {sup 32}P and two busulphan. In two cases the clone appeared to develop after treatment. A similar anomaly has been reported in several cases of idiopathic sideroblastic anaemia who had not been irradiated. Progression into the leukaemic phase of the disease is associated in some cases with gross chromosomal abnormalities, such as shift of the stem line chromosome number and bizarre chromosome 'markers'. In other cases, some of whom have not been irradiated for several years, the chromosomal changes are less pronounced and may result from non-disjunctional gain of one or more chromosomes or chromosome loss. One case showed a step-by-step clonal evolution over a two-year period. None of the chromosomal abnormalities in the 'leukaemic' phase appear to be a

  10. Localization of preferential sites of rearrangement within the BCR gene in Philadelphia chromosome-positive acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Denny, C.T.; Shah, N.P.; Ogden, S.; Willman, C.; McConnell, T.; Crist, W.; Carroll, A.; Witte, O.N.

    1989-01-01

    The Philadelphia chromosome associated with acute lymphoblastic leukemia (ALL) has been linked to a hybrid BCR/ABL protein product that differs from that found in chronic myelogenous leukemia. This implies that the molecular structures of the two chromosomal translocations also differ. Localization of translocation breakpoints in Philadelphia chromosome-positive ALL has been impeded due to the only partial characterization of the BCR locus. The authors have isolated the entire 130-kilobase BCR genomic locus from a human cosmid library. They have demonstrated that these breakpoints are all located at the 3' end of the intron around an unusual restriction fragment length polymorphism caused by deletion of a 1-kilobase fragment containing Alu family reiterated sequences. This clustering is unexpected in light of previous theories of rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia that would have predicted a random dispersion of breakpoints in the first intron in Philadelphia chromosome-positive ALL. The proximity of the translocation breakpoints to this constitutive deletion may indicate shared mechanisms of rearrangement or that such polymorphisms mark areas of the genome prone to recombination

  11. Enhanced stimulation of chromosomal translocations and sister chromatid exchanges by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces cerevisiae yku70 mutants

    International Nuclear Information System (INIS)

    Fasullo, Michael; St Amour, Courtney; Zeng Li

    2005-01-01

    DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MAT a and MATα inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-Δ5' and his3-Δ3'::HOcs is enhanced in haploids and diploids expressing both MAT a and MATα genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-Δ3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent

  12. Chromosome Banding in Amphibia. XXXII. The Genus Xenopus (Anura, Pipidae).

    Science.gov (United States)

    Schmid, Michael; Steinlein, Claus

    2015-01-01

    Mitotic chromosomes of 16 species of the frog genus Xenopus were prepared from kidney and lung cell cultures. In the chromosomes of 7 species, high-resolution replication banding patterns could be induced by treating the cultures with 5-bromodeoxyuridine (BrdU) and deoxythymidine (dT) in succession, and in 6 of these species the BrdU/dT-banded chromosomes could be arranged into karyotypes. In the 3 species of the clade with 2n = 20 and 4n = 40 chromosomes (X. tropicalis, X. epitropicalis, X. new tetraploid 1), as well as in the 3 species with 4n = 36 chromosomes (X. laevis, X. borealis, X. muelleri), the BrdU/dT-banded karyotypes show a high degree of homoeology, though differences were detected between these groups. Translocations, inversions, insertions or sex-specific replication bands were not observed. Minor replication asynchronies found between chromosomes probably involve heterochromatic regions. BrdU/dT replication banding of Xenopus chromosomes provides the landmarks necessary for the exact physical mapping of genes and repetitive sequences. FISH with an X. laevis 5S rDNA probe detected multiple hybridization sites at or near the long-arm telomeric regions in most chromosomes of X. laevis and X. borealis, whereas in X. muelleri, the 5S rDNA sequences are located exclusively at the long-arm telomeres of a single chromosome pair. Staining with the AT base pair-specific fluorochrome quinacrine mustard revealed brightly fluorescing heterochromatic regions in the majority of X. borealis chromosomes which are absent in other Xenopus species.

  13. Sperm FISH analysis of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat complex chromosome rearrangement.

    Science.gov (United States)

    Ferfouri, F; Boitrelle, F; Clement, P; Molina Gomes, D; Selva, J; Vialard, F

    2014-06-01

    Complex chromosome rearrangements (CCR) with two independent chromosome rearrangements are rare. Although CCRs lead to high unbalanced gamete rates, data on meiotic segregation in this context are scarce. A male patient was referred to our clinic as part of a family screening programme prompted by the observation of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat karyotype in his brother. Karyotyping identified the same CCR. Sperm FISH (with locus-specific probes for the segments involved in the translocations and nine chromosomes not involved in both rearrangements) was used to investigate the rearrangements meiotic segregation products and establish whether or not an inter-chromosomal effect was present. Sperm nuclear DNA fragmentation was also evaluated. For rob(13;14) and der(Y), the proportions of unbalanced products were, respectively, 26.4% and 60.6%. Overall, 70.3% of the meiotic segregation products were unbalanced. No evidence of an inter-chromosomal effect was found, and the sperm nuclear DNA fragmentation rate was similar to our laboratory's normal cut-off value. In view of previously published sperm FISH analyses of Robertsonian translocations (and even though the mechanism is still unknown), we hypothesise that cosegregation of der(Y) and rob(13;14) could modify rob(13;14) meiotic segregation. © 2013 Blackwell Verlag GmbH.

  14. Colocalization of somatic and meiotic double strand breaks near the Myc oncogene on mouse chromosome 15.

    Science.gov (United States)

    Ng, Siemon H; Maas, Sarah A; Petkov, Petko M; Mills, Kevin D; Paigen, Kenneth

    2009-10-01

    Both somatic and meiotic recombinations involve the repair of DNA double strand breaks (DSBs) that occur at preferred locations in the genome. Improper repair of DSBs during either mitosis or meiosis can lead to mutations, chromosomal aberration such as translocations, cancer, and/or cell death. Currently, no model exists that explains the locations of either spontaneous somatic DSBs or programmed meiotic DSBs or relates them to each other. One common class of tumorigenic translocations arising from DSBs is chromosomal rearrangements near the Myc oncogene. Myc translocations have been associated with Burkitt lymphoma in humans, plasmacytoma in mice, and immunocytoma in rats. Comparing the locations of somatic and meiotic DSBs near the mouse Myc oncogene, we demonstrated that the placement of these DSBs is not random and that both events clustered in the same short discrete region of the genome. Our work shows that both somatic and meiotic DSBs tend to occur in proximity to each other within the Myc region, suggesting that they share common originating features. It is likely that some regions of the genome are more susceptible to both somatic and meiotic DSBs, and the locations of meiotic hotspots may be an indicator of genomic regions more susceptible to DNA damage. (c) 2009 Wiley-Liss, Inc.

  15. Trisomy 10p and translocation of 10q to 4p associated with selective dysgenesis of IgA-producing cells in lymphoid tissue.

    Science.gov (United States)

    Saiga, Tatsuyoshi; Hashimoto, Kazuhiro; Kimura, Nobusuke; Ono, Hisako; Hiai, Hiroshi

    2007-01-01

    A combined chromosomal abberation trisomy of the short arm of chromosome 10 associated with translocation of 10q to chromosome 4p was found in a 14-month-old boy, who died after repeated bouts of pneumonia. The translocation involved the target region 4p16.3 of Wolf-Hirschhorn syndrome and/or Pitt-Rogers-Danks syndrome. The karyotype was 46,XY,der(4)t(4;10)(p16;q11.2),i(10)(p10),ish der(4)t(4;10)(p16.3;q11.2) (D4S96+,D4Z1+),i(10) (pter ++). In addition to growth retardation and external as well as internal dysmorphism, the patient had abnormalities of the immune system, such as thymic involution, generalized lymph node enlargement, unusual distribution of T cells in lymphoid follicles, and selective IgA deficiency. The IgA-producing cells were rarely found in lymph nodes but normally in intestinal mucosa. In contrast, in the lymph nodes, the paracortical T-lymphocytes were hyperplastic, but they rarely entered the primary follicles. It is assumed that the chromosomal abnormality may lead to the dysfunction of T lymphocytes and, further, to the dysgenesis of IgA-producing cells in lymph nodes but not in intestinal mucosa. This suggests that the thymus may differentially control the subsets of IgA-producing cells in lymph nodes and intestinal mucosa.

  16. Chromosome reduction in Eleocharis maculosa (Cyperaceae).

    Science.gov (United States)

    da Silva, C R M; González-Elizondo, M S; Laforga Vanzela, A L

    2008-01-01

    Chromosome numbers in Cyperaceae lower than the typical basic number x = 5 have been described for only three species: Rhynchospora tenuis (n = 2), Fimbristylis umbellaris (n = 3) and Eleocharis subarticulata (n = 3). Eleocharis maculosa is recorded here as the fourth species of Cyperaceae that has a chromosome number lower than 2n = 10, with 2n = 8, 7 and 6. The karyotype differentiation in E. maculosa was studied using conventional staining (mitosis and meiosis), FISH with 45S and 5S rDNA and telomere probes. The results allow us to determine which chromosomes of the chromosome race with 2n = 10 fused to form the remaining reduced numbers, as well as to understand how the symploidy and translocation mechanisms were important in karyotype differentiation and the formation of chromosome races in Eleocharis. Copyright 2008 S. Karger AG, Basel.

  17. DNA rearrangement in human follicular lymphoma can involve the 5' or the 3' region of the bcl-2 gene

    International Nuclear Information System (INIS)

    Tsujimoto, Y.; Bashir, M.M.; Givol, I.; Cossman, J.; Jaffe, E.; Croce, C.M.

    1987-01-01

    In most human lymphomas, the chromosome translocation t(14;18) occurs within two breakpoint clustering regions on chromosome 18, the major one at the 3' untranslated region of the bcl-2 gene and the minor one at 3' of the gene. Analysis of a panel of follicular lymphoma DNAs using probes for the first exon of the bcl-2 gene indicates that DNA rearrangements may also occur 5' to the involved bcl-2 gene. In this case the IgH locus and the bcl-2 gene are found in an order suggesting that an inversion also occurred during the translocation process. The coding region of the bcl-2 gene, however, are left intact in all cases of follicular lymphoma studied to date

  18. A correlative study on the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of mammals

    International Nuclear Information System (INIS)

    Buul, P.P.W. van

    1976-01-01

    A series of investigations on the correlation between the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of mouse and rhesus monkey is described. In the mouse the induction of reciprocal translocations in bone-marrow cells was compared with that in spermatogonia (as scored in the descending spermatocytes). In the rhesus monkey frequencies of radiation-induced chromosome aberrations in spermatogonia and peripheral blood lymphocytes were studied. Furthermore the effect of multigeneration irradiation (69 generations with 200 rads X-rays) on the sensitivity for translocation induction in spermatogonia of male mice was studied. Frequencies of dicentric chromosomes and chromosomal deletions in cultured peripheral blood lymphocytes of 5 different types of mice were determined following in vitro irradiation with doses of 100 and/or 200 rad X-rays. To obtain more insight into the processes underlying translocation induction in spermatogonia of the mouse, fractionation experiments were conducted

  19. mFISH analysis of chromosome aberrations in workers occupationally exposed to mixed radiation

    Energy Technology Data Exchange (ETDEWEB)

    Sotnik, Natalia V.; Osovets, Sergey V.; Azizova, Tamara V. [Southern Urals Biophysics Institute (SUBI), Ozyorsk, Chelyabinsk Region (Russian Federation); Scherthan, Harry [Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Munich (Germany)

    2014-05-15

    We performed a study on the presence of chromosome aberrations in a cohort of plutonium workers of the Mayak production association (PA) with a mean age of 73.3 ± 7.2 years to see whether by multi-color fluorescence in situ hybridization (mFISH) translocation analysis can discriminate individuals who underwent occupational exposure with internal and/or external exposure to ionizing radiation 40 years ago. All Mayak PA workers were occupationally exposed to chronic internal alpha-radiation due to incorporated plutonium-239 and/or to external gamma-rays. First, we obtained the translocation yield in control individuals by mFISH to chromosome spreads of age-matched individuals and obtained background values that are similar to previously published values of an international study (Sigurdson et al. in Mutat Res 652:112-121, 2008). Workers who had absorbed a total dose of >0.5 Gy external gamma-rays to the red bone marrow (RBM) displayed a significantly higher frequency of stable chromosome aberrations relative to a group of workers exposed to <0.5 Gy gamma-rays total absorbed RBM dose. Thus, the translocation frequency may be considered to be a biological marker of external radiation exposure even years after the exposure. In a group of workers who were internally exposed and had incorporated plutonium-239 at a body burden >1.48 kBq, mFISH revealed a considerable number of cells with complex chromosomal rearrangements. Linear associations were observed for translocation yield with the absorbed RBM dose from external gamma-rays as well as for complex chromosomal rearrangements with the plutonium-239 body burden. (orig.)

  20. The effect of X-irradiation on the fertility and the induction of meiotic chromosome rearrangements in mice and their first generation

    International Nuclear Information System (INIS)

    Savkovic, N.; Pecevski, J.; Maric, N.; Radivojevic, D.

    1978-01-01

    The effect of whole-body and local irradiation with a dose of 600 X-rays on the induction of chromosomal translocations in Diakinesis-Metaphase I of meiosis in treated and F 1 males and their fertility have been examined. Our results showed the high percentage of mortality in whole-body irradiated mice. The percentage of fertility was 25% in whole-body, and 93,7% in locally irradiated males. The testis weight was also reduced. The percentage of chromosomal translocations in Diakinesis-Metaphase I of meiosis was greater after whole-body than after local irradiation. In F 1 males both types of irradiation induced chromosomal translocations. (orig.) [de

  1. Rapid mapping of chromosomal breakpoints: from blood to BAC in 20 days.

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chun-Mei; Kwan, Johnson; Weier, Jingly F.; Baumgartner, Aldof; Wang, Mei; Escudero, Tomas; Munne, Santiago; Weier, Heinz-Ulrich

    2009-02-25

    Structural chromosome aberrations and associated segmental or chromosomal aneusomies are major causes of reproductive failure in humans. Despite the fact that carriers of reciprocal balanced translocation often have no other clinical symptoms or disease, impaired chromosome homologue pairing in meiosis and karyokinesis errors lead to over-representation of translocations carriers in the infertile population and in recurrent pregnancy loss patients. At present, clinicians have no means to select healthy germ cells or balanced zygotes in vivo, but in vitro fertilization (IVF) followed by preimplantation genetic diagnosis (PGD) offers translocation carriers a chance to select balanced or normal embryos for transfer. Although a combination of telomeric and centromeric probes can differentiate embryos that are unbalanced from normal or unbalanced ones, a seemingly random position of breakpoints in these IVF-patients poses a serious obstacle to differentiating between normal and balanced embryos, which for most translocation couples, is desirable. Using a carrier with reciprocal translocation t(4;13) as an example, we describe our state-of-the-art approach to the preparation of patient-specific DNA probes that span or 'extent' the breakpoints. With the techniques and resources described here, most breakpoints can be accurately mapped in a matter of days using carrier lymphocytes, and a few extra days are allowed for PGD-probe optimization. The optimized probes will then be suitable for interphase cell analysis, a prerequisite for PGD since blastomeres are biopsied from normally growing day 3 - embryos regardless of their position in the mitotic cell cycle. Furthermore, routine application of these rapid methods should make PGD even more affordable for translocation carriers enrolled in IVF programs.

  2. Cytogenetic study of stable chromosome aberrations in residents of a high background radiation area in China

    International Nuclear Information System (INIS)

    Zhang Wei; Wang Chunyan; Chen Deqing; Wei Lvxin

    2004-01-01

    Objective: To investigate the effect of high background radiation on the induction of stable chromosome aberrations. Methods: By fluorescence in situ hybridization (FISH) technique chromosome Nos. 1, 2 and 4 were painted using specific biotin-labeled whole chromosome painting probes. Peripheral blood specimens were taken from 31 individuals living in the high background radiation area (HRBA) and 29 individuals in the control area. Results: No significant difference was found in the frequencies of translocations between HBRA and the control (P>0.05, Mann-Whitney U test) for both children and elderly individuals. On the other hand, correlation between age and translocation frequencies was significant at the 1% level (r s =0.388 with 56DF). Conclusion: There are no differences in the frequencies of translocations between HBRA and the control area. The present result indicates that the contribution of an elevated level of natural radiation in HBRA in China to the induction rate of stable type aberrations (translocations) dose not have a significant effect compared with the contributions from all other sources such as chemical mutagens and(or) metabolic factors. (authors)

  3. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Li, Yilong; Schwab, Claire; Ryan, Sarra; 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; 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.

  4. [The molecular-cytogenetic characterization and tyrosine kinase inhibitors efficacy in newly diagnosed chronic phase CML patients with variant Philadelphia chromosomes].

    Science.gov (United States)

    Zhao, J J; Zhang, Y L; Zhang, S J; Zhou, J; Yu, F K; Zu, Y L; Zhao, H F; Li, Z; Song, Y P

    2018-03-14

    Objective: To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh). Methods: The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210. Results: There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients. 3(9.4%) of the 32 vPh cases were simple variant translocations. Among the remaining 29 cases with complex variant translocations, 28 cases (87.5%) involved 3 chromosomes, and only 1 (3.1%) involved 4 chromosomes. Except for 8, 15, 18, X, and Y chromosomes, the other chromosomes were involved. The frequency of chromosome 12q(15.5%) and 1p (12.1%) were higher involved. The most common FISH signal pattern was 2G2R1Y (74.1%), followed by 1G1R2F (14.8%), 2G1R1Y (3.7%), 1G2R1Y (3.7%), 1G1R1Y (3.7%). The comparison of complete cytogenetic response (CCyR) ( P =0.269), major molecular response (MMR) ( P =0.391) were carried out between simple and complex mechanisms, without difference. Compared with the classic Ph, the patients with vPh had higher IM primary resistance rate ( χ 2 =3.978, P =0.046), especially primary hematological resistance ( χ 2 =7.870, P =0.005), but the difference of CCyR ( χ 2 =0.192, P =0.661), MMR ( χ 2 =0.822, P =0.365), EFS ( χ 2 =0.509, P =0.476), OS ( χ 2 =3.485, P =0.062) were not statistically significant, and multivariate analysis showed that the presence of vPh did not affect OS ( RR =0.692, 95% CI 0.393-1.765, P =0.658)、EFS ( RR =0.893, 95% CI 0.347-2.132, P =0.126) and PFS ( RR =1.176, 95% CI 0.643-2.682, P =0.703). Conclusion: CML-CP patients with vPh and classic Ph had similar demographic and hematological characteristics. Except for 22q11, 9q34, the

  5. High rate of translocation-based gene birth on the Drosophila Y chromosome.

    Science.gov (United States)

    Tobler, Ray; Nolte, Viola; Schlötterer, Christian

    2017-10-31

    The Y chromosome is a unique genetic environment defined by a lack of recombination and male-limited inheritance. The Drosophila Y chromosome has been gradually acquiring genes from the rest of the genome, with only seven Y-linked genes being gained over the past 63 million years (0.12 gene gains per million years). Using a next-generation sequencing (NGS)-powered genomic scan, we show that gene transfers to the Y chromosome are much more common than previously suspected: at least 25 have arisen across three Drosophila species over the past 5.4 million years (1.67 per million years for each lineage). The gene transfer rate is significantly lower in Drosophila melanogaster than in the Drosophila simulans clade, primarily due to Y-linked retrotranspositions being significantly more common in the latter. Despite all Y-linked gene transfers being evolutionarily recent (Drosophila Y chromosome to be more dynamic than previously appreciated. Our analytical method provides a powerful means to identify Y-linked gene transfers and will help illuminate the evolutionary dynamics of the Y chromosome in Drosophila and other species. Copyright © 2017 the Author(s). Published by PNAS.

  6. First description of multivalent ring structures in eutherian mammalian meiosis: new chromosomal characterization of Cormura brevirostris (Emballonuridae, Chiroptera).

    Science.gov (United States)

    de Araújo, Ramon Everton Ferreira; Nagamachi, Cleusa Yoshiko; da Costa, Marlyson Jeremias Rodrigues; Noronha, Renata Coelho Rodrigues; Rodrigues, Luís Reginaldo Ribeiro; Pieczarka, Julio César

    2016-08-01

    Twelve specimens of the bat Cormura brevirostris (Emballonuridae: Chiroptera) were collected from four localities in the Brazilian Amazon region and analyzed by classical and molecular cytogenetics. The diploid number and autosomal fundamental number were as previously reported (2n = 22 and FNa = 40, respectively). Fluorescence in situ hybridization using rDNA probes and silver nitrate technique demonstrated the presence of two NOR sites and the presence of internal telomeric sequences at pericentromeric regions of all chromosomes with exception of Y. Based on meiotic studies and chromosome banding we suggest that the sex chromosome pair of C. brevirostris was equivocally identified as it appears in the literature. Meiotic analysis demonstrated that at diplotene-diakinesis the cells had a ring conformation involving four chromosome pairs. This suggests the occurrence of multiple reciprocal translocations among these chromosomes, which is a very rare phenomenon in vertebrates, and has never been described in Eutheria.

  7. Changes in Nuclear Orientation Patterns of Chromosome 11 during Mouse Plasmacytoma Development

    Directory of Open Access Journals (Sweden)

    Ann-Kristin Schmälter

    2015-10-01

    Full Text Available Studying changes in nuclear architecture is a unique approach toward the understanding of nuclear remodeling during tumor development. One aspect of nuclear architecture is the orientation of chromosomes in the three-dimensional nuclear space. We studied mouse chromosome 11 in lymphocytes of [T38HxBALB/c]N mice with a reciprocal translocation between chromosome X and 11 (T38HT(X;11 exhibiting a long chromosome T(11;X and a short chromosome T(X;11 and in fast-onset plasmacytomas (PCTs induced in the same strain. We determined the three-dimensional orientation of chromosome 11 using a mouse chromosome 11 specific multicolor banding probe. We also examined the nuclear position of the small translocation chromosome T(X;11 which contains cytoband 11E2 and parts of E1. Chromosomes can point either with their centromeric or with their telomeric end toward the nuclear center or periphery, or their position is found in parallel to the nuclear border. In T38HT(X;11 nuclei, the most frequently observed orientation pattern was with both chromosomes 11 in parallel to the nuclear border (“PP”. PCT cells showed nuclei with two or more copies of chromosome 11. In PCTs, the most frequent orientation pattern was with one chromosome in parallel and the other pointing with its centromeric end toward the nuclear periphery (“CP”. There is a significant difference between the orientation patterns observed in T38HT(X;11 and in PCT nuclei (P < .0001.

  8. Putative cruciform DNA structures at BCL6 breakpoint region may explain BCL6 translocation in diffuse large B-Cell lymphoma

    International Nuclear Information System (INIS)

    Bhatelia, Khyati D.; Nambiar, Mridula; Choudhary, Bibha; Raghvan, Sathees C.

    2010-01-01

    Cancer is a disease characterized by uncontrolled proliferation of cells, caused by genetic alterations such as chromosomal translocations, which are present in almost all hematological malignancies. Diffuse Large B-cell Lymphoma (DLBL) is the most common non-Hodgkin's lymphoma, comprising 40-50% of all lymphomas both in India and worldwide, and is characterized by BCL6 chromosomal translocation. However, the mechanism of this translocation is completely unknown. By mapping of translocation breakpoints from patients, we have identified three breakpoint cluster regions at 5' UTR of BCL6 gene. Bioinformatics analysis of cluster II, which possesses majority of breakpoints, this region may form cruciform DNA structures. Gel mobility shift assays using oligomeric DNA from the region suggested that a portion of cluster II folded into hairpin structures. Mutations to the wild type sequences disrupted hairpin formation. Circular dichroism studies on BCL6 oligomers resulted in a spectra containing two overlapping peaks at 265 nm and 285 nm, confirming hairpin structure. Further, the structure was destroyed upon heating, and reformed when appropriate conditions were provided. P1 nuclease assay in conjunction with KMnO 4 probing suggested that the structure possessed an eight nucleotide double-stranded stem and a nine nucleotide loop. To further understand the mechanism of BCL6 translocation in vivo, human cells were transfected with episomes harboring cluster II region and the results obtained will be discussed. Hence, our results suggest the formation of a putative cruciform DNA structure at BCL6 breakpoint region and that may facilitate breakage at BCL6 gene explaining chromosomal translocations in DLBL. (author)

  9. Study of chromosome aberrations on the workers occupationally exposed to thorium and rare earth mixed dust

    International Nuclear Information System (INIS)

    Zhang Wei; Wang Chunyan; Lv Huiming; Zhang Cuilan; Hao Shuxia; Su Xu; Jia Kejun; Liu Yufei

    2008-01-01

    Objective: To study the effect of thorium and rare earth mixed dust on chromosome aberrations in the lymphocytes of occupational exposed workers. Methods: Analyses of unstable chromosome aberrations on 53 occupational exposed workers and 58 control workers were carried out by the conventional Giemsa staining method. Fluorescence in situ hybridization method was performed to analyze the chromosome stable aberrations on 10 occupational exposed workers and l0 control workers. Results: The frequencies of chromosomal aberration cells, dicentrics plus rings, total aberrations in exposed workers were significantly higher than those in controls. No significant difference was found in the frequency of acentric aberrations between exposed and non-exposed workers. No significant difference was found in the frequency of translocations between exposed and non-exposed workers. Conclusions: Chronically occupational exposure to thorium and rare earth mixed dust can increase the induction of unstable chromosome aberration, but the increase of stable chromosome aberrations (translocation) can not be observed. (authors)

  10. Sequence-Based Analysis of Translocations and Inversions in Bread Wheat (Triticum aestivum L.)

    Czech Academy of Sciences Publication Activity Database

    Ma, J.; Stiller, J.; Berkman, P.J.; Wei, Y.M.; Rogers, J.; Feuillet, C.; Doležel, Jaroslav; Mayer, K. F.; Eversole, K.; Zheng, Y.L.; Liu, C.L.

    2013-01-01

    Roč. 8, č. 11 (2013) E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z50380511 Keywords : CHROMOSOMAL TRANSLOCATIONS * HOMOEOLOGOUS GROUP-4 * EVOLUTION Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.534, year: 2013

  11. A new 2DS·2RL Robertsonian translocation transfers stem rust resistance gene Sr59 into wheat.

    Science.gov (United States)

    Rahmatov, Mahbubjon; Rouse, Matthew N; Nirmala, Jayaveeramuthu; Danilova, Tatiana; Friebe, Bernd; Steffenson, Brian J; Johansson, Eva

    2016-07-01

    A new stem rust resistance gene Sr59 from Secale cereale was introgressed into wheat as a 2DS·2RL Robertsonian translocation. Emerging new races of the wheat stem rust pathogen (Puccinia graminis f. sp. tritici), from Africa threaten global wheat (Triticum aestivum L.) production. To broaden the resistance spectrum of wheat to these widely virulent African races, additional resistance genes must be identified from all possible gene pools. From the screening of a collection of wheat-rye (Secale cereale L.) chromosome substitution lines developed at the Swedish University of Agricultural Sciences, we described the line 'SLU238' 2R (2D) as possessing resistance to many races of P. graminis f. sp. tritici, including the widely virulent race TTKSK (isolate synonym Ug99) from Africa. The breakage-fusion mechanism of univalent chromosomes was used to produce a new Robertsonian translocation: T2DS·2RL. Molecular marker analysis and stem rust seedling assays at multiple generations confirmed that the stem rust resistance from 'SLU238' is present on the rye chromosome arm 2RL. Line TA5094 (#101) was derived from 'SLU238' and was found to be homozygous for the T2DS·2RL translocation. The stem rust resistance gene on chromosome 2RL arm was designated as Sr59. Although introgressions of rye chromosome arms into wheat have most often been facilitated by irradiation, this study highlights the utility of the breakage-fusion mechanism for rye chromatin introgression. Sr59 provides an additional asset for wheat improvement to mitigate yield losses caused by stem rust.

  12. Severe hemophilia A in a female by cryptic translocation: Order and orientation of factor VIII within Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Migeon, B.R.; McGinniss, M.J.; Antonarakis, S.E.; Axelman, J.; Stasiowski, B.A.; Youssoufian, H.; Kearns, W.G.; Chung, A.; Pearson, P.L.; Kazazian, H.H. Jr. (Johns Hopkins Univ., Baltimore, MD (United States)); Muneer, R.S. (Univ. of Oklahoma, Norman (United States))

    1993-04-01

    The authors report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X; 17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1--15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5[prime] end of F8C, but left the more proximal G6PD locus intact on the der(17)chromosome. As the deleted segment includes the 5[prime] half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5[prime] region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3[prime]F8C-5[prime]F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the pro-band, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X. 27 refs., 5 figs., 1 tab.

  13. Investigating the role of X chromosome breakpoints in premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Baronchelli Simona

    2012-07-01

    Full Text Available Abstract The importance of the genetic factor in the aetiology of premature ovarian failure (POF is emphasized by the high percentage of familial cases and X chromosome abnormalities account for 10% of chromosomal aberrations. In this study, we report the detailed analysis of 4 chromosomal abnormalities involving the X chromosome and associated with POF that were detected during a screening of 269 affected women. Conventional and molecular cytogenetics were valuable tools for locating the breakpoint regions and thus the following karyotypes were defined: 46,X,der(Xt(X;19(p21.1;q13.42mat, 46,X,t(X;2(q21.33;q14.3dn, 46,X,der(Xt(X;Y(q26.2;q11.223mat and 46,X,t(X;13(q13.3;q31dn. A bioinformatic analysis of the breakpoint regions identified putative candidate genes for ovarian failure near the breakpoint regions on the X chromosome or on autosomes that were involved in the translocation event. HS6ST1, HS6ST2 and MATER genes were identified and their functions and a literature review revealed an interesting connection to the POF phenotype. Moreover, the 19q13.32 locus is associated with the age of onset of the natural menopause. These results support the position effect of the breakpoint on flanking genes, and cytogenetic techniques, in combination with bioinformatic analysis, may help to improve what is known about this puzzling disorder and its diagnostic potential.

  14. Translocation of cell-penetrating peptides into Candida fungal pathogens.

    Science.gov (United States)

    Gong, Zifan; Karlsson, Amy J

    2017-09-01

    Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

  15. Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

    Directory of Open Access Journals (Sweden)

    Sun Jian-Sheng

    2006-01-01

    Full Text Available Abstract Background Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL, considers the spatial proximity of loci in interphase nuclei (static "contact first" model. The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model. Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4 and a less frequent partner gene (ENL, should elucidate the MLL translocation mechanism. Methods Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. Results In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value loci would indicate a greater probability of the occurrence of t(11;19(q23;p13.3 compared to t(4;11(q21;q23. However this is in contradiction to the epidemiology of 11q23 translocation. Conclusion The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation.

  16. Sorting genomes by reciprocal translocations, insertions, and deletions.

    Science.gov (United States)

    Qi, Xingqin; Li, Guojun; Li, Shuguang; Xu, Ying

    2010-01-01

    The problem of sorting by reciprocal translocations (abbreviated as SBT) arises from the field of comparative genomics, which is to find a shortest sequence of reciprocal translocations that transforms one genome Pi into another genome Gamma, with the restriction that Pi and Gamma contain the same genes. SBT has been proved to be polynomial-time solvable, and several polynomial algorithms have been developed. In this paper, we show how to extend Bergeron's SBT algorithm to include insertions and deletions, allowing to compare genomes containing different genes. In particular, if the gene set of Pi is a subset (or superset, respectively) of the gene set of Gamma, we present an approximation algorithm for transforming Pi into Gamma by reciprocal translocations and deletions (insertions, respectively), providing a sorting sequence with length at most OPT + 2, where OPT is the minimum number of translocations and deletions (insertions, respectively) needed to transform Pi into Gamma; if Pi and Gamma have different genes but not containing each other, we give a heuristic to transform Pi into Gamma by a shortest sequence of reciprocal translocations, insertions, and deletions, with bounds for the length of the sorting sequence it outputs. At a conceptual level, there is some similarity between our algorithm and the algorithm developed by El Mabrouk which is used to sort two chromosomes with different gene contents by reversals, insertions, and deletions.

  17. The effect of X-irradiation on the fertility and on the induction of meiotic chromosome rearrangements in mice and their first generation

    International Nuclear Information System (INIS)

    Savkovic, N.; Pecevski, J.; Maric, N.; Radivojevic, D.

    1980-01-01

    The effect of whole-body or local irradiation with X-rays at a dose of 600 R on the induction of chromosomal translocations in the diakinesis metaphase I of the meiosis in treated and F 1 males has been examined along with their fertility. Our results show the high percentage of mortality in whole-body irradiated mice. The percentage of the fertility was 25% in whole-body, and 93.7% in locally irradiated males. The testis weight was also reduced. The percentage of chromosomal translocations in diakinesis, metaphase I, of the meiosis was higher after whole-body irradiation than after local irradiation. In F 1 males both types of irradiation induced chromosomal translocations. (orig.) [de

  18. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation: Comprehensive progress report, January 1986--June 1988

    International Nuclear Information System (INIS)

    Rowley, J.D.

    1988-06-01

    I purchased one of the few available prototypes of the pulse field gel electrophoresis (PFGE) apparatus. We used PFGE and its various modifications to map the human Abelson protooncogene (ABL) and to show that the two alternative first exons (Ia and Ib) are separated by at least 200 kilobases (kb). This has provided the first evidence that alternative splicing from exon Ib to the common splice acceptor site (exon II) could occur over such very large distances. We are actively using vertical field gel electrophoresis, a modification of PFGE, for mapping various DNA probes on chromosome 5. Another major advance has been the development of the polymerase chain reaction (PCR). We are currently using this to define the breakpoints in the BCR gene in the 9; 22 translocation in chronic myeloid leukemia (CML) and in Ph 1 -positive acute lymphoblastic leukemia (ALL). I had expected to be able to describe major progress in cloning the chromosome translocation breakpoints in ANLL, and this has not occurred. Our laboratory knows how to solve the problem. We successfully cloned a new translocation breakpoint in B cell chronic lymphatic leukemia involving Nos. 14 and 19. 22 refs., 2 figs., 5 tabs

  19. Chronic Myeloid Leukemia with Variant Chromosomal Translocations: Results of Treatment with Imatinib Mesylate

    Directory of Open Access Journals (Sweden)

    Rohan Bhise

    2013-01-01

    Full Text Available Objective: To evaluate the efficacy of imatinib in chronic myeloid leukemia patients with variant translocations. Methods: Forty eight chronic myeloid leukemia patients carrying variant translocations and treated with imatinib at our institute were considered for the study. Survival and response rates were evaluated. Results: The median follow up was 48 months(m. Forty three (89.58% patients achieved complete hematologic response. Thirty one (64.58% patients achieved complete cytogenetic response and 19(39.58% achieved major molecular response anytime during their follow up period. Only 18.75% of the patients achieved complete cytogenetic response and major molecular response within the stipulated time frames.The estimated overall survival at 48 m median follow up was 81.2%.The progression free survival was also 81.2% and the event free survival was 79.1%.There was no significant survival difference between low vs intermediate and high risk sokal group. Conclusion: We report suboptimal responses to imatinib in chronic myeloid leukemia with variant translocations. Further studies with imatinib and the newer more active drugs dasatinib and nilotinib are justified.

  20. Chromosome abnormalities in atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Tomonaga, Y [Nagasaki Univ. (Japan). School of Medicine

    1976-09-01

    Chromosome abnormalities in bone marrow cells were recognized in 6 cases which consisted of one case of chronic myelogenous leukemia, two cases of acute myelogenous leukemia, one case of sideroblastic anemia, and two cases of myelodysplasis. Frequency of stable type chromosome abnormalities in bone marrow cells was investigated in 45 atomic bomb survivors without hematologic disorders and 15 controls. It was 1.4% (15 cases) in the group exposed to atomic bomb within 1 km from the hypocenter, which was significantly higher as compared with 0.1% (15 cases) in the group exposed to atomic bomb over 2.5 km from the hypocenter and 0.2% in normal controls. Examination of chromosome was also made on 2 of 3 cases which were the seconds born of female with high chromosome abnormality, who was exposed to within 1 km from the hypocenter, and healthy male exposed 3 km from the hypocenter. These two cases showed chromosome of normal male type, and balanced translocation was not recognized. There was not a significant difference in chromosome abnormalities between the seconds of atomic bomb survivors and controls.

  1. Impact of various parameters in detecting chromosomal aberrations by FISH to describe radiosensitivity

    International Nuclear Information System (INIS)

    Keller, U.; Mueller, E.; Grabenbauer, G.; Sauer, R.; Distel, L.; Kuechler, A.; Liehr, T.

    2004-01-01

    Background and purpose: analysis of radiation-induced chromosomal aberrations is regarded as the ''gold standard'' for classifying individual radiosensitivity. A variety of different parameters can be used. The crucial question, however, is to explore which parameter is suited best to describe the differences between patients with increased radiosensitivity and healthy individuals. Patients and methods: in this study, five patients with severe radiation-induced late effects of at least grade 3, classified according to the Radiation Therapy Oncology Group (RTOG), and eleven healthy individuals were examined retrospectively. Peripheral blood lymphocytes were irradiated in vitro with 0.7 Gy and 2.0 Gy prior to cultivation and stained by means of three-color fluorescence in situ hybridization (FISH). The detailed analysis was focused on the number of breaks per metaphase, on breaks from complex chromosomal rearrangements per metaphase, as well as on the percentage of translocations, dicentric chromosomes, breaks, and excess acentric fragments - each in comparison with the total number of mitoses analyzed. Results: using the number of breaks from complex chromosomal rearrangements after 2.0 Gy, radiosensitive patients as endpoint were clearly to be distinguished (p = 0.001) from healthy individuals. Translocations (p = 0.001) as well as breaks per metaphase (p = 0.002) were also suitable indicators for detecting differences between patients and healthy individuals. The parameters ''percentage of dicentric chromosomes'', ''breaks'', and ''excess acentric fragments'' in comparison to the total number of mitoses analyzed could neither serve as meaningful nor as significant criteria, since they showed a strong interindividual variability. Conclusion: to detect a difference in chromosomal aberrations between healthy and radiosensitive individuals, the parameters ''frequency of breaks per metaphase'', ''complex chromosomal rearrangements'', and ''translocations'' are most

  2. Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

    International Nuclear Information System (INIS)

    Gué, Michaël; Sun, Jian-Sheng; Boudier, Thomas

    2006-01-01

    Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static 'contact first' model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic 'breakage first' model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static 'contact first' model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static 'contact first' model of translocation. The recently proposed dynamic 'breakage first' model offers an attractive alternative explanation

  3. Chromosomal duplication strains of Aspergillus nidulans and their instability

    International Nuclear Information System (INIS)

    Azevedo, J.L. de; Almeida Okino, L.M. de

    1981-01-01

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

  4. Recurrence of Chromosome Rearrangements and Reuse of DNA Breakpoints in the Evolution of the Triticeae Genomes

    Directory of Open Access Journals (Sweden)

    Wanlong Li

    2016-12-01

    Full Text Available Chromosomal rearrangements (CRs play important roles in karyotype diversity and speciation. While many CR breakpoints have been characterized at the sequence level in yeast, insects, and primates, little is known about the structure of evolutionary CR breakpoints in plant genomes, which are much more dynamic in genome size and sequence organization. Here, we report identification of breakpoints of a translocation between chromosome arms 4L and 5L of Triticeae, which is fixed in several species, including diploid wheat and rye, by comparative mapping and analysis of the draft genome and chromosome survey sequences of the Triticeae species. The wheat translocation joined the ends of breakpoints downstream of a WD40 gene on 4AL and a gene of the PMEI family on 5AL. A basic helix-loop-helix transcription factor gene in 5AL junction was significantly restructured. Rye and wheat share the same position for the 4L breakpoint, but the 5L breakpoint positions are not identical, although very close in these two species, indicating the recurrence of 4L/5L translocations in the Triticeae. Although barley does not carry the translocation, collinearity across the breakpoints was violated by putative inversions and/or transpositions. Alignment with model grass genomes indicated that the translocation breakpoints coincided with ancient inversion junctions in the Triticeae ancestor. Our results show that the 4L/5L translocation breakpoints represent two CR hotspots reused during Triticeae evolution, and support breakpoint reuse as a widespread mechanism in all eukaryotes. The mechanisms of the recurrent translocation and its role in Triticeae evolution are also discussed.

  5. Sex chromosome diversity in Armenian toad grasshoppers (Orthoptera, Acridoidea, Pamphagidae)

    Science.gov (United States)

    Bugrov, Alexander G.; Jetybayev, Ilyas E.; Karagyan, Gayane H.; Rubtsov, Nicolay B.

    2016-01-01

    Abstract Although previous cytogenetic analysis of Pamphagidae grasshoppers pointed to considerable karyotype uniformity among most of the species in the family, our study of species from Armenia has discovered other, previously unknown karyotypes, differing from the standard for Pamphagidae mainly in having unusual sets of sex chromosomes. Asiotmethis turritus (Fischer von Waldheim, 1833), Paranocaracris rubripes (Fischer von Waldheim, 1846), and Nocaracris cyanipes (Fischer von Waldheim, 1846) were found to have the karyotype 2n♂=16+neo-XY and 2n♀=16+neo-XX, the neo-X chromosome being the result of centromeric fusion of an ancient acrocentric X chromosome and a large acrocentric autosome. The karyotype of Paranothrotes opacus (Brunner von Wattenwyl, 1882) was found to be 2n♂=14+X1X2Y and 2n♀=14+X1X1X2X2., the result of an additional chromosome rearrangement involving translocation of the neo-Y and another large autosome. Furthermore, evolution of the sex chromosomes in these species has involved different variants of heterochromatinization and miniaturization of the neo-Y. The karyotype of Eremopeza festiva (Saussure, 1884), in turn, appeared to have the standard sex determination system described earlier for Pamphagidae grasshoppers, 2n♂=18+X0 and 2n♀=18+XX, but all the chromosomes of this species were found to have small second C-positive arms. Using fluorescent in situ hybridization (FISH) with 18S rDNA and telomeric (TTAGG)n DNA repeats to yield new data on the structural organization of chromosomes in the species studied, we found that for most of them, clusters of repeats homologous to 18S rDNA localize on two, three or four pairs of autosomes and on the X. In Eremopeza festiva, however, FISH with labelled 18S rDNA painted C-positive regions of all autosomes and the X chromosome; clusters of telomeric repeats localized primarily on the ends of the chromosome arms. Overall, we conclude that the different stages of neo-Y degradation revealed in

  6. Characterization of a panel of somatic cell hybrids for regional mapping of the mouse X chromosome

    International Nuclear Information System (INIS)

    Avner, P.; Arnaud, D.; Amar, L.; Cambrou, J.; Winking, H.; Russell, L.B.

    1987-01-01

    A panel of five hybrid cell lines containing mouse X chromosomes with various deletions has been obtained by fusing splenocytes from male mice carrying one of a series of reciprocal X-autosome translocations with the azaguanine-resistant Chinese hamster cell line CH3g. These hybrids have been extensively characterized by using the allozymes hypoxanthine/guanine phosphoribosyltransferase (encoded by the Hprt locus) and α-galactosidase (Ags) and a series of 11 X-chromosome-specific DNA probes whose localization had been previously established by linkage studies. Such studies have established the genetic breakpoints of the T(X;12)13R1 and T(X;2)14R1 X-autosome translocations on the X chromosome and provided additional information as to the X-chromosome genetic breakpoints of the T(X;16)16H, T(X;4)7R1, and T(X;7)6R1 translocations. The data establish clearly that both the T(X;7)5RI and T(X;12)13R1 X-chromosome breakpoints are proximal to Hprt, the breakpoint of the former being more centromeric, lying as it does in the 9-centimorgan interval between the ornithine transcarbamoylase (Otc) and DXPas7 (M2C) loci. These five hybrid cell lines provide, with the previously characterized EBS4 hybrid cell line, a nested series of seven mapping intervals distributed along the length of the mouse X chromosome. Their characterization not only allows further correlation of the genetic and cytological X-chromosome maps but also should permit the rapid identification of DNA probes specific for particular regions of the mouse X chromosome

  7. Polytene chromosome analysis in relation to genetic sex separation in the Mediterranean fruit fly, Ceratitis capitata (Wied.)

    International Nuclear Information System (INIS)

    Kerremans, P.; Busch-Petersen, E.

    1990-01-01

    The development of stable genetic sexing strains in the Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann), is hampered by the presence of low levels of male recombination. Such recombination may be reduced by minimizing the distance between the translocation breakpoint and the translocated 'sexing' allele. Cytogenetic analysis of mitotic/meiotic and polytene chromosomes could provide information on the selection of such potentially stable genetic sexing strains. Translocation breakpoints in two genetic sexing strains in the medfly, based on a white female/brown male pupal colour dimorphism, have been determined. Preliminary results are described and the advantages and limitations of polytene chromosome analysis for the isolation of stable genetic sexing strains of the medfly are discussed. (author). 31 refs

  8. Development of T. aestivum L.-H. californicum alien chromosome lines and assignment of homoeologous groups of Hordeum californicum chromosomes.

    Science.gov (United States)

    Fang, Yuhui; Yuan, Jingya; Wang, Zhangjun; Wang, Haiyan; Xiao, Jin; Yang, Zhixi; Zhang, Ruiqi; Qi, Zengjun; Xu, Weigang; Hu, Lin; Wang, Xiu-E

    2014-08-20

    Hordeum californicum (2n = 2x = 14, HH) is resistant to several wheat diseases and tolerant to lower nitrogen. In this study, a molecular karyotype of H. californicum chromosomes in the Triticum aestivum L. cv. Chinese Spring (CS)-H. californicum amphidiploid (2n = 6x = 56, AABBDDHH) was established. By genomic in situ hybridization (GISH) and multicolor fluorescent in situ hybridization (FISH) using repetitive DNA clones (pTa71, pTa794 and pSc119.2) as probes, the H. californicum chromosomes could be differentiated from each other and from the wheat chromosomes unequivocally. Based on molecular karyotype and marker analyses, 12 wheat-alien chromosome lines, including four disomic addition lines (DAH1, DAH3, DAH5 and DAH6), five telosomic addition lines (MtH7L, MtH1S, MtH1L, DtH6S and DtH6L), one multiple addition line involving H. californicum chromosome H2, one disomic substitution line (DSH4) and one translocation line (TH7S/1BL), were identified from the progenies derived from the crosses of CS-H. californicum amphidiploid with common wheat varieties. A total of 482 EST (expressed sequence tag) or SSR (simple sequence repeat) markers specific for individual H. californicum chromosomes were identified, and 47, 50, 45, 49, 21, 51 and 40 markers were assigned to chromosomes H1, H2, H3, H4, H5, H6 and H7, respectively. According to the chromosome allocation of these markers, chromosomes H2, H3, H4, H5, and H7 of H. californicum have relationship with wheat homoeologous groups 5, 2, 6, 3, and 1, and hence could be designated as 5H(c), 2H(c), 6H(c), 3H(c) and 1H(c), respectively. The chromosomes H1 and H6 were designated as 7H(c) and 4H(c), respectively, by referring to SSR markers located on rye chromosomes. Copyright © 2014 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  9. Chromosomal phylogeny of Lagothrix, Brachyteles, and Cacajao.

    Science.gov (United States)

    Viegas Péquignot, E; Koiffmann, C P; Dutrillaux, B

    1985-01-01

    Based on a comparison of the karyotypes of two Plathyrrhini species, Cacajao melanocephalus (Pitheciinae) and Brachyteles arachnoides (Atelinae), with those of two previously studied species, Lagothrix lagothrica (Atelinae) and C calvus rubicundus (Pitheciinae), it appears that the two Cacajao species have undergone the same number of chromosome rearrangements since they diverged from their common ancestor and that the karyotype of Brachyteles is ancestral to that of Lagothrix. The chromosomal phylogeny of these four species is proposed. A Y-autosome translocation is present in the karyotypes of the two Cacajao species.

  10. Mechanisms of induction of chromosomal aberrations and their detection by fluorescence in situ hybridization

    International Nuclear Information System (INIS)

    Natarajan, A.T.

    2002-01-01

    Recently introduced fluorescence in situ hybridization (FISH) technique employing chromosome specific DNA libraries as well as region specific DNA probes (e.g., centromere, telomere) have helped to analyse chromosomal aberrations in great detail and thus have given some new insights into the mechanisms of induction of chromosomal aberrations. The relative proportion of induction of translocations and dicentrics by ionising radiation was studied in human, mice and Chinese hamster cells. Many of the studies point to the differences between the mechanisms of induction of dicentrics and translocations. Preliminary results obtained in our laboratory using arm specific probes for human chromosomes 1 and 3 indicate that the aberrations between the arms appear to be more than expected on a random basis. By employing telomeric probes the frequencies of interstitial deletions were found to be high and similar to the frequencies of dicentrics both in human and mouse lymphocytes. A recent study with human chromosome specific probes clearly shows variation of sensitivity of chromosomes for the induction of exchange aberrations. Radiation response studies with Chinese hamster cells using telomeric probes, suggest that telomeric sequences, especially interstitial ones appear to be an important factor in the origin of both spontaneous and induced chromosomal aberrations

  11. Molecular mechanisms involved in the production of chromosomal aberrations. I

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Obe, G.

    1978-01-01

    Chinese hamster ovary cells (CHO) were X-irradiated in G2 stage of the cell cycle and immediately treated, in the presence of inactivated Sendai virus, with Neurospora endonuclease (E.C. 3.1.4.), an enzyme which is specific for cleaving single-stranded DNA. With this treatment, the frequencies of all types of chromosome aberrations increased when compared to X-irradiated controls. These results are interpreted as due to the conversion of some of the X-ray induced single-stranded DNA breaks into double-strand breaks by this enzyme. Similar enhancement due to this enzyme was found following treatment with methyl methanesulfonate (MMS) and bleomycin, but not following UV and mitomycin C. Addition of Micrococcus endonuclease and Neurospora endonuclease to the cells did not alter the frequencies of aberrations induced by UV. The introduction of enzymes with specific DNA-repair function offers possibilities to probe into the molecular events involved in the formation of structural chromosome aberrations induced by different classes of physical and chemical mutagens. (Auth.)

  12. A case of an atypically large proximal 15q deletion as cause for Prader-Willi syndrome arising from a de novo unbalanced translocation.

    Science.gov (United States)

    Hickey, Scott E; Thrush, Devon Lamb; Walters-Sen, Lauren; Reshmi, Shalini C; Astbury, Caroline; Gastier-Foster, Julie M; Atkin, Joan

    2013-09-01

    We describe an 11 month old female with Prader-Willi syndrome (PWS) resulting from an atypically large deletion of proximal 15q due to a de novo 3;15 unbalanced translocation. The 10.6 Mb deletion extends from the chromosome 15 short arm and is not situated in a region previously reported as a common distal breakpoint for unbalanced translocations. There was no deletion of the reciprocal chromosome 3q subtelomeric region detected by either chromosomal microarray or FISH. The patient has hypotonia, failure to thrive, and typical dysmorphic facial features for PWS. The patient also has profound global developmental delay consistent with an expanded, more severe, phenotype. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Chromosomal aberrations induced by low-dose γ-irradiation: Study of R-banded chromosomes of human lymphocytes

    International Nuclear Information System (INIS)

    Al-Achkar, W.; Lefrancois, D.; Aurias, A.

    1991-01-01

    The effect of low-dose (0-0.5 Gy) γ-radiations was studied on R-banded chromosomes from lymphocytes of healthy donors of various ages. In cells from newborns, an increase of chromosome damage roughly proportional to the dose was found. In lymphocytes from young adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults not even at 0.2 Gy. The difficulty in detecting aberrations in lymphocytes from adults is largely due to a considerable background of chromosomal anomalies which should be borne in mind in dosimetry studies. The rate of induction largely depends on the types of rearrangements. One-break terminal deletions are efficiently induced at 0.1 and 0.2 Gy and are the best indicators of exposure at these doses. At 0.5 Gy, the frequencies of 2-break lesions, i.e., dicentrics and reciprocal translocations, increase, whereas the of deletions decreases. (author). 6 refs., 3 figs., 2 tabs

  14. Chromosomal Diversity and Karyotype Evolution in South American Macaws (Psittaciformes, Psittacidae.

    Directory of Open Access Journals (Sweden)

    Ivanete de Oliveira Furo

    Full Text Available Most species of macaws, which represent the largest species of Neotropical Psittacidae, characterized by their long tails and exuberant colours, are endangered, mainly because of hunting, illegal trade and habitat destruction. Long tailed species seem to represent a monophyletic group within Psittacidae, supported by cytogenetic data. Hence, these species show karyotypes with predominance of biarmed macrochromosomes, in contrast to short tailed species, with a predominance of acro/telocentric macrochromosomes. Because of their similar karyotypes, it has been proposed that inversions and translocations may be the main types of rearrangements occurring during the evolution of this group. However, only one species of macaw, Ara macao, that has had its genome sequenced was analyzed by means of molecular cytogenetics. Hence, in order to verify the rearrangements, we analyzed the karyotype of two species of macaws, Ara chloropterus and Anodorhynchus hyacinthinus, using cross-species chromosome painting with two different sets of probes from chicken and white hawk. Both intra- and interchromosomal rearrangements were observed. Chicken probes revealed the occurrence of fusions, fissions and inversions in both species, while the probes from white hawk determined the correct breakpoints or chromosome segments involved in the rearrangements. Some of these rearrangements were common for both species of macaws (fission of GGA1 and fusions of GGA1p/GGA4q, GGA6/GGA7 and GGA8/GGA9, while the fissions of GGA 2 and 4p were found only in A. chloropterus. These results confirm that despite apparent chromosomal similarity, macaws have very diverse karyotypes, which differ from each other not only by inversions and translocations as postulated before, but also by fissions and fusions.

  15. Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hengwen [Department of Radiation, Cancer Center of Guangdong General Hospital (Guangdong Academy of Medical Science), Guangzhou, 510080, Guangdong (China); Yang, Shana; Li, Jianhua [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Gao, Dongsheng [Department of Oncology, Guangdong Medical College Affiliated Pengpai Memorial Hospital, Hai Feng, 516400, Gungdong (China); Zhao, Shenting, E-mail: zhaoshenting@126.com [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China)

    2016-03-25

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.

  16. Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

    International Nuclear Information System (INIS)

    Sun, Hengwen; Yang, Shana; Li, Jianhua; Zhang, Yajie; Gao, Dongsheng; Zhao, Shenting

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.

  17. A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

    Energy Technology Data Exchange (ETDEWEB)

    Naiel, Abdulbasit [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom); Vetter, Michael [MetaSystems, Altlussheim 68804 (Germany); Plekhanova, Olga [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Fleischman, Elena; Sokova, Olga [N.N. Blokhin Russian Cancer Research Center Russian Academy of Medical Science, Moscow 115478 (Russian Federation); Tsaur, Grigory [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Research Institute of Medical Cell Technologies, Ekaterinburg 620149 (Russian Federation); Harbott, Jochen [Oncogenetic Laboratory, Department of Paediatric Haematology and Oncology, Justus Liebig University, Giessen 35392 (Germany); Tosi, Sabrina, E-mail: sabrina.tosi@brunel.ac.uk [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom)

    2013-03-11

    The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting.

  18. Clinical Utility of Array Comparative Genomic Hybridization for Detection of Chromosomal Abnormalities in Pediatric Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Rabin, Karen R.; Man, Tsz-Kwong; Yu, Alexander; Folsom, Matthew R.; Zhao, Yi-Jue; Rao, Pulivarthi H.; Plon, Sharon E.; Naeem, Rizwan C.

    2014-01-01

    Background Accurate detection of recurrent chromosomal abnormalities is critical to assign patients to risk-based therapeutic regimens for pediatric acute lymphoblastic leukemia (ALL). Procedure We investigated the utility of array comparative genomic hybridization (aCGH) for detection of chromosomal abnormalities compared to standard clinical evaluation with karyotype and fluorescent in-situ hybridization (FISH). Fifty pediatric ALL diagnostic bone marrows were analyzed by bacterial artificial chromosome (BAC) array, and findings compared to standard clinical evaluation. Results Sensitivity of aCGH was 79% to detect karyotypic findings other than balanced translocations, which cannot be detected by aCGH because they involve no copy number change. aCGH also missed abnormalities occurring in subclones constituting less than 25% of cells. aCGH detected 44 additional abnormalities undetected or misidentified by karyotype, 21 subsequently validated by FISH, including abnormalities in 4 of 10 cases with uninformative cytogenetics. aCGH detected concurrent terminal deletions of both 9p and 20q in three cases, in two of which the 20q deletion was undetected by karyotype. A narrow region of loss at 7p21 was detected in two cases. Conclusions An array with increased BAC density over regions important in ALL, combined with PCR for fusion products of balanced translocations, could minimize labor- and time-intensive cytogenetic assays and provide key prognostic information in the approximately 35% of cases with uninformative cytogenetics. PMID:18253961

  19. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  20. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  1. Comparative physical mapping between wheat chromosome arm 2BL and rice chromosome 4.

    Science.gov (United States)

    Lee, Tong Geon; Lee, Yong Jin; Kim, Dae Yeon; Seo, Yong Weon

    2010-12-01

    Physical maps of chromosomes provide a framework for organizing and integrating diverse genetic information. DNA microarrays are a valuable technique for physical mapping and can also be used to facilitate the discovery of single feature polymorphisms (SFPs). Wheat chromosome arm 2BL was physically mapped using a Wheat Genome Array onto near-isogenic lines (NILs) with the aid of wheat-rice synteny and mapped wheat EST information. Using high variance probe set (HVP) analysis, 314 HVPs constituting genes present on 2BL were identified. The 314 HVPs were grouped into 3 categories: HVPs that match only rice chromosome 4 (298 HVPs), those that match only wheat ESTs mapped on 2BL (1), and those that match both rice chromosome 4 and wheat ESTs mapped on 2BL (15). All HVPs were converted into gene sets, which represented either unique rice gene models or mapped wheat ESTs that matched identified HVPs. Comparative physical maps were constructed for 16 wheat gene sets and 271 rice gene sets. Of the 271 rice gene sets, 257 were mapped to the 18-35 Mb regions on rice chromosome 4. Based on HVP analysis and sequence similarity between the gene models in the rice chromosomes and mapped wheat ESTs, the outermost rice gene model that limits the translocation breakpoint to orthologous regions was identified.

  2. X-autosome translocation and low fertility in a family of crossbred cattle.

    Science.gov (United States)

    Basrur, P K; Reyes, E R; Farazmand, A; King, W A; Popescu, P C

    2001-07-03

    An investigation was carried out on a family of Limousin-Jersey crossbreds exhibiting low fertility in the females, to determine the impact of a previously identified X-autosome translocation (X-AT) on the reproductive performance of the carrier cows. Three of the identified translocation carriers, including a cow and two of her daughters, were maintained at our University Research Station and artificially inseminated periodically with semen from different bulls of known fertility. Attempts to breed the X-AT carriers resulted in high rates of return to estrus between days 28 and 60, abortions between days 121 and 235 after insemination, and a total of 13 live births including 4 translocation carrier calves. Results of superovulation and embryo retrieval trials on X-AT carriers revealed significantly higher proportions of unfertilized and uncleaved ova and abnormal embryos compared to those from normal cows, and no pregnancy in the recipients transferred with morphologically normal blastocysts from X-AT carriers. While the higher rates of failed fertilization and cleavage, abnormal embryos and return to estrus in X-AT carriers could be attributed to chromosome imbalance expected in their gametes, the relatively high prevalence of abortion (late in gestation) was unexpected. Our observations on the fetuses expelled by X-AT carriers after 5 months of gestation indicated that a majority (three out of four) of these fetuses were products of abnormal (3:1) segregation in meiosis I and that these chromosomally unbalanced (hyperdiploid) conceptuses were able to survive early embryogenesis and fetal life up to the end of the second trimester. We hypothesize that their relatively long in utero life and the absence of any overt birth defects may be attributable to the type of chromosomes over-represented in these fetuses and that their eventual expulsion may have been the result of selection against the clonal population of cells in which the altered X carrying a segment of

  3. Complex distal 10q rearrangement in a girl with mild intellectual disability: follow up of the patient and review of the literature of non-acrocentric satellited chromosomes.

    Science.gov (United States)

    Sarri, Catherine; Douzgou, Sofia; Gyftodimou, Yolanda; Tümer, Zeynep; Ravn, Kirstine; Pasparaki, Angela; Sarafidou, Theologia; Kontos, Harry; Kokotas, Haris; Karadima, Georgia; Grigoriadou, Maria; Pandelia, Effie; Theodorou, Virginia; Moschonas, Nicholas K; Petersen, Michael B

    2011-11-01

    We report on an intellectually disabled girl with a de novo satellited chromosome 10 (10qs) and performed a review of the literature of the non-acrocentric satellited chromosomes (NASC). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited non-acrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is, to our knowledge, the third report of a 10qs chromosome. The phenotype observed in the proband prompted a search for a structural rearrangement of chromosome 10q. By microsatellite analysis we observed a 4 Mb deletion on the long arm of chromosome 10, approximately 145 kb from the telomere. FISH and array CGH analyses revealed a complex rearrangement involving in range from the centromere to the telomere: A 9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region with no copy number change, followed by a 5.62 Mb 10q26.2-q26.3 deletion and a translocation of satellite material. The homology between the repeat sequences at 10q subtelomere region and the sequences on the acrocentric short arms may explain the origin of the rearrangement and it is likely that the submicroscopic microdeletion and microduplication are responsible for the abnormal phenotype in our patient. The patient presented here, with a 15-year follow-up, manifests a distinct phenotype different from the 10q26 pure distal monosomy and trisomy syndromes. Copyright © 2011 Wiley Periodicals, Inc.

  4. Verification by the FISH translocation assay of historic doses to Mayak workers from external gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Sotnik, Natalia V.; Azizova, Tamara V. [Southern Urals Biophysics Institute (SUBI), Ozyorsk, Chelyabinsk Region (Russian Federation); Darroudi, Firouz [Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); College of North Atlantic, Department of Health Science, Centre for Human Safety and Environmental Research, Doha (Qatar); Ainsbury, Elizabeth A.; Moquet, Jayne E.; Lloyd, David C.; Hone, Pat A.; Edwards, Alan A. [Public Health England, Chilton, Oxfordshire (United Kingdom); Fomina, Janna [Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands)

    2015-11-15

    The aim of this study was to apply the fluorescence in situ hybridization (FISH) translocation assay in combination with chromosome painting of peripheral blood lymphocytes for retrospective biological dosimetry of Mayak nuclear power plant workers exposed chronically to external gamma radiation. These data were compared with physical dose estimates based on monitoring with badge dosimeters throughout each person's working life. Chromosome translocation yields for 94 workers of the Mayak production association were measured in three laboratories: Southern Urals Biophysics Institute, Leiden University Medical Center and the former Health Protection Agency of the UK (hereinafter Public Health England). The results of the study demonstrated that the FISH-based translocation assay in workers with prolonged (chronic) occupational gamma-ray exposure was a reliable biological dosimeter even many years after radiation exposure. Cytogenetic estimates of red bone marrow doses from external gamma rays were reasonably consistent with dose measurements based on film badge readings successfully validated in dosimetry system ''Doses-2005'' by FISH, within the bounds of the associated uncertainties. (orig.)

  5. Chromosome abnormalities in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tomonaga, Yu

    1976-01-01

    Chromosome abnormalities in bone marrow cells were recognized in 6 cases which consisted of one case of chronic myelogenous leukemia, two cases of acute myelogenous leukemia, one case of sideroblastic anemia, and two cases of myelodysplasis. Frequency of stable type chromosome abnormalities in bone marrow cells was investigated in 45 atomic bomb survivors without hematologic disorders and 15 controls. It was 1.4% (15 cases) in the group exposed to atomic bomb within 1 km from the hypocenter, which was significantly higher as compared with 0.1% (15 cases) in the group exposed to atomic bomb over 2.5 km from the hypocenter and 0.2% in normal controls. Examination of chromosome was also made on 2 of 3 cases which were the seconds born of female with high chromosome abnormality, who was exposed to within 1 km from the hypocenter, and healthy male exposed 3 km from the hypocenter. These two cases showed chromosome of normal male type, and balanced translocation was not recognized. There was not a significant difference in chromosome abnormalities between the seconds of atomic bomb survivors and controls. (Kanao, N.)

  6. Molecular breakpoint cloning and gene expression studies of a novel translocation t(4;15(q27;q11.2 associated with Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Slater Howard R

    2005-05-01

    Full Text Available Abstract Background Prader-Willi syndrome (MIM #176270; PWS is caused by lack of the paternally-derived copies, or their expression, of multiple genes in a 4 Mb region on chromosome 15q11.2. Known mechanisms include large deletions, maternal uniparental disomy or mutations involving the imprinting center. De novo balanced reciprocal translocations in 5 reported individuals had breakpoints clustering in SNRPN intron 2 or exon 20/intron 20. To further dissect the PWS phenotype and define the minimal critical region for PWS features, we have studied a 22 year old male with a milder PWS phenotype and a de novo translocation t(4;15(q27;q11.2. Methods We used metaphase FISH to narrow the breakpoint region and molecular analyses to map the breakpoints on both chromosomes at the nucleotide level. The expression of genes on chromosome 15 on both sides of the breakpoint was determined by RT-PCR analyses. Results Pertinent clinical features include neonatal hypotonia with feeding difficulties, hypogonadism, short stature, late-onset obesity, learning difficulties, abnormal social behavior and marked tolerance to pain, as well as sticky saliva and narcolepsy. Relative macrocephaly and facial features are not typical for PWS. The translocation breakpoints were identified within SNRPN intron 17 and intron 10 of a spliced non-coding transcript in band 4q27. LINE and SINE sequences at the exchange points may have contributed to the translocation event. By RT-PCR of lymphoblasts and fibroblasts, we find that upstream SNURF/SNRPN exons and snoRNAs HBII-437 and HBII-13 are expressed, but the downstream snoRNAs PWCR1/HBII-85 and HBII-438A/B snoRNAs are not. Conclusion As part of the PWCR1/HBII-85 snoRNA cluster is highly conserved between human and mice, while no copy of HBII-438 has been found in mouse, we conclude that PWCR1/HBII-85 snoRNAs is likely to play a major role in the PWS- phenotype.

  7. Frequencies of X-ray induced chromosome aberrations in lymphocytes of xeroderma pigmentosum and Fanconi anemia patients estimated by Giemsa and fluorescence in situ hybridization staining techniques

    Directory of Open Access Journals (Sweden)

    Saraswathy Radha

    2000-01-01

    Full Text Available Blood lymphocytes from xeroderma pigmentosum (XP and Fanconi anemia (FA patients were assessed for their sensitivity to ionizing radiation by estimating the frequency of X-ray (1 and 2 Gy-induced chromosome aberrations (CA. The frequencies of aberrations in the whole genome were estimated in Giemsa-stained preparations of lymphocytes irradiated at G0 or G2 stages. The frequencies of translocations and dicentrics involving chromosomes 1 and 3 as well as the X-chromosome were determined in slides stained by fluorescence in situ hybridization (FISH technique. An increase in all types of CA was observed in XP and FA lymphocytes irradiated at G0 when compared to controls. The frequency of dicentrics and rings was 6 to 27% higher (at 1 and 2 Gy in XP lymphocytes and 37% higher (at 2 Gy in FA lymphocytes than in controls, while chromosome deletions were higher in irradiated (30% in 1 Gy and 72% in 2 Gy than in control XP lymphocytes and 28 to 102% higher in FA lymphocytes. In G2-irradiated lymphocytes the frequency of CA was 24 to 55% higher in XP lymphocytes than in controls. In most cases the translocation frequencies were higher than the frequencies of dicentrics (21/19.

  8. Chromosomal Abnormalities Associated With Omphalocele

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-03-01

    Full Text Available Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q, dup(11p, inv(11, dup(1q, del(1q, dup(4q, dup(5p, dup(6q, del(9p, dup(15q, dup(17q, Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.

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

    Science.gov (United States)

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

    1992-11-01

    We report two families with a satellited chromosome 4 short arm (4ps). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited nonacrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is the first report of 4ps chromosomes. Our families are remarkable in that both unaffected and affected individuals carry the 4ps chromosome. The phenotypes observed in affected individuals, although dissimilar, were sufficient to encourage a search for a deletion of chromosome 4p. By Southern blot analysis and fluorescence in situ hybridization, a deletion of material mapping approximately 150 kb from chromosome 4pter was discovered. This deletion is notable because it does not result in the Wolf-Hirschhorn syndrome and can result in an apparently normal phenotype. We speculate that homology between subterminal repeat sequences on 4p and sequences on the acrocentric short arms may explain the origin of the rearrangement and that position effect may play a role in the expression of the abnormal phenotype.

  10. Estudo cromossômico no sangue periférico de pacientes com diferentes tipos de leucemia do Hospital de Base, São José do Rio Preto - SP Chromosomal study of peripheral blood in patients with different types of leukemia from Hospital de Base, São José do Rio Preto - SP

    Directory of Open Access Journals (Sweden)

    Agnes C. Fett-Conte

    2000-12-01

    Full Text Available A análise das alterações cromossômicas em leucemias tem uma aplicação direta no diagnóstico, prognóstico e tratamento dos pacientes. Além disso, permite o entendimento dos processos biológicos envolvidos na carcinogênese. Este trabalho apresenta os resultados do estudo cariotípico de 51 casos de diferentes tipos de leucemias. Os cromossomos foram obtidos através de cultura de células de sangue periférico, realizadas por 24 ou 48 horas, sem estimulação mitogênica. Em 74% dos pacientes foram observadas anomalias cromossômicas clonais como translocações, deleções, monossomias e trissomias. Muitas alterações foram compatíveis com outras previamente descritas e outras não, como a translocação envolvendo os cromossomos 9 e 22, que origina o cromossomo Philadelphia e uma translocação complexa envolvendo os cromossomos 4, 7 e 11. Os resultados reforçam a importância da análise cromossômica em leucemia e seus benefícios para o paciente.The analysis of chromosomal changes in leukemia has had a direct involvement in the diagnosis, prognosis and treatment of patients. Furthermore, it has allowed the understanding of biological processes involved in carcinogenesis. This work presents the results of a kariotypic study of 51 cases of different types of leukemia. The chromosomes were obtained through a 24 or 48 hour culture of cells of the peripheral blood with no mitogenic stimulation. In 74,5% of patients clonal chromosomic abnormalities were observed such as translocations, deletions, monosomies and trisomies. Many of the alterations were similar to results previously published and others were not such as the translocation involving the chromosomes 9 and 22, which leads to the Philadelphia chromosome and the complex translocation involving the chromosomes 4, 7 and 11. The results emphasized the importance of chromosomal analysis in leukemia, its benefits to the patient and to the knowledge of the biological mechanisms

  11. Characterization of human chromosome 22 : Cloning of breakpoints of the constitutional translocation t(11;22)(q23;q11) and detection of small constitutional delections by microarray CGH

    OpenAIRE

    Tapia Paez, Isabel

    2003-01-01

    Chromosome 22 is the second smallest human chromosome, composing approximately 1.5% of the genome. The short arm of this acrocentric chromosome harbors ribosomal genes and the long arm contains the protein coding genes. This chromosome is gene-rich in comparison to the majority of other chromosomes, containing approximately 600 so far characterized genes. Many of these are involved in the etiology of a wide spectrum of diseases such as congenital and psychiatric disorders as...

  12. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L Is Associated with Chromosome Rearrangements.

    Directory of Open Access Journals (Sweden)

    Laura B Dickson

    2016-04-01

    staining was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3.

  13. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements

    Science.gov (United States)

    Dickson, Laura B.; Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Fleming, Karen L.; Caspary, Alex; Sylla, Massamba; Black, William C.

    2016-01-01

    was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere) inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3. PMID:27105225

  14. Aberrations of holokinetic chromosomes and associated lethality after X-irradiation of meiotic stages in Tetranychus urticae Koch (acari, tetranychidae)

    International Nuclear Information System (INIS)

    Tempelaar, M.J.

    1979-01-01

    Chromosomes of the holokinetic organization type were irradiated with X-rays in various stages of meiosis in unfertillized eggs of Tetranychus urticae Koch. Visible cytological aberrations, lethality and sterility were investigated in subsequent generations. Chromosome fragments are the most frequently occuring light-microscopically visible chromosome aberrations; bridges are not formed. Contrary to expectations, the presence of fragments appears to be positively correlated with the occurrence of lethality; loss of fragments, missegregation and the measure of damage of the broken chromosome parts are involved. In contrast with monokinetic chromosomes the earliest lethality occurs only after about 10 divisions. The ratios between different embryonic lethality types (early vs. late) differ depending on the stage irradiated: in more compact chromatin, more serious damage (i.e. more early lethality syndromes) is induced than in less compact chromatin. In the progeny of the surviving males, neither translocations nor independent fragments are found; indirect evidence indicated the occasional presence of inversions. The presumtive inversions are induced more frequently in a chromatin-compact stage (metaphase I) than in a less compact one (telophase I). (Auth.)

  15. Chromosome aberrations in cultured skin cells obtained from atomic bomb survivors

    International Nuclear Information System (INIS)

    Honda, Takeo; Sadamori, Naoki.

    1989-01-01

    Skin specimens were obtained from 11 A-bomb survivors, 10 of whom had been exposed at ≤2300 m from the hypocenter, and 7 non-exposed controls. There was a higher frequency (12%, 147/1222 cells) of chromosome aberrations in the exposed group compared with 1.2% (4/341 cells) in the control group. This suggests that aberrant cells are still present in the skin tissue 40 years or more after the bombing. Of 147 cells, 136 cells (91.3%) showed translocation of chromosome. Other aberrations, such as inversion, deletion, dicentric chromosome and acentric fragment, were observed in only 3.8%. These aberrant cells tended to be observed in A-bomb survivors exposed to high doses and with a history of severe acute symptoms. One hundred and twenty two (83%) of 136 aberrant cells were obtained from 3 A-bomb survivors, which has important implications for marked proliferation of specific clone cells. In an analysis by B-band staining technique for the 122 cells, band sites of break point were found to correspond to loci of protooncogenes, suggesting the involvement in aggressive proliferation of clone cells. (Namekawa, K)

  16. Meiotic and mitotic analyses of a reciprocal translocation in pisum sativum

    International Nuclear Information System (INIS)

    Muller, D.

    1974-01-01

    After X-irradiation of air-dried seeds of Pisum sativum, mutant 210 A was selected on the basis of the characteristic 'low number of seeds per pod', that segregates during following generations. Studies of pollen show a reduced fertility of 49.4% in about 50% of the plants. In meiotic metaphase I association of 4 chromosomes were observed in about 90% PMC in which more than half showed co-orientation of centromeres. A 3:1 segregation of the 4 linking chromosomes appeared in about 24% of all cases. Laggards, bridges and fragments reached a frequency of 11% in anaphase II. Seed production per pod in 2 vegetative periods varied from 63-67%; seed setting per plant fluctuated in the same year, between 55% and 43%. The analysis of karyotype proved the presumption of a simple reciprocal translocation. The exchange occurred between the long arms of the chromosomes 3 and 5. The break position is believed to be situated near the centromers of chromosome 3 and the lower half of the long arm of chromosome 5. (author)

  17. Influence of chromosome territory morphology and nuclear distribution on exchange frequencies: comparison between experiment and simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kreth, G.; Hase, J.V.; Finsterle, J.; Cremer, C. [Kirchhoff Institute for Physics, INF, Heidelber (Germany); Greulich, K. [German Cancer Research Center, INF, Heidelberg (Germany); Cremer, M. [Institute of Anthropology and Human Genetics, Muenchen (Germany)

    2003-07-01

    To explore the influence of chromosome territory morphology and the positioning of certain chromosomes in the nuclear volume on aberration frequencies, in the present study geometric computer models of all Chromosome Territories (CTs) in a human cell nucleus were used to investigate these constraints quantitatively. For this purpose a geometric representation of a CT in a given nuclear volume was approximated by a linear polymer chain of 500 nm sized spherical 1 Mbp domains connected by entropic spring potentials. The morphology aspect was investigated for the active and inactive X-chromosome of female cells. Assuming a statistical distribution of Xa, Xi and the autosomes a quite good agreement of virtually calculated translocation break frequencies with observed frequencies determined from Hiroshima A-bomb survivors was found. To regard in a first step the aspect of the experimentally observed different locations of certain chromosomes, a simulated gene density correlated distribution of modeled lymphocytes was realized. The respective calculated translocation frequencies were compared with fish experiments of irradiated lymphocyte cells. (author)

  18. Retrospective Dose Reconstruction for Medical Diagnostic X Ray Workers in China using Stable Chromosome Aberrations

    International Nuclear Information System (INIS)

    Wang, Q.; Liu, P.; Li, J.; Wang, Q.; Tang, S.; Sun, M.; Wang, L.; Aoyama, T.; Sugahara, T.

    1998-01-01

    The chromosome rearrangements in medical diagnostic X ray workers were analysed using the G-banding technique and evaluated collectively in accumulated doses. A total of 9102 metaphase spreads from 84 medical diagnostic X ray workers and 17 controls were scored. The results showed that: (1) the frequencies of translocation, stable chromosome aberration and total aberration in X ray workers were significantly higher than those of controls (P < 0.05 γ 0.005), unstable chromosome aberrations (including dicentric and acentric aberration) tended upwards; (2) the main aberration in stable aberrations was reciprocal translocation; (3) the stable aberration predominated strikingly in total aberrations. The medical diagnostic X ray workers were divided into three groups according to calendar year of entry. The data showed that the frequencies of translocation, stable aberration and total aberration increased with earlier year of entry, especially in two groups who started working before 1970. According to the equation recommended by Straume et al, linear coefficient (α) in the linear quadratic model provided by Fernandez's experiment, their collective accumulation doses calculated were 0.53, 0.26 and 0.06 Gy for calendar year of entry before 1960, 1960-1969, and after 1970, in X ray workers, respectively. (author)

  19. A High-Density Genetic Map of Wild Emmer Wheat from the Karaca Dağ Region Provides New Evidence on the Structure and Evolution of Wheat Chromosomes

    Directory of Open Access Journals (Sweden)

    Chad Jorgensen

    2017-10-01

    Full Text Available Wild emmer (Triticum turgidum ssp. dicoccoides is a progenitor of all cultivated wheat grown today. It has been hypothesized that emmer was domesticated in the Karaca Dağ region in southeastern Turkey. A total of 445 recombinant inbred lines of T. turgidum ssp. durum cv. ‘Langdon’ x wild emmer accession PI 428082 from this region was developed and genotyped with the Illumina 90K single nucleotide polymorphism Infinium assay. A genetic map comprising 2,650 segregating markers was constructed. The order of the segregating markers and an additional 8,264 co-segregating markers in the Aegilops tauschii reference genome sequence was used to compare synteny of the tetraploid wheat with the Brachypodium distachyon, rice, and sorghum. These comparisons revealed the presence of 15 structural chromosome rearrangements, in addition to the already known 4A-5A-7B rearrangements. The most common type was an intra-chromosomal translocation in which the translocated segment was short and was translocated only a short distance along the chromosome. A large reciprocal translocation, one small non-reciprocal translocation, and three large and one small paracentric inversions were also discovered. The use of inversions for a phylogeny reconstruction in the Triticum–Aegilops alliance was illustrated. The genetic map was inconsistent with the current model of evolution of the rearranged chromosomes 4A-5A-7B. Genetic diversity in the rearranged chromosome 4A showed that the rearrangements might have been contemporary with wild emmer speciation. A selective sweep was found in the centromeric region of chromosome 4A in Karaca Dağ wild emmer but not in 4A of T. aestivum. The absence of diversity from a large portion of chromosome 4A of wild emmer, believed to be ancestral to all domesticated wheat, is puzzling.

  20. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  1. Comparison of the chromosomal radiosensitivity of blood lymphocytes and stem-cell spermatogonia in the rhesus monkey and the mouse

    International Nuclear Information System (INIS)

    Buul, P.P.W. van; Richardson, J.F.; Boer, P. de; Zwanenburg, S.

    1980-01-01

    By experiments similar to those with the mouse we studied, in the rhesus monkey (Macaca mulatta), the induction by X-rays of reciprocal translocations in steam-cell spermatogonia and of dicentric chromosomes in blood lymphocytes. Human blood lymphocytes and rhesus monkey lymphocytes showed about equal sensitivity to dicentric induction. This equal radiosensitivity of somatic cells, however, provides no clue to the quantitative extrapolation to the human situation of the data obtained on translocation induction in stem-cell spermatogonia of the rhesus monkey. In our opinion, only direct observations on induced chromosomal aberrations in germ cells of higher primates and man can play a decisive role in estimating human genetic radiation risks arising from chromosomal aberrations. (orig./AJ)

  2. Correlation of chromosome patterns in leukemic cells of patients with exposure to chemicals and/or radiation

    International Nuclear Information System (INIS)

    Rowley, J.D.

    1989-10-01

    We have identified two new recurring translocations involving chromosome 5; one is a 3;5 translocation and the other involves a rearrangement between chromosomes 5 and 7. The first is t(3;5)(q25.1;q35). We studied five patients with AML and a t(3;5) in their leukemic cells. At diagnosis, four of the patients had a t(3;5) as their sole karyotypic anomaly; the remaining patient had additional structural and numerical abnormalities. Careful cytogenetic analysis indicated that the breakpoints of this rearrangement were 3q25.1 and 5q34, in contrast to the various breakpoints reported in earlier studies (3q21 to 3q25 and 5q31 to 5q35). The karyotypic, morphologic, and clinical characteristics of this group, as well as those of 15 previously reported patients with the t(3;5), were compared to identify any features that might warrant consideration of this anomaly as a specific syndrome. The median age of the group, 37 years, as younger than that of all patients with AML, 49 years. A preceding myelodysplastic syndrome was observed in three patients. We have no information regarding the occupation of most of these patients. Except for acute promyelocytic leukemia, each morphologic subtype occurred in these patients; however, the frequency of erythroleukemia (M6) was much greater than expected. 11 refs., 2 figs., 5 tabs

  3. Prader-Willi syndrome due to an unbalanced de novo translocation [t(15;19)(q12;p13.3)

    Science.gov (United States)

    Dang, Vy; Surampalli, Abhilasha; Manzardo, Ann M; Youn, Stephanie; Butler, Merlin G; Gold, June-Anne; Kimonis, Virginia

    2018-01-01

    Background and Aims Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic and behavioral abnormalities. We report the first case of an unbalanced de-novo reciprocal translocation of chromosome 15 and 19: 45,XY,-15, der (19)t(15;19)(q12;p13.3) resulting in monosomy for the PWS chromosome critical region. We performed high resolution SNP microarray to characterize the breakpoints. Case report Our patient had several typical features for PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet and food seeking but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. Results High resolution SNP microarray analysis identified an atypical PWS Type I deletion of chromosome 15 involving proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11-q13 region and GABRA5, GABRG3 and OCA2 genes were intact. Conclusion We report a case with atypical features for PWS associated with an unbalanced de-novo reciprocal translocation resulting in monosomy for the 15q11.1–15q12 with intact GABRA5, GABRG3 and OCA2 genes. No deletion of 19p13.3 band was detected therefore the patient was not at an increased risk of tumors from Peutz-Jeghers syndrome associated with a deletion of the STK11 gene. PMID:27894106

  4. DNA Probe Pooling for Rapid Delineation of Chromosomal Breakpoints

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chun-Mei; Kwan, Johnson; Baumgartner, Adolf; Weier, Jingly F.; Wang, Mei; Escudero, Tomas; Munne' , Santiago; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich

    2009-01-30

    Structural chromosome aberrations are hallmarks of many human genetic diseases. The precise mapping of translocation breakpoints in tumors is important for identification of genes with altered levels of expression, prediction of tumor progression, therapy response, or length of disease-free survival as well as the preparation of probes for detection of tumor cells in peripheral blood. Similarly, in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for carriers of balanced, reciprocal translocations benefit from accurate breakpoint maps in the preparation of patient-specific DNA probes followed by a selection of normal or balanced oocytes or embryos. We expedited the process of breakpoint mapping and preparation of case-specific probes by utilizing physically mapped bacterial artificial chromosome (BAC) clones. Historically, breakpoint mapping is based on the definition of the smallest interval between proximal and distal probes. Thus, many of the DNA probes prepared for multi-clone and multi-color mapping experiments do not generate additional information. Our pooling protocol described here with examples from thyroid cancer research and PGD accelerates the delineation of translocation breakpoints without sacrificing resolution. The turnaround time from clone selection to mapping results using tumor or IVF patient samples can be as short as three to four days.

  5. Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome-positive acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Rubin, C.M.; Carrino, J.J.; Dickler, M.N.; Leibowitz, D.; Smith, S.D.; Westbrook, C.A.

    1988-01-01

    Philadelphia chromosome-positive acute lymphoblastic leukemia occurs in two molecular forms, those with and those without rearrangement of the breakpoint cluster region on chromosome 22. The molecular abnormality in the former group is similar to that found in chronic myelogenous leukemia. To characterize the abnormality in the breakpoint cluster region-unrearranged form, the authors have mapped a 9; 22 translocation from the Philadelphia chromosome-positive acute lymphoblastic leukemia cell line SUP-B13 by using pulsed-field gel electrophoresis and have cloned the DNA at the translocation junctions. They demonstrate a BCR-ABL fusion gene on the Philadelphia chromosome. The exons from ABL are the same. Analysis of leukemic cells from four other patients with breakpoint cluster region-unrearranged Philadelphia chromosome-positive acute lymphoblastic leukemia revealed a rearrangement on chromosome 22 close to the breakpoint in SUP-B13 in only one patient. These data indicate that breakpoints do not cluster tightly in this region but are scattered, possibly in a large intron. Given the large size of BCR and the heterogeneity in breakpoint location, detection of BCR rearrangement by standard Southern blot analysis is difficult. Pulsed-field gel electrophoresis should allow detection at the DNA level in every patient and thus will permit clinical correlation of the breakpoint location with prognosis

  6. Genome Organization Drives Chromosome Fragility.

    Science.gov (United States)

    Canela, Andres; Maman, Yaakov; Jung, Seolkyoung; Wong, Nancy; Callen, Elsa; Day, Amanda; Kieffer-Kwon, Kyong-Rim; Pekowska, Aleksandra; Zhang, Hongliang; Rao, Suhas S P; Huang, Su-Chen; Mckinnon, Peter J; Aplan, Peter D; Pommier, Yves; Aiden, Erez Lieberman; Casellas, Rafael; Nussenzweig, André

    2017-07-27

    In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements. VIDEO ABSTRACT. Published by Elsevier Inc.

  7. Rapid detection of chromosome rearrangement in medical diagnostic X-ray workers by using fluorescence in situ hybridization and study on dose estimation

    International Nuclear Information System (INIS)

    Wang Zhiquan; Sun Yuanming; Li Jin

    1998-01-01

    Objective: Biological doses were estimated for medical diagnostic X-ray workers. Methods: Chromosome rearrangements in X-ray workers were analysed by fluorescence in situ hybridization (FISH) with composite whole chromosome paintings number 4 and number 7. Results: The frequency of translocation in medical diagnostic X-ray workers was much higher than that in control group (P<0.01). The biological doses to individual X-ray workers were calculated by their translocation frequency. The translocation frequencies of both FISH and G-banding were in good agreement. Conclusion: The biological doses to X-ray workers are estimated by FISH first when their dosimetry records are not documented

  8. Relations between ultrastructure of mitotic spindle and chromosome translocation

    OpenAIRE

    Jadwiga A. Tarkowska

    2014-01-01

    Dividing endosperm cells of Haemanthus katherinae Bak. treated with an 0.25 per cent mixture of water-soluble glycosides from Nerium oleander were insepected in a light microscope (LM) and severe disturbances were found in all phases of mitosis. The same cells were observed in the electron microscope (EM) and relations were noted and analysed between the chromosome arrangement and the submicroscopic structure of the mitotuc spindle. The successive steps in the disintegration of the formed spi...

  9. A novel Robertsonian translocation event leads to transfer of a stem rust resistance gene (Sr52) effective against race Ug99 from Dasypyrum villosum into bread wheat.

    Science.gov (United States)

    Qi, L L; Pumphrey, M O; Friebe, Bernd; Zhang, P; Qian, C; Bowden, R L; Rouse, M N; Jin, Y; Gill, B S

    2011-06-01

    Stem rust (Puccinia graminis f. sp. tritici Eriks. & E. Henn.) (the causal agent of wheat stem rust) race Ug99 (also designated TTKSK) and its derivatives have defeated several important stem rust resistance genes widely used in wheat (Triticum aestivum L.) production, rendering much of the worldwide wheat acreage susceptible. In order to identify new resistance sources, a large collection of wheat relatives and genetic stocks maintained at the Wheat Genetic and Genomic Resources Center was screened. The results revealed that most accessions of the diploid relative Dasypyrum villosum (L.) Candargy were highly resistant. The screening of a set of wheat-D. villosum chromosome addition lines revealed that the wheat-D. villosum disomic addition line DA6V#3 was moderately resistant to race Ug99. The objective of the present study was to produce and characterize compensating wheat-D. villosum whole arm Robertsonian translocations (RobTs) involving chromosomes 6D of wheat and 6V#3 of D. villosum through the mechanism of centric breakage-fusion. Seven 6V#3-specific EST-STS markers were developed for screening F(2) progeny derived from plants double-monosomic for chromosomes 6D and 6V#3. Surprisingly, although 6D was the target chromosome, all recovered RobTs involved chromosome 6A implying a novel mechanism for the origin of RobTs. Homozygous translocations (T6AS·6V#3L and T6AL·6V#3S) with good plant vigor and full fertility were selected from F(3) families. A stem rust resistance gene was mapped to the long arm 6V#3L in T6AS·6V#3L and was designated as Sr52. Sr52 is temperature-sensitive and is most effective at 16°C, partially effective at 24°C, and ineffective at 28°C. The T6AS·6V#3L stock is a new source of resistance to Ug99, is cytogenetically stable, and may be useful in wheat improvement.

  10. Evolutionary trends in the family Curimatidae (Characiformes): inferences from chromosome banding.

    Science.gov (United States)

    Sampaio, Tatiane Ramos; Pires, Larissa Bettin; Venturelli, Natália Bortolazzi; Usso, Mariana Campaner; da Rosa, Renata; Dias, Ana Lúcia

    2016-01-01

    The family Curimatidae is a fish group usually considered chromosomally conserved in their diploid number. However, some studies show small changes in the karyotype microstructure, and the presence of B chromosomes, indicating a chromosomal diversification within the group, even if structural changes in the karyotypes are not visible. Few studies associate this trait with an evolutionary pattern within the family. This study aimed to characterize the karyotype, nucleolus organizer regions (NORs), and heterochromatin distribution of six species of Curimatidae of the genera Cyphocharax Fowler, 1906 and Steindachnerina Fowler, 1906: Cyphocharax voga (Hensel, 1870), Cyphocharax spilotus (Vari, 1987), Cyphocharax saladensis (Meinken, 1933), Cyphocharax modestus (Fernández-Yépez, 1948), Steindachnerina biornata (Braga et Azpelicueta, 1987) and Steindachnerina insculpta (Fernández-Yépez, 1948) and contribute data to a better understanding of the mechanisms involved in the chromosomal evolution of this group of fish. All specimens had 2n=54, m-sm, and B microchromosomes. Five species exhibited single NORs, except for Steindachnerina biornata, which showed a multiple pattern of ribosomal sites. NORs were chromomycin A3 positive (CMA3 (+)) and 4'-6-diamino-2-phenylindole (DAPI(-)) negative, exhibiting differences in the pair and chromosomal location of each individual of the species. FISH with 5S rDNA probe revealed sites in the pericentrometic position of a pair of chromosomes of five species. However, another site was detected on a metacentric chromosome of Cyphocharax spilotus. Heterochromatin distributed both in the pericentromeric and some terminal regions was revealed to be CMA3 (+)/DAPI(-). These data associated with the previously existing ones confirm that, although Curimatidae have a very conservative karyotype macrostructure, NORs and heterochromatin variability are caused by mechanisms of chromosome alterations, such as translocations and/or inversions

  11. Studies on chromosomal aberrations and dominant lethal mutations induced by x irradiation in germ cells of male mice

    International Nuclear Information System (INIS)

    Wang Xianli; Wang Mingdong; Wang Bin; Sun Shuqing

    1992-01-01

    After male mice irradiated by 2 Gy X rays mated to normal virginal females superovulated with PMSG and HCG, pronuclei chromosome spreading of first-cleavage embryos were prepared and chromosomal aberrations of paternal pronuclei were observed. The results showed that the frequency of chromosomal aberrations was highest irradiated at spermatic stage among different stages of spermatogenesis. The sequence of radiosensitivity in spermatogenesis was as follows: spermatids > mature sperm > spermatocyte > spermatogonia and stem spermatogonia. The frequencies of paternal chromosomal aberrations resulted from irradiation at spermatids and mature sperms were significantly higher than that in control. The reciprocal translocations of stem spermatogonia induced by 2 Gy X rays in those male mice were also examined in the preparations of diakinesis-metaphase I. The frequency of reciprocal translocations were 0.0429 per cell and significantly higher than that in control. The proportion of unbalanced gametes, resulting in lethal embryos after fertilization, was 0.02145 to be predicted. At the same time, the dominant lethality induced by X rays in stem spermatogonia was measured, being 0.0371. The frequency of dead fetuses in irradiation group was about twice as in control. The regression analysis was found that the reciprocal translocations was markedly related to the dominant lethality

  12. Problem-elephant translocation: translocating the problem and the elephant?

    Directory of Open Access Journals (Sweden)

    Prithiviraj Fernando

    Full Text Available Human-elephant conflict (HEC threatens the survival of endangered Asian elephants (Elephas maximus. Translocating "problem-elephants" is an important HEC mitigation and elephant conservation strategy across elephant range, with hundreds translocated annually. In the first comprehensive assessment of elephant translocation, we monitored 16 translocations in Sri Lanka with GPS collars. All translocated elephants were released into national parks. Two were killed within the parks where they were released, while all the others left those parks. Translocated elephants showed variable responses: "homers" returned to the capture site, "wanderers" ranged widely, and "settlers" established home ranges in new areas soon after release. Translocation caused wider propagation and intensification of HEC, and increased elephant mortality. We conclude that translocation defeats both HEC mitigation and elephant conservation goals.

  13. A constitutional translocation t(1;17(p36.2;q11.2 in a neuroblastoma patient disrupts the human NBPF1 and ACCN1 genes.

    Directory of Open Access Journals (Sweden)

    Karl Vandepoele

    Full Text Available The human 1p36 region is deleted in many different types of tumors, and so it probably harbors one or more tumor suppressor genes. In a Belgian neuroblastoma patient, a constitutional balanced translocation t(1;17(p36.2;q11.2 may have led to the development of the tumor by disrupting or activating a gene. Here, we report the cloning of both translocation breakpoints and the identification of a novel gene that is disrupted by this translocation. This gene, named NBPF1 for Neuroblastoma BreakPoint Family member 1, belongs to a recently described gene family encoding highly similar proteins, the functions of which are unknown. The translocation truncates NBPF1 and gives rise to two chimeric transcripts of NBPF1 sequences fused to sequences derived from chromosome 17. On chromosome 17, the translocation disrupts one of the isoforms of ACCN1, a potential glioma tumor suppressor gene. Expression of the NBPF family in neuroblastoma cell lines is highly variable, but it is decreased in cell lines that have a deletion of chromosome 1p. More importantly, expression profiling of the NBPF1 gene showed that its expression is significantly lower in cell lines with heterozygous NBPF1 loss than in cell lines with a normal 1p chromosome. Meta-analysis of the expression of NBPF and ACCN1 in neuroblastoma tumors indicates a role for the NBPF genes and for ACCN1 in tumor aggressiveness. Additionally, DLD1 cells with inducible NBPF1 expression showed a marked decrease of clonal growth in a soft agar assay. The disruption of both NBPF1 and ACCN1 genes in this neuroblastoma patient indicates that these genes might suppress development of neuroblastoma and possibly other tumor types.

  14. Translocation t(11;14 (q13;q32 and genomic imbalances in multi-ethnic multiple myeloma patients: a Malaysian study

    Directory of Open Access Journals (Sweden)

    Ivyna Bong Pau Ni

    2012-09-01

    Full Text Available More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR-based translocation detection assay to detect BCL1/JH t(11;14 (q13;q32 in 105 myeloma patients, and randomly selected 8 translocation positive samples for array comparative genomic hybridization (aCGH analysis. Our findings revealed 14.3% of myeloma samples were positive for BCL1/JH t(11;14 (q13;q32 translocation (n=15 of 105. We found no significant correlation between this translocation with age (P=0.420, gender (P=0.317, ethnicity (P=0.066 or new/relapsed status of multiple myeloma (P=0.412 at 95% confidence interval level by x2 test. In addition, aCGH results showed genomic imbalances in all samples analyzed. Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q. Copy number variations at genetic loci that contain NAMPT, IVNS1ABP and STK17B genes are new findings that have not previously been reported in myeloma patients. Besides fluorescence in situ hybridization, PCR is another rapid, sensitive and simple technique that can be used for detecting BCL1/JH t(11;14(q13;q32 translocation in multiple myeloma patients. Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14 (q13;q32 translocation.

  15. Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

    DEFF Research Database (Denmark)

    Aristidou, Constantia; Koufaris, Costas; Theodosiou, Athina

    2017-01-01

    Familial apparently balanced translocations (ABTs) segregating with discordant phenotypes are extremely challenging for interpretation and counseling due to the scarcity of publications and lack of routine techniques for quick investigation. Recently, next generation sequencing has emerged...... and non-affected members carrying the same translocations. PTCD1, ATP5J2-PTCD1, CADPS2, and STPG1 were disrupted by the translocations in three families, rendering them initially as possible disease candidate genes. However, subsequent mutation screening and structural variant analysis did not reveal any...... can also be used in routine clinical investigation of ABT cases. Unlike de novo translocations, no associations were determined here between familial two-way ABTs and the phenotype of the affected members, in which the presence of cryptic imbalances and complex chromosomal rearrangements has been...

  16. Chromosome aberrations in human lymphocytes for investigation of individual radiosensitivity; Chromosomenaberrationen in peripheren Lymphozyten zur Untersuchung der individuellen Strahlenempfindlichkeit

    Energy Technology Data Exchange (ETDEWEB)

    Zitzelsberger, H. [LMU Muenchen (Germany). Strahlenbiologisches Inst.; Bauchinger, M. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Oberschleissheim (Germany). Inst. fuer Strahlenbiologie

    2000-07-01

    Stable translocations and insertions which are not selected against during cell proliferation can be reliably scored by use of fluorescence in situ hybridisation (FISH) which allows painting of selected chromosomes along their entire length. This temporal persistence makes them particulary valuable for quantifying post human radiation exposures ('biodosimetry'). A disadvantage of this approach is that for routine use only a partial genome analysis can be performed which is mostly based on triple combinations of DNA probes for particular chromosomes. Translocation frequencies from partial genome analysis are often scaled-up to equal the full genome. Basic assumptions for such scaling are, that double strand breaks leading to translocations must be distributed randomly throughout the genome and no preferential interaction between particular pairs of chromosomes occurs. Thus, the probability of a particular chromosome being involved in an exchange is proportional to its DNA content. However, this is not always supported by experimental findings and may thus indicate a differential radiosensitivity of particular chromosomes. Translocation measurements in peripheral blood of different healthy donors irradiated in vitro with the same dose revealed also some evidence for the existence of interindividual differences in radiosensitivity. Similar findings have been already demonstrated after therapeutic irradiation of tumour patients. Consequences thereof may result for long-term retrospective biodosimetry. In order to provide reliable estimates of an individual's exposure to ionising radiation, the extent, distribution and dose-dependence of the observed variability has to be carefully examined in larger groups of persons and larger sets of calibration data. (orig.) [German] Durch die Anfaerbung kompletter Chromosomen mit Hilfe der Fluoreszenz-in-situ Hybridisierung (FISH) lassen sich die waehrend der Zellproliferation als stabil angesehenen Translokationen

  17. Sirenomelia with a de novo balanced translocation 46,X,t(X;16)(p11.23;p12.3).

    Science.gov (United States)

    Kurosawa, Kenji; Tanoshima-Takei, Miki; Yamamoto, Toshiyuki; Ishikawa, Hiroshi; Masuno, Mitsuo; Tanaka, Yukichi; Yamanaka, Michiko

    2012-06-01

    We report a female fetus with sirenomelia with 46,X,t(X;16)(p11.23;p12.3) de novo. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes were employed for narrowing down the breakpoint regions. On chromosome 16, the breakpoint was mapped in the region of RP11-453F10 (19 920 640-20 118 153 bp from 16pter). On chromosome X, the breakpoint was mapped in the region of RP11-794A15 (47 333 744-47 524 066 bp from Xpter). This is the first case report of sirenomelia associated with translocations. The abnormal phenotype, associated with a balanced translocation, was caused by deletion or breakage of dosage-sensitive genes of the breakpoint, disruption of an imprinted gene, or uniparental disomy. Although the parental origin of normal 16 and der(16) remained undetermined, this case will provide insight into the pathogenetic mechanism of sirenomelia. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

  18. Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.

    Science.gov (United States)

    Calton, Christine M; Bronnimann, Matthew P; Manson, Ariana R; Li, Shuaizhi; Chapman, Janice A; Suarez-Berumen, Marcela; Williamson, Tatum R; Molugu, Sudheer K; Bernal, Ricardo A; Campos, Samuel K

    2017-05-01

    The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of this critical process remain poorly characterized. We have developed a system based on subcellular compartmentalization of the enzyme BirA and its cognate substrate to detect membrane translocation of L2-BirA from incoming virions. We find that L2 translocation requires transport to the TGN and is strictly dependent on entry into mitosis, coinciding with mitotic entry in synchronized cells. Cell cycle arrest causes retention of L2/vDNA at the TGN; only release and progression past G2/M enables translocation across the limiting membrane and subsequent infection. Microscopy of EdU-labeled vDNA reveals a rapid and dramatic shift in vDNA localization during early mitosis. At late G2/early prophase vDNA egresses from the TGN to a pericentriolar location, accumulating there through prometaphase where it begins to associate with condensed chromosomes. By metaphase and throughout anaphase the vDNA is seen bound to the mitotic chromosomes, ensuring distribution into both daughter nuclei. Mutations in a newly defined chromatin binding region of L2 potently blocked translocation, suggesting that translocation is dependent on chromatin binding during prometaphase. This represents the first time a virus has been shown to functionally couple the penetration of limiting membranes to cellular mitosis, explaining in part the tropism of HPV for mitotic basal keratinocytes.

  19. Sequencing of individual chromosomes of plant pathogenic Fusarium oxysporum.

    Science.gov (United States)

    Kashiwa, Takeshi; Kozaki, Toshinori; Ishii, Kazuo; Turgeon, B Gillian; Teraoka, Tohru; Komatsu, Ken; Arie, Tsutomu

    2017-01-01

    A small chromosome in reference isolate 4287 of F. oxysporum f. sp. lycopersici (Fol) has been designated as a 'pathogenicity chromosome' because it carries several pathogenicity related genes such as the Secreted In Xylem (SIX) genes. Sequence assembly of small chromosomes in other isolates, based on a reference genome template, is difficult because of karyotype variation among isolates and a high number of sequences associated with transposable elements. These factors often result in misassembly of sequences, making it unclear whether other isolates possess the same pathogenicity chromosome harboring SIX genes as in the reference isolate. To overcome this difficulty, single chromosome sequencing after Contour-clamped Homogeneous Electric Field (CHEF) separation of chromosomes was performed, followed by de novo assembly of sequences. The assembled sequences of individual chromosomes were consistent with results of probing gels of CHEF separated chromosomes with SIX genes. Individual chromosome sequencing revealed that several SIX genes are located on a single small chromosome in two pathogenic forms of F. oxysporum, beyond the reference isolate 4287, and in the cabbage yellows fungus F. oxysporum f. sp. conglutinans. The particular combination of SIX genes on each small chromosome varied. Moreover, not all SIX genes were found on small chromosomes; depending on the isolate, some were on big chromosomes. This suggests that recombination of chromosomes and/or translocation of SIX genes may occur frequently. Our method improves sequence comparison of small chromosomes among isolates. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Dek-can rearrangement in translocation (6;9)(p23;q34)

    NARCIS (Netherlands)

    Soekarman, D.; von Lindern, M.; van der Plas, D. C.; Selleri, L.; Bartram, C. R.; Martiat, P.; Culligan, D.; Padua, R. A.; Hasper-Voogt, K. P.; Hagemeijer, A.

    1992-01-01

    The translocation (6;9)(p23;q34) is mainly found in specific subtypes of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The diagnosis of this translocation is not easy since the cytogenetic change is quite subtle. The two genes involved in this translocation were recently isolated

  1. Survival and transmission of symmetrical chromosomal aberrations

    International Nuclear Information System (INIS)

    Savage, J.R.K.

    1979-01-01

    The interaction between the lesions to produce chromosomal structural changes may be either asymmetrical (A) or symmetrical (S). In A, one or more acentric fragments are always produced, and there may also be the mechanical separation problems resulting from bridges at anaphase, while S-changes never produce fragment, and pose no mechanical problem in cell division. If A and S events occur with equal frequency, it might be an indication that they are truly the alternative modes of lesion interaction. Unstimulated lymphocytes were irradiated with 2.68 Gy 250 kV X-ray, and metaphases were sampled at 50 h after the stimulation. Preparations were complete diploid cells, and any obvious second division cells were rejected. So far as dermal repair and fibroblast functions are concerned, aberration burden seems to have little consequence from the view-point of the long-term survival in vivo. Large numbers of aberrations (mainly S translocation and terminal deletion) were found in the samples taken up to 60 years after therapy. Skin biopsies were removed 1 day and 6 months after irradiation and cultured. In irradiated cells, reciprocal translocations dominated, followed by terminal deletions, then inversions, while no chromosome-type aberration was seen in the control cells. a) The relative occurrence of A : S changes, b) long-term survival in vivo, c) the possibility of in vivo repair, and d) some unusual features of translocation found in Syrian hamsters are reviewed. The relevance or importance of major S events is clearly dependent upon the cells, the tissues or the organisms in which they occur. (Yamashita, S.)

  2. Leukemia-related clonal chromosome aberrations observed in A-bomb survivors. Deletion in chromosome 5 and inversion in chromosome 14

    International Nuclear Information System (INIS)

    Ohtaki, Kazuo

    1999-01-01

    Chromosome aberrations were analyzed by G differentiation staining method on about 5,400 peripheral lymphocytes of 168 A-bomb survivors, of whom 143 had been exposed to mean DS86 dose of 2.05 Gy (exposed group) and of 25, 0 Gy (control) and results concerning clonal growth of abnormal cells were described in this paper. G band analysis of the aberrations in T-lymphocytes revealed that frequency of translocation in the exposed group increased to 17 times of the control and deletion, 5 times. Deletion in chromosome 5 where tumor-suppressor gene was present, [del(5q-)], was found in about 30% of total deletions. Since patients of myelodysplasia syndrome and acute myelogenic leukemia had the deletion in more than 50%, growth of cells possessing it was suggestive of the progression of pre-leukemic step. Frequency of inversion in chromosome 14, inv(14)(q11q32), was as high as 80% of total 118 inversions of T-ALL (T-acute lymphocyte leukemia) and T-CLL (T-chronic LL) types in the exposed group. Therefore, the inversion also can be a pre-leukemic step. However, it was suggested that these aberrations were not sufficient for crisis of the disease, which required other factors.(K.H.)

  3. Effects of long-term radiation exposure on chromosomal aberrations in radiological technologists

    International Nuclear Information System (INIS)

    Kumagai, Etsuko; Onomichi, Mitsukazu; Tanaka, Ryuji; Kumagai, Takashi; Sawada, Shozo.

    1990-01-01

    Chromosomal aberrations in the lymphocytes of radiation technologists (RT) were analyzed by the trypsin G-banding method to study the late effects of long-term exposure to low doses of radiation. Structural aberrations were identified in 384 (2.5%) of 15442 cells analyzed from 53 RT as compared to 177 (1.6%) of 11136 cells from 36 healthy controls. Stable aberrations were the most frequent in both groups and were either translocations or deletions. Unstable aberrations were mainly acentric fragments in both groups. The frequency of translocations and acentric fragments was significantly higher in the RT than in the controls and was highest in the RT over 50 years. The highest frequency observed in the >50 age group was attributed to the unknown for cumulative dose prior to introduction of film badges. Frequency of chromosomal aberrations correlated with the estimated dose from the film badges and years of experience of each RT based on the equation y=0.22+0.37D+4.35D 2 , where y is overall frequency of chromosomal aberrations and D is the estimated radiation dose in Sv. (author)

  4. A comparative study on the frequencies of radiation-induced chromosome aberrations in the somatic and germ cells in mouse and monkey

    International Nuclear Information System (INIS)

    Sobels, F.H.

    1976-06-01

    Two systems were mainly used for studying the relationship between radiation induced chromosome aberration frequencies in somatic and germ cells. The first consists of reciprocal translocation induced in bone-marrow cells of mice compared to reciprocal translocation induced spermatogonia (scored in descending spermatocytes) of the same mice. Dose-response curves for induced aberrations in both cell types (0-100-200-300-400-500 and 600 R X-rays) and dose rate effects indicated that (130-1.92-0.0287 R/min) of a 400 R γ-ray exposure of the two cell types mitotically dividing germ cells respond to radiation similarly to mitotic dividing germ cells. Clonal proliferation or selective elimination of aberration-carrying cells, and other post-irradiation factors can, however, cause great differences in absolute aberration frequencies. A similar study was attempted, using the rhesus monkey as a second system. Its bone-marrow cells were proved unsuitable for induced reciprocal translocations. Stimulated peripheral blood lymphocytes were studied instead. Following 100, 200 and 300 R of X-rays, the frequencies of induced dicentric chromosomes were compared to those of induced reciprocal translocations in spermatogonia. Human peripheral blood was studied similarly. It was concluded that: (a) The absolute frequencies of chromosome aberrations in somatic and germ cells of the rhesus monkey are low compared to most other mammalian species. (b) The ratio between dicentric frequencies and reciprocal translocation frequencies at 100 R and 200 R differed significantly from 4:1 reported for mouse and Chinese hamster and 2:1 for marmoset and man. (c) Although the numbers of 'effective chromosome arms' in man and rhesus monkey are similar (81 vs 83), the rhesus monkey showed at all doses a lower rate of induction of dicentrics in blood lymphocytes than man, reaching statistical significance at the 300 R level

  5. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Can epigenetic control explain pronounced within plant heterogeneity of meiosis in a translocation trisome of Secale L.?

    NARCIS (Netherlands)

    Sybenga, J.

    2012-01-01

    Meiotic metaphase I configuration frequencies were determined in different tillers of genetically related plants of rye (Secale cereale L.) heterozygous for reciprocal translocation T248W (between chromosome arms 1RS and 6RS) and with an additional (telocentric) arm 1RS. Seventeen different

  7. Descriptive evaluation of chromosome aberrations in blood lymphocytes due to gamma-irradiation

    International Nuclear Information System (INIS)

    Medina III, F.S.; Gregorio, J.S.; Vinoya, P.C.; Panlaque, C.A.

    1983-01-01

    To induce and evaluate the effect of radiation among Filipinos, frequencies and types of ν-ray induced chromosome aberrations were studied with peripheral lymphocytes from 19 donors. Peripheral blood samples were irradiated at 0 Gray, 500 mGy, 1 Gy, 2 Gy, 3 Gy and 4 Gy. Irradiated blood samples were cultured by the same standard technique as that commonly used for human blood lymphocytes. Our observations showed that irradiation causes chromosomal aberration similar to effects observed in Caucasians. Our study confirm that irradiation causes an increase of the chromosome aberrations types normally found in the control (gaps, chromatid breaks and chromosome fragments) and can induce aberrations which are rarely observed in non-exposed individual (deletions, translocations, polycentrics, rings, and despiralizations). (author)

  8. Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

    Science.gov (United States)

    George, K. A.; Hada, M.; Patel, Z.; Huff, J.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase, DNA-PK activity. Chromosomes were analyzed using the fluorescence in-situ hybridization (FISH) chromosome painting method in cells at the first division post-irradiation and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma radiation induced higher yields of both simple and complex exchanges in the DSB repair defective cells than in the normal cells. The quadratic dose-response terms for both chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further

  9. Chromosomal investigations in patients with mental retardation and/or congenital malformations

    Directory of Open Access Journals (Sweden)

    Santos C.B.

    2000-01-01

    Full Text Available We investigated the chromosomal constitution of patients with mental retardation and/or congenital malformations in order to determine genetic causes for such disturbances. The GTG and CBG banding patterns were studied using phytohemagglutinin M-stimulated lymphocytes cultured from peripheral blood. Among 98 individuals with mental retardation and/or congenital malformations who were analyzed there were 12 cases of Down's syndrome, two of Edward's syndrome, one of Patau's syndrome, five of Turner's syndrome, two of Klinefelter's syndrome, one of "cri-du-chat" syndrome, one case of a balanced translocation between chromosomes 13 and 14, one case of a derivative chromosome and one of a marker chromosome. We found abnormal chromosomes in 26% of the patients, 82% of which were numerical abnormalities, with the remaining 18% being structural variants. We conclude that patients with mental retardation and/or congenital malformations should be routinely karyotyped.

  10. DNA hybridization sensing for cytogenetic analysis

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dapra, Johannes; Brøgger, Anna Line

    2013-01-01

    are rearrangements between two chromosome arms that results in two derivative chromosomes having a mixed DNA sequence. The current detection method is a Fluorescent In situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the DNA sequences of two chromosomes involved...... in the translocation (Kwasny et al., 2012). We have developed a new double hybridization assay that allows for sorting of the DNA chromosomal fragments into separate compartment, moreover allowing for detection of the translocation. To detect the translocation it is necessary to determine that the two DNA sequences...... forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The first example of the translocation detection was presented on lab-on-a-disc using fluorescently labeled DNA fragments, representing the derivative chromosome (Brøgger et al., 2012). To allow...

  11. Altered DNA methylation associated with a translocation linked to major mental illness

    OpenAIRE

    McCartney, Daniel L; Walker, Rosie M; Morris, Stewart W; Anderson, Susan M; Duff, Barbara J; Marioni, Riccardo E; Millar, J Kirsty; McCarthy, Shane E; Ryan, Niamh M; Lawrie, Stephen M; Watson, Andrew R; Blackwood, Douglas H R; Thomson, Pippa A; McIntosh, Andrew M; McCombie, W Richard

    2018-01-01

    Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumin...

  12. Conversion and non-conversion approach to preimplantation diagnosis for chromosomal rearrangements in 475 cycles.

    Science.gov (United States)

    Kuliev, Anver; Janzen, Jeanine Cieslak; Zlatopolsky, Zev; Kirillova, Irina; Ilkevitch, Yury; Verlinsky, Yury

    2010-07-01

    Due to the limitations of preimplantation genetic diagnosis (PGD) for chromosomal rearrangements by interphase fluorescent in-situ hybridization (FISH) analysis, a method for obtaining chromosomes from single blastomeres was introduced by their fusion with enucleated or intact mouse zygotes, followed by FISH analysis of the resulting heterokaryons. Although this allowed a significant improvement in the accuracy of testing of both maternally and paternally derived translocations, it is still labour intensive and requires the availability of fertilized mouse oocytes, also creating ethical issues related to the formation of interspecies heterokaryons. This method was modified with a chemical conversion procedure that has now been clinically applied for the first time on 877 embryos from PGD cycles for chromosomal rearrangements and has become the method of choice for performing PGD for structural rearrangements. This is presented within the context of overall experience of 475 PGD cycles for translocations with pre-selection and transfer of balanced or normal embryos in 342 (72%) of these cycles, which resulted in 131 clinical pregnancies (38%), with healthy deliveries of 113 unaffected children. The spontaneous abortion rate in these cycles was as low as 17%, which confirms an almost five-fold reduction of spontaneous abortion rate following PGD for chromosomal rearrangements. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  13. Some characteristics and its influence factors of chromosome aberrations of germ cells induced by ionizing radiation in mice

    International Nuclear Information System (INIS)

    Jin Yuke; Cai Lu; Wang Xianli

    1995-01-01

    The chromosome aberrations of germ cells in mice by low LET ionizing radiation were systematically studied. The study demonstrated that the chromosome aberrations were linear or linearly square correlated with X-ray doses in large doses; that was linear correlated with X-ray doses in low doses. In addition, there were many factors directly influencing chromosome aberrations. The aberrations of the germ cells in males were 4.4 times of that in females. The aberrations in the germ cells were significantly higher after meiosis than before. The aberrations in secondary spermatocytes were 3.6 times of that in spermatogonia and 10 times of that in primary spermatocytes, respectively. In different phases of meiosis, the amount of chromosome aberrations in leptotene was the least, that in diaknesis was the most. The spermatogonic translocation rate receiving a whole body X-irradiation was 1.74 times of that receiving a local testis X-irradiation. The spermatogonic translocation rate of acute X-irradiation was 4.6∼6.3 times of that of chronic γ-irradiation

  14. Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Khandogina, E K; Mutovin, G R; Filyushkin, I V; Akif' ev, A P

    1980-02-01

    The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during ..gamma..-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source /sup 60/Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed.

  15. Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

    International Nuclear Information System (INIS)

    Khandogina, E.K.; Mutovin, G.R.; Filyushkin, I.V.; Akif'ev, A.P.

    1980-01-01

    The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during γ-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source 60 Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed

  16. Leiomyoma of uterus in a patient with ring chromosome 12: Case presentation and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Hajianpour, M.J.; Habibian, R.; Hajianpour, A.K. [Children`s Hospital, Los Angeles, CA (United States)] [and others

    1996-05-17

    We report on a 30-year-old woman with de novo ring chromosome 12 mosaicism, 46,XX,r(12)(p13.3q24.3)/46,XX. In addition to the clinical manifestations generally observed in {open_quotes}ring syndrome{close_quotes} cases such as growth retardation, short stature, microcephaly, and mental deficiency, she had a broad nasal bridge, micrognathia with overbite, underdeveloped breasts, mild dorsal scoliosis, clinodactyly of the fifth fingers with a single interdigital crease, symphalangism of thumbs, tapering fingers, mild cutaneous syndactyly between the second and third toes, multiple cafe-au-lait spots, sebaceous acne on the face and back, and mild dystrophic toenails. She developed a large, pedunculated uterine leiomyoma at age 28 years. To our knowledge, uterine leiomyoma in association with r(12) has not been reported previously. However, a gain of chromosome 12 and translocations involving 12q14-15 have been described. 12 refs., 5 figs., 2 tabs.

  17. Entropic effects in formation of chromosome territories: towards understanding of radiation-induced gene translocation frequency

    Science.gov (United States)

    Gudowska-Nowak, Ewa; Ritter, Sylvia; Durante, Marco; Deperas-Standylo, Joanna; Ciesla, Michal

    2012-07-01

    A detailed understanding of structural organization of biological target, such as geometry of an inter-phase chromosome, is an essential prerequisite for gaining deeper insight into relationship between radiation track structure and radiation-induced biological damage [1]. In particular, coupling of biophysical models aimed to describe architecture of chromosomes and their positioning in a cell nucleus [2-4] with models of local distribution of ionizations caused by passing projectiles, are expected to result in more accurate estimates of aberration induction caused by radiation. There is abundant experimental evidence indicating that arrangements of chromosomes in eukaryotic cell nucleus is non-random and has been evolutionary conserved in specific cell types. Moreover, the radial position of a given chromosome territory (CT) within the cell nucleus has been shown to correlate with its size and gene density. Usually it is assumed that chromosomal geometry and positioning result from the action of specific forces acting locally, such as hydrogen bonds, electrostatic, Van der Waals or hydrophobic interactions operating between nucleosomes and within their interiors. However, it is both desirable and instructive to learn to what extend organization of inter-phase chromosomes is affected by nonspecific entropic forces. In this study we report results of a coarse-grained analysis of a chromatin structure modeled by two distinct approaches. In the first method, we adhere to purely statistical analysis of chromatin packing within a chromosome territory. On the basis of the polymer theory, the chromatin fiber of diameter 30nm is approximated by a chain of spheres, each corresponding to about 30 kbp. Random positioning of the center of the domain is repeated for 1000 spherical nuclei. Configuration of the domain is determined by a random packing of a polymer (a string of identical beads) in estimated fraction of space occupied by a chromosome of a given length and mass

  18. Inter-chromosomal heterogeneity in the formation of radiation induced chromosomal aberrations

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Vermeulen, S.; Boei, J.J.W.A.

    1997-01-01

    It is generally assumed that radiation induced chromosomal lesions are distributed randomly and repaired randomly among the genome. Recent studies using fluorescent in situ hybridization (FISH) and chromosome specific DNA libraries indicate that some chromosomes are more sensitive for radiation induced aberration formation than others. Chromosome No. 4 in human and chromosome No. 8 in Chinese hamster have been found to involve more in exchange aberrations than others, when calculated on the basis of their DNA content. Painting with arm specific chromosome libraries indicate that the frequencies of radiation induced intra-chromosome exchanges (i.e., between the arms of a chromosome, such as centric rings and inversions) are far in excess than one would expect on the basis of the frequencies of observed inter-chromosomal exchanges. The possible factors leading to the observed heterogeneity will be discussed

  19. Multiple aspects of ATP-dependent nucleosome translocation by RSC and Mi-2 are directed by the underlying DNA sequence.

    Directory of Open Access Journals (Sweden)

    Joke J F A van Vugt

    Full Text Available BACKGROUND: Chromosome structure, DNA metabolic processes and cell type identity can all be affected by changing the positions of nucleosomes along chromosomal DNA, a reaction that is catalysed by SNF2-type ATP-driven chromatin remodelers. Recently it was suggested that in vivo, more than 50% of the nucleosome positions can be predicted simply by DNA sequence, especially within promoter regions. This seemingly contrasts with remodeler induced nucleosome mobility. The ability of remodeling enzymes to mobilise nucleosomes over short DNA distances is well documented. However, the nucleosome translocation processivity along DNA remains elusive. Furthermore, it is unknown what determines the initial direction of movement and how new nucleosome positions are adopted. METHODOLOGY/PRINCIPAL FINDINGS: We have used AFM imaging and high resolution PAGE of mononucleosomes on 600 and 2500 bp DNA molecules to analyze ATP-dependent nucleosome repositioning by native and recombinant SNF2-type enzymes. We report that the underlying DNA sequence can control the initial direction of translocation, translocation distance, as well as the new positions adopted by nucleosomes upon enzymatic mobilization. Within a strong nucleosomal positioning sequence both recombinant Drosophila Mi-2 (CHD-type and native RSC from yeast (SWI/SNF-type repositioned the nucleosome at 10 bp intervals, which are intrinsic to the positioning sequence. Furthermore, RSC-catalyzed nucleosome translocation was noticeably more efficient when beyond the influence of this sequence. Interestingly, under limiting ATP conditions RSC preferred to position the nucleosome with 20 bp intervals within the positioning sequence, suggesting that native RSC preferentially translocates nucleosomes with 15 to 25 bp DNA steps. CONCLUSIONS/SIGNIFICANCE: Nucleosome repositioning thus appears to be influenced by both remodeler intrinsic and DNA sequence specific properties that interplay to define ATPase

  20. Sex reversal in the mouse (Mus musculus) is caused by a recurrent nonreciprocal crossover involving the x and an aberrant y chromosome.

    Science.gov (United States)

    Singh, L; Jones, K W

    1982-02-01

    Satellite DNA (Bkm) from the W sex-determining chromosome of snakes, which is related to sequences on the mouse Y chromosome, has been used to analyze the DNA and chromosomes of sex-reversed (Sxr) XXSxr male mice. Such mice exhibit a male-specific Southern blot Bkm hybridization pattern, consistent with the presence of Y-chromosome DNA. In situ hybridization of Bkm to chromosomes of XXSxr mice shows an aberrant concentration of related sequences on the distal terminus of a large mouse chromosome. The XYSxr carrier male, however, shows a pair of small chromosomes, which are presumed to be aberrant Y derivatives. Meiosis in the XYSxr mouse involves transfer of chromatin rich in Bkm-related DNA from the Y-Y1 complex to the X distal terminus. We suggest that this event is responsible for the transmission of the Sxr trait.

  1. Interstitial deletion 1p as a result of a de novo reciprocal 1p;2p translocation

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Jensen, P H

    1985-01-01

    A 5-month-old female patient with psychomotor retardation and minor dysmorphisms is described. Cytogenetic analysis using high-resolution banding technique revealed an interstitial deletion of the short arm of one chromosome 1 (p21----p22.2) resulting from a de novo translocation t(1;2)(p22;p25)....

  2. Late and latent effects of atomic bomb on chromosomes in the exposed population

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, R; Kamada, N [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1976-09-01

    Cytogenetic changes of exposed individuals, and the diseases and cytogenetic changes of the F/sub 1/ were discussed. The subjects exposed within 0.5 km. from the hypocenter revealed chromosomal aberration of the bone marrow in 83 per cent and those within 0.5 to 1.0 km. from the hypocenter revealed it in 47 per cent. The aberration was mostly the stable type, and was frequent in deletion, balanced-type translocation, unbalanced-type translocation, and inversion, in the order named. The number of abnormal clone varied with year. The chromosomes of the lymphocytes in the peripheral blood also showed high rate of stable type aberration, and the chromosomes were also aberrant in the fibroblasts of the keloid lesion. However, there were no abnormalities in the spermatogonium. Thirty seven subjects of F/sub 1/ group included 13 subjects whose father had been exposed, 19 subjects whose mother had been exposed, and 5 subjects whose both parents had been exposed. The diseases seen in the F/sub 1/ subjects were hematonosis in 28 subjects, autoimmune diseases in 5 subjects, and hypertension and lymphadenitis in 4 cases. Acute myelogenic leukemia (AML) showed normal chromosomes in all the 3 cases, the acute lymphatic leukemia (ALL), showed abnormal clones in 2 of 3 cases. Chronic myelogenic leukemia (CML) revealed abnormal chromosomes in all the 3 cases. The cytogenetic changes of abnormal clone in the F/sub 1/ of non-exposed were 60 per cent in AML, 57 per cent, in ALL and 100 per cent in CML.

  3. Late and latent effects of atomic bomb on chromosomes in the exposed population

    International Nuclear Information System (INIS)

    Tanaka, Ryuji; Kamada, Nanao

    1976-01-01

    Cytogenetic changes of exposed individuals, and the diseases and cytogenetic changes of the F 1 were discussed. The subjects exposed within 0.5 km. from the hypocenter revealed chromosomal aberration of the bone marrow in 83 per cent and those within 0.5 to 1.0 km. from the hypocenter revealed it in 47 per cent. The aberration was mostly the stable type, and was frequent in deletion, balanced-type translocation, unbalanced-type translocation, and inversion, in the order named. The number of abnormal clone varied with year. The chromosomes of the lymphocytes in the peripheral blood also showed high rate of stable type aberration, and the chromosomes were also aberrant in the fibroblasts of the keloid lesion. However, there were no abnormalities in the spermatogonium. Thirty seven subjects of F 1 group included 13 subjects whose father had been exposed, 19 subjects whose mother had been exposed, and 5 subjects whose both parents had been exposed. The diseases seen in the F 1 subjects were hematonosis in 28 subjects, autoimmune diseases in 5 subjects, and hypertension and lymphadenitis in 4 cases. Acute myelogenic leukemia (AML) showed normal chromosomes in all the 3 cases, the acute lymphatic leukemia (ALL), showed abnormal clones in 2 of 3 cases. Chronic myelogenic leukemia (CML) revealed abnormal chromosomes in all the 3 cases. The cytogenetic changes of abnormal clone in the F 1 of non-exposed were 60 per cent in AML, 57 per cent, in ALL and 100 per cent in CML. (Mukohata, S.)

  4. Interchromosomal insertional translocation at Xq26.3 alters SOX3 expression in an individual with XX male sex reversal.

    Science.gov (United States)

    Haines, Bryan; Hughes, James; Corbett, Mark; Shaw, Marie; Innes, Josie; Patel, Leena; Gecz, Jozef; Clayton-Smith, Jill; Thomas, Paul

    2015-05-01

    46,XX male sex reversal occurs in approximately 1: 20 000 live births and is most commonly caused by interchromosomal translocations of the Y-linked sex-determining gene, SRY. Rearrangements of the closely related SOX3 gene on the X chromosome are also associated with 46,XX male sex reversal. It has been hypothesized that sex reversal in the latter is caused by ectopic expression of SOX3 in the developing urogenital ridge where it triggers male development by acting as an analog of SRY. However, altered regulation of SOX3 in individuals with XX male sex reversal has not been demonstrated. Here we report a boy with SRY-negative XX male sex reversal who was diagnosed at birth with a small phallus, mixed gonads, and borderline-normal T. Molecular characterization of the affected individual was performed using array comparative genomic hybridization, fluorescent in situ hybridization of metaphase chromosomes, whole-genome sequencing, and RT-PCR expression analysis of lymphoblast cell lines. The affected male carries ∼774-kb insertion translocation from chromosome 1 into a human-specific palindromic sequence 82 kb distal to SOX3. Importantly, robust SOX3 expression was identified in cells derived from the affected individual but not from control XX or XY cells, indicating that the translocation has a direct effect on SOX3 regulation. This is the first demonstration of altered SOX3 expression in an individual with XX male sex reversal and suggests that SOX3 can substitute for SRY to initiate male development in humans.

  5. A Newborn with Genital Ambiguity, 45,X/46,XY Mosaicism, a Jumping Chromosome Y, and Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2013-01-01

    Full Text Available Disorders of sex development (DSD, formerly termed “intersex” conditions, arise from numerous causes. CAH secondary to 21-hydroxylase deficiency is the most common cause of DSD. Sex chromosome disorders, including sex chromosome mosaicism, are the second most common cause of DSD. We discuss a medically complex neonate with DSD presenting with ambiguous genitalia. Hormone levels suggested 21-hydroxylase deficiency. Molecular analysis revealed compound heterozygous mutations in the 21-hydroxylase gene (CYP21A2, confirming the diagnosis of CAH. Chromosome analysis revealed sex chromosome mosaicism with three cell lines: 45,X[8]/45,X,tas(Y;16(p11.32;p13.3[8]/45,X,t(Y;8(p11.32;p23.3[4] with the Y chromosome in telomere association with chromosomes 8p and 16p in different cell lines, a “jumping translocation.” Histologically, the right gonad had irregular, distended seminiferous tubules with hyperplastic germ cells contiguous with ovarian stroma and primordial follicles. The left gonad had scant ovarian stroma and embryonic remnants. Chromosome analyses showed mosaicism in both gonads: 45,X[17]/45,X,tas(Y;8(p11.32;p23.3[3]. This is the first case of coexisting CAH and 45,X/46,XY mosaicism reported in the English literature and the third case of a constitutional chromosome Y “jumping translocation.” Our report documents the medical and genetic complexity of children such as this one with ambiguous genitalia and discusses the need for a multidisciplinary team approach.

  6. 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.

  7. Use of a human chromosome 11 radiation hybrid panel to map markers at 11q13

    International Nuclear Information System (INIS)

    Withers, D.; Richard, C. III; Meeker, T.C.; Maurer, S.; Evans, G.; Myers, R.M.; Cox, D.R.

    1990-01-01

    A human/hamster hybrid cell line containing human chromosome 11 was X-irradiated and 102-independent derivative lines were recovered. These 'radiation hybrids' contain random fragments of human chromosome 11. This radiation hybrid panel was used to score the retention of markers at band 11q13. Statistical analysis of marker co-retention patterns in the radiation hybrid panel permits a preliminary ordering and mapping of the markers used. The best order for six scored markers is: proximal - CD5 - CD20 - PGA - HST - BCL1 - SEA - distal. Additional markers are currently being scored. The six 11q13 markers above are spread over approximately 10-12 mB of DNA. The mapping data has implications for the identification of the bcl-1 gene. bcl-1 is the site of chromosome breakage in translocations associated with B lymphocytic malignancy. bcl-1 markers map at least 4 Mb away from any of four genes previously hypothesized to be activated by such translocations, thereby making them unlikely candidates for activation

  8. Determining the role of skewed X-chromosome inactivation in developing muscle symptoms in carriers of Duchenne muscular dystrophy.

    Science.gov (United States)

    Viggiano, Emanuela; Ergoli, Manuela; Picillo, Esther; Politano, Luisa

    2016-07-01

    Duchenne and Becker dystrophinopathies (DMD and BMD) are X-linked recessive disorders caused by mutations in the dystrophin gene that lead to absent or reduced expression of dystrophin in both skeletal and heart muscles. DMD/BMD female carriers are usually asymptomatic, although about 8 % may exhibit muscle or cardiac symptoms. Several mechanisms leading to a reduced dystrophin have been hypothesized to explain the clinical manifestations and, in particular, the role of the skewed XCI is questioned. In this review, the mechanism of XCI and its involvement in the phenotype of BMD/DMD carriers with both a normal karyotype or with X;autosome translocations with breakpoints at Xp21 (locus of the DMD gene) will be analyzed. We have previously observed that DMD carriers with moderate/severe muscle involvement, exhibit a moderate or extremely skewed XCI, in particular if presenting with an early onset of symptoms, while DMD carriers with mild muscle involvement present a random XCI. Moreover, we found that among 87.1 % of the carriers with X;autosome translocations involving the locus Xp21 who developed signs and symptoms of dystrophinopathy such as proximal muscle weakness, difficulty to run, jump and climb stairs, 95.2 % had a skewed XCI pattern in lymphocytes. These data support the hypothesis that skewed XCI is involved in the onset of phenotype in DMD carriers, the X chromosome carrying the normal DMD gene being preferentially inactivated and leading to a moderate-severe muscle involvement.

  9. Robin sequence associated with karyotypic mosaicism involving chromosome 22 abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Salinas, C.F.; Jastrzab, J.M.; Centu, E.S. [Medical Univ. of South Carolina, Charleston, SC (United States)

    1994-09-01

    Robin sequence is characterized by cleft palate, hypoplastic mandible, glossoptosis and respiratory difficulties. The Robin sequence may be observed as an isolated defect or as part of about 33 syndromes; however, to our knowledge, it has never been reported associated with chromosome 22 abnormalities. We examined a two-month-old black boy with a severe case of Robin sequence. Exam revealed a small child with hypoplastic mandible, glossoptosis, high palate and respiratory difficulty with continuous apnea episodes resulting in cyanotic lips and nails. In order to relieve the upper airway obstruction, his tongue was attached to the lower lip. Later a tracheostomy was performed. On follow-up exam, this patient was found to have developmental delay. Cytogenetic studies of both peripheral blood and fibroblast cells showed mosaicism involving chromosome 22 abnormalities which were designated as follows: 45,XY,-22/46,XY,-22,+r(22)/46,XY. Fluorescence in situ hybridization (FISH) studies confirmed the identity of the r(22) and showed the presence of the DiGeorge locus (D22575) but the absence of the D22539 locus which maps to 22q13.3. Reported cases of r(22) show no association with Robin sequence. However, r(22) has been associated with flat bridge of the nose, bulbous tip of the nose, epicanthus and high palate, all characteristics that we also observed in this case. These unusual cytogenetic findings may be causally related to the dysmorphology found in the patient we report.

  10. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2008-01-01

    Full Text Available Background/Aim. Intrauterine growth retardation (IUGR is a pathological condition of pregnancy characterised by birth weight below the 10th centile. A number of fetal, placental and maternal causes can lead to IUGR; although, in most cases no specific causes can be identified. The aim of this study was to determine the part of chromosomal abnormalities in IUGR etiology. Methods. Fetal blood karyotype taken by cordocentesis from 168 fetuses with diagnosed IUGR was analyzed. Results. Chromosomal rearrangements both numerical and structural were detected in 14 cases (12.2%. Two cases were triploid. Patau syndrome, Edwards syndrome and Down syndrome were found in two cases each. There was one case of trisomy 7 (47, XY, +7 and one case of trisomy 16 (47, XX, +16; one translocation, 46, XY, t (2; 14(q23; q32 and a deletion 46, XYdel (12 (p12 as well as two cases of sex chromosomes abnormalities, 45, X (Turner syndrome and 47, XYY. Conclusion. These findings suggest that a consistent number of symmetrical IUGR cases (about 12% can be associated with chromosomal rearrangements. Chromosomal aberrations that cause IUGR are heterogeneous, aberration of autosomes, mostly autosomal trisomies, being the most common.

  11. Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients

    International Nuclear Information System (INIS)

    Walker, B A; Wardell, C P; Brioli, A; Boyle, E; Kaiser, M F; Begum, D B; Dahir, N B; Johnson, D C; Ross, F M; Davies, F E; Morgan, G J

    2014-01-01

    Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including IGH, IGK and IGL, which juxtapose the immunoglobulin (Ig) enhancers next to MYC in 8/23 samples. The remaining samples had partner loci including XBP1, FAM46C, CCND1 and KRAS, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of MYC in these samples. Patients with MYC translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near MYC result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of MYC and an aggressive disease phenotype

  12. Chromosomal aberration

    International Nuclear Information System (INIS)

    Ishii, Yutaka

    1988-01-01

    Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G 2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G 2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G 2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G 1 phase. (author)

  13. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

    Directory of Open Access Journals (Sweden)

    Qiong Pan

    Full Text Available Complex chromosome rearrangements (CCRs, which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques.

  14. 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....

  15. The Relationship between the (In-)Stability of NORs and Their Chromosomal Location: The Example of Cercopithecidae and a Short Review of Other Primates.

    Science.gov (United States)

    Gerbault-Seureau, Michèle; Cacheux, Lauriane; Dutrillaux, Bernard

    2017-01-01

    Amongst Cercopithecidae, the species of the Cercopithecini tribe underwent a very active chromosome evolution, principally by fissions, which increased their chromosome number up to 72. In contrast, all the species of Papionini have fairly similar karyotypes with 42 chromosomes. In animals, nucleolus organizer regions (NORs) are generally considered as instable structures, which frequently vary in size, number, and location at both infra- and interspecific levels. Although in Cercopithecinae the NORs, involved in breaks, exchanges, and translocations, behave like fragile sites in somatic cells, their number and location appear to be very stable between species. Fluorescence in situ hybridization of a 28S rDNA probe on metaphase chromosomes displayed a unique interstitial location in either an acrocentric pair (in 12 species of Cercopithecini) or a metacentric pair (in 6 species of Papionini). A non-exhaustive survey of literature data on NOR location in other primates shows that numerical variations of the NORs principally depend on their location: most multiple NORs are in terminal positions, while almost all unique NORs are in interstitial positions. We propose that this correlation is the consequence of the selection against gametic imbalances involving the chromosomal material distal to the NORs, which is effective when they are interstitially, but not terminally, located. Thus, the consequences of the interstitial NOR instability for reproduction are essentially limited to their size variations, as observed in Cercopithecidae. © 2018 S. Karger AG, Basel.

  16. Non-homologous chromosome synapsis during mouse meiosis : consequences for male fertility and survival of progeny

    NARCIS (Netherlands)

    Peters, A.H.F.M.

    1997-01-01

    In the mouse, heterozygosity for several reciprocal and Robertsonian translocations is associated with impairment of chromosome synapsis and suppression of crossover formation in segments near the points of exchange during prophase of meiosis. This thesis describes the analysis of the consequences

  17. High-speed detection of DNA translocation in nanopipettes

    Science.gov (United States)

    Fraccari, Raquel L.; Ciccarella, Pietro; Bahrami, Azadeh; Carminati, Marco; Ferrari, Giorgio; Albrecht, Tim

    2016-03-01

    We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface.We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface. Electronic supplementary information (ESI) available: Gel electrophoresis confirming lengths and purity of DNA samples, comparison between Axopatch 200B and custom-built setup, comprehensive low-noise amplifier characterization, representative I-V curves of nanopipettes used, typical scatter plots of τ vs. peak amplitude for the four LDNA's used, table of most probable τ values, a comparison between different fitting models for the DNA translocation time distribution, further details on the stochastic numerical simulation of the scaling statistics and the derivation of the extended

  18. Synaptonemal complex analysis of X-7 translocations in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Ashley, T. (Univ. of Tennessee, Knoxville); Russell, L.B.; Cacheiro, N.L.A.

    1982-01-01

    The synaptonemal complexes of surface-spread spermatocytes of mice heterozygous for one of two reciprocal translations (R3 and R5) between the X and chromosome 7 have been examined by light and electron microscopy (EM). The break points of R3 were determined to be at 70% of chromosome 7, as measured from the centromere, and at 22% of the X. Translocation quadrivalents were formed almost exclusively. The break points of R5 were at 21% of chromosome 7 as measured from the centromere, and at 83% of the X. There was little indication that the break in the X interfered with sex-chromosome synapis between the 7X and Y. Univalent Y's were not observed in R3, and only seldom observed (8-14%) in R5. However, in contrast to R3, R5 formed quadrivalents relatively rarely (20% in the EM study of 100 nuclei), and hetermorphic bivalents of 7X-Y and X7-7 quite frequently (72%). Possible causes of this high bivalent frequency are discussed. Light-microsope (LM) analysis alone was found to be inadequate for interpreting synaptic configurations (quadrivalents vs. bivalents) in R5. The LM analysis was further complicated by the occurrence of nonhomologous synapsis in the heteromorphic bivalents of R5, a phenomonon easily recognized and interpreted in the EM portion of the study.

  19. Ribosomal DNA, tri- and bi-partite pericentromeres in the permanent translocation heterozygote Rhoeo spathacea.

    Science.gov (United States)

    Golczyk, Hieronim; Hasterok, Robert; Szklarczyk, Marek

    2010-12-01

    High- and low-stringency FISH and base-specific fluorescence were performed on the permanent translocation heterozygote Rhoeo spathacea (2n = 12). Our results indicate that 45S rDNA arrays, rDNA-related sequences and other GC-rich DNA fraction(s) are located within the pericentromeric regions of all twelve chromosomes, usually colocalizing with the chromomycin A(3)-positive bands. Homogenization of the pericentromeric regions appears to result from the concerted spread of GC-rich sequences, with differential amplification likely. We found new 5S rDNA patterns, which suggest a variability in the breakpoints and in the consequent chromosome reorganizations. It was found that the large 5S rDNA locus residing on each of the 8E and 9E arms consisted of two smaller loci. On each of the two chromosome arms 3b and 4b, in addition to the major subtelomeric 5S rDNA locus, a new minor locus was found interstitially about 40% along the arm length. The arrangement of cytotogenetic landmarks and chromosome arm measurements are discussed with regard to genome repatterning in Rhoeo.

  20. Three patients with Wolf-Hirschhorn syndrome carrying a satellited chromosome 4p.

    Science.gov (United States)

    Liang, Desheng; Zhou, Zhongmin; Meng, Dahua; Du, Juan; Wen, Juan; Niikawa, Norio; Wu, Lingqian

    2012-07-01

    Wolf-Hirschhorn syndrome (WHS) is caused by a deletion involving the 4p16.3 region. Approximately 70% of WHS patients have a de novo isolated deletion and 22% involve unbalanced translocations. However, WHS with unbalanced rearrangements involving the short arm of an acrocentric chromosome are infrequently reported. Cytogenetic and molecular analyses by using standard G-banding, argyrophilic nucleolar organiser region (Ag-NOR) staining, fluorescence in situ hybridization, and single nucleotide polymorphism array for copy number detection were performed in three patients with WHS phenotype from two Chinese families. A heterozygous 2,767,380-bp terminal 4p deletion was detected in patients 1 and 2 and a heterozygous 5,047,291-bp terminal 4p deletion was detected in patient3. Clinical comparisons among our patients and previously reported cases have been reviewed. Two terminal 4p deletions were identified in three WHS patients with a satellited 4p and an attempt was made to refine the genotypic-phenotypic correlations of the deleted regions. Copyright © 2012 Wiley Periodicals, Inc.

  1. [Involvement of distal fragment of chromosome 13 in the regulation of sensitivity to ethanol in mice].

    Science.gov (United States)

    Bazovkina, D V; Kulikov, A V

    2015-01-01

    The role of the fragment 57-65 cM of mouse chromosome 13 was studied in the regulation of ethanol action on locomotor activity, anxiety and sensitivity to hypnotic and hypothermic effects of ethanol. We used male mice of recombinant lines AKR/J and AKR.CBA-D13Mit76C, differing only in this fragment. After acute administration of ethanol only AKR mice showed the increase in the length of traveled distance in the open-field test (p mice demonstrated the increase the time spent in the center of open-field arena (p mice. The results suggest the involvement of the distal fragment 57-65 cM of chromosome 13 in the mechanisms of ethanol action in mice.

  2. Mapping EBNA-1 Domains Involved in Binding to Metaphase Chromosomes

    Science.gov (United States)

    Marechal, Vincent; Dehee, Axelle; Chikhi-Brachet, Roxane; Piolot, Tristan; Coppey-Moisan, Maité; Nicolas, Jean-Claude

    1999-01-01

    The Epstein-Barr virus (EBV) genome can persist in dividing human B cells as multicopy circular episomes. Viral episomes replicate in synchrony with host cell DNA and are maintained at a relatively constant copy number for a long time. Only two viral elements, the replication origin OriP and the EBNA-1 protein, are required for the persistence of viral genomes during latency. EBNA-1 activates OriP during the S phase and may also contribute to the partition and/or retention of viral genomes during mitosis. Indeed, EBNA-1 has been shown to interact with mitotic chromatin. Moreover, viral genomes are noncovalently associated with metaphase chromosomes. This suggests that EBNA-1 may facilitate the anchorage of viral genomes on cellular chromosomes, thus ensuring proper partition and retention. In the present paper, we have investigated the chromosome-binding activity of EBV EBNA-1, herpesvirus papio (HVP) EBNA-1, and various derivatives of EBV EBNA-1, fused to a variant of the green fluorescent protein. The results show that binding to metaphase chromosomes is a common property of EBV and HVP EBNA-1. Further studies indicated that at least three independent domains (CBS-1, -2, and -3) mediate EBNA-1 binding to metaphase chromosomes. In agreement with the anchorage model, two of these domains mapped to a region that has been previously demonstrated to be required for the long-term persistence of OriP-containing plasmids. PMID:10196336

  3. Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(15;19)(q12;p13.3).

    Science.gov (United States)

    Dang, Vy; Surampalli, Abhilasha; Manzardo, Ann M; Youn, Stephanie; Butler, Merlin G; Gold, June-Anne; Kimonis, Virginia E

    2016-01-01

    Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. High-resolution SNP microarray analysis identified an atypical PWS type I deletion in chromosome 15 involving the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was detected; therefore, the patient was not at an increased risk of tumors from the Peutz-Jeghers syndrome associated with a deletion of the STK11 gene. © 2016 S. Karger AG, Basel.

  4. Simple and Rapid In Vivo Generation of Chromosomal Rearrangements using CRISPR/Cas9 Technology

    Directory of Open Access Journals (Sweden)

    Rafael B. Blasco

    2014-11-01

    Full Text Available Generation of genetically engineered mouse models (GEMMs for chromosomal translocations in the endogenous loci by a knockin strategy is lengthy and costly. The CRISPR/Cas9 system provides an innovative and flexible approach for genome engineering of genomic loci in vitro and in vivo. Here, we report the use of the CRISPR/Cas9 system for engineering a specific chromosomal translocation in adult mice in vivo. We designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the murine endogenous Eml4 and Alk loci in order to generate the Eml4-Alk gene rearrangement recurrently found in non-small-cell lung cancers (NSCLCs. Intratracheal or intrapulmonary inoculation of lentiviruses induced Eml4-Alk gene rearrangement in lung cells in vivo. Genomic and mRNA sequencing confirmed the genome editing and the production of the Eml4-Alk fusion transcript. All mice developed Eml4-Alk-rearranged lung tumors 2 months after the inoculation, demonstrating that the CRISPR/Cas9 system is a feasible and simple method for the generation of chromosomal rearrangements in vivo.

  5. P chromosomes involved in intergenomic rearrangements of ...

    Indian Academy of Sciences (India)

    2014-04-08

    Apr 8, 2014 ... [Wang Q., Han H., Gao A., Yang X. and Li L. 2014 P chromosomes ... Y, were affected predominantly by ecological factors and altitude in nine populations of Kengyilia thoroldiana (Wang et al. 2012). To investigate the effects of different altitudes on .... AB51 0LX, UK) for improving the article linguistically.

  6. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Science.gov (United States)

    Mukesh; Sharma, Lalit Kumar; Charoo, Samina Amin; Sathyakumar, Sambandam

    2015-01-01

    The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears) returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  7. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Directory of Open Access Journals (Sweden)

    Mukesh

    Full Text Available The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  8. Influence of different chromosomal abnormalities in Ph-positive bone marrow cells on the chronic myeloid leukemia course during tyrosine kinase inhibitors therapy

    Directory of Open Access Journals (Sweden)

    O. Yu. Vinogradova

    2014-07-01

    Full Text Available The additional molecular and chromosomal abnormalities (ACA in Phositive cells usually considered as a genetic marker of chronic myeloid leukemia (CML progression. 457 patients in different CML phases received tyrosine kinase inhibitors (1st and 2nd generation were studied. During therapy 50 cases with additional chromosomal abnormalities in Ph+ clone (22 of them in chronic CML phase were revealed (median follow-up from CML diagnosis – 117 months, median imatinib therapy – 62 months. 86 % of patients in chronic phase with Ph+- cell abnormalities were cytogenetic resistance, and their 5-years overall survival was 80 % which was significantly lower than in patients without ACA (p < 0.005. The treatment results depend on chromosomal abnormalities detected. In patients with additional chromosome 8 imatinib therapy is effective, although complete cytogenetic response (CCR is achieved only in the later therapy stages. In patients with additional translocations CCR also achieved with imatinib or 2nd generation TKI. Only a third of patients with additional Ph-chromosome or BCR/ABL amplification achieved complete suppression of Ph+ clone using 2nd generation TKI. The presence of additional chromosome 7 abnormalities and complex karyotype disorders involving isochromosome i(17(q10 are poor prognostic factors of TKI treatment failures.

  9. Molecular and genetic characterization of a radiation-induced structural rearrangement in mouse chromosome 2 causing mutations at the limb deformity and agouti loci

    International Nuclear Information System (INIS)

    Woychik, R.P.; Generoso, W.M.; Russell, L.B.; Cain, K.T.; Cacheiro, N.L.; Bultman, S.J.; Selby, P.B.; Dickinson, M.E.; Hogan, B.L.

    1990-01-01

    Molecular characterization of mutations in the mouse, particularly those involving agent-induced major structural alterations, is proving to be useful for correlating the structure and expression of individual genes with their function in the whole organism. Here we present the characterization of a radiation-induced mutation that simultaneously generated distinct alleles of both the limb deformity (ld) and agouti (a) loci, two developmentally important regions of chromosome 2 normally separated by 20 centimorgans. Cytogenetic analysis revealed that an interstitial segment of chromosome 17 (17B- 17C; or, possibly, 17A2-17B) had been translocated into the distal end of chromosome 2, resulting in a smaller-than-normal chromosome 17 (designated 17del) and a larger form of chromosome 2 designated 2(17). Additionally, a large interstitial segment of the 2(17) chromosome, immediately adjacent and proximal to the insertion site, did not match bands 2E4-2H1 at corresponding positions on a normal chromosome 2. Molecular analysis detected a DNA rearrangement in which a portion of the ld locus was joined to sequences normally tightly linked to the a locus. This result, along with the genetic and cytogenetic data, suggests that the alleles of ld and a in this radiation-induced mutation, designated ldIn2 and ajIn2, were associated with DNA breaks caused by an inversion of an interstitial segment in the 2(17) chromosome

  10. Relations between ultrastructure of mitotic spindle and chromosome translocation

    Directory of Open Access Journals (Sweden)

    Jadwiga A. Tarkowska

    2014-01-01

    Full Text Available Dividing endosperm cells of Haemanthus katherinae Bak. treated with an 0.25 per cent mixture of water-soluble glycosides from Nerium oleander were insepected in a light microscope (LM and severe disturbances were found in all phases of mitosis. The same cells were observed in the electron microscope (EM and relations were noted and analysed between the chromosome arrangement and the submicroscopic structure of the mitotuc spindle. The successive steps in the disintegration of the formed spindle are described: fragmentatiun of all microtubules (MTs starting from the poles, disappearance of non-kinetachore MTs and further the external MTs of the kineto,chore bundle. The central (internal parallel ones remain the longest at the kinerf,ochares. Oleander glycosides cause disintegration of the existing MTs and prevent formation of new ones. The causes of restitution transformations in the successive phases of mitosis are discussed.

  11. Mechanism for translocation of fluoroquinolones across lipid membranes

    DEFF Research Database (Denmark)

    Cramariuc, O.; Rog, T.; Javanainen, M.

    2012-01-01

    Classical atom-scale molecular dynamics simulations, constrained free energy calculations, and quantum mechanical (QM) calculations are employed to study the diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is considered here as a representative of the fluoroquinolone...... antibiotics class. Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being predominant. Simulations reveal that only the neutral form permeates the bilayer, and it does so through a novel mechanism that involves dissolution of concerted stacks of zwitterionic ciprofloxacins....... Subsequent QM analysis of the observed molecular stacking shows the important role of partial charge neutralization in the stacks, highlighting how the zwitterionic form of the drug is neutralized for translocation. The findings propose a translocation mechanism in which zwitterionic CPFX molecules approach...

  12. Adaptation of the Pivotal-Differential Genome Pattern for the Induction of Intergenomic Chromosome Recombination in Hybrids of Synthetic Amphidiploids within Triticeae Tribe

    Directory of Open Access Journals (Sweden)

    Michal T. Kwiatek

    2017-07-01

    Full Text Available A pivotal-differential evolution pattern is when two allopolyploids share a common genome, which is called pivotal, and differ with respect to the other genome or genomes, called differential. This feature induces the intergenomic recombination between chromosomes of differential genomes, which can lead to speciation. Our study is a cytomolecular insight into this mechanism which was adapted for the induction of intergenomic chromosome recombination in hybrids of synthetic amphidiploids Aegilops biuncialis × S. cereale (UUMMRR and triticale (AABBRR where R-genome was pivotal. We observed chromosome recombination events which were induced by both: (1 random chromosome fragmentation and non-homologous chromosome end joining at mitosis of root meristem cells and (2 intergenomic chromosome associations at meiosis of pollen mother cells (PMCs of F1 hybrids. Reciprocal chromosome translocations were identified in six F1 plants and 15 plants of F2 generation using fluorescence in situ hybridization (FISH with DNA clones (pTa-86, pTa-k374, pTa-465, pTa-535, pTa-k566, and pTa-713. We observed signals of pTa-86, pTa-535, and pTa-k566 probes in several chromosome breakpoints. The comparison of the DNA clone sequences distinguished a number of common motifs, which can be considered as characteristics of chromosome breakpoint loci. Immunodetection of synaptonemal complex proteins and genomic in situ hybridization analysis at meiosis of PMCs of F1 hybrids showed, that the homologous pairing of pivotal R—genome chromosomes is crucial for the fertility of F1 hybrids, however, these chromosomes can be also involved in the intergeneric recombination.

  13. Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.

    Science.gov (United States)

    Johansson, Anna-Mia; Stenberg, Per; Bernhardsson, Carolina; Larsson, Jan

    2007-05-02

    Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome.

  14. Multiple mouse chromosomal loci for dynein-based motility

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, K.T.; Mikami, Atsushi; Paschal, B.M. [Worcester Foundation for Biomedical Research, Shrewsbury, MA (United States)] [and others

    1996-08-15

    Dyneins are multisubunit mechanochemical enzymes capable of interacting with microtubules to generate force. Axonemal dyneins produce the motive force for ciliary and flagellar beating by inducing sliding between adjacent microtubules within the axoneme. Cytoplasmic dyneins translocate membranous organelles and chromosomes toward the minus ends of cytoplasmic microtubules. Dynactin is an accessory complex implicated in tethering cytoplasmic dynein to membranous organelles and mitotic kinetochores. In the studies described here, we have identified a number of new dynein genes and determined their mouse chromosomal locations by interspecific backcross analysis. We have also mapped several dynein and dynactin genes cloned previously. Our studies provide the first comprehensive attempt to map dynein and dynactin genes in mammals and provide a basis for the further analysis of dynein function in development and disease. 65 refs., 6 figs., 1 tab.

  15. Preimplantation genetic diagnosis for chromosomal rearrangements with the use of array comparative genomic hybridization at the blastocyst stage.

    Science.gov (United States)

    Christodoulou, Christodoulos; Dheedene, Annelies; Heindryckx, Björn; van Nieuwerburgh, Filip; Deforce, Dieter; De Sutter, Petra; Menten, Björn; Van den Abbeel, Etienne

    2017-01-01

    To establish the value of array comparative genomic hybridization (CGH) for preimplantation genetic diagnosis (PGD) in embryos of translocation carriers in combination with vitrification and frozen embryo transfer in nonstimulated cycles. Retrospective data analysis study. Academic centers for reproductive medicine and genetics. Thirty-four couples undergoing PGD for chromosomal rearrangements from October 2013 to December 2015. Trophectoderm biopsy at day 5 or day 6 of embryo development and subsequently whole genome amplification and array CGH were performed. This approach revealed a high occurrence of aneuploidies and structural rearrangements unrelated to the parental rearrangement. Nevertheless, we observed a benefit in pregnancy rates of these couples. We detected chromosomal abnormalities in 133/207 embryos (64.2% of successfully amplified), and 74 showed a normal microarray profile (35.7%). In 48 of the 133 abnormal embryos (36.1%), an unbalanced rearrangement originating from the parental translocation was identified. Interestingly, 34.6% of the abnormal embryos (46/133) harbored chromosome rearrangements that were not directly linked to the parental translocation in question. We also detected a combination of unbalanced parental-derived rearrangements and aneuploidies in 27 of the 133 abnormal embryos (20.3%). The use of trophectoderm biopsy at the blastocyst stage is less detrimental to the survival of the embryo and leads to a more reliable estimate of the genomic content of the embryo than cleavage-stage biopsy. In this small cohort PGD study, we describe the successful implementation of array CGH analysis of blastocysts in patients with a chromosomal rearrangement to identify euploid embryos for transfer. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Karyotypic evolution in family Hipposideridae (Chiroptera, Mammalia) revealed by comparative chromosome painting, G- and C-banding.

    Science.gov (United States)

    Mao, Xiu-Guang; Wang, Jin-Huan; Su, Wei-Ting; Wang, Ying-Xiang; Yang, Feng-Tang; Nie, Wen-Hui

    2010-10-01

    Comparing to its sister-family (Rhinolophidae), Hipposideridae was less studied by cytogenetic approaches. Only a few high-resolution G-banded karyotypes have been reported so far, and most of the conclusions on the karyotypic evolution in Hipposideridae were based on conventional Giemsa-staining. In this study, we applied comparative chromosome painting, a method of choice for genome-wide comparison at the molecular level, and G- and C-banding to establish comparative map between five hipposiderid species from China, using a whole set of chromosome-specific painting probes from one of them (Aselliscus stoliczkanus). G-band and C-band comparisons between homologous segments defined by chromosome painting revealed that Robertsonian translocations, paracentric inversions and heterochromatin addition could be the main mechanism of chromosome evolution in Hipposideridae. Comparative analysis of the conserved chromosomal segments among five hipposiderid species and outgroup species suggests that bi-armed chromosomes should be included into the ancestral karyotype of Hipposideridae, which was previously believed to be exclusively composed of acrocentric chromosomes.

  17. A 45 X male patient with 7q distal deletion and rearrangement with SRY gene translocation: a case report.

    Science.gov (United States)

    Bilen, S; Okten, A; Karaguzel, G; Ikbal, M; Aslan, Y

    2013-01-01

    Here we present a male newborn with multiple congenital anomalies who also has an extremely rare form of testicular disorder of sex development (DSD). His karyotype was 45X, without any mosaicism. SRY gene was positive by polymerase chain reaction (PCR), and rearranged on distal part of the 7th chromosome by fluorescence in situ hybridization (FISH) analysis. SRY, normally located on the Y chromosome, is the most important gene that plays a role in the development of male sex. SRY gen may be translocated onto another chromosome, mostly X chromosome in the XX testicular DSD. On the other hand very few cases of 45 X testicular DSD were published to date. Other clinical manifestations of our patient were compatible with distal 7 q deletion syndrome. To the best of our knowledge this is the first case of 45 X testicular DSD with SRY gene rearranged on the 7th autosomal chromosome.

  18. Regulation of CD95 expression and CD95-mediated cell death by interferon-gamma in acute lymphoblastic leukemia with chromosomal translocation t(4;11).

    Science.gov (United States)

    Dörrie, J; Schuh, W; Keil, A; Bongards, E; Greil, J; Fey, G H; Zunino, S J

    1999-10-01

    The regulatory effects of IFNgamma on CD95 expression and CD95-mediated cell death were investigated in three high-risk pro-B acute lymphoblastic leukemia (ALL) lines that carry the chromosomal translocation t(4;11)(q21;q23). These leukemias are characteristically refractory to conventional chemotherapeutic treatments operating through the induction of apoptosis. However, the mechanisms leading to increased cell survival and resistance to cell death in these leukemias are largely unknown. Interferon-gamma (IFNgamma), a potent inhibitor of hematopoiesis, acts in part by upregulating CD95 and sensitizing cells to CD95-induced apoptosis. The t(4;11) lines SEM, RS4;11, and MV4;11 expressed low levels of CD95, but were completely resistant to CD95-mediated death. Addition of IFNgamma markedly upregulated CD95 expression in SEM (8-9-fold), RS4;11 (2-3-fold), and MV4;11 (2-3-fold) lines. However, after treatment with IFNgamma, only an 11% increase in sensitivity to CD95-mediated cell death was observed in SEM cells, whereas RS4;11 and MV4;11 cells remained resistant. Cycloheximide, but not actinomycin D or brefeldin A, increased CD95-specific cell death only in IFNgamma-treated RS4;11 cells by approximately 12%. Abundant levels of Bcl-2 and Bcl-XL, known to inhibit CD95-signaling in some cells, were present suggesting a possible role for both molecules in the resistance to CD95-mediated cell death. Resistance of the leukemic blasts to CD95-mediated cell death and the failure of IFNgamma to substantially sensitize the CD95-signaling pathway may contribute to the highly malignant phenotype of pro-B ALL with translocation t(4;11).

  19. Chromatin structure and ionizing-radiation-induced chromosome aberrations

    International Nuclear Information System (INIS)

    Muehlmann-Diaz, M.C.

    1993-01-01

    The possible influence of chromatic structure or activity on chromosomal radiosensitivity was studied. A cell line was isolated which contained some 10 5 copies of an amplified plasmid in a single large mosquito artificial chromosome (MAC). This chromosome was hypersensitive to DNase I. Its radiosensitivity was some three fold greater than normal mosquito chromosomes in the same cell. In cultured human cells irradiated during G 0 , the initial breakage frequency in chromosome 4, 19 and the euchromatic and heterochromatic portions of the Y chromosome were measured over a wide range of doses by inducing Premature Chromosome Condensation (PCC) immediately after irradiation with Cs-137 gamma rays. No evidence was seen that Y heterochromatin or large fragments of it remained unbroken. The only significant deviation from the expected initial breakage frequency per Gy per unit length of chromosome was that observed for the euchromatic portion of the Y chromosome, with breakage nearly twice that expected. The development of aberrations involving X and Y chromosomes at the first mitosis after irradation was also studied. Normal female cells sustained about twice the frequency of aberrations involving X chromosomes for a dose of 7.3 Gy than the corresponding male cells. Fibroblasts from individuals with supernumerary X chromosomes did not show any further increase in X aberrations for this dos. The frequency of aberrations involving the heterochromatic portion of the long arm of the Y chromosome was about what would be expected for a similar length of autosome, but the euchromatic portion of the Y was about 3 times more radiosensitive per unit length. 5-Azacytidine treatment of cultured human female fibroblasts or fibroblasts from a 49,XXXXY individual, reduced the methylation of cytosine residues in DNA, and resulted in an increased chromosomal radiosensitivity in general, but it did not increase the frequency of aberrations involving the X chromosomes

  20. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1...... using death (P = 0.015) and recurrence (P = 0.002) as outcome. The combined mutation score is strongly associated to upregulation of several growth factor pathways....

  1. New wheat-rye 5DS-4RS·4RL and 4RS-5DS·5DL translocation lines with powdery mildew resistance.

    Science.gov (United States)

    Fu, Shulan; Ren, Zhenglong; Chen, Xiaoming; Yan, Benju; Tan, Feiquan; Fu, Tihua; Tang, Zongxiang

    2014-11-01

    Powdery mildew is one of the serious diseases of wheat (Triticum aestivum L., 2 n = 6 × = 42, genomes AABBDD). Rye (Secale cereale L., 2 n = 2 × = 14, genome RR) offers a rich reservoir of powdery mildew resistant genes for wheat breeding program. However, extensive use of these resistant genes may render them susceptible to new pathogen races because of co-evolution of host and pathogen. Therefore, the continuous exploration of new powdery mildew resistant genes is important to wheat breeding program. In the present study, we identified several wheat-rye addition lines from the progeny of T. aestivum L. Mianyang11 × S. cereale L. Kustro, i.e., monosomic addition lines of the rye chromosomes 4R and 6R; a disomic addition line of 6R; and monotelosomic or ditelosomic addition lines of the long arms of rye chromosomes 4R (4 RL) and 6R (6 RL). All these lines displayed immunity to powdery mildew. Thus, we concluded that both the 4 RL and 6 RL arms of Kustro contain powdery mildew resistant genes. It is the first time to discover that 4 RL arm carries powdery mildew resistant gene. Additionally, wheat lines containing new wheat-rye translocation chromosomes were also obtained: these lines retained a short arm of wheat chromosome 5D (5 DS) on which rye chromosome 4R was fused through the short arm 4 RS (designated 5 DS-4 RS · 4 RL; 4 RL stands for the long arm of rye chromosome 4R); or they had an extra short arm of rye chromosome 4R (4 RS) that was attached to the short arm of wheat chromosome 5D (5 DS) (designated 4 RS-5 DS · 5 DL; 5 DL stands for the long arm of wheat chromosome 5D). These two translocation chromosomes could be transmitted to next generation stably, and the wheat lines containing 5 DS-4 RS · 4 RL chromosome also displayed immunity to powdery mildew. The materials obtained in this study can be used for wheat powdery mildew resistant breeding program.

  2. Translocation and gross deletion breakpoints in human inherited disease and cancer II: Potential involvement of repetitive sequence elements in secondary structure formation between DNA ends.

    Science.gov (United States)

    Chuzhanova, Nadia; Abeysinghe, Shaun S; Krawczak, Michael; Cooper, David N

    2003-09-01

    Translocations and gross deletions are responsible for a significant proportion of both cancer and inherited disease. Although such gene rearrangements are nonuniformly distributed in the human genome, the underlying mutational mechanisms remain unclear. We have studied the potential involvement of various types of repetitive sequence elements in the formation of secondary structure intermediates between the single-stranded DNA ends that recombine during rearrangements. Complexity analysis was used to assess the potential of these ends to form secondary structures, the maximum decrease in complexity consequent to a gross rearrangement being used as an indicator of the type of repeat and the specific DNA ends involved. A total of 175 pairs of deletion/translocation breakpoint junction sequences available from the Gross Rearrangement Breakpoint Database [GRaBD; www.uwcm.ac.uk/uwcm/mg/grabd/grabd.html] were analyzed. Potential secondary structure was noted between the 5' flanking sequence of the first breakpoint and the 3' flanking sequence of the second breakpoint in 49% of rearrangements and between the 5' flanking sequence of the second breakpoint and the 3' flanking sequence of the first breakpoint in 36% of rearrangements. Inverted repeats, inversions of inverted repeats, and symmetric elements were found in association with gross rearrangements at approximately the same frequency. However, inverted repeats and inversions of inverted repeats accounted for the vast majority (83%) of deletions plus small insertions, symmetric elements for one-half of all antigen receptor-mediated translocations, while direct repeats appear only to be involved in mediating simple deletions. These findings extend our understanding of illegitimate recombination by highlighting the importance of secondary structure formation between single-stranded DNA ends at breakpoint junctions. Copyright 2003 Wiley-Liss, Inc.

  3. Persistence of translocations detected by means of fluorescence in situ hybridization in peripheral lymphocytes of accidentally exposed radiation workers

    International Nuclear Information System (INIS)

    Pressl, S.; Stephan, G.

    1997-01-01

    The translocation frequency in lymphocytes of radiation workers accidentally exposed a number of years earlier was determined by means of fluorescence in situ hybridization. Chromosomes 2, 4 and 8 were painted, and simultaneously the centromeres. The genomic frequency of translocations is between 1.7 and 17.9 per 1000 cells. This variation is not significantly different from the level in healthy control subjects. Therefore, no radiation exposure could be detected retrospectively. On the other hand, the frequency of dicentrics in these radiation workers measured by means of fluorescence plus Giemsa staining shortly after the exposure was significantly increased, and whole body doses between 0.2 and 0.3 Gy could be calculated. Consequently, it would seem that dicentrics measured shortly after an exposure are a more sensitive indicator than translocations which are determined years later. (author)

  4. [Clinical characteristics and preimplantation genetic diagnosis for male Robertsonian translocations].

    Science.gov (United States)

    Huang, Jin; Lian, Ying; Qiao, Jie; Liu, Ping

    2012-08-18

    To explore the clinical characteristics and the preimplantation genetic diagnosis (PGD) for male Robertsonian translocations. From Jan 2005 to Oct 2011, 96 PGD cycles of 80 male Robertsonian translocations were performed at the Center of Reproductive Medicine of Peking University Third Hospital, Beijing. All the couples were involved in assisted reproductive therapy because of oligozoospermia or repeated abortions. Pregnancy results and clinical characteristics were analyzed in this study. Of all the 80 Robertsonian translocation couples, 62 (77.50%, 62/80) couples suffered from primary infertility due to severe oligoospermia and 8 (10%, 8/80) couples suffered from secondary infertility due to oligoospermia. Moreover, 10 (12.50%, 10/80) couples had recurrent spontaneous abortion. Of all the 80 male Robertsonian translocations, 50 were (13; 14) translocations and 15 (14; 21) translocations. The study showed that 79 PGD cycles had the balanced embryos to transfer and 25 cycles resulted in clinical pregnancies. The clinical pregnancy rate per transfer cycle was 31.65% (25 of 79). Now, 18 couples had 21 viable infants and 3 were ongoing pregnant. Oligozoospermia is the main factor for the infertility of the male Robertsonian translocations. Artificial reproductive techniques can solve their reproductive problems. Moreover, PGD will decrease the risk of recurrent spontaneous abortion and the malformations.

  5. New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22(q34;p11;q11

    Directory of Open Access Journals (Sweden)

    Abdeljabar El Andaloussi

    2007-01-01

    Full Text Available A Chronic myeloid leukaemia (CML case with a new complex t(9;18;22(q34;p11;q11 of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH. In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML.

  6. Chromosomal mosaicism in mouse two-cell embryos after paternal exposure to acrylamide

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Bishop, Jack; Lowe, Xiu; Wyrobek, Andrew J

    2008-10-14

    Chromosomal mosaicism in human preimplantation embryos is a common cause ofspontaneous abortions, however, our knowledge of its etiology is limited. We used multicolor fluorescence in situ hybridization (FISH) painting to investigate whether paternally-transmitted chromosomal aberrations result in mosaicism in mouse 2-cell embryos. Paternal exposure to acrylamide, an important industrial chemical also found in tobacco smoke and generated during the cooking process of starchy foods, produced significant increases in chromosomally defective 2-cell embryos, however, the effects were transient primarily affecting the postmeiotic stages of spermatogenesis. Comparisons with our previous study of zygotes demonstrated similar frequencies of chromosomally abnormal zygotes and 2-cell embryos suggesting that there was no apparent selection against numerical or structural chromosomal aberrations. However, the majority of affected 2-cell embryos were mosaics showing different chromosomal abnormalities in the two blastomeric metaphases. Analyses of chromosomal aberrations in zygotes and 2-cell embryos showed a tendency for loss of acentric fragments during the first mitotic division ofembryogenesis, while both dicentrics and translocations apparently underwent propersegregation. These results suggest that embryonic development can proceed up to the end of the second cell cycle of development in the presence of abnormal paternal chromosomes and that even dicentrics can persist through cell division. The high incidence of chromosomally mosaic 2-cell embryos suggests that the first mitotic division of embryogenesis is prone to missegregation errors and that paternally-transmitted chromosomal abnromalities increase the risk of missegregation leading to embryonic mosaicism.

  7. Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett syndrome

    DEFF Research Database (Denmark)

    Borg, Isabella; Freude, Kristine; Kübart, Sabine

    2005-01-01

    with different C-termini: one membrane bound through a glycosylphosphatidylinositol anchor and the other soluble. The membrane-bound protein isoform would be affected by the breakpoint, whereas the soluble form would remain intact. Our results suggest that the central nervous system is sensitive to NTNG1...... hybridisations, utilizing probes derived from breakpoint spanning BACs, detected several aberrant fragments specific for the patient. Sequence analysis of the cloned junction fragment indicated that on chromosome 1 the predominantly brain-expressed Netrin G1 (NTNG1) gene is disrupted, whereas on chromosome 7...... there was no indication for a truncated gene. The chromosome 1 breakpoint lies within the 3' part of NTNG1 and affects alternatively spliced transcripts, suggesting that the phenotype in this patient is the result of disturbed NTNG1 expression. In silico translation of the NTNG1 splice variants predicted protein isoforms...

  8. Preferential selection and transfer of euploid noncarrier embryos in preimplantation genetic diagnosis cycles for reciprocal translocations.

    Science.gov (United States)

    Wang, Li; Shen, Jiandong; Cram, David S; Ma, Minyue; Wang, Hui; Zhang, Wenke; Fan, Junmei; Gao, Zhiying; Zhang, Liwen; Li, Zhifeng; Xu, Mengnan; Leigh, Don A; Trounson, Alan O; Liu, Jiayin; Yao, Yuanqing

    2017-10-01

    To develop and validate a new strategy to distinguish between balanced/euploid carrier and noncarrier embryos in preimplantation genetic diagnosis (PGD) cycles for reciprocal translocations and to successfully achieve a live birth after selective transfer of a noncarrier embryo. Retrospective and prospective study. In vitro fertilization (IVF) units. Eleven patients undergoing mate pair sequencing for identification of translocation breakpoints, followed by clinical PGD cycles. Embryo biopsy with 24-chromosome testing to determine carrier status of balanced/euploid embryos. Definition of translocation breakpoints and polymerase chain reaction (PCR) diagnostic primers, correct diagnosis of euploid embryos for carrier status, and a live birth with a normal karyotype after transfer of a noncarrier embryo. In 9 of 11 patients (82%), translocation breakpoints were successfully identified. In four patients with a term PGD pregnancy established with a balanced/euploid embryo of unknown carrier status, the correct carrier status was retrospectively determined, matching with the cytogenetic karyotype of the resulting newborns. In a prospective PGD cycle undertaken by a patient with a 46,XY,t(7;14)(q22;q24.3) translocation, the four balanced/euploid embryos identified comprised three carriers and one noncarrier. Transfer of the noncarrier embryo resulted in birth of a healthy girl who was subsequently confirmed with a normal 46,XX karyotype. The combination of mate pair sequencing and PCR breakpoint analysis of balanced reciprocal translocation derivatives is a novel, reliable, and accurate strategy for distinguishing between carrier and noncarrier balanced/euploid embryos. The method has potential application in clinical PGD cycles for patients with reciprocal translocations or other structural rearrangements. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells.

    Science.gov (United States)

    Schwer, Bjoern; Wei, Pei-Chi; Chang, Amelia N; Kao, Jennifer; Du, Zhou; Meyers, Robin M; Alt, Frederick W

    2016-02-23

    High-throughput, genome-wide translocation sequencing (HTGTS) studies of activated B cells have revealed that DNA double-strand breaks (DSBs) capable of translocating to defined bait DSBs are enriched around the transcription start sites (TSSs) of active genes. We used the HTGTS approach to investigate whether a similar phenomenon occurs in primary neural stem/progenitor cells (NSPCs). We report that breakpoint junctions indeed are enriched around TSSs that were determined to be active by global run-on sequencing analyses of NSPCs. Comparative analyses of transcription profiles in NSPCs and B cells revealed that the great majority of TSS-proximal junctions occurred in genes commonly expressed in both cell types, possibly because this common set has higher transcription levels on average than genes transcribed in only one or the other cell type. In the latter context, among all actively transcribed genes containing translocation junctions in NSPCs, those with junctions located within 2 kb of the TSS show a significantly higher transcription rate on average than genes with junctions in the gene body located at distances greater than 2 kb from the TSS. Finally, analysis of repair junction signatures of TSS-associated translocations in wild-type versus classical nonhomologous end-joining (C-NHEJ)-deficient NSPCs reveals that both C-NHEJ and alternative end-joining pathways can generate translocations by joining TSS-proximal DSBs to DSBs on other chromosomes. Our studies show that the generation of transcription-associated DSBs is conserved across divergent cell types.

  10. 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.

  11. Chromosome survey for children of A-bomb survivors

    International Nuclear Information System (INIS)

    Awa, Akio

    1992-01-01

    To investigate chromosomes from children of A-bomb survivors, cytogenetic survey has been started in 1967 by the ABCC and completed in 1985 by the succeeding RERF. This paper is designed to overview the cytogenetic survey and to discuss the cytogenetic effects of A-bomb radiation. A cohort of 16,298 children of A-bomb survivors, which were collected from mortality survey population in 1974, was enrolled in this survey and was divided into two groups: the proximally exposed group (n=8,322, whose parents exposed to estimated doses of 0.01 Gy or more within 2,000 m from the hypocenter) and the distally exposed group (n=7,976, those exposed to 0.005 Gy or less far from 2,500 m or not in the city). Three chromosomal aberrations were identified: sex chromosome aberrations consisting mainly of XYY, XXY, and mosaic; structural abnormality of autosomes consisting mainly of translocation and inversion; and trisomy of autosomes. Overall, the incidence of chromosomal aberrations was higher in the distally exposed group (6.39%) than the proximally exposed group (5.17%). According to the type of chromosomal aberrations, the incidences of both sex chromosomes and structural abnormality of autosomes were slightly higher in the distally exposed group (0.30% and 0.34%) than the proximally exposed group (0.23% and 0.28%). Trisomy of autosomes was identified in only one child in the proximally exposed group. These findings failed to demonstrate the rationale for the cytogenetic effects of A-bomb radiation; however, cytogenetic risk of radiation has not been denied completely. (N.K.)

  12. Chromosomal changes in maize induced by hydrogen fluoride gas

    Energy Technology Data Exchange (ETDEWEB)

    Mohamed, A H

    1970-01-01

    Maize seedlings were fumigated in growth chambers with hydrogen fluoride at a concentration of about 3 ..mu..g/m/sup 3/. The experiment was run for 10 days, with the first group of treated plants removed from the chambers after 4 days and then at intervals of 2 days. Microsporocyte smears from the treated plants revealed chromosomal aberrations that included asynaptic regions, translocations, inversions, and bridges plus fragments or fragments by themselves. It is believed that these abnormalities were due to the physiological effect of HF causing the chromosomes to become sticky and/or to the occurrence of chromatid breakage followed by reunion to sticky and/or to the occurrence of chromatid breakage followed by reunion to form structural changes. These findings indicate that HF is a mutagenic agent.

  13. Cytogenetic and molecular characteristics of 25 Chilean patients with a variant Ph translocation.

    Science.gov (United States)

    Legues, Maria E; Encina, Andrea; Valenzuela, Mercedes; Palma, Tamara; Undurraga, Maria S

    2011-07-01

    Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome (Ph), which results from a balanced translocation between chromosomes 9 and 22, the t(9;22)(q34;q11.2). In 5-10% of the cases, variants of the Ph (vPh) are detected, involving various breakpoints in addition to 9q34 and 22q11.2. Deletions on the der(9) and der(22) can be detected in approximately 10-15% of CML patients. The frequency of a deletion of the der(9) in vPh CML is variable. Most studies have shown high frequencies (30-45%) in this subgroup. We report the cytogenetic evaluation of 25 vPh cases, which represents 6.8% of the CML cases diagnosed at one institution in 20 years. The breakpoints of the partners of the vPh in our patients agree with those reported previously, except for a novel 18q23. We found a low incidence of deletions of the der(9) (10%) and der(22) (5%) in these patients, contrasting with several reports in the literature. This finding may reflect the extensive spectrum of aberrations in vPh, and the possibility that a considerable group of these aberrations may not affect the genetic stability of 5'ABL1 and 3'BCR. Epidemiologic differences may also exist and could explain our results. These differences would require further investigation. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. A voltage-gated pore for translocation of tRNA

    Energy Technology Data Exchange (ETDEWEB)

    Koley, Sandip; Adhya, Samit, E-mail: nilugrandson@gmail.com

    2013-09-13

    Highlights: •A tRNA translocating complex was assembled from purified proteins. •The complex translocates tRNA at a membrane potential of ∼60 mV. •Translocation requires Cys and His residues in the Fe–S center of RIC6 subunit. -- Abstract: Very little is known about how nucleic acids are translocated across membranes. The multi-subunit RNA Import Complex (RIC) from mitochondria of the kinetoplastid protozoon Leishmania tropica induces translocation of tRNAs across artificial or natural membranes, but the nature of the translocation pore remains unknown. We show that subunits RIC6 and RIC9 assemble on the membrane in presence of subunit RIC4A to form complex R3. Atomic Force Microscopy of R3 revealed particles with an asymmetric surface groove of ∼20 nm rim diameter and ∼1 nm depth. R3 induced translocation of tRNA into liposomes when the pH of the medium was lowered to ∼6 in the absence of ATP. R3-mediated tRNA translocation could also be induced at neutral pH by a K{sup +} diffusion potential with an optimum of 60–70 mV. Point mutations in the Cys{sub 2}–His{sub 2} Fe-binding motif of RIC6, which is homologous to the respiratory Complex III Fe–S protein, abrogated import induced by low pH but not by K{sup +} diffusion potential. These results indicate that the R3 complex forms a pore that is gated by a proton-generated membrane potential and that the Fe–S binding region of RIC6 has a role in proton translocation. The tRNA import complex of L. tropica thus contains a novel macromolecular channel distinct from the mitochondrial protein import pore that is apparently involved in tRNA import in some species.

  15. Chromosomal abnormalities and environmental exposures in acute nonlymphocytic leukemia

    International Nuclear Information System (INIS)

    Crane, M.M.; Keating, M.J.; Trujillo, J.M.; Labarthe, D.R.

    1988-01-01

    Chromosomal abnormalities are present in bone marrow of approximately 50% of newly diagnostic acute nonlymphatic leukemia (ANLL) patients, but their etiologic significance, if any, is unclear. The frequency of environmental exposures, gathered by questionnaire from patients or relatives, was compared in 127 newly diagnosed ANLL patients with marrow abnormalities (AA) and 109 ANLL patients with cytogenetically normal marrow. These represented 73% of de novo patients treated at M. D. Anderson Hospital between 1976 and 1983. AA patients were more likely than NN patients to: report cytotoxic treatment for prior medical conditions, smoke cigarettes, drink alcoholic beverages, and work at occupations with possible exposure to mutagens. No statistically significant associations between aneuploidy and use of other tobacco, avocational exposure to chemicals or exposure to animals were present. Associations between specific abnormalities and prior cytotoxic therapy (deletion of chromosome 7), smoking (extra chromosome 8, inversion chromosome 16), and occupation at the time of diagnosis (translocation between chromosomes 8 and 21) were noted. No association between occupational exposure to benzene or ionizing radiation and the 6 most common chromosomal abnormalities in ANLL patients were noted, although these agents are known to be leukemogenic. Problems with interpreting the above associations, including the high nonresponse rate, a high proportion of surrogate respondents, and the large number of significance tests that were performed, are discussed. These results are consistent with those from previously reported series, and suggest that tumor-specific markers may be present for some exposures in this disease

  16. Physical Mapping of Bread Wheat Chromosome 5A: An Integrated Approach

    Directory of Open Access Journals (Sweden)

    Delfina Barabaschi

    2015-11-01

    Full Text Available The huge size, redundancy, and highly repetitive nature of the bread wheat [ (L.] genome, makes it among the most difficult species to be sequenced. To overcome these limitations, a strategy based on the separation of individual chromosomes or chromosome arms and the subsequent production of physical maps was established within the frame of the International Wheat Genome Sequence Consortium (IWGSC. A total of 95,812 bacterial artificial chromosome (BAC clones of short-arm chromosome 5A (5AS and long-arm chromosome 5A (5AL arm-specific BAC libraries were fingerprinted and assembled into contigs by complementary analytical approaches based on the FingerPrinted Contig (FPC and Linear Topological Contig (LTC tools. Combined anchoring approaches based on polymerase chain reaction (PCR marker screening, microarray, and sequence homology searches applied to several genomic tools (i.e., genetic maps, deletion bin map, neighbor maps, BAC end sequences (BESs, genome zipper, and chromosome survey sequences allowed the development of a high-quality physical map with an anchored physical coverage of 75% for 5AS and 53% for 5AL with high portions (64 and 48%, respectively of contigs ordered along the chromosome. In the genome of grasses, [ (L. Beauv.], rice ( L., and sorghum [ (L. Moench] homologs of genes on wheat chromosome 5A were separated into syntenic blocks on different chromosomes as a result of translocations and inversions during evolution. The physical map presented represents an essential resource for fine genetic mapping and map-based cloning of agronomically relevant traits and a reference for the 5A sequencing projects.

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

    International Nuclear Information System (INIS)

    Massenkeil, G.; Zschieschang, P.; Thiel, G.; Hemmati, P. G.; Budach, V.; Dörken, B.; Pross, J.; Arnold, R.

    2015-01-01

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

  18. Cold-inhibited phloem translocation in sugar beet

    International Nuclear Information System (INIS)

    Grusak, M.A.

    1985-01-01

    Experimental studies were undertaken on a simplified single source leaf-single sink leaf, or single source leaf-double sink leaf sugar beet system to investigate the responsive nature of the long-distance phloem translocation system to localized cooling perturbations on the source leaf petiole. Experiments were performed by using a steady state [ 14 C]-labelling system for the source leaf, and translocation into the sink leaf (leaves) was monitored with a Geiger-Mueller system. A specially designed Peltier apparatus enabled cooling of the source petiole to 1 0 C (or other desired temperatures) at various positions on the petiole, over different lengths, and at different rates of cooling. Initial experiment were designed to test the predictions of a mathematical recovery model of translocation inhibited by cold. The results did not support the mathematical model, but did suggest that vascular anastomoses may be involved in the recovery response. Selective petiolar incision/excision experiments showed that anastomoses were capable of re-establishing translocation following a disruption of flow. Studies with two monitored sink levels suggested that the inhibition to slow-coolings was not due to reduced translocation through the cooled source petiole region, but rather, was due to a repartitioning of flow among the terminal sinks (sink leaves and hypocotyl/crown region above the heat-girdled root). This repartitioning occurred via a redirection of flow through the vascular connections in the crown region of the plant, and appeared to be promoted by rapid, physical signals originating from the cooled region of the petiole

  19. Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3

    Energy Technology Data Exchange (ETDEWEB)

    Greger, V.; Knoll, J.H.M.; Wagstaff, J.; Lalande, M. [and others

    1997-03-01

    Angelman syndrome (AS) most frequently results from large ({ge}5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located {approximately}25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within {approximately}1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype. 47 refs., 3 figs.

  20. Phenolic content variability and its chromosome location in tritordeum

    Science.gov (United States)

    Navas-Lopez, José F.; Ostos-Garrido, Francisco J.; Castillo, Almudena; Martín, Antonio; Gimenez, Maria J.; Pistón, Fernando

    2014-01-01

    For humans, wheat is the most important source of calories, but it is also a source of antioxidant compounds that are involved in the prevention of chronic disease. Among the antioxidant compounds, phenolic acids have great potential to improve human health. In this paper we evaluate the effect of environmental and genetic factors on the phenolics content in the grain of a collection of tritordeums with different cytoplasm and chromosome substitutions. To this purpose, tritordeum flour was used for extraction of the free, conjugates and bound phenolic compounds. These phenolic compounds were identified and quantified by RP-HPLC and the results were analyzed by univariate and multivariate methods. This is the first study that describes the composition of phenolic acids of the amphiploid tritordeum. As in wheat, the predominant phenolic compound is ferulic acid. In tritordeum there is great variability for the content of phenolic compounds and the main factor which determines its content is the genotype followed by the environment, in this case included in the year factor. Phenolic acid content is associated with the substitution of chromosome DS1D(1Hch) and DS2D(2Hch), and the translocation 1RS/1BL in tritordeum. The results show that there is high potential for further improving the quality and quantity of phenolics in tritordeum because this amphiploid shows high variability for the content of phenolic compounds. PMID:24523725

  1. Duplication 4p and deletion 4p (Wolf-Hirschhorn syndrome) due to complementary gametes from a 3:1 segregation of a maternal balanced t(4;13)(p16;q11) translocation.

    Science.gov (United States)

    Takeno, S S; Corbani, M; Andrade, J A D; Smith, M de A C; Brunoni, D; Melaragno, M I

    2004-08-30

    We present clinical and cytogenetic data on a family with a t(4;13)(p16;q11) translocation present in four generations. The balanced translocation resulted in one individual with monosomy 4p and one individual with trisomy 4p, due to 3:1 segregation. The male patient with trisomy 4p was fertile and transmitted the extra chromosome to his daughter. Copyright 2004 Wiley-Liss, Inc.

  2. Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms.

    Directory of Open Access Journals (Sweden)

    James A Fraser

    2004-12-01

    Full Text Available Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen Cryptococcus revealed sequential evolutionary events that fashioned this large, highly unusual region. We hypothesize that MAT evolved via four main steps, beginning with acquisition of genes into two unlinked sex-determining regions, forming independent gene clusters that then fused via chromosomal translocation. A transitional tripolar intermediate state then converted to a bipolar system via gene conversion or recombination between the linked and unlinked sex-determining regions. MAT was subsequently subjected to intra- and interallelic gene conversion and inversions that suppress recombination. These events resemble those that shaped mammalian sex chromosomes, illustrating convergent evolution in sex-determining structures in the animal and fungal kingdoms.

  3. Repair of x-ray induced chromosomal damage in trisomy 2- and normal diploid lymphocytes

    International Nuclear Information System (INIS)

    Countryman, P.I.; Heddle, J.A.; Crawford, E.

    1977-01-01

    The frequency of chromosomal aberrations produced by x-rays is greater in lymphocytes cultured from trisomy 21 patients (Down's syndrome) than from normal diploid donors. This increase, which can be detected by a micronucleus assay for chromosomal damage, was postulated by us to result from a defect in the rejoining system which repairs chromosomal breaks. The postulated defect would result in a longer rejoining time, therapy permitting more movement of broken ends and thus enhancing the frequency of exchanges. To test this possibility, the time required for the rejoining (repair) of chromosome breaks was measured in lymphocytes from five Down's syndrome (four trisomy 21 and one D/G translocation partial trisomy 21) donors, from a monosomy 21 donor, and from five diploid donors. The rejoining time was reduced in the Down's syndrome lymphocytes in comparison to the normal diploid and monosomy 21 lymphocytes. Thus the repair of chromosome breaks, far from being defective as evidenced by a longer rejoining time in Down's syndrome cells, occurred more rapidly than in normal cells

  4. Characterization of a t(5;8)(q31;q21) translocation in a patient with mental retardation and congenital heart disease: implications for involvement of RUNX1T1 in human brain and heart development

    DEFF Research Database (Denmark)

    Zhang, Litu; Tümer, Zeynep; Møllgård, Kjeld

    2009-01-01

    The chromosome break points of the t(8;21)(q21.3;q22.12) translocation associated with acute myeloid leukemia disrupt the RUNX1 gene (also known as AML1) and the RUNX1T1 gene (also known as CBFA2T3, MTG8 and ETO) and generate a RUNX1-RUNX1T1 fusion protein. Molecular characterization of the trans...... development and support the notion that disruption of the RUNX1T1 gene is associated with the patient's phenotype.European Journal of Human Genetics advance online publication, 28 January 2009; doi:10.1038/ejhg.2008.269....

  5. In-situ fluorescence hybridization applied to biological dosimetry: contribution of automation to the counting of radio-induced chromosome aberrations

    International Nuclear Information System (INIS)

    Germain Thomas Roy, Laurence

    1999-01-01

    The frequency of chromosome aberrations on peripheral blood lymphocytes is a dose indicator in the case of ionizing radiations over-exposure. Stable chromosome aberrations (translocations, insertions) are visualized after labelling of some chromosomes using the fluorescence in-situ hybridization (FISH). The study of the use of the FISH technique in biological dosimetry is done with dose-effect curves. It seems that a bias is introduced during the observation of chromosome aberrations involving only 3 pairs of chromosomes. In order to avoid this bias, it would be useful to test the feasibility of using the multi-FISH technique in biological dosimetry. Moreover, this type of chromosome aberration changes with the type of irradiation. It is thus important to define the aberrations to be considered when the FISH technique is used. In order to reduce the time of image analysis, the CYTOGEN system, developed by IMSTAR company (Paris, France) has been adapted to the needs of biological dosimetry. This system allows to localize automatically the metaphases on the slide, which reduces the observation time by 2 or 4. An automatic detection protocol for chromosome aberrations has been implemented. It comprises the image capture, the contours detection and the classification of some chromosome aberrations. The different steps of this protocol have been tested in order to check that no bias is introduced by the automation. However, because radio-induced aberrations are rare events, it seems that a totally automatic system is not foreseeable. A semi-automatic analysis is more suitable. The use of the Slit-Scan technology (Laboratory of applied physics, Heidelberg, Germany) in biological dosimetry has been studied too. This technique allows to analyze rapidly a huge number of chromosomes. A good correlation has been observed between the dicentric frequency measured automatically and by manual counting. The system is under development and should be adapted to the detection of

  6. Using 3-color chromosome painting to decide between chromosome aberration models

    International Nuclear Information System (INIS)

    Lucas, J.N.; Sachs, R.K.

    1993-01-01

    Ionizing radiation produces chromosome aberrations when DNA double strand breaks (DSB) interact pairwise. For more than 30 years there have been two main, competing theories of such binary DSB interactions. The classical theory asserts that an unrepaired DSB makes two ends which separate, with each end subsequently able to join any similar (non-telomeric) end. The exchange theory asserts that the two DSB ends remain associated until repair or a reciprocal chromosome exchange involving a second DSB occurs. The authors conducted an experiment to test these models, using 3-color chromosome painting. After in vitro irradiation of resting human lymphocytes, they observed cells with three-color triplets at first metaphase: three derivative chromosomes having permuted colors, as if three broken chromosomes had played musical chairs. On the exchange model in its standard form such 3-color triplets cannot occur. On the classical model the expected frequency can be calculated. They report data and computer calculations which exclude the exchange model and favor the classical model

  7. Dose Assessment using Chromosome Aberration Analyses in Human Peripheral Blood Lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin-Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    The healthy five donors were recruited to establish the dose-response calibration curve for chromosomal aberrations by ionizing radiation exposure. Our cytogenetic results revealed that the mean frequency of chromosome aberration increased with increasing radiation dose. In this study, dicentric assay and CBMN assay were compared considering the sensitivity and accuracy of dose estimation. Therefore, these chromosome aberration analyses will be the foundation for biological dosimetric analysis with additional research methods such as translocation and PCC assay. The conventional analysis of dicentric chromosomes in HPBL was suggested by Bender and Gooch in 1962. This assay has been for many years, the golden standard and the most specific method for ionizing radiation damage. The dicentric assay technique in HPBL has been shown as the most sensitive biological method and reliable bio-indicator of quantifying the radiation dose. In contrast, the micronucleus assay has advantages over the dicentric assay since it is rapid and requires less specialized expertise, and accordingly it can be applied to monitor a big population. The cytokinesis-block micronucleus (CBMN) assay is a suitable method for micronuceli measurement in cultured human as well as mammalian cells. The aim of our study was to establish the dose response curve of radiation-induced chromosome aberrations in HPBL by analyzing the frequency of dicentrics and micronuclei.

  8. Comparison of type and frequency of chromosome aberrations by conventional and G-staining methods in Hiroshima atomic bomb survivors

    International Nuclear Information System (INIS)

    Ohtaki, Kazuo; Shimba, Hachiro; Sofuni, Toshio; Awa, A.A.

    1982-07-01

    Somatic chromosomes derived from cultured lymphocytes of 23 atomic bomb survivors of Hiroshima were analyzed to determine the type and frequency of radiation-induced structural aberrations, using in sequence the ordinary staining method (O-method) and the trypsin G-banding method (G-method). Of 896 cells examined, 342 were found to contain induced aberrations, including 31 cells in which the precise identification of the type of aberrations was not possible even by the G-method. The number of chromosome aberrations observed was 376 in the 311 cells where aberrant precise identification was possible. The majority (288 or 76.6%) were intra- or inter-chromosomal symmetric exchanges due to a two-break event, while only 24 were found to be asymmetric exchanges (dicentrics, rings, and interstitial deletions). Further, there were 28 aberrations showing acentric fragments and terminal deletions, and the remaining 36 were complex intra- and inter-chromosomal exchanges involving three or more breaks which result in insertions and double translocations. A comparative karyotype analysis of the same metaphases examined by the sequential 0- And G-methods was carried out independently on 361 aberrations, mostly of the symmetric type. It was found that 78 (21.6%) of the 361 were detected only by the G-method; among these were 14 paracentric inversions, 48 reciprocal interchanges of chromosome segments with either equal length (11) or un