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Sample records for chromosome alterations frequency

  1. Analysis of unstable chromosome alterations frequency induced by neutron-gamma mixed field radiation

    International Nuclear Information System (INIS)

    Nowadays monitoring chromosome alterations in peripheral blood lymphocytes have been used to access the radiation absorbed dose in individuals exposed accidental or occupationally to gamma radiation. However there are not many studies based on the effects of mixed field neutron-gamma. The radiobiology of neutrons has great importance because in nuclear factories worldwide there are several hundred thousand individuals monitored as potentially receiving doses of neutron. In this paper it was observed the frequencies of unstable chromosome alterations induced by a gamma-neutron mixed field. Blood was obtained from one healthy donor and exposed to mixed field neutron-gamma sources 241AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphases were analyzed for the presence of chromosome alterations by two experienced scorers. The results suggest that there is the possibility of a directly proportional relationship between absorbed dose of neutron-gamma mixed field radiation and the frequency of unstable chromosome alterations analyzed in this paper. (author)

  2. Preliminary study about frequencies of unstable chromosome alterations induced by gamma beam and neutron-gamma mixed field

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Mariana E.; Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F. [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Calixto, Merilane S.; Santos, Neide [Universidade Federal de Pernanmbuco (CCB/UFPE), Recife, PE (Brazil). Centro de Ciencias Biologicas. Dept. de Genetica

    2011-07-01

    The estimate on approximate dose in exposed individual can be made through conventional cytogenetic analysis of dicentric, this technique has been used to support physical dosimetry. It is important to estimate the absorbed dose in case of accidents with the aim of developing an appropriate treatment and biological dosimetry can be very useful in case where the dosimetry is unavailable. Exposure to gamma and neutron radiation leads to the same biological effects such as chromosomal alterations and cancer. However, neutrons cause more genetic damage, such as mutation or more structural damage, such as chromosome alterations. The aim of research is to compare frequencies of unstable chromosome alterations induced by a gamma beam with those from neutron-gamma mixed field. Two blood samples were obtained from one healthy donor and irradiated at different sources. The first sample was exposed to mixed field neutron-gamma sources {sup 241}AmBe at the Neutron Calibration Laboratory (NCL - CRCN/NE - PE - Brazil) and the second one was exposed to {sup 137}Cs gamma rays at {sup 137}Cs Laboratory (CRCN/NE - PE - Brazil), both exposures resulting in an absorbed dose of 0.66Gy. Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. These preliminary results showed a similarity in associated dicentrics frequency per cell (0.041 and 0.048) after {sup 137}Cs and {sup 241}AmBe sources irradiations, respectively. However, it was not observed centric rings frequency per cell (0.0 and 0.027). This study will be continue to verify the frequencies of unstable chromosome alterations induced by only gamma beam and neutron-gamma mixed field. (author)

  3. Origin and significance of chromosomal alterations

    International Nuclear Information System (INIS)

    The spontaneous frequency of chromsomal changes (structural and numerical aberations) in humans is in the order of 6 in 1,000 newborn. Chromosomal analysis of spontaneous abortuses indicate that about 50% of all spontaneous abortions are chromsomally abnormal. Populations exposed to ionizing radiations (atom bomb survivors) or chemical mutagens (e.g., workers occupational.y exposed to vinyl chloride or benzene) show increased frequencies of chromosomal aberrations in their peripheral blood lymphocytes. Many types of human cancer are associated with specific or non-specific chromosomal aberrations. Several human recessive diseases, such as ataxia telangiectasia (A-T), Faconi's anemia (FA) and Bloom's syndrome (BS) are associated with increased frequencies of chromosomal aberrations. However, no detectable increase in the frequency of spontaneous point mutations in human populations exposed to ionizing radiations or chemical mutagens has been demonstrated so far. These observations point to the importance of understanding the mechanism involved in the origin of chromosomal alterations and their significance, which the author discusses in this paper

  4. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

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    Sarah Derks

    2006-01-01

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

  5. Frequency and distribution studies of asymmetrical versus symmetrical chromosome aberrations

    International Nuclear Information System (INIS)

    Two aspects of the relationship between Asymmetrical (A) and Symmetrical (S) radiation-induced chromosomal aberrations are considered in this paper. (1) Are A and S truly alternative modes of lesion interaction. Relative frequencies for chromatid-type and chromosome-type are examined, and new lymphocyte data using banding is used to look at this, and also for parallelism in chromosome participation of the two forms for various aberration categories. All the tests applied suggest that A and S are alternative interaction modes. (2) The long-term survival characteristics of A and S are discussed, and the differences in expected frequencies of derived S per surviving cell from chromosome-type and chromatid-types are stressed. Since many in vivo tissues have varying mixtures of potential chromatid and chromosome aberration-bearing target cells, ultimate cell survival and derived S frequencies may differ between tissues for the same absorbed dose. An Appendix gives Relative Corrected Lengths (RCL) for chromosomes of the human karyotype which should be used when testing the various exchange aberration categories for random chromosome participation. (orig.)

  6. Detection of Chromosomal Structural Alterations in Single Cells by SNP Arrays: A Systematic Survey of Amplification Bias and Optimized Workflow

    Science.gov (United States)

    Iwamoto, Kazuya; Bundo, Miki; Ueda, Junko; Nakano, Yoko; Ukai, Wataru; Hashimoto, Eri; Saito, Toshikazu; Kato, Tadafumi

    2007-01-01

    Background In single-cell human genome analysis using whole-genome amplified product, a strong amplification bias involving allele dropout and preferential amplification hampers the quality of results. Using an oligonucleotide single nucleotide polymorphism (SNP) array, we systematically examined the nature of this amplification bias, including frequency, degree, and preference for genomic location, and we assessed the effects of this amplification bias on subsequent genotype and chromosomal copy number analyses. Methodology/Principal Findings We found a large variability in amplification bias among the amplified products obtained by multiple displacement amplification (MDA), and this bias had a severe effect on the genotype and chromosomal copy number analyses. We established optimal experimental conditions for pre-screening for high-quality amplified products, processing array data, and analyzing chromosomal structural alterations. Using this optimized protocol, we successfully detected previously unidentified chromosomal structural alterations in single cells from a lymphoblastoid cell line. These alterations were subsequently confirmed by karyotype analysis. In addition, we successfully obtained reproducible chromosomal copy number profiles of single cells from the cell line with a complex karyotype, indicating the applicability and potential of our optimized workflow. Conclusions/Significance Our results suggest that the quality of amplification products should be critically assessed before using them for genomic analyses. The method of MDA-based whole-genome amplification followed by SNP array analysis described here will be useful for exploring chromosomal alterations in single cells. PMID:18074030

  7. Frequency of primary amenorrhea due to chromosomal aberration

    International Nuclear Information System (INIS)

    Objective: To find out the frequency of primary amenorrhea due to chromosomal aberration and the different options available for management. Subjects and Methods: All patients with primary amenorrhea due to chromosomal aberrations were included in study. Patient's detailed history, general physical examination, presence or absence of secondary sexual characteristics, abdominal and pelvic examination finding were noted. Targeted investigations, including ultrasound, hormonal assay, buccal smear and karyotyping results were recorded. The management options were individually tailored with focus n psychological management. Results: Eighteen patients out of 30,000 patients were diagnosed as having primary amenorrhea. Six had primary amenorrhea due to chromosomal aberrations with the frequency of 0.02%. The age at presentation was 20 years and above in 50%. The most common cause was Turner's syndrome seen in 4 out of 6. The presenting symptoms were delay in onset of menstruation in 05 patients and primary infertility in 01 patient. Conclusion: Primary amenorrhea due to chromosomal aberration is an uncommon condition requiring an early and accurate diagnosis. Turner's syndrome is a relatively common cause of this condition. Management should be multi-disciplinary and individualized according to the patient's age and symptom at presentation. Psychological management is very important and counselling throughout treatment is recommended. (author)

  8. Occupational risk factors and frequency of sex chromosome disomy.

    Science.gov (United States)

    Radwan, Michał; Jurewicz, Joanna; Radwan, Paweł; Ulańska, Anna; Jakubowski, Lucjusz; Hanke, Wojciech

    2015-09-01

    Possible reproductive toxicants such as occupational factors may affect the normal disjunction of chromosomes during meiosis, thereby altering the number of chromosomes in sperm nuclei. The purpose of the present analysis was to determine whether exposure to occupational factors existing in a contemporary work setting affected sperm aneuploidy. The study population consisted of 212 men who attended the infertility clinic for diagnostic purposes. The men either had a normal semen concentration of 20-300 million/ml or slight oligozoospermia (semen concentration of 15-20 million/ml) ( WHO 1999 ). All participants were interviewed and provided a semen sample. Sperm aneuploidy was assessed using multicolor FISH. After adjustment for potential confounders, positive associations were found between disomy XY18, 18, and sex chromosome disomy and exposure to mechanical vibrations (p = 0.03, p = 0.04, p = 0.03, respectively). In addition, sitting for more than 6 h at work increased X and Y disomy (p = 0.03, p = 0.04, respectively). To the best of our knowledge, this is the first study to show a significant effect of occupational factors on sperm aneuploidy. As such, the results need to be confirmed in larger studies.

  9. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer

    DEFF Research Database (Denmark)

    Bonassi, Stefano; Norppa, Hannu; Ceppi, Marcello;

    2008-01-01

    incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence...... for stomach cancer [RR(medium) = 1.17 (95% CI = 0.37-3.70), RR(high) = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information......Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single...

  10. Altered Crossover Distribution and Frequency in Spermatocytes of Infertile Men with Azoospermia.

    Science.gov (United States)

    Ren, He; Ferguson, Kyle; Kirkpatrick, Gordon; Vinning, Tanya; Chow, Victor; Ma, Sai

    2016-01-01

    During meiosis, homologous chromosomes pair to facilitate the exchange of DNA at crossover sites along the chromosomes. The frequency and distribution of crossover formation are tightly regulated to ensure the proper progression of meiosis. Using immunofluorescence techniques, our group and others have studied the meiotic proteins in spermatocytes of infertile men, showing that this population displays a reduced frequency of crossovers compared to fertile men. An insufficient number of crossovers is thought to promote chromosome missegregation, in which case the faulty cell may face meiotic arrest or contribute to the production of aneuploid sperm. Increasing evidence in model organisms has suggested that the distribution of crossovers may also be important for proper chromosome segregation. In normal males, crossovers are shown to be rare near centromeres and telomeres, while frequent in subtelomeric regions. Our study aims to characterize the crossover distribution in infertile men with non-obstructive (NOA) and obstructive azoospermia (OA) along chromosomes 13, 18 and 21. Eight of the 16 NOA men and five of the 21 OA men in our study displayed reduced crossover frequency compared to control fertile men. Seven NOA men and nine OA men showed altered crossover distributions on at least one of the chromosome arms studied compared to controls. We found that although both NOA and OA men displayed altered crossover distributions, NOA men may be at a higher risk of suffering both altered crossover frequencies and distributions compared to OA men. Our data also suggests that infertile men display an increase in crossover formation in regions where they are normally inhibited, specifically near centromeres and telomeres. Finally, we demonstrated a decrease in crossovers near subtelomeres, as well as increased average crossover distance to telomeres in infertile men. As telomere-guided mechanisms are speculated to play a role in crossover formation in subtelomeres, future

  11. Chromosome Structural Alteration an Unusual Abnormality Characterizing Human Neoplasia

    Directory of Open Access Journals (Sweden)

    Abolfazl Movafagh

    2016-04-01

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

  12. Alteration of chromosome behavior and synchronization of parental chromosomes after successive generations in Brassica napus x Orychophragmus violaceus hybrids.

    Science.gov (United States)

    Zhao, Zhigang; Ma, Ni; Li, Zaiyun

    2007-02-01

    In an earlier study, the progenies of intergeneric hybrids Brassica napus (2n = 38) x Orychophragmus violaceus (2n = 24) were investigated in successive generations (F1-F4) for the cytological phenomenon of parental genome separation during mitotic and meiotic division. In the present study, inbred lines (F5-F8) derived from 1 such hybrid were characterized for morphology, chromosome pairing behaviour, and genome composition. One F5 plant (2n = 31) with slightly yellow petals and 12:19 and 15:16 segregation ratios in its pollen mother cells (PMCs) produced F6 plants with distinct morphological characteristics and wide variations in fertility and chromosome numbers (2n = 25-38). F7 and F8 lines with distinctive morphology and wide ranges in chromsome numbers were established. In PMCs of F7 plants from 4 F6 plants, 0-12 labelled chromosomes from O. violaceus, which predominantly appeared as bivalents, were identified by genomic in situ hybridization. They behaved synchronously with B. napus chromosomes during meiotic division. The results provide molecular cytogenetic evidence of the inclusion of O. violaceus chromosomes in the original hybrids and the cytology in the hybrids documented earlier. They also show that chromosome behaviour was altered and the parental chromosomes became synchronized after successive generations.

  13. Frequencies of fetal chromosomal abnormalities at prenatal diagnosis: 10 years experiences in a single institution.

    OpenAIRE

    Park, S. Y.; J.W. Kim; Y.M. Kim; Kim, J.M.; Lee, M. H.; Lee, B. Y.; Han, J. Y.; Kim, M. Y.; Yang, J. H.; Ryu, H. M.

    2001-01-01

    We present frequencies of fetal chromosomal abnormalities in 4,907 prenatal cytogenetic examinations at Samsung Cheil Hospital from 1988 to 1997 for 10 yr duration. Prenatal karyotypes were undertaken in 3,913 amniotic fluid samples, 800 chorionic villi samples, and 194 percutaneous umbilical blood samples. The frequency of fetal abnormal karyotypes was 3.1% (150 cases). Numerical chromosome abnormalities were 87 cases (1.8%) and structural aberrations of chromosomes were 63 cases (1.3%). In ...

  14. Identification of a high frequency of chromosomal rearrangements in the centromeric regions of prostate cancer patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation,inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investigation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 1, 3, 5, 6, 7, 9, 13, 16, 18 and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in prostate cancer tumorigenesis. Identification of chromosome alterations may be helpful in understanding the molecular basis of the disease in better manner.

  15. Novel and highly recurrent chromosomal alterations in Sezary syndrome

    NARCIS (Netherlands)

    Vermeer, Maarten H.; van Doorn, Remco; Dijkman, Remco; Mao, Xin; Whittaker, Sean; Vader, Pieter C. van Voorst; Gerritsen, Marie-Jeanne P.; Geerts, Marie-Louise; Gellrich, Sylke; Soderberg, Ola; Leuchowius, Karl-Johan; Landegren, Ulf; Out-Luiting, Jacoba J.; Knijnenburg, Jeroen; Ijszenga, Marije; Szuhai, Karoly; Willemze, Rein; Tensen, Cornelis P.

    2008-01-01

    This study was designed to identify highly recurrent genetic alterations typical of Sezary syndrome (Sz), an aggressive cutaneous T-cell lymphoma/leukemia, possibly revealing pathogenetic mechanisms and novel therapeutic targets. High-resolution array-based comparative genomic hybridization was done

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

    International Nuclear Information System (INIS)

    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 G0 -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

  17. Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud’s phenomenon

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    L. Migliore

    2011-09-01

    Full Text Available Objective: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud’s phenomenon (RP, by means of molecular cytogenetic analysis. Methods: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH analysis using a pancentromeric DNA probe was also performed. Results: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39±15.2 vs 10±2.1 and 9.8±3.5 respectively p<0.0001. Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44±8.1 as compared to subjects with different antibody pattern (26±7.1. Conclusions: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP.

  18. Altered Chromosomal Positioning, Compaction, and Gene Expression with a Lamin A/C Gene Mutation

    Science.gov (United States)

    Abuisneineh, Fida; Fahrenbach, John P.; Zhang, Yuan; MacLeod, Heather; Dellefave, Lisa; Pytel, Peter; Selig, Sara; Labno, Christine M.; Reddy, Karen; Singh, Harinder; McNally, Elizabeth

    2010-01-01

    Background Lamins A and C, encoded by the LMNA gene, are filamentous proteins that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations cause multiple human diseases including cardiac and skeletal myopathies. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene expression. Methods/Findings To investigate the hypothesis that mutant lamin A/C changes the lamina's ability to interact with chromatin, we studied gene misexpression resulting from the cardiomyopathic LMNA E161K mutation and correlated this with changes in chromosome positioning. We identified clusters of misexpressed genes and examined the nuclear positioning of two such genomic clusters, each harboring genes relevant to striated muscle disease including LMO7 and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA-mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart and fibroblasts, we found that chromosome 13 had a disproportionately high fraction of misexpressed genes. Using three-dimensional fluorescence in situ hybridization we found that the entire territory of chromosome 13 was displaced towards the center of the nucleus in LMNA mutant fibroblasts. Additional cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning of chromosome 13, although in the opposite direction. Conclusions These data support a model in which LMNA mutations perturb the intranuclear positioning and compaction of chromosomal domains and provide a mechanism by which gene expression may be altered. PMID:21179469

  19. Altered chromosomal positioning, compaction, and gene expression with a lamin A/C gene mutation.

    Directory of Open Access Journals (Sweden)

    Stephanie K Mewborn

    Full Text Available BACKGROUND: Lamins A and C, encoded by the LMNA gene, are filamentous proteins that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations cause multiple human diseases including cardiac and skeletal myopathies. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene expression. METHODS/FINDINGS: To investigate the hypothesis that mutant lamin A/C changes the lamina's ability to interact with chromatin, we studied gene misexpression resulting from the cardiomyopathic LMNA E161K mutation and correlated this with changes in chromosome positioning. We identified clusters of misexpressed genes and examined the nuclear positioning of two such genomic clusters, each harboring genes relevant to striated muscle disease including LMO7 and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA-mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart and fibroblasts, we found that chromosome 13 had a disproportionately high fraction of misexpressed genes. Using three-dimensional fluorescence in situ hybridization we found that the entire territory of chromosome 13 was displaced towards the center of the nucleus in LMNA mutant fibroblasts. Additional cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning of chromosome 13, although in the opposite direction. CONCLUSIONS: These data support a model in which LMNA mutations perturb the intranuclear positioning and compaction of chromosomal domains and provide a mechanism by which gene expression may be altered.

  20. Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ubol Chuensumran; Sopit Wongkham; Chawalit Pairojkul; Siri Chauin; Songsak Petmitr

    2007-01-01

    AIM: To characterize and evaluate DNA alterations among intrahepatic cholangiocarcinoma (ICC) patients.METHODS: DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that alters most frequently in ICC was cloned, sequenced, and identified by comparison with known nucleotide sequences in the genome database (www.ncbi.nlm.nih.gov). The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by x2-test.The Kaplan-Meier method was used to analyze survival rates.RESULTS: From 33 primers, an altered DNA fragment (518 bp) amplified from BC17 random primer was found frequently in the tumors analyzed and mapped to chromosome 17p13.2. Sixteen of 52 (31%) cases showed DNA amplification, while 7 (13%) showed allelic loss. Interestingly, DNA amplification on chromosome 17p13.2 was associated with a good prognosis, median survival time (wk) of amp vs no amp was 44.14 vs 24.14,P = 0.002; whereas allelic loss of this DNA sequence corresponded with a poor prognosis, median survival time (wk) of loss vs no loss was 18.00 vs 28.71, P =0.019). Moreover, Kaplan-Meier curves comparing the DNA alterations with survival depicted highly significant separation that the median survival time equal to DNA amplification, allelic loss, and normal was 44.14 wk,18.00 wk, and 24.29 wk, respectively (P = 0.005).CONCLUSION: Alterations in the DNA sequence on chromosome 17p13.2 may be involved in cholangiocarcinogenesis, and could be used as a prognostic marker in the treatment of ICC patients.

  1. Prognostic values of chromosome 18q microsatellite alterations in stage Ⅱ colonic carcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the prognostic value of chromosome 18q microsatellite alterations (MA) in stage Ⅱ colon cancer. METHODS: One hundred and six patients with sporadic stage Ⅱ colon cancer were enrolled in this study. DNA was extracted from formalin-fixed, paraffin-embedded tumor and adjacent normal mucosal tissue samples. MA, including loss of heterozygosity (LOH) and microsatellite instability (MSI), was analyzed by polymerase chain reaction, polyacrylamide gel-electrophoresis and DNA sequencing at 5 micr...

  2. Chromosome

    Science.gov (United States)

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

  3. Frequency of fragile X chromosome in normal females.

    Science.gov (United States)

    Abuelo, D; Castree, K; Pueschel, S; Padre-Mendoza, T; Zolnierz, K

    1985-08-01

    Because of the ambiguities in diagnosing carriers of the fragile X syndrome, we studied thirty-six normal females to determine whether the fragile site at Xq27 can be seen in noncarrier females and at what frequency. A fragile site at Xq27 was identified in one out of thirty-six females, occurring at a frequency of 0.5% in her peripheral lymphocytes. We conclude that the fragile Xq27 site occurs only rarely in noncarrier females and that each laboratory should determine its own baseline frequencies of fragile X in order to most accurately distinguish between normal and carrier women.

  4. Squeezing Alters Frequency Tuning of WGM Optical Resonator

    Science.gov (United States)

    Mohageg, Makan; Maleki, Lute

    2010-01-01

    Mechanical squeezing has been found to alter the frequency tuning of a whispering-gallery-mode (WGM) optical resonator that has an elliptical shape and is made of lithium niobate. It may be possible to exploit this effect to design reconfigurable optical filters for optical communications and for scientific experiments involving quantum electrodynamics. Some background information is prerequisite to a meaningful description of the squeezing-induced alteration of frequency tuning: The spectrum of a WGM resonator is represented by a comblike plot of intensity versus frequency. Each peak of the comblike plot corresponds to an electromagnetic mode represented by an integer mode number, and the modes are grouped into sets represented by integer mode indices. Because lithium niobate is an electro-optically active material, the WGM resonator can be tuned (that is, the resonance frequencies can be shifted) by applying a suitable bias potential. The frequency shift of each mode is quantified by a tuning rate defined as the ratio between the frequency shift and the applied potential. In the absence of squeezing, all modes exhibit the same tuning rate. This concludes the background information. It has been demonstrated experimentally that when the resonator is squeezed along part of either of its two principal axes, tuning rates differ among the groups of modes represented by different indices (see figure). The differences in tuning rates could be utilized to configure the resonance spectrum to obtain a desired effect; for example, through a combination of squeezing and electrical biasing, two resonances represented by different mode indices could be set at a specified frequency difference something that could not be done through electrical biasing alone.

  5. Evaluation of radioprotection properties of propolis by chromosomal alterations, cell proliferation kinetics, mitotic index and sister chromatid exchange

    International Nuclear Information System (INIS)

    A consequence of ionizing radiation is the induction of chromosomal alterations. This causality relation involves that chromosomal alterations can be considered a good indicator of the radiological damage. Some chemical agents can modulate the tissue response to radiation. These compounds are useful because they show certain selectivity, protecting the healthy tissues (radioprotectors) or increasing the sensibility of tissues to radiations (radiosensibilizators). Propolis substance has showed radioprotection properties which are performed in the following study. Propolis is a product of extraordinary interest for both medicine and pharmaceutical industry, since it is assumed to show diverse beneficial health effects. Among many other attributes of EEP (propolis ethanolic extract), it exhibits antioxidant and radical free scavenger properties. In a previous study, human peripheral blood lymphocytes were exposed to 2 Gy of γ rays in presence and absence of EEP, and the analysis showed a reduction in the frequency of dicentrics and rings, with a maximum protection of 50%. The proposed concentration for radioprotection would be between 120-500 μg.ml-1. The cytotoxic effect has been evaluated analyzing the EEP effect in the cellular division cycle. Propolis ethanolic extract (EEP) has been obtained and samples of peripheral blood have been cultured in the presence of increasing concentrations of EEP. In order to quantify it, two indexes have been used, the mitotic index and cell proliferation index. For both indexes the cytotoxic effect takes place from 750 μg.ml-1 concentrations onwards. Similar results were obtained for the analysis of chromosomal aberrations. Finally, propolis effect in lymphocytes by sister chromatid exchange test has been presented for higher concentrations of EEP. (author)

  6. Jasplakinolide, an actin stabilizing agent, alters anaphase chromosome movements in crane-fly spermatocytes.

    Science.gov (United States)

    Xie, Lele; Forer, Arthur

    2008-11-01

    We added jasplakinolide to anaphase crane-fly spermatocytes and determined its effects on chromosome movement. Previous work showed that the actin depolymerizing agents cytochalasin D or latrunculin B blocked or slowed chromosome movements. We studied the effects of jasplakinolide, a compound that stabilizes actin filaments. Jasplakinolide had the same effect on movements of each half- bivalent in a separating pair of half-bivalents, but different half-bivalent pairs in the same cell often responded differently, even when the concentrations of jasplakinolide varied by a factor of two. Jasplakinolide had no effect on about 20% of the pairs, but otherwise caused movements to slow, or to stop, or, rarely, to accelerate. When cells were kept in jasplakinolide, stopped pairs eventually resumed movement; slowed pairs did not change their speeds. Confocal microscopy indicated that neither the distributions of spindle actin filaments nor the distributions of spindle microtubules were altered by the jasplakinolide. It is possible that jasplakinolide binds to spindle actin and blocks critical binding sites, but we suggest that jasplakinolide affects anaphase chromosome movement by preventing actin-filament depolymerization that is necessary for anaphase to proceed. Overall, our data indicate that actin is involved in one of the redundant mechanisms cells use to move chromosomes. PMID:18688844

  7. Increased risk of cancer in radon-exposed miners with elevated frequency of chromosomal aberrations.

    Science.gov (United States)

    Smerhovsky, Zdenek; Landa, Karel; Rössner, Pavel; Juzova, Dagmar; Brabec, Marek; Zudova, Zdena; Hola, Nora; Zarska, Hana; Nevsimalova, Emilie

    2002-02-15

    In spite of the extensive use of cytogenetic analysis of human peripheral blood lymphocytes in the biomonitoring of exposure to various mutagens and carcinogens, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 1323 cytogenetic assays and 225 subjects examined because of occupational exposures to radon (range of exposure from 1.7 to 662.3 working level month (WLM)). Seventy-five subjects were non-smokers. We found 36 cases of cancer in this cohort. Chromatid breaks were the most frequently observed type of aberrations (mean frequency 1.2 per 100 cells), which statistically significantly correlated with radon exposure (Spearman's correlation coefficient R=0.22, P<0.001). Also, the frequency of aberrant cells (median of 2.5%) correlated with radon exposure (Spearman's correlation coefficient R=0.16, P<0.02). Smoking and silicosis were not associated with results of cytogenetic analyses. The Cox regression models, which accounted for the age at time of first cytogenetic assay, radon exposure, and smoking showed strong and statistically significant associations between cancer incidence and frequency of chromatid breaks and frequency of aberrant cells, respectively. A 1% increase in the frequency of aberrant cells was paralleled by a 62% increase in risk of cancer (P<0.000). An increase in frequency of chromatid breaks by 1 per 100 cells was followed by a 99% increase in risk of cancer (P<0.000). We obtained similar results when we analyzed the incidence of lung cancer and the incidence other than lung cancer separately. Contrary to frequency of chromatid breaks and frequency of aberrant cells, the frequency of chromatid exchanges, and chromosome-type aberrations were not predictive of cancer.

  8. Alteration of Terminal Heterochromatin and Chromosome Rearrangements in Derivatives of Wheat-Rye Hybrids

    Institute of Scientific and Technical Information of China (English)

    Shulan Fu; Zhenling Lv; Xiang Guo; Xiangqi Zhang; Fangpu Han

    2013-01-01

    Wheat-rye addition and substitution lines and their self progenies revealed variations in telomeric heterochromatin and centromeres.Furthermore,a mitotically unstable dicentric chromosome and stable multicentric chromosomes were observed in the progeny of a Chinese Spring-Imperial rye 3R addition line.An unstable multicentric chromosome was found in the progeny of a 6R/6D substitution line.Drastic variation of terminal heterochromatin including movement and disappearance of terminal heterochromatin occurred in the progeny of wheatrye addition line 3R,and the 5RS ditelosomic addition line.Highly stable minichromosomes were observed in the progeny of a monosomic 4R addition line,a ditelosomic 5RS addition line and a 6R/6D substitution line.Minichromosomes,with and without the FISH signals for telomeric DNA (TTTAGGG)n,derived from a monosomic 4R addition line are stable and transmissible to the next generation.The results indicated that centromeres and terminal heterochromatin can be profoundly altered in wheat-rye hybrid derivatives.

  9. Frequency of Chromosomally-Integrated Human Herpesvirus 6 in Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Annie Gravel; Daniel Sinnett; Louis Flamand

    2013-01-01

    Introduction Human herpesvirus 6 (HHV-6) is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6). The biological consequences of chromosomal integration by HHV-6 remain unknown. Objective To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors. Methodology A total of 293 DNA samples from children with pre-B (n = 255), ...

  10. MYC, TP53, and Chromosome 17 Copy-Number Alterations in Multiple Gastric Cancer Cell Lines and in Their Parental Primary Tumors

    Directory of Open Access Journals (Sweden)

    Mariana Ferreira Leal

    2011-01-01

    Full Text Available We evaluated whether MYC, TP53, and chromosome 17 copy-number alterations occur in ACP02, ACP03, and AGP01 gastric cancer cell lines and in their tumor counterpart. Fluorescence in situ hybridization for MYC and TP53 genes and for chromosome 17 was applied in the 6th, 12th, 60th, and 85th passages of the cell lines and in their parental primary tumors. We observed that three and four MYC signals were the most common alterations in gastric cell lines and tumors. ACP02 presented cells with two copies of chr17 and loss of one copy of TP53 more frequently than ACP03 and AGP01. Only ACP03 and AGP01 presented clonal chr17 trisomy with three or two TP53 copies. The frequency of MYC gain, TP53 loss, and chromosome 17 trisomy seems to increase in gastric cell lines compared to their parental tumors. Our findings reveal that these cell lines retain, in vitro, the genetic alterations presented in their parental primary tumors.

  11. Unique association between global DNA hypomethylation and chromosomal alterations in human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Naoshi Nishida

    Full Text Available Global DNA hypomethylation is a characteristic feature of cancer cells that closely associates with chromosomal instability (CIN. However, the association between these characteristics during hepatocarcinogenesis remains unclear. Herein, we determined the relationship between hypomethylation and CIN in human hepatocellular carcinoma (HCC by analyzing 179 HCCs, 178 matched non-tumor livers and 23 normal liver tissues. Hypomethylation at three different repetitive DNA (rDNA sequences and hypermethylation of 12 CpG loci, including 11 tumor suppressor gene (TSG promoters, were quantified using MethyLight or combined bisulfite restriction analysis. Fractional allelic loss (FAL was used as a marker for CIN, calculated by analyzing 400 microsatellite markers. Gains and losses at each chromosome were also determined using semi-quantitative microsatellite analysis. The associations between rDNA hypomethylation and FAL, as well as between TSG hypermethylation and FAL were investigated. Significantly more hypomethylation was observed in HCC tissues than in normal liver samples. Progression of hypomethylation during carcinogenesis was more prominent in hepatitis C virus (HCV-negative cases, which was in contrast to our previous reports of significantly increased TSG methylation levels in HCV-positive tumors. Absence of liver cirrhosis and higher FAL scores were identified as independent contributors to significant hypomethylation of rDNA in HCC. Among the chromosomal alterations frequently observed in HCC, loss of 8p, which was unique in the earliest stages of hepatocarcinogenesis, was significantly associated with hypomethylation of rDNA by multivariable analysis (p=0.0153. rDNA hypomethylation was also associated with a high FAL score regardless of tumor differentiation (p=0.0011, well-differentiated; p=0.0089, moderately/poorly-differentiated HCCs. We conclude that DNA hypomethylation is an important cause of CIN in the earliest step of HCC, especially

  12. Chromosomal and Nuclear Alterations in Root Tip Cells of Allium Cepa L. Induced by Alprazolam

    Science.gov (United States)

    Nefic, Hilada; Musanovic, Jasmin; Metovic, Azra; Kurteshi, Kemajl

    2013-01-01

    ABSTRACT Introduction: Alprazolam is a triazolobenzodiazepine used in panic disorders and other anxiety states. Target organ of Alprazolam is CNS, causing depression of respiration and consciousness. Aim: This study aimed to estimate the genotoxic potential of Alprazolam using Allium cepa test. Methods: Allium cepa is one of the most suitable plants for detecting different types of xenobiotics. The test enables the assessment of different genetic endpoints making possible damage to the DNA of humans to be predicted. Results: Alprazolam induced chromosomal (anaphase bridges, breaks, lagging and stickiness, abnormal spiralisation, multipolarity and polyploidy) and cytological aberrations, especially nuclear alterations (nuclear buds, fragmented nucleus and apoptotic bodies, cells without nucleus, binucleated and micronucleated cells), morphological alterations in shape and size of cells, spindle disturbance and polar deviation in root tip meristem cells of Allium cepa at all tested concentrations. Alprazolam also caused significant inhibition of mitotic index in these cells. Conclusion: These changes in cells are indicators of genotoxic potential of Alprazolam suggesting a need for further in vitro studies on animal and human lymphocytes as well as in vivo studies. PMID:25568504

  13. Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications.

    Science.gov (United States)

    Chang, Yi Shin; Owen, Julia P; Pojman, Nicholas J; Thieu, Tony; Bukshpun, Polina; Wakahiro, Mari L J; Marco, Elysa J; Berman, Jeffrey I; Spiro, John E; Chung, Wendy K; Buckner, Randy L; Roberts, Timothy P L; Nagarajan, Srikantan S; Sherr, Elliott H; Mukherjee, Pratik

    2016-08-01

    Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers. We find associations of these white matter alterations with cognitive and behavioral impairments. We further demonstrate the value of imaging metrics for characterizing the copy number variant phenotype by employing linear discriminant analysis to predict the gene dosage status of the study subjects. These results show an effect of 16p11.2 gene dosage on white matter microstructure, and further suggest that opposite changes in diffusion tensor imaging metrics can lead to similar cognitive and behavioral deficits. Given the large effect sizes found in this study, our results support the view that specific genetic variations are more strongly associated with specific brain alterations than are shared neuropsychiatric diagnoses. Hum Brain Mapp 37:2833-2848, 2016. © 2016 Wiley Periodicals, Inc. PMID:27219475

  14. Greig cephalopolysyndactyly syndrome: Altered phenotype of a contiguous gene syndrome by the presence of a chromosomal deletion

    Energy Technology Data Exchange (ETDEWEB)

    Hersh, J.H.; Williams, P.G.; Yen, F.F. [Univ. of Louisville, KY (United States)] [and others

    1994-09-01

    Greig cephalopolysyndactyly syndrome (GCPS) is characterized by craniofacial anomalies, broad thumbs and halluces, polydactyly of the hands and feet, and variable syndactyly. Intellectual abilities are usually normal. Inheritance is in an autosomal dominant fashion. The disorder has been mapped to chromosome 7p13, suggesting that the condition represents a contiguous gene syndrome (CGS). A male infant presented with multiple congenital anomalies, including omphalocele, dysgenesis of the corpus callosum, hydrocephalus, esotropia, broad thumbs and halluces, syndactyly, polydactyly of one foot, hypotonia and developmental delay. A de novo interstitial deletion of chromosome 7p was detected, 46,XY,del(7)(p13p15). Although clinical findings in this case were reminiscent of GCPS, and the chromosomal abnormality included the region assigned to the candidate gene for this syndrome, additional physical abnormalities were present, as well as cognitive deficits. Some of these features have been previously described in patients with chromosomal deletions of 7p. The chromosomal abnormality in our case provides supportive evidence of the gene locus in GCPS, and that GCPS represents a new CGS. However, a larger deletion, extending beyond the limits of the gene, significantly altered the phenotype. Isolation of the gene responsible for GCPS, and identification of additional patients with chromosomal abnormalities in this region of chromosome 7, should help to provide more accurate genotype-phenotype correlations.

  15. Role of 239Pu-induced chromosome alterations and mutated Ki-v-ras oncogene during liver-cancer induction in Chinese hamsters and mice

    International Nuclear Information System (INIS)

    Chromosome aberrations and mutated oncogenes can cause important changes during carcinogenesis. Model systems are being studied in which defined cellular and molecular changes can be quantitated and altered, and tumor frequency, type, and time of appearance can be evaluated. Dose-response relationships for Pu Citrate-induced chromosome aberrations and liver cancer were measured in Chinese hamsters. Chromosome aberrations increased linearly according to dose, with a slope of 4.8 x 10-1 aberrations/cell/Gy; liver-tumor incidence was 1.1 x 10-1 tumors/animal/Gy. The dose was calculated at the 50% survival time. The interaction between Pu and Ki-v-ras, an altered, dominant-acting oncogene, on the induction of liver cancer was measured in B6C3F1 mice. The neo oncogene was used as a negative control in these studies. The Ki-v-ras oncogene was inserted into a viral vector and incorporated into the livers of mice either 30 days before or after the incorporation of 239Pu. Compared with both the controls and the mice injected with a single insult, mortality increased in groups of animals that received combined exposure to oncogenes, CCl4, and 239Pu. The relationships between molecular and cellular damage and the induction of cancer is being defined in both mice and Chinese hamsters

  16. Frequency of chromosomally-integrated human herpesvirus 6 in children with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Annie Gravel

    Full Text Available INTRODUCTION: Human herpesvirus 6 (HHV-6 is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6. The biological consequences of chromosomal integration by HHV-6 remain unknown. OBJECTIVE: To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors. METHODOLOGY: A total of 293 DNA samples from children with pre-B (n=255, pre-pre-B (n=4, pre-T (n=26 and undetermined (n=8 leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content. RESULTS: Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35% contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6. CONCLUSION: The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p=0.5 to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.

  17. Universal spectrum for DNA base C+G frequency distribution in Human chromosomes 1 to 24

    CERN Document Server

    Selvam, A M

    2007-01-01

    Power spectra of human DNA base C+G frequency distribution in all available contiguous sections exhibit the universal inverse power law form of the statistical normal distribution for the 24 chromosomes. Inverse power law form for power spectra of space-time fluctuations is generic to dynamical systems in nature and indicate long-range space-time correlations. A recently developed general systems theory predicts the observed non-local connections as intrinsic to quantumlike chaos governing space-time fluctuations of dynamical systems. The model predicts the following. (1) The quasiperiodic Penrose tiling pattern for the nested coiled structure of the DNA molecule in the chromosome resulting in maximum packing efficiency. (2) The DNA molecule functions as a unified whole fuzzy logic network with ordered two-way signal transmission between the coding and non-coding regions. Recent studies indicate influence of non-coding regions on functions of coding regions in the DNA molecule.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  20. DNA methylation patterns of Brachypodium distachyon chromosomes and their alteration by 5-azacytidine treatment

    OpenAIRE

    Borowska, Natalia; Idziak, Dominika; Hasterok, Robert

    2011-01-01

    Sequential immunolocalisation of 5-methylcytosine (5-MeC) and fluorescence in situ hybridisation with chromosome-specific BAC clones were performed on Brachypodium distachyon mitotic metaphase chromosomes to determine specific DNA methylation patterns of each chromosome in the complement. In the majority of cells examined, chromosomes Bd4 and Bd5, which bear the loci of 5S and 35S ribosomal DNA, respectively, had characteristic 5-MeC patterns. In contrast, the distribution of 5-MeC along the ...

  1. Altered metaphase chromosome structure in xrs-5 cells is not related to its radiation sensitivity or defective DNA break rejoining

    International Nuclear Information System (INIS)

    The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive derivative of CHO-K1 cells. The xrs-5 cells have a defect in DNA double-strand break rejoining and show alterations in chromosome structure and nuclear morphology. The relationship between radiation sensitivity and metaphase chromosome morphology was examined in 12 'revertant' xrs-5 clones isolated following treatment with 5-azacytidine. Nine of the clones were radioresistant while the other three retained xrs-5-like radiation sensitivity. Chromosome morphology reverted to CHO-K1-like characteristics in three of the radioresistant clones and one of the radiosensitive clones suggesting that the over-condensed metaphase chromosome morphology of xrs-5 cells does not underlie its radiation sensitivity. Radiation sensitivity did correlate with DNA double-strand break rejoining ability. The radioresistant clones showing the over-condensed xrs-5-like chromosome morphology were also slightly more sensitive to the topoisomerase II inhibitor etoposide (VP-16) than CHO-K1, suggesting that the over-condensed morphology might be due to alterations in the phosphorylation of chromatin proteins

  2. Frequency of Cancer Genes on the Chicken Z Chromosome and Its Human Homologues: Implications for Sex Chromosome Evolution

    Directory of Open Access Journals (Sweden)

    Rami Stiglec

    2007-01-01

    Full Text Available It has been suggested that there are special evolutionary forces that act on sex chromosomes. Hemizygosity of the X chromosome in male mammals has led to selection for male-advantage genes, and against genes posing extreme risks of tumor development. A similar bias against cancer genes should also apply to the Z chromosome that is present as a single copy in female birds. Using comparative database analysis, we found that there was no significant underrepresentation of cancer genes on the chicken Z, nor on the Z-orthologous regions of human chromosomes 5 and 9. This result does not support the hypothesis that genes involved in cancer are selected against on the sex chromosomes.

  3. Investigation of the frequency of chromosomal aneuploidy using triple fluorescence in situ hybridization in 12 Chinese infertile men

    Institute of Scientific and Technical Information of China (English)

    张群芳; 卢光琇

    2004-01-01

    Background Chromosomal aberrations are the major cause of pre-and post-implantation embryo wastage and some studies suggest that half of all human conceptions have a chromosomal abnormality. A chromosomal aberration in human sperms is also one of the causes of failure of in vitro fertilization. This study was designed to ascertain whether chromosomal aneuploidy in spermatozoa is a risk factor for male infertility.Methods Twelve infertile men were divided into two groups: 10 with oligoasthenoteratozoospermia (OAT, Group A) and two with a normal semen analysis (Group B). Two normal healthy sperm donors acted as controls (Group C). We used fluorescence in situ hybridization (FISH) and probes for chromosomes X, Y and 18 to determine the frequency of aneuploidy.Results The frequencies of spermatozoa disomy for chromosomes X, Y and 18 were 0.30% and 0.30%, respectively, in Group B. The percentages were not significantly different from those of Group C (0.15% and 0. 16%). The frequencies of nullisomy for chromosomes X, Y and 18 were 0.15%and 0 for Group B, and 0 and 0.15% for Group C (P>0.05). In Group A, the incidences of disomy were 1.13% and 0. 96% and the frequencies of nullisomy were 1.13% and 1.60%. In these three groups, the incidences of diploidy were 0.60%, 1.00%, and 0.30%, respectively. Both the frequencies of disomic and nullisomic spermatozoa for chromosomes X, Y, and 18 and of diploid spermatozoa were significantly higher in Group A than in Groups B and C. The estimated total aneuploidy rates in the sperm from the three groups were 42.44%, 6.05%, and 2.59%,respectively.Conclusion These results indicate that chromosomal aneuploidy in spermatozoa may be a risk factor for infertility.

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

    International Nuclear Information System (INIS)

    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

  5. Detection of numerical alterations of chromosome 1 in cytopathological specimens of breast tumors by chromogen in situ hybridization.

    Science.gov (United States)

    Takarabe, T; Tsuda, H; Okada, S; Fukutomi, T; Hirohashi, S

    2001-10-01

    To investigate the effectiveness of chromogen in situ hybridization (CISH) in the diagnosis of breast tumors, numerical alterations of chromosome 1 were examined by CISH and fluorescence in situ hybridization (FISH) methods, and the presence of der(16)t(1;16) was also examined by FISH in imprinted cytology specimens from resected tissues of 14 carcinomas and five non-malignant lesions. The modal signal counts of chromosome 1 were compared between the specimens processed by CISH and FISH for each case. Aneusomies of the long arm of chromosome 1 were detected in 10 (71%) carcinomas as the major clones by both methods. In addition, one atypical papilloma demonstrated tetrasomy of 1q12 as a major clone by CISH, but such a clone was at first overlooked by FISH. Four other benign lesions showed disomic 1q12 signals as a major clone by both CISH and FISH. As additional information from FISH, eight cancers showed structural or numerical alterations of chromosome 16, and four showed der(16)t(1;16). In total, 10 carcinomas showed chromosome 16 alterations, and all of these overlapped with the carcinomas with 1q12 aneusomies. The CISH method provided almost the same results as the FISH method, and both methods were considered applicable in supportive diagnosis of cytological specimens of breast tumors. In addition, the CISH method was superior in the detection of numerical alterations in carcinoma cells by referring to the morphology of cells and in the detection of significant clones which might be missed under dark-field microscopy. PMID:11881731

  6. Frequency of unstable chromosome aberrations in peripheral lymphocytes of women with breast cancer treated with radiotherapy

    International Nuclear Information System (INIS)

    This study proposes to obtain information about the behavior of the frequency and distribution of radiation induced lymphocyte dicentric chromosome aberrations with therapeutic doses in women with breast cancer treated only with radiotherapy, about which there are no existing works in Chile. Blood samples were taken from 6 women volunteers included in the study, with their informed consent, treated in the Fundacion Arturo Lopez Perez, aged 24 to 65 years old, without prior or parallel chemotherapy, nor prior radiotherapy. Three peripheral blood samples were taken from each patient in 0, 16.2 and 43.2 Gy doses. The lymphocytes obtained from each sample were cultivated using the micro-culture technique following the protocol in IAEA Technical Report No. 405, 2001. The samples were evaluated under a microscope and the unstable chromosome aberrations for lymphocytes were counted. A total of 500 cells per sample was evaluated in most cases, which were distributed depending on the number of aberrations that they had. The results were analyzed by treatment dose for each of the study patients, using the Papworth u test, Dolphin's 'Contaminated Poisson' method and Sasaki's 'QDR'. Great variations were observed in the frequency distribution of aberrations among the patients studied, which could be due to the influence of factors related to the patients' partial irradiations (C.Wood)

  7. Determination of the relationship between genotypes and chromosomal aberration frequencies in a normal population

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey, M.; Tucker, J. [Lawrence Livermore National Lab., CA (United States)

    1997-10-01

    Individual differences in cancer susceptibility may be attributed in part to genetic differences in the genes which code for enzymes involved in metabolic activation and detoxification of environmental procarcinogens. Polymorphisms of certain genes functioning in this manner (CYP2D6, CYP1A1, CYP2E1, NAT1, NAT2, GSTT1, GSTM1) have been linked to an increased risk of some cancers. An increased level of genomic instability, often reflected as an increase in chromosomal aberrations (CA), has also been associated with an elevated risk of cancer. Accurate polymorphism frequency determinations for these genes in a normal population is needed to establish whether these frequencies are different in a diseased population. In this work, analyses are being performed on over 100 normal individuals, ranging from 0 to 80 years of age, to determine CA frequency and genotypes. Individual exposure and health data have also been obtained from all individuals in the study. These analyses will provide a baseline frequency for the various gene polymorphisms in a normal (mainly Caucasian) population, and will determine whether a relationship between the CA frequency and certain polymorphisms and or genotypes exists. In addition the interaction between environmental exposures (such as smoking), genotypes and CA frequencies are being examined. At present 24 individuals have been genotyped for GSTT1, GSTM1 and CYP2D6(T) and their CA frequencies determined. Genotype frequencies of 21% for GSTM1 B, 4% for GSTM1 null, 29% for GSTM1 A, 21% for GSTM1 B, 4% for GSTM1 A,B, and 0% for CYP2D6(T) have been determined from the small sample analyzed to date. We plan to extend our genotype analysis to include the remaining CYP2D6 polymorphisms, CYP2E1, CYP1A1, NAT1 and NAT2.

  8. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    OpenAIRE

    Geísa Pinheiro Paes; José Marcelo Soriano Viana; Fabyano Fonseca e Silva; Gabriel Borges Mundim

    2016-01-01

    Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kerne...

  9. 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 < median intake of whole grains (P = 0·03) and red and processed meat (P = 0·01): 0·69 (95 % CI 0·50, 0·96) and 1·56 (95 % CI 1·13, 2·16), respectively. Our data suggest that a high intake of niacin from 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.

  10. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma.

    OpenAIRE

    Pelicci, P.G.; Knowles, D M; Magrath, I; Dalla-Favera, R

    1986-01-01

    We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines. This panel includes the two pathogenetic forms of BL: the endemic (African-type) BL (eBL) and sporadic (American-type) BL (sBL). In all cases tested, including fresh samples and cell lines, structural alterations of the 5' portion of the gene were detected...

  11. Rainfall-driven sex-ratio genes in African buffalo suggested by correlations between Y-chromosomal haplotype frequencies and foetal sex ratio

    OpenAIRE

    Greyling Barend J; van Wieren Sipke E; Jolles Anna E; Getz Wayne M; Prins Herbert HT; van Hooft Pim; van Helden Paul D; Bastos Armanda DS

    2010-01-01

    Abstract Background The Y-chromosomal diversity in the African buffalo (Syncerus caffer) population of Kruger National Park (KNP) is characterized by rainfall-driven haplotype frequency shifts between year cohorts. Stable Y-chromosomal polymorphism is difficult to reconcile with haplotype frequency variations without assuming frequency-dependent selection or specific interactions in th...

  12. Temporalchanges in relative frequencies of third chromosome inversions of Drosophila pseudoobscura in Mexican populations

    Directory of Open Access Journals (Sweden)

    Salceda Victor M.

    2008-01-01

    Full Text Available Variations in relative frequencies of third chromosome inversions during 1974-2000 in three populations of D. pseudoobscura from Mexico were analyzed. The general constitution of these populations is formed from ten up to 15 different inversions, been prevalent, as data shows, the gene arrangements CU, TL, SC, OA, EP, and OL as main components of the studied populations. In Amecameca and Tulancingo we observed that they were constituted by a dominant pair in both cases represented by such partners as CU-TL inside each pair, in Amecameca the superior partner was CU and in Tulancingo TL. In Zirahuén two dominant pairs form the constitution they are SC-OA and CU-TL been the former superior. In all cases sporadic increases of some of inversions were observed. No directional changes were observed. The cyclic pattern is show within periods of 4-5 years.

  13. The frequency of chromosome exchanges in critical groups of Chernobyl accident victims according to conventional chromosome analysis and FISH method

    International Nuclear Information System (INIS)

    Conventional cytogenetic with group karyotyping and FISH analyses were performed in 16 Chernobyl accident liquidators diagnosed in 1986 with acute radiation sickness of different degree of severity. The data received confirmed the validity of FISH both as for evaluation of stable chromosome aberrations in peripheral lymphocytes of irradiated persons as enough high sensitivity of FISH for the tentative retrospective dose evaluation in the remote period after acute irradiation and during chronic radiation exposure in doses above 0.25 Gy

  14. Dynamics of rye chromosome 1R regions with high or low crossover frequency in homology search and synapsis development.

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    Nohelia T Valenzuela

    Full Text Available In many organisms, homologous pairing and synapsis depend on the meiotic recombination machinery that repairs double-strand DNA breaks (DSBs produced at the onset of meiosis. The culmination of recombination via crossover gives rise to chiasmata, which locate distally in many plant species such as rye, Secale cereale. Although, synapsis initiates close to the chromosome ends, a direct effect of regions with high crossover frequency on partner identification and synapsis initiation has not been demonstrated. Here, we analyze the dynamics of distal and proximal regions of a rye chromosome introgressed into wheat to define their role on meiotic homology search and synapsis. We have used lines with a pair of two-armed chromosome 1R of rye, or a pair of telocentrics of its long arm (1RL, which were homozygous for the standard 1RL structure, homozygous for an inversion of 1RL that changes chiasma location from distal to proximal, or heterozygous for the inversion. Physical mapping of recombination produced in the ditelocentric heterozygote (1RL/1RL(inv showed that 70% of crossovers in the arm were confined to a terminal segment representing 10% of the 1RL length. The dynamics of the arms 1RL and 1RL(inv during zygotene demonstrates that crossover-rich regions are more active in recognizing the homologous partner and developing synapsis than crossover-poor regions. When the crossover-rich regions are positioned in the vicinity of chromosome ends, their association is facilitated by telomere clustering; when they are positioned centrally in one of the two-armed chromosomes and distally in the homolog, their association is probably derived from chromosome elongation. On the other hand, chromosome movements that disassemble the bouquet may facilitate chromosome pairing correction by dissolution of improper chromosome associations. Taken together, these data support that repair of DSBs via crossover is essential in both the search of the homologous partner

  15. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.

    Science.gov (United States)

    Darrow, Emily M; Huntley, Miriam H; Dudchenko, Olga; Stamenova, Elena K; Durand, Neva C; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P; Lander, Eric S; Chadwick, Brian P; Aiden, Erez Lieberman

    2016-08-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  16. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture

    Science.gov (United States)

    Darrow, Emily M.; Huntley, Miriam H.; Dudchenko, Olga; Stamenova, Elena K.; Durand, Neva C.; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L.; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P.; Lander, Eric S.; Chadwick, Brian P.; Aiden, Erez Lieberman

    2016-01-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the “Barr body.” Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called “superdomains,” such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called “superloops.” DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4. We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  17. Characterization of Common Chromosomal Translocations and Their Frequencies in Acute Myeloid Leukemia Patients of Northwest Iran

    Directory of Open Access Journals (Sweden)

    Elnaz Amanollahi Kamaneh

    2016-04-01

    Full Text Available Objective: Detection of chromosomal translocations has an important role in diagnosis and treatment of hematological disorders. We aimed to evaluate the 46 new cases of de novo acute myeloid leukemia (AML patients for common translocations and to assess the effect of geographic and ethnic differences on their frequencies. Materials and Methods: In this descriptive study, reverse transcriptase-polymerase chain reaction (RT-PCR was used on 46 fresh bone marrow or peripheral blood samples to detect translocations t (8; 21, t (15; 17, t (9; 11 and inv (16. Patients were classified using the French-American-British (FAB criteria in to eight sub-groups (M0-M7. Immunophenotyping and biochemical test results of patients were compared with RT-PCR results. Results: Our patients were relatively young with a mean age of 44 years. AML was relatively predominant in female patients (54.3% and most of patients belonged to AML-M2. Translocation t (8; 21 had the highest frequency (13% and t (15; 17 with 2.7% incidence was the second most frequent. CD19 as an immunophenotypic marker was at a relatively high frequency (50% in cases with t (8; 21, and patients with this translocation had a specific immunophenotypic pattern of complete expression of CD45, CD38, CD34, CD33 and HLA-DR. Conclusion: Similarities and differences of results in Iran with different parts of the world can be explained with ethnic and geographic factors in characterizations of AML. Recognition of these factors especially in other comprehensive studies may aid better diagnosis and management of this disease.

  18. Nursing frequency alters circadian patterns of mammary gene expression in lactating mice

    Science.gov (United States)

    Milking frequency impacts lactation in dairy cattle and in rodent models of lactation. The role of circadian gene expression in this process is unknown. The hypothesis tested was that changing nursing frequency alters the circadian patterns of mammary gene expression. Mid-lactation CD1 mice were stu...

  19. Chromosome Specific Substitution Lines of Aegilops geniculata Alter Parameters of Bread Making Quality of Wheat

    Science.gov (United States)

    Tsujimoto, Hisashi; Gupta, Raj Kumar; Kumar, Aman; Kaur, Navneet; Kumar, Rohit; Chunduri, Venkatesh; Sharma, Nand Kishor; Chawla, Meenakshi; Sharma, Saloni; Mundey, Jaspreet Kaur

    2016-01-01

    Wheat cultivars with wide introgression have strongly impacted global wheat production. Aegilops geniculata (MgUg) is an important wild relative with several useful traits that can be exploited for wheat improvement. Screening of Ae. geniculata addition lines indicated a negative effect of 1Ug and the positive effect of 1Mg chromosome on wheat dough strength. Negative effect of 1Ug is probably associated with variation in number and position of the tripeptide repeat motif in the high molecular weight glutenin (HMW-G) gene. To utilize the positive potential of 1Mg chromosome, three disomic substitution lines (DSLs) 1Mg(1A), 1Mg(1B) and 1Mg(1D) were created. These lines were characterized for morphological, cytogenetic properties and biochemical signatures using FISH, 1D-, 2D-PAGE and RP-HPLC. Contribution of wheat 1A, 1B and 1D chromosomes towards dough mixing and baking parameters, chapatti quality, Fe/Zn content and glume color were identified. Observed order of variation in the dough mixing and baking parameters {1Mg(1D) ≤wheat ≤1Mg(1B) ≤1Mg(1A)} indicated that chromosome specific introgression is desirable for best utilization of wild species’ potential. PMID:27755540

  20. Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy

    Directory of Open Access Journals (Sweden)

    Olla Carlo

    2007-08-01

    Full Text Available Abstract Background The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21 genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy. Results Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21 were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects. Conclusion We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.

  1. What the Erythrocytic Nuclear Alteration Frequencies Could Tell Us about Genotoxicity and Macrophage Iron Storage?

    Science.gov (United States)

    Gomes, Juliana M. M.; Ribeiro, Heder J.; Procópio, Marcela S.; Alvarenga, Betânia M.; Castro, Antônio C. S.; Dutra, Walderez O.; da Silva, José B. B.; Corrêa Junior, José D.

    2015-01-01

    Erythrocytic nuclear alterations have been considered as an indicative of organism’s exposure to genotoxic agents. Due to their close relationship among their frequencies and DNA damages, they are considered excellent markers of exposure in eukaryotes. However, poor data has been found in literature concerning their genesis, differential occurrence and their life span. In this study, we use markers of cell viability; genotoxicity and cellular turn over in order to shed light to these events. Tilapia and their blood were exposed to cadmium in acute exposure and in vitro assays. They were analyzed using flow cytometry for oxidative stress and membrane disruption, optical microscopy for erythrocytic nuclear alteration, graphite furnace atomic absorption spectrometry for cadmium content in aquaria water, blood and cytochemical and analytical electron microscopy techniques for the hemocateretic aspects. The results showed a close relationship among the total nuclear alterations and cadmium content in the total blood and melanomacrophage centres area, mismatching reactive oxygen species and membrane damages. Moreover, nuclear alterations frequencies (vacuolated, condensed and blebbed) showed to be associated to cadmium exposure whereas others (lobed and bud) were associated to depuration period. Decrease on nuclear alterations frequencies was also associated with hemosiderin increase inside spleen and head kidney macrophages mainly during depurative processes. These data disclosure in temporal fashion the main processes that drive the nuclear alterations frequencies and their relationship with some cellular and systemic biomarkers. PMID:26619141

  2. Altered Frequency Distribution in the Electroencephalogram is Correlated to the Analgesic Effect of Remifentanil

    DEFF Research Database (Denmark)

    Graversen, Carina; Malver, Lasse P; Kurita, Geana P;

    2015-01-01

    Opioids alter resting state brain oscillations by multiple and complex factors, which are still to be elucidated. To increase our knowledge, multi-channel electroencephalography (EEG) was subjected to multivariate pattern analysis (MVPA), to identify the most descriptive frequency bands and scalp...... individual changes in heat pain in the delta (p = 0.045), theta (p = 0.038) and alpha (p = 0.039) bands and to bone pain in the alpha band (p = 0.0092). Hence, MVPA of multi-channel EEG was able to identify frequency bands and corresponding channels most sensitive to altered brain activity during...... locations altered by remifentanil in healthy volunteers. Sixty-two channels of resting EEG followed by independent measures of pain scores to heat and bone pain were recorded in 21 healthy males before and during remifentanil infusion in a placebo-controlled, double-blind crossover study. EEG frequency...

  3. Detection of numerical and structural alterations and fusion of chromosomes 16 and 1 in low-grade papillary breast carcinoma by fluorescence in situ hybridization.

    OpenAIRE

    Tsuda, H; Takarabe, T.; Susumu, N; Inazawa, J; Okada, S.; Hirohashi, S

    1997-01-01

    Intracystic papillary breast tumors, including intraductal papilloma and low-grade intracystic papillary carcinoma, constitute a group for which differential diagnosis is frequently difficult. We examined the status of chromosomes 16 and 1 by multicolor fluorescence in situ hybridization (FISH) analyses and the DNA ploidy patterns by flow cytometry in 26 intracystic papillary tumors. Alterations of chromosomes 16 and 1 were detected by FISH in 93 and 85%, respectively, of 14 low-grade papilla...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  5. The frequency of chromosomal aberrations in sheep from the area contaminated by depleted uranium during NATO air strikes in 1999

    OpenAIRE

    Fišter Svetlana L.; Jović Slavoljub Z.

    2014-01-01

    This paper presents the results of cytogenetic studies in sheep from the region of Bujanovac that was contaminated by depleted uranium during the NATO air strikes in 1999. The study was conducted on sheep blood lymphocytes, in order to determine the frequency of chromosomal aberrations and to assess the presence of genetic risk as a result of the possible impact of depleted uranium. Blood samples for lymphocyte cultures were taken at random from the 20 anim...

  6. The effects of biological and life-style factors on baseline frequencies of chromosome aberrations in human lymphocytes

    Directory of Open Access Journals (Sweden)

    Hilada Nefic

    2014-01-01

    Full Text Available Objective: This study investigated the influence of sex and ageing on chromosomal damage and the role of life-style habits on the frequency of chromosomal aberrations (CAs in peripheral blood lymphocytes (PBLs of healthy Bosnian subjects. Materials and Methods: Peripheral blood samples were obtained from 100 healthy, unrelated individuals in Bosnia and Herzegovina during 2010 and 2011. Chromosome preparations were made by dropping and air drying and slides were stained with 10% Giemsa solution (pH 6.8. The cytogenetic analysis was carried out in a cytogenetic laboratory in the Department of Biology of the Faculty of Science in Sarajevo. The category of total structural CAs was sub classified as chromosome-type aberrations (CSAs and chromatid-type aberrations (CTAs while the category of total numerical CAs was sub classified as aneuploid and polyploid mitoses. All statistical analyses were carried out using Microsoft Excel 2010 (Microsoft Corporation and the Windows Kwikstat Winks SDA 7.0.2 statistical software package (Texa Soft Cedar Hill, Texas. Results: Cytogenetic analysis revealed the average number of structural CAs was 2.84 and of numerical CAs was 9.56. There was a significant increase in the frequency of chromosome-type aberrations (1.92 compared with chromatid-type aberrations (CTAs (0.92 and a significant increase in the frequency of aneuploid (8.83 compared with polyploid (0.73 mitoses. Significant positive correlations between age and CTAs in human PBLs were also demonstrated. Additional statistical analysis showed that ageing increase number of numerical CAs in lymphocytes of drinkers. The frequency of structural CAs of females exposed to radiation was significantly greater than in males. Analysis indicates the presence of a positive association between CAs and smoking in younger subjects but a negative correlation between aberrant cells frequencies and alcohol in older drinkers. Conclusion: The results of the study support the

  7. Geographical changes in relative frequency of inversions in chromosome III of Drosophila pseudoobscura among natural populations from Mexico

    Directory of Open Access Journals (Sweden)

    Salceda Víctor M.

    2009-01-01

    Full Text Available Chromosomal polymorphism in natural populations of Drosophila pseudoobscura have been broadly studied in the USA but scarcely in Mexico where only about 60 localities have been analyzed. Differences among both regions are notorious with respect to their chromosomal constitution. Northern populations, those of USA, have as representative inversions the sequences ST, AR and CH contrasting with those in Southern populations (Mexico in which prevail the gene arrangements TL, CU and SC. Assuming as a probable mechanism that has allowed these substitutions the flow generated by the presence of a North - South clines, we took as a goal find out if such clines really exist. With that objective in mind we studied 29 populations of this species distributed along four North - South transects. Specimens of D. pseudoobscura caught by attracting them with fermenting bananas were carried to the laboratory where from each female an isofemale line was established. When their offspring appeared a single larva from each isofemale was taken, its salivary glands extracted and stained with a solution of lacto-aceto- orcein, by these means the polytene chromosomes were obtained. On these chromosomes we identified, for each larva, the inversion (s carried in the third chromosome, in such a way 3439 third chromosomes were analyzed. Among the 29 localities we identified 17 different inversions but the number of them varied from population to population from three to eleven. Relative frequencies of each inversion at every location were calculated and with them for each transect the presence or absence of clines was determined. Among each transect the existence of clines was observed only between two or three near by populations, but we were not able to find a clear manifestation of the presence of clines along a complete transect. Our results at this respect are similar to those previously reported for USA populations. A mechanism that explains North - South substitutions

  8. Higher frequencies of chromosomal aberrations in lymphocytes of children with acute lymphoblastic leukemia after in vitro gamma irradiation

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    A Ramyar

    2012-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood, characterized by excess lymphoblasts, and immature white blood cells that are continuously multiplying and overproducing in the bone marrow. The aim of this investigation was to measure the sensitivity of lymphocytes against gamma irradiation in patients with acute lymphoblastic leukemia, and also find out the effect of such irradiations in causing chromosomal abnormalities.Methods: In this investigation performed between April 2010 and July 2011, at the Department of Genetics, Cancer Institute of Iran, we studied the effects of gamma irradiation on the lymphocytes of 20 children with acute lymphoblastic leukemia. The lymphocytes of 30 healthy donors were used to establish as a normal response to gamma irradiation and seven age-matched ataxia telangiectasia patients were recruited as positive control. The chromosomal radiosensitivity was assessed with the G2- and the G0-assay. We compared the mean number of chromosomal abnormalities such as chromosome and chromatid breakages, chromosome and chromatid gaps, and chromatid exchanges in one-hundred metaphases of patients and control groups.Results: The frequency of chromosomal aberrations was statistically higher among patients with acute lymphoblastic leukemia than the normal controls (P<0.01. In total, 65% of the patients were sensitive to gamma irradiation, but the remaining 35% were similar to the normal controls. Patients with ataxia telangiectasia showed the highest sensitivity to gamma irradiation (P=0.001.Conclusion: Our results showed that a high percentage of patients with acute lymphoblastic leukemia were sensitive to irradiation, meaning that maximum care should be taken during their treatment to avoid unnecessary X-rays or radiotherapies.

  9. Detection of numerical and structural alterations and fusion of chromosomes 16 and 1 in low-grade papillary breast carcinoma by fluorescence in situ hybridization.

    Science.gov (United States)

    Tsuda, H; Takarabe, T; Susumu, N; Inazawa, J; Okada, S; Hirohashi, S

    1997-10-01

    Intracystic papillary breast tumors, including intraductal papilloma and low-grade intracystic papillary carcinoma, constitute a group for which differential diagnosis is frequently difficult. We examined the status of chromosomes 16 and 1 by multicolor fluorescence in situ hybridization (FISH) analyses and the DNA ploidy patterns by flow cytometry in 26 intracystic papillary tumors. Alterations of chromosomes 16 and 1 were detected by FISH in 93 and 85%, respectively, of 14 low-grade papillary carcinomas, and the latter alterations always concurred with the former. Two-color FISH using probes for the D1Z1 (1q12) and D16Z2 (16cen) loci or the D1Z1 and D16Z3 (16q11) loci showed that fusion of chromosomes 16 and 1, mostly with breakpoints distal to 16q11.2 and proximal to 1q12, occurred in 77% of the papillary carcinomas. DNA aneuploidy was detected in 6% of these carcinomas. No papilloma showed these chromosome alterations or DNA aneuploidy. Chromosome 16 and 1 fusions appeared to occur frequently in diploid breast carcinomas and to be involved in the acquisition of a malignant phenotype by duct epithelial cells. We suggest that two-color FISH methods for detecting 1;16 fusions might be applicable as supportive methods for the differential diagnosis of intracystic papillary breast tumors. PMID:9327736

  10. Pacifier-sucking habit duration and frequency on occlusal and myofunctional alterations in preschool children

    Directory of Open Access Journals (Sweden)

    Valdeane Simone Cenci NIHI

    2015-01-01

    Full Text Available The objective of this study was to evaluate the association of pacifier-sucking habit with occlusal and oral myofunctional alterations in preschool children. Eighty-four 2- to 5-year-old children participated in the study. Data on duration and frequency of pacifier use were collected from parents or guardians. Occlusal and oral myofunctional characteristics were examined by a dentist and a speech therapist, respectively. Chi-square tests and Poisson regression were used to analyze the data. The occlusal characteristics that were significantly associated with a pacifier-sucking habit were anterior open bite, altered canine relation, posterior crossbite, increased overjet, and malocclusion. The oral myofunctional characteristics that were significantly associated with a pacifier-sucking habit were resting lip position, resting tongue position, shape of the hard palate, and swallowing pattern. The strongest associations were for anterior open bite (prevalence ratio [PR] = 11.33, malocclusion (PR = 2.33, altered shape of the hard palate (PR = 1.29, and altered swallowing pattern (PR = 1.27. Both duration and frequency of pacifier-sucking habit were associated with occlusal and oral myofunctional alterations. These results emphasize the need for pediatric dentists to advise parents and caregivers about the risks of prolonged pacifier use and refer children to professionals for multidisciplinary assistance to minimize these risks whenever necessary.

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

    Science.gov (United States)

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

    1997-05-01

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

  12. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    Directory of Open Access Journals (Sweden)

    Geísa Pinheiro Paes

    2016-03-01

    Full Text Available Abstract The objectives of this study were to assess linkage disequilibrium (LD and selection-induced changes in single nucleotide polymorphism (SNP frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D, the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis.

  13. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    Science.gov (United States)

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca e; Mundim, Gabriel Borges

    2016-01-01

    Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

  14. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits.

    Science.gov (United States)

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca E; Mundim, Gabriel Borges

    2016-03-01

    The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

  15. Rainfall-driven sex-ratio genes in African buffalo suggested by correlations between Y-chromosomal haplotype frequencies and foetal sex ratio

    Directory of Open Access Journals (Sweden)

    Greyling Barend J

    2010-04-01

    Full Text Available Abstract Background The Y-chromosomal diversity in the African buffalo (Syncerus caffer population of Kruger National Park (KNP is characterized by rainfall-driven haplotype frequency shifts between year cohorts. Stable Y-chromosomal polymorphism is difficult to reconcile with haplotype frequency variations without assuming frequency-dependent selection or specific interactions in the population dynamics of X- and Y-chromosomal genes, since otherwise the fittest haplotype would inevitably sweep to fixation. Stable Y-chromosomal polymorphism due one of these factors only seems possible when there are Y-chromosomal distorters of an equal sex ratio, which act by negatively affecting X-gametes, or Y-chromosomal suppressors of a female-biased sex ratio. These sex-ratio (SR genes modify (suppress gamete transmission in their own favour at a fitness cost, allowing for stable polymorphism. Results Here we show temporal correlations between Y-chromosomal haplotype frequencies and foetal sex ratios in the KNP buffalo population, suggesting SR genes. Frequencies varied by a factor of five; too high to be alternatively explained by Y-chromosomal effects on pregnancy loss. Sex ratios were male-biased during wet and female-biased during dry periods (male proportion: 0.47-0.53, seasonally and annually. Both wet and dry periods were associated with a specific haplotype indicating a SR distorter and SR suppressor, respectively. Conclusions The distinctive properties suggested for explaining Y-chromosomal polymorphism in African buffalo may not be restricted to this species alone. SR genes may play a broader and largely overlooked role in mammalian sex-ratio variation.

  16. Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.

    OpenAIRE

    Fatma, N; Jain, A. K.; Rahman, Q

    1991-01-01

    Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and...

  17. Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.

    Science.gov (United States)

    Tsuda, H; Takarabe, T; Shimamura, K; Hirohashi, S

    1998-01-01

    Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone. On the other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal for malignancy and 1 marked adenosis with atypia which was judged as malignant by fine-needle aspiration cytology, the majority of constituent tumor cells showed fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1 as a predominant clone was suggested to be an indicator of lesion malignancy even though the grade of malignancy may not be high. As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer. PMID:9769473

  18. Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    Yuan-Yuan Qin; Ya-Peng Li; Shun Zhang; Ying Xiong; Lin-Ying Guo; Shi-Qi Yang; Yi-Hao Yao

    2015-01-01

    Background:Previous studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network.However,whether the selection of a specific frequency band could impact the topological properties is still not clear.Our hypothesis is that the topological properties of AD patients are also frequency-specific.Methods:Resting state functional magnetic resonance imaging data from l0 right-handed moderate AD patients (mean age:64.3 years; mean mini mental state examination [MMSE]:18.0) and 10 age and gender-matched healthy controls (mean age:63.6 years; mean MMSE:28.2) were enrolled in this study.The global efficiency,the clustering coefficient (CC),the characteristic path length (CpL),and "small-world" property were calculated in a wide range of thresholds and averaged within each group,at three different frequency bands (0.01-0.06 Hz,0.06-0.11 Hz,and 0.11-0.25 Hz).Results:At lower-frequency bands (0.01-0.06 Hz,0.06-0.11 Hz),the global efficiency,the CC and the "small-world" properties of AD patients decreased compared to controls.While at higher-frequency bands (0.11-0.25 Hz),the CpL was much longer,and the "small-world" property was disrupted in AD,particularly at a higher threshold.The topological properties changed with different frequency bands,suggesting the existence of disrupted global and local functional organization associated with AD.Conclusions:This study demonstrates that the topological alterations of large-scale functional brain networks inAD patients are frequency dependent,thus providing fundamental support for optimal frequency selection in future related research.

  19. [Chromosome aberration frequency in workers in tire and industrial ruber manufacture].

    Science.gov (United States)

    Aleksandrov, S E

    1982-01-01

    A cytogenetic study was carried out with the view to analyse blood and embryonic tissue cultures taken from female workers of various shops of tyre and rubber industry. In workers of preparation shops the level of chromosome aberrations in blood was equal to 2.63%, while in embryonic tissues the value was 6.33%. The number of aberrations on blood and embryonic tissue exhibited by workers of chemical shops was equal to 1.34 and 2.79%, respectively. No specific differences were observed in the sub-group of women having been in frequent contacts with gasoline or curing gases, as compared with the group on the whole. Curing accelerators which are ingredients of toxic dust in preparation shops of tyre and rubber industry cause a sharp increase in the number of chromosome aberrations both in blood and in the embryonic tissues of women. Data on induced abortions may be used for evaluation of the influence of chemicals on the developing fetus and can serve as a test models of mutagenic and embryotoxic effect. They also may be regarded as a part of the general system of the evaluation of mutagenic effects of chemicals in humans. PMID:7199008

  20. 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.

  1. ALTERATIONS IN FREQUENCY OF ULNAR LOOPS AND ‘ATD’ ANGLE IN CONGENITAL HEART DISEASE

    Directory of Open Access Journals (Sweden)

    Jaywant

    2016-01-01

    Full Text Available INTRODUCTION Dermatoglyphics is a scientific study of epidermal ridge configuration on palm, soles and fingertips valuable for medico legal and genetic investigations. Dermatoglyphics form in utero during early gestation and may be influenced by genetic and environmental factors operating at that time. Present investigation was undertaken to study alterations in dermatoglyphic patterns with special reference to various congenital heart diseases (CHD. The study involved 102 cases of CHD and 100 cases of normal individuals. It was observed that percent frequency of ulnar loops significantly increased in CHD group as compared to control group. Mean 'atd' angle was also increased in CHD group as compared to control group indicating distal displacement of palmar axial triradius (t. Thus, rise in frequency of ulnar loops and increase in 'atd' angle can be considered as one of the diagnostic criteria for CHD.

  2. Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

    Directory of Open Access Journals (Sweden)

    Bertrand Degos

    Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

  3. Frequency of climbing behavior as a predictor of altered motor activity in rat forced swimming test.

    Science.gov (United States)

    Vieira, Cíntia; De Lima, Thereza C M; Carobrez, Antonio de Pádua; Lino-de-Oliveira, Cilene

    2008-11-14

    Previous work has shown that the frequency of climbing behavior in rats submitted to the forced swimming test (FST) correlated to the section's crosses in the open field test, which suggest it might be taken as a predictor of motor activity in rat FST. To investigate this proposal, the frequency, duration, as well as the ratio duration/frequency for each behavior expressed in the FST (immobility, swimming and climbing) were compared in animals treated with a motor stimulant, caffeine (CAF), and the antidepressant, clomipramine (CLM). Male Wistar rats were submitted to 15min of forced swimming (pre-test) and 24h later received saline (SAL, 1ml/kg, i.p.) or CAF (6.5mg/kg, i.p.) 30min prior a 5-min session (test) of FST. To validate experimental procedures, an additional group of rats received three injections of SAL (1ml/kg, i.p.) or clomipramine (CLM, 10mg/kg, i.p.) between the pre-test and test sessions. The results of the present study showed that both drugs, CLM and CAF, significantly reduced the duration of immobility and significantly increased the duration of swimming. In addition, CAF significantly decreased the ratio of immobility, and CLM significantly increased the ratio of swimming and climbing. Moreover, CLM significantly increased the duration of climbing but only CAF increased the frequency of climbing. Thus, it seems that the frequency of climbing could be a predictor of altered motor activity scored directly in the FST. Further, we believe that this parameter could be useful for fast and reliable discrimination between antidepressant drugs and stimulants of motor activity.

  4. Extra-Low-Frequency Magnetic Fields alter Cancer Cells through Metabolic Restriction

    CERN Document Server

    Li, Ying

    2012-01-01

    Background: Biological effects of extra-low-frequency (ELF) magnetic fields (MF) have lacked a credible mechanism of interaction between MFs and living material. Objectives: Examine the effect of ELF-MFs on cancer cells. Methods: Five cancer cell lines were exposed to ELF-MFs within the range of 0.025 to 5 microT, and the cells were examined for karyotype changes after 6 days. Results: All cancer cells lines lost chromosomes from MF exposure, with a mostly flat dose-response. Constant MF exposures for three weeks allow a rising return to the baseline, unperturbed karyotypes. From this point, small MF increases or decreases are again capable of inducing karyotype contractions. Our data suggests that the karyotype contractions are caused by MF interference with mitochondria's ATP synthase (ATPS), compensated by the action of AMP-activated Protein Kinase (AMPK). The effects of MFs are similar to those of the ATPS inhibitor oligomycin. They are amplified by metformin, an AMPK stimulator, and attenuated by resisti...

  5. Factor interaction analysis for chromosome 8 and DNA methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer

    Directory of Open Access Journals (Sweden)

    Lengauer Thomas

    2007-02-01

    Full Text Available Abstract Background Alterations of chromosome 8 and hypomethylation of LINE-1 retrotransposons are common alterations in advanced prostate carcinoma. In a former study including many metastatic cases, they strongly correlated with each other. To elucidate a possible interaction between the two alterations, we investigated their relationship in less advanced prostate cancers. Results In 50 primary tumor tissues, no correlation was observed between chromosome 8 alterations determined by comparative genomic hybridization and LINE-1 hypomethylation measured by Southern blot hybridization. The discrepancy towards the former study, which had been dominated by advanced stage cases, suggests that both alterations converge and interact during prostate cancer progression. Therefore, interaction analysis was performed on microarray-based expression profiles of cancers harboring both alterations, only one, or none. Application of a novel bioinformatic method identified Gene Ontology (GO groups related to innate immunity, cytoskeletal organization and cell adhesion as common targets of both alterations. Many genes targeted by their interaction were involved in type I and II interferon signaling and several were functionally related to hereditary prostate cancer genes. In addition, the interaction appeared to influence a switch in the expression pattern of EPB41L genes encoding 4.1 cytoskeleton proteins. Real-time RT-PCR revealed GADD45A, MX1, EPB41L3/DAL1, and FBLN1 as generally downregulated in prostate cancer, whereas HOXB13 and EPB41L4B were upregulated. TLR3 was downregulated in a subset of the cases and associated with recurrence. Downregulation of EPB41L3, but not of GADD45A, was associated with promoter hypermethylation, which was detected in 79% of carcinoma samples. Conclusion Alterations of chromosome 8 and DNA hypomethylation in prostate cancer probably do not cause each other, but converge during progression. The present analysis implicates their

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

    International Nuclear Information System (INIS)

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

  7. Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: Pathological significance in early- and late-onset breast carcinoma

    Directory of Open Access Journals (Sweden)

    Roychoudhury Susanta

    2008-11-01

    Full Text Available Abstract Introduction Younger women with breast carcinoma (BC exhibits more aggressive pathologic features compared to older women; young age could be an independent predictor of adverse prognosis. To find any existing differences in the molecular pathogenesis of BC in both younger and older women, alterations at chromosomal (chr. 9q22.32-22.33 region were studied owing to its association in wide variety of tumors. Present work focuses on comparative analysis of alterations of four candidate genes; PHF2, FANCC, PTCH1 and XPA located within 4.4 Mb region of the afore-said locus in two age groups of BC, as well as the interrelation and prognostic significance of alterations of these genes. Methods Deletion analysis of PHF2, FANCC, PTCH1 and XPA were examined in a subset of 47 early-onset (group-A: ≤ 40 years and 59 late-onset (group-B: > 40 years breast carcinomas using both microsatellite and exonic markers. Methylation Sensitive Restriction analysis (MSRA was done to check for promoter methylation. Quantitative real-time polymerase chain reaction (Q-PCR and immunohistochemisty (IHC was done in some genes to see their relative mRNA and protein expressions respectively. Clinico-pathological correlation of different parameters as well as patient survival was calculated using different statistical softwares like EpiInfo 6.04b, SPSS 10.0 etc. Results Either age group exhibited high frequency of overall alterations in PHF2, FANCC and PTCH1 compared to XPA. Samples with alteration (deletion/methylation in these genes showed reduced level of mRNA expression as seen by Q-PCR. Immunohistochemical analysis of FANCC and PTCH1 also supported this observation. Poor patient survival was noted in both age groups having alterations in FANCC. Similar result was also seen with PTCH1 and XPA alterations in group-A and PHF2 alterations in group-B. This reflected their roles as prognostic tools in the respective groups in which they were altered. Conclusion Overall

  8. Use of high frequency ultrasound to monitor cervical lymph node alterations in mice.

    Directory of Open Access Journals (Sweden)

    Elyse L Walk

    Full Text Available Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC, provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl. Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy.

  9. Use of high frequency ultrasound to monitor cervical lymph node alterations in mice.

    Science.gov (United States)

    Walk, Elyse L; McLaughlin, Sarah; Coad, James; Weed, Scott A

    2014-01-01

    Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO) and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular) lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA) biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl). Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy. PMID:24955984

  10. 肝细胞癌8号染色体微卫星变异的研究%Microsatellite Alterations on Chromosome 8 of Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    张树辉; 冼志红; 丛文铭; 吴孟超

    2004-01-01

    目的探讨肝细胞癌(HCC)8号染色体微卫星变异的特点及其与临床病理的相关性.方法采用MegaBACE 500型自动化DNA分析系统,对56例HCC中8号染色体上10个微卫星的杂合性缺失(LOH)、微卫星不稳定性(MSI)和等位基因失衡(AI)3种变异特征进行检测.结果56例HCC在8号染色体上10个基因座发生LOH的总频率为66.1%(37/56),MSI的频率为12.5%(7/56),AI的频率为19.6%(11/56).LOH以D8S261最高为53.5%(23/43),其次为D8S1721(52.5%)和D8S1771(52.5%).D8S277基因座,血清HBsAg阳性患者的LOH频率显著高于HBsAg阴性者(P<0.01),D8S261、D8S298和D8S1733基因座,血清HBsAg阴性患者的LOH频率显著高于HBsAg阳性者(P<0.01);D8S298和D8S1771基因座,肿瘤直径>3cm的LOH率明显高于≤3cm组(P<0.05和P<0.01);在D8S1721基因座,无包膜或包膜不完整的肿瘤的LOH显著高于包膜完整的肿瘤(P<0.01);D8S298和D8S1771基因座,肝内转移者的LOH明显高于无肝内转移者(P<0.05).MSI和AI与HCC临床病理学特点无明显相关性.结论HCC的8号染色体上存在广泛的微卫星变异,其中以代表肿瘤抑制基因路径的LOH方式在HCC的发生和发展过程中起重要作用,代表错配修复基因路径的MSI的作用次之.特定基因座的LOH与临床和病理学参数有一定的相关性.%Objective: To study the features of microsatellite alterations on chromosome 8 and their asso-ciation with clinicopathological characteristics of hepatocellular carcinoma (HCC). Methods: Ten highly-polymorphic microsatellite markers on chromosome 8 were selected to be detected for loss of heterozygosity(LOH), microsatellite instability (MSI) and allelic imbalance (AI) in 56 HCC using MegaBACE 500 auto-matic DNA analysis system. Results: LOH was found in 37 of 56 HCC (66.1%) on at least 1 locus, and the top three loci were D8S261(53.5%), D8S1721(52.5%) and D8S1771(52.5%). LOH frequency on D8S277 was significantly higher in cases positive for serum HBs

  11. The frequency of chromosomal aberrations in sheep from the area contaminated by depleted uranium during NATO air strikes in 1999

    Directory of Open Access Journals (Sweden)

    Fišter Svetlana L.

    2014-01-01

    Full Text Available This paper presents the results of cytogenetic studies in sheep from the region of Bujanovac that was contaminated by depleted uranium during the NATO air strikes in 1999. The study was conducted on sheep blood lymphocytes, in order to determine the frequency of chromosomal aberrations and to assess the presence of genetic risk as a result of the possible impact of depleted uranium. Blood samples for lymphocyte cultures were taken at random from the 20 animals of the households in the village of Borovac, near Bujanovac. The animals were chosen because they were pastured, fed, and watered in the NATO bombing area. With the purpose of comparing the results two control groups were cytogenetically analyzed, each consisted of 20 sheep from Zemun and Ovča, two northern localities that were not contaminated with depleted uranium. The established structural chromosomal changes were of breaks and gap types, and their frequencies in sheep of all surveyed localities were within the range of basic level values that are commonly found in the sheep lymphocyte cultures analyses. Significant differences are apparent between the values defined in the sheep from Bujanovac compared to those obtained in the sheep from the northern locality (Zemun, probably as a result of breeding of animals in the farm conditions and their being less exposed to the impact of environmental agents. There were neither elevated values of polyploid and aneuploid cells nor significant differences between the sites. According to earlier known data, depleted uranium was below the detection limit of the method applied both in the soil and feed given to cytogenetically analyzed animals. Based on the low-level changes that are in the range of the basic level changes, commonly observed in sheep lymphocytes control cultures, it cannot be said with certainty that it was depleted uranium that caused the changes, or that it is wide-spread in the region of Bujanovac. [Projekat Ministarstva nauke

  12. Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production

    Directory of Open Access Journals (Sweden)

    Longo Dan L

    2011-03-01

    Full Text Available Abstract Background Intermittent fasting (IF improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects. Objective A study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects. Design In a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15 were maintained for 2 months on controlled on-site one meal per day (OMD or three meals per day (TMD isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay. Results There were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets. Lower levels of TNF-α, IL-17, MCP-1 and MIP-1β were produced by PBMCs from subjects on the OMD versus TMD diet. Conclusions PBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines.

  13. The rad52-Y66A allele alters the choice of donor template during spontaneous chromosomal recombination

    DEFF Research Database (Denmark)

    de Mayolo, A.A.; Sunjevaric, I.; Reid, R.;

    2010-01-01

    Spontaneous mitotic recombination is a potential source of genetic changes Such as loss of heterozygosity and chromosome translocations, which may lead to genetic disease. In this study we have used a rad52 hyper-recombination mutant, rad52-Y66A, to investigate the process of spontaneous heteroal...

  14. Nicotine-induced Disturbances of Meiotic Maturation in Cultured Mouse Oocytes: Alterations of Spindle Integrity and Chromosome Alignment

    Directory of Open Access Journals (Sweden)

    Zenzes Maria

    2004-09-01

    Full Text Available Abstract We investigated whether nicotine exposure in vitro of mouse oocytes affects spindle and chromosome function during meiotic maturation (M-I and M-II. Oocytes in germinal vesicle (GV stage were cultured in nicotine for 8 h or for 16 h, to assess effects in M-I and in metaphase II (M-II. The latter culture setting used the three protocols: 8 h nicotine then 8 h medium (8N + 8M; 16 h nicotine (16N; 8 h medium then 8 h nicotine (8M + 8N. Non-toxic concentrations of nicotine at 1.0, 2.5, 5.0 and 10.0 mmol/L were used. Spindle-chromosome configurations were analyzed with wide-field optical sectioning microscopy. In 8 h cultures, nicotine exposure resulted in dose-related increased proportions of M-I oocytes with defective spindle-chromosome configurations. A dose-related delayed entry into anaphase I was also detected. In 16 h cultures, nicotine exposure for the first 8 h (8N + 8M, or for 16 h (16N, resulted in dose- and time-related increased proportions of oocytes arrested in M-I (10 mmol/L; 8 h: 53.2%, controls 9.6%; 16 h: 87.6%, controls 8.5%. Defects in M-I spindles and chromosomes caused M-I arrest leading to dose-related decreased proportions of oocytes that reached metaphase-II (10 mmol/L 8 h: 46.8%, controls 90.4%;16 h: 12.4%, controls 91.5%. A delayed anaphase-I affected the normal timing of M-II, leading to abnormal oocytes with dispersed chromosomes, or with double spindles and no polar body. Nicotine exposure during the second 8 h (8M + 8N resulted in dose-related, increased proportions of M-II oocytes with defective spindles and chromosomes (10 mmol/L: 42.9%, controls 2.0%. Nicotine has no adverse effects on GV break down, but induces spindle and chromosome defects compromising oocyte meiotic maturation and development.

  15. Reversal of DNA methylation with 5-azacytidine alters chromosome replication patterns in human lymphocyte and fibroblast cultures.

    OpenAIRE

    Shafer, D A; Priest, J H

    1984-01-01

    Prior studies demonstrated that developmental or induced methylation of DNA can inactivate associated gene loci. Such DNA methylation can be reversed and specific genes reactivated by treatment with 5-azacytidine (5- azaC ). The present cytogenetic studies using replication banding methods show that 5- azaC treatment also results in an increase or decrease in replication staining at one or more band locations in human lymphocyte and fibroblast chromosomes. New replication band locations are n...

  16. Radiation-induced chromosome aberrations in ataxia telangiectasia cells: high frequency of deletions and misrejoining detected by fluorescence in situ hybridization

    Science.gov (United States)

    Kawata, Tetsuya; Ito, Hisao; George, Kerry; Wu, Honglu; Uno, Takashi; Isobe, Kouichi; Cucinotta, Francis A.

    2003-01-01

    The mechanisms underlying the hyper-radiosensitivity of AT cells were investigated by analyzing chromosome aberrations in the G(2) and M phases of the cell cycle using a combination of chemically induced premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with chromosome painting probes. Confluent cultures of normal fibroblast cells (AG1522) and fibroblast cells derived from an individual with AT (GM02052) were exposed to gamma rays and allowed to repair at 37 degrees C for 24 h. At doses that resulted in 10% survival, GM02052 cells were approximately five times more sensitive to gamma rays than AG1522 cells. For a given dose, GM02052 cells contained a much higher frequency of deletions and misrejoining than AG1522 cells. For both cell types, a good correlation was found between the percentage of aberrant cells and cell survival. The average number of color junctions, which represent the frequency of chromosome misrejoining, was also found to correlate well with survival. However, in a similar surviving population of GM02052 and AG1522 cells, induced by 1 Gy and 6 Gy, respectively, AG1522 cells contained four times more color junctions and half as many deletions as GM02052 cells. These results indicate that both repair deficiency and misrepair may be involved in the hyper-radiosensitivity of AT cells.

  17. Effects of hepatitis B virus infection on human sperm chromosomes

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Huang; Tian-Hua Huang; Huan-Ying Qiu; Xiao-Wu Fang; Tian-Gang Zhuang; Hong-Xi Liu; Yong-Hua Wang; Li-Zhi Deng; Jie-Wen Qiu

    2003-01-01

    AIM: To evaluate the level of sperm chromosome aberrations in male patients with hepatitis B, and to directly detect whether there are HBV DNA integrations in sperm chromosomes of hepatitis B patients.METHODS: Sperm chromosomes of 14 tested subjects (5healthy controls, 9 patients with HBV infection, including 1with acute hepatitis B, 2 with chronic active hepatitis B, 4with chronic persistent hepatitis B, 2 chronic HBsAg carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free golden hamster ova and human spermatozoa, and the frequencies of aberration spermatozoa were compared between subjects of HBV infection and controls. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes.RESULTS: The total frequency of sperm chromosome aberrations in HBV infection group (14.8%, 33/223) was significantly higher than that in the control group (4.3%,5/116). Moreover, the sperm chromosomes in HBV infection patients commonly presented stickiness, clumping, failure to staining, etc, which would affect the analysis of sperm chromosomes. Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis. In 9 (9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots, others presented 2 to 4signals. There was significant difference of fluorescence intensity among the signal spots. The distribution of signal sites among chromosomes was random.CONCLUSION: HBV infection can bring about mutagenic effects on sperm chromosomes. Integrations of viral DNA into sperm chromosomes which are multisites and nonspecific, can further increase the instability of sperm chromosomes. This study suggested that HBV infection can create extensively hereditary effects by alteration genetic constituent and

  18. Influence of DNA repair gene polymorphisms of hOGG1, XRCC1, XRCC3, ERCC2 and the folate metabolism gene MTHFR on chromosomal aberration frequencies.

    Science.gov (United States)

    Skjelbred, Camilla Furu; Svendsen, Marit; Haugan, Vera; Eek, Anette Kildal; Clausen, Kjell Oskar; Svendsen, Martin Veel; Hansteen, Inger-Lise

    2006-12-01

    We have studied the effect of genetic polymorphisms in the DNA repair genes hOGG1, XRCC1, XRCC3, ERCC2 and the MTHFR gene in the folate metabolism on the frequencies of cells with chromosomal aberrations (CA), chromosome-type aberrations (CSA), chromatid-type aberrations (CTA), chromatid breaks (CTB) and chromatid gaps (CTG) scored in peripheral blood lymphocytes from 651 Norwegian subjects of Caucasian descendant. DNA was extracted from fixed cell suspensions. The log-linear Poisson regression model was used for the combined data which included age, smoking, occupational exposure and genotype for 449 subjects. Our results suggest that individuals carrying the hOGG1 326Cys or the XRCC1 399Gln allele have an increased risk of chromosomal damage, while individuals carrying the XRCC1 194Trp or the ERCC2 751Gln allele have a reduced risk regardless of smoking habits and age. Individuals carrying the XRCC1 280His allele had an increased risk of CSA which was only apparent in non-smokers. This was independent of age. A protective effect of the XRCC3 241Met allele was only found in the older age group in non-smokers for CA, CSA and CTA, and in smokers for CSA. In the youngest age group, the opposite effect was found, with an increased risk for CA, CTA and CTG in smokers. Carrying the MTHFR 222Val allele gave an increased risk for chromosome and chromatid-type aberrations for both non-smokers and smokers, especially for individuals in the older age group, and with variable results in the youngest age group. The variables included in the different regression models accounted, however, for only 4-10% of the variation. The frequency ratio for CTG was significantly higher than for CTA and CTB for only 7 of the 43 comparisons performed. Some of the gap frequencies diverge from the trend in the CA, CSA, CTA and CTB results.

  19. Frequency-specific alterations in the fractional amplitude of low-frequency fluctuations in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ma, Xujing; Zhang, Jiuquan; Zhang, Youxue; Chen, Heng; Li, Rong; Long, Zhiliang; Zheng, Junjie; Wang, Jian; Chen, Huafu

    2016-08-01

    This study used resting-state functional magnetic resonance imaging and fractional amplitude of low-frequency fluctuations (fALFF) method to investigate low-frequency spontaneous neural activity at the bands of slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) in 20 patients with amyotrophic lateral sclerosis (ALS) and 20 healthy controls. We determined that, at slow-5 band, patients with ALS showed increased fALFF in the right middle frontal gyrus and decreased fALFF in the left middle occipital gyrus. However, compared with healthy controls, patients with ALS exhibited higher fALFF in the right caudate nucleus, left superior frontal gyrus, and right anterior cingulate cortex and lower fALFF in the right inferior occipital gyrus and bilateral middle occipital gyrus at slow-4 band. Furthermore, the fALFF value in the left superior frontal gyrus at slow-4 band was negatively correlated with functional rating scale-revised score. Our results demonstrated that the fALFF changes in ALS were widespread and frequency dependent. These findings may provide a novel way to look into the pathophysiology mechanisms underlying ALS. PMID:27139743

  20. Frequency and pattern of cytogenetic alterations in primary amenorrhea cases of Kashmir, North India

    Directory of Open Access Journals (Sweden)

    Tahir M. Malla

    2016-01-01

    Conclusion: The results of the present study indicate that chromosomal analysis of females with PA, after the exclusion of non-genetic causes, should be essentially considered for the precise diagnosis and the development of more successful treatment. The study being the first of its kind in this part of the world forms the basis for further studies of the PA cases of this region. The precise molecular characterization of the unique breakpoint regions reported in our study can possibly help in the identification of new genes involved in primary amenorrhea.

  1. Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self

    OpenAIRE

    D. Lehmann(Darmstadt, GSI); Faber, P L; Achermann, P.; Jeanmonod, D; Gianotti, L. R.; Pizzagalli, D.

    2001-01-01

    Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal popu...

  2. Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22

    Directory of Open Access Journals (Sweden)

    Volfovsky Natalia

    2009-01-01

    Full Text Available Abstract Background Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes. Results Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb region, (ii those with at least one exact copy found nearby, and (iii those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429 were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans. Conclusion Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are

  3. Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

    Science.gov (United States)

    Gericke, G S

    2010-05-01

    Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

  4. Frequency of chromosome aberration and dose/dose rate effects in the mouse exposed to long-term low dose radiation

    International Nuclear Information System (INIS)

    Authors have been conducting long term irradiation experiments in the mouse with the dose rate as low as unreported hitherto and have shown with highly sensitive methods to detect chromosomal aberration, that there is the positive dose rate effect under even such a condition, of which details are described herein. According to the definition of United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCER) (1993), the low dose rate is 137Cs-gamma-ray at the low dose rate of 1 or 20 mGy/22 h/day (total, 125-615 or 100-8000 mGy, respectively). Other groups received radiations of 0 Gy (non-irradiated, age-matched control), 200-8000 mGy at 200 mGy/22 h/day, 400-8000 mGy at 400 mGy/22 h/day, or 250-2000 mGy at 890 mGy/min. At the defined days after exposure, mice were sacrificed, their spleens were dissected out, splenic cells were cultured for 48 hr, and their chromosome specimens were prepared to be stained with Giemsa or FISH (fluorescence in situ hybridization). Dicentric (dic) and translocation chromosomal aberrations were found to increase even with the lowest total (accumulated) dose, where the frequency was significantly higher than that in control. Comparison of the regression slopes at each dose rate of the relation between dose and aberration revealed the difference dependent on the rate, thus demonstrating the presence of dose rate effect. Dose/dose rate effect factor (DDREF) calculated by authors' procedure (at 1000-100 mGy: DDREF=17.8-4.5 for dic by FISH; 24.5-5.2 for dic+ring chromosome by Giemsa) was thought important in the risk assessment of low dose radiation and also revealed a problem in International Commission on Radiological Protection (ICRP) (1991) calculation of the factor. (K.T.)

  5. Subthalamic Nucleus High-Frequency Stimulation Restores Altered Electrophysiological Properties of Cortical Neurons in Parkinsonian Rat

    OpenAIRE

    Bertrand Degos; Jean-Michel Deniau; Mario Chavez; Nicolas Maurice

    2013-01-01

    Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized...

  6. Cold-induced alteration in the global structure of the male sex chromosome of In(1)B$^{M2}$(reinverted) of Drosophila melanogaster is associated with increased acetylation of histone 4 at lysine 16

    Indian Academy of Sciences (India)

    S. Kulkarni-Shukla; A. P. Barge; R. S. Vartak; Anita Kar

    2008-12-01

    In Drosophila melanogaster, dosage compensation occurs through hypertranscription of sex-linked genes in males. The hypertranscription involves acetylation of histone 4 at lysine 16 (H4K16) on amale X-chromosome, brought about by a histone acetyltransferase encoded by the dosage compensation gene, males absent on the first (mof). We report a phenomenon in the strain In(1)B$^{M2}$(reinverted) of D. melanogaster where the global structure of the male X-chromosome can be altered at the third instar larval stage through a 4-h cold shock at 12±1°C. We show that the cold shock results in a transient hyperacetylation of H4K16 and an increased expression of MOF. Control proteins H4 acetylated at lysine 5, and the dosage compensation gene msl-2, do not show any change in expression after cold shock. Cytology of the male X-chromosome at different time points during cold shock and recovery, suggests that the hyperacetylation of H4 at lysine 16 causes the X-chromosome to corkscrew into itself, thereby achieving the cold-induced change in the higher order structure of the male polytene X-chromosome. Our studies suggest a role for H4K16 in maintaining the structure of the male X-chromosome in Drosophila.

  7. Observation on the Frequency of Chromosomal Aberration and Changes in Number of Peripheral Lymphocytes in Radioactive Iodine Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Chun Hee; Shin, Min Ho; Park, Young Ju; Lee, Jung Yim; Park, Tae Yong; Lee, Jae Yong; Kim, Chong Soon; Han, Seung Soo; Kim, Kwang Hoe [Hanil General Hospital, Seoul (Korea, Republic of); Kim, Hee Gun; Kang, Duck Won; Song, Myung Jae [Korean Electric Power Corporation Research-Development Center, Daejeon (Korea, Republic of)

    1995-06-15

    For biological dosimetry of radiation exposure, both observing hematologic change and calculating Ydr by chromosomal analysis as biological indicators are widely used. However, due to the lack of studies on biological dosimetry of radiation dose absorbed in the body such as in the cases of radioactive iodine therapy, the maximal and safe dose is not well known, nor is the extent to which the body can safely endure radiation exposure. To investigate the practical applicability of hematologic changes and Ydr as an indicator for estimating radiation exposure, to patients with thyroid diseases after doses of radioactive iodine. 5 patients with hyperthyroidism and 35 patients who have had thyroid cancer operation were under treatment with radioactive iodine, changes in number of lymphocytes were tracked and Ydr was calculated for more than 2 months by chromosomal analysis in peripheral lymphocytes. 1) The number of lymphocytes began to decrease 2 weeks after doses of radioactive iodine, and reached the nadir after 6 and 8 weeks, then gradually recovered. 2) The nadir count of lymphocytes was reversely correlated with the administered dosage of radioactive iodine. 3) Ydr was generally stable between 2 and 8 weeks. 4) The maximal value of Ydr was correlated with the administered dosage of radioactive iodine. 5) Ydr value at the 2nd week increased with augmented dosage of radioactive iodine. 6) Ydr value at the 2nd week was correlated with fall of lymphocyte count. Patients must be closely observed, because temporary bone marrow suppression and slight chromosomal aberration can be produced by even generally used dosages of radioactive iodine for diagnosis and therapy. Maximal percent fall of lymphocyte count, Ydr at the 2 week interval and maximal Ydr can be used as the biological predictor of administered dosage of radioactive iodine.

  8. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

    Directory of Open Access Journals (Sweden)

    Héctor Rincón-Arévalo

    2016-06-01

    Full Text Available Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/− mice fed or not with high-fat diet (HFD, by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410 [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia.

  9. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

    Science.gov (United States)

    Rincón-Arévalo, Héctor; Castaño, Diana; Villa-Pulgarín, Janny; Rojas, Mauricio; Vásquez, Gloria; Correa, Luis A.; Ramírez-Pineda, José R.; Yassin, Lina M.

    2016-01-01

    Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/−) mice fed or not with high-fat diet (HFD), by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410) [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia. PMID:27081674

  10. Multisensory stimuli elicit altered oscillatory brain responses at gamma frequencies in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    David B. Stone

    2014-11-01

    Full Text Available Deficits in auditory and visual unisensory responses are well documented in patients with schizophrenia; however, potential abnormalities elicited from multisensory audio-visual stimuli are less understood. Further, schizophrenia patients have shown abnormal patterns in task-related and task-independent oscillatory brain activity, particularly in the gamma frequency band. We examined oscillatory responses to basic unisensory and multisensory stimuli in schizophrenia patients (N = 46 and healthy controls (N = 57 using magnetoencephalography (MEG. Time-frequency decomposition was performed to determine regions of significant changes in gamma band power by group in response to unisensory and multisensory stimuli relative to baseline levels. Results showed significant behavioral differences between groups in response to unisensory and multisensory stimuli. In addition, time-frequency analysis revealed significant decreases and increases in gamma-band power in schizophrenia patients relative to healthy controls, which emerged both early and late over both sensory and frontal regions in response to unisensory and multisensory stimuli. Unisensory gamma-band power predicted multisensory gamma-band power differently by group. Furthermore, gamma-band power in these regions predicted performance in select measures of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS test battery differently by group. These results reveal a unique pattern of task-related gamma-band power in schizophrenia patients relative to controls that may indicate reduced inhibition in combination with impaired oscillatory mechanisms in patients with schizophrenia.

  11. An association, in adult Japanese, between the occurrence of rogue cells among cultured lymphocytes (JC virus activity) and the frequency of "simple" chromosomal damage among the lymphocytes of persons exhibiting these rogue cells.

    OpenAIRE

    Neel, J V

    1998-01-01

    Data from a previous study of the cytogenetic effects, in cultured lymphocytes, of exposure to the atomic bomb in Hiroshima have been reanalyzed to determine the relationship between the occurrence of "rogue" cells in an individual and the frequency of "simple" chromosomal damage in the nonrogue cells of the same individual. Rogue cells are cells with complex chromosomal damage, currently believed to be a manifestation of the activity of a human polyoma virus termed "JC." Among a total of 1,8...

  12. Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward.

    Science.gov (United States)

    Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; Nichols, Weston A; Moaddel, Ruin; Xiao, Cheng; Lester, Henry A

    2016-03-01

    Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway.

  13. Analysis of the frequency of unstable chromosome aberrations in human lymphocytes irradiated with {sup 60}Co; Analise da frequencia de alteracoes cromossomicas instaveis em linfocitos humanos irradiados com {sup 60}Co

    Energy Technology Data Exchange (ETDEWEB)

    Mendonca, Julyanne C.G.; Mendes, Mariana E.; Lima, Fabiana F., E-mail: july_cgm@hotmail.com, E-mail: mendes_sb@hotmail.com [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Santos, Neide, E-mail: santos_neide@yahoo.com.br [Universidade Federal de Pernambuco (CCB/UFPE), Recife, PE (Brazil). Departamento de Genetica

    2013-07-01

    The aim of this study was to analyze the frequency of unstable chromosomal aberrations induced by gamma radiation from a {sup 60}Co source at two different doses. Samples were obtained from a healthy donor and exposed to {sup 60}Co source (Gammacel 220 ) located in the Department of Nuclear Energy of Pernambuco Federal University (DEN/UFPe/Brazil) with a rate of air Kerma to 3,277 Gy/h. Exposures resulted in absorbed dose 0.51 Gy and 0.77 Gy. Mitotic metaphases were obtained by culturing lymphocytes for chromosome analysis and the slides were stained with 5% Giemsa. Among the unstable chromosomal aberrations the dicentric chromosomes, ring chromosomes and acentric fragments were analyzed. To calculate the significance level the chi - square test was used, considering relevant differences between the frequencies when the value of p < 0.05. To calculate the significance level of the chi - square test was used, considering relevant differences between the frequencies when the value of p < 0.05. The results showed that there was significant difference of the frequencies of dicentric chromosomes (from 0.18 to 0.51 to 0.37 Gy to 0.77 Gy), however there was no statistically significant difference between the frequencies of acentric fragments ( 0.054 to 0, 51 Gy to 0.063 to 0.77 Gy) and ring chromosomes (0.001 to 0.51 Gy to 0.003 to 0.77 Gy). The low number of rings is found justified, considering that in irradiated human lymphocytes, its appearance is rare relative to dicentrics. The results confirm that dicentrics are the most reliable biomarkers in estimating dose after exposure to gamma radiation. These two points will make the calibration curve dose-response being built for Biological Dosimetry Laboratory of CRCN-NE/CNEN.

  14. Metabolic impacts of altering meal frequency and timing - Does when we eat matter?

    Science.gov (United States)

    Hutchison, Amy T; Heilbronn, Leonie K

    2016-05-01

    Obesity prevalence continues to rise throughout the developed world, as a result of positive energy balance and reduced physical activity. At present, there is still a perception within the general community, and amongst some nutritionists, that eating multiple small meals spaced throughout the day is beneficial for weight control and metabolic health. However, intervention trials do not generally support the epidemiological evidence, and data is emerging to suggest that increasing the fasting period between meals may beneficially impact body weight and metabolic health. To date, this evidence is of short term duration, and it is becoming increasingly apparent that meal timing must also be considered if we are to ensure optimal health benefits in response to this dietary pattern. The purpose of this review is to summate the existing human literature on modifying meal frequency and timing on body weight control, appetite regulation, energy expenditure, and metabolic health under conditions of energy balance, restriction and surplus.

  15. High frequency application of nanosecond pulsed electric fields alters cellular membrane disruption and fluorescent dye uptake

    Science.gov (United States)

    Steelman, Zachary A.; Tolstykh, Gleb P.; Beier, Hope T.; Ibey, Bennett L.

    2016-03-01

    Cells exposed to nanosecond-pulsed electric fields (nsPEF) exhibit a wide variety of nonspecific effects, including blebbing, swelling, intracellular calcium bursts, apoptotic and necrotic cell death, formation of nanopores, and depletion of phosphatidylinositol 4,5-biphosphate (PIP2) to induce activation of the inositol trisphosphate/diacylglycerol pathway. While several studies have taken place in which multiple pulses were delivered to cells, the effect of pulse repetition rate (PRR) is not well understood. To better understand the effects of PRR, a laser scanning confocal microscope was used to observe CHO-K1 cells exposed to ten 600ns, 200V pulses at varying repetition rates (5Hz up to 500KHz) in the presence of either FM 1-43, YO-PRO-1, or Propidium Iodide (PI) fluorescent dyes, probes frequently used to indicate nanoporation or permeabilization of the plasma membrane. Dye uptake was monitored for 30 seconds after pulse application at a rate of 1 image/second. In addition, a single long pulse of equivalent energy (200V, 6 μs duration) was applied to test the hypothesis that very fast PRR will approximate the biological effects of a single long pulse of equal energy. Upon examination of the data, we found strong variation in the relationship between PRR and uptake in each of the three dyes. In particular, PI uptake showed little frequency dependence, FM 1-43 showed a strong inverse relationship between frequency and internal cell fluorescence, and YO-PRO-1 exhibited a "threshold" point of around 50 KHz, after which the inverse trend observed in FM 1-43 was seen to reverse itself. Further, a very high PRR of 500 KHz only approximated the biological effects of a single 6 μs pulse in cells stained with YO-PRO-1, suggesting that uptake of different dyes may proceed by different physical mechanisms.

  16. Effect of post-treatments with caffeine during G2 on the frequencies of chromosome-type aberrations produced by X-rays in human lymphocytes during G0 and G1

    International Nuclear Information System (INIS)

    Human lymphocytes were irradiated with X-rays in G0 and G1, grown in the presence of 5-bromodeoxyuridine, and harvested at different times from 48 to 80 h after stimulation. Some cultures were exposed to 2.5-5 mM caffeine during the last 3 h before harvesting. The frequencies of chromosome-type aberrations were scored in first division (M1) metaphases. The post-treatment with caffeine increased the frequencies of mitoses and chromosome-type aberrations in irradiated cultures. The results suggest that cells carrying chromosome-type aberrations are delayed in G2 and that caffeine increases the frequencies of aberrations in dividing cells by removing this G2-block. (author)

  17. [Biological effects in natural populations of small rodents in radiation-polluted territories. Dynamics of chromosome aberration frequency in a number of generations of European bank vole (Clethrionomys glareolus, Schreber)].

    Science.gov (United States)

    Goncharova, R I; Riabokon', N I

    1998-01-01

    The dynamics of chromosome aberration frequency in bone marrow cells of many generations (14) of bank vole living in the radioactive trace of the Chernobyl catastrophe (1986-1992) has been analysed. The study revealed that the chromosome aberration frequency in voles in the areas with radio-contamination density 220 and 1526 kBq/m2 (for 137Cs) significantly exceeds the control level 3-7 times over the whole period under investigation. The dynamics of the frequency of structural chromosome injuries from 1986 to 1991-1992 is characterised by the tendency to increase in all populations inhabiting the areas with various radio-contamination density (8-1526 kBq/m2).

  18. Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization

    Directory of Open Access Journals (Sweden)

    Chia-Hsiung Cheng

    2015-01-01

    Full Text Available Sensory gating (SG, referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII. However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1- induced event-related desynchronization (ERD contributes to a less-suppressed stimulus 2- (S2- evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc. Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity.

  19. Acupuncture induces divergent alterations of functional connectivity within conventional frequency bands: evidence from MEG recordings.

    Directory of Open Access Journals (Sweden)

    Youbo You

    Full Text Available As an ancient Chinese healing modality which has gained increasing popularity in modern society, acupuncture involves stimulation with fine needles inserted into acupoints. Both traditional literature and clinical data indicated that modulation effects largely depend on specific designated acupoints. However, scientific representations of acupoint specificity remain controversial. In the present study, considering the new findings on the sustained effects of acupuncture and its time-varied temporal characteristics, we employed an electrophysiological imaging modality namely magnetoencephalography with a temporal resolution on the order of milliseconds. Taken into account the differential band-limited signal modulations induced by acupuncture, we sought to explore whether or not stimulation at Stomach Meridian 36 (ST36 and a nearby non-meridian point (NAP would evoke divergent functional connectivity alterations within delta, theta, alpha, beta and gamma bands. Whole-head scanning was performed on 28 healthy participants during an eyes-closed no-task condition both preceding and following acupuncture. Data analysis involved calculation of band-limited power (BLP followed by pair-wise BLP correlations. Further averaging was conducted to obtain local and remote connectivity. Statistical analyses revealed the increased connection degree of the left temporal cortex within delta (0.5-4 Hz, beta (13-30 Hz and gamma (30-48 Hz bands following verum acupuncture. Moreover, we not only validated the closer linkage of the left temporal cortex with the prefrontal and frontal cortices, but further pinpointed that such patterns were more extensively distributed in the ST36 group in the delta and beta bands compared to the restriction only to the delta band for NAP. Psychophysical results for significant pain threshold elevation further confirmed the analgesic effect of acupuncture at ST36. In conclusion, our findings may provide a new perspective to lend

  20. Subpopulations of lymphocytes and their bearing on the radiation dose-response of the human lymphocyte (cell survival, mitogenic stimulation and chromosome aberration frequency)

    International Nuclear Information System (INIS)

    To determine whether in the lymphocyte the frequency of chromosome aberrations might be influenced by a differential radiation response of the varying types of cells, as well as interactions among them, subpopulations were separated on the basis of differences in cell surface receptors. The subpopulations, namely, T and B lymphocytes and three T subsets, T-M, T-G, T-null, were found to differ in radiosensitivity as measured by survival in culture and mitotic index after PHA stimulation. All the populations studied are represented to varying degrees among the mitotic cells of unirradiated samples 48 hours after PHA stimulation. At increasing doses of 6Co gamma rays (50, 100, 250, 500 rads), however, their proportions change both as a direct result of irradiation, such as cell killing, and as an indirect effect, such as the reduction in suppressor cell action

  1. Point process time-frequency analysis of respiratory sinus arrhythmia under altered respiration dynamics.

    Science.gov (United States)

    Kodituwakku, Sandun; Lazar, Sara W; Indic, Premananda; Brown, Emery N; Barbieri, Riccardo

    2010-01-01

    Respiratory sinus arrhythmia (RSA) is largely mediated by the autonomic nervous system through its modulating influence on the heartbeat. We propose an algorithm for quantifying instantaneous RSA as applied to heart beat interval and respiratory recordings under dynamic respiration conditions. The blood volume pressure derived heart beat series (pulse intervals, PI) are modeled as an inverse gaussian point process, with the instantaneous mean PI modeled as a bivariate regression incorporating both past PI and respiration values observed at the beats. A point process maximum likelihood algorithm is used to estimate the model parameters, and instantaneous RSA is estimated by a frequency domain transfer function approach. The model is statistically validated using Kolmogorov-Smirnov (KS) goodness-of-fit analysis, as well as independence tests. The algorithm is applied to subjects engaged in meditative practice, with distinctive dynamics in the respiration patterns elicited as a result. Experimental results confirm the ability of the algorithm to track important changes in cardiorespiratory interactions elicited during meditation, otherwise not evidenced in control resting states.

  2. Detecting chromosomal alterations at 1p and 19q by FISH and DNA fragment analysis - a comparative study in human gliomas

    DEFF Research Database (Denmark)

    Broholm, H.; Born, P.W.; Guterbaum, D.;

    2008-01-01

    Histological classification of gliomas is important for treatment and as a prognostic predictor, but classification by histology alone can be a challenge. Molecular genetic investigations, in particular the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 (LOH1p/19...

  3. Influence of GSTM1, GSTT1, GSTP1, NAT1, NAT2, EPHX1, MTR and MTHFR polymorphism on chromosomal aberration frequencies in human lymphocytes.

    Science.gov (United States)

    Skjelbred, Camilla Furu; Svendsen, Marit; Haugan, Vera; Eek, Anette Kildal; Clausen, Kjell Oskar; Kure, Elin H; Tuimala, Jarno T; Svendsen, Martin Veel; Norppa, Hannu; Hansteen, Inger-Lise

    2011-03-01

    We have studied the influence of genetic polymorphisms in the xenobiotic-metabolizing genes GSTM1, GSTP1, GSTT1, EPHX1, NAT1 and NAT2 and the folate-metabolizing genes MTR and MTHFR on the frequencies of cells with chromosomal aberrations (CAs) in peripheral lymphocytes of Norwegian men. Log-linear Poisson regression models were applied on 357 subjects of whom data on all the polymorphisms examined were available. Total CAs and chromosome-type aberrations (CSAs) were significantly increased by higher age alone, whereas chromatid-type aberrations (CTAs) were elevated by the GSTT1-null genotype and MTHFR codon 222 variant allele and chromatid gaps (CTGs) by EPHX1 high activity genotype and occupational exposure. Stratification by smoking and age (<40 and ≥40 years) showed that the effect of the GSTT1 null and EPHX1 high activity genotypes only concerned (older) smokers, in agreement with the roles of the respective enzymes in detoxification and metabolic activation. The MTHFR codon 222 variant allele was associated with high CTGs in smokers, the MTR codon 919 variant allele with high CTAs in older smokers and the NAT2 fast acetylator genotype with high CTGs in older subjects. Among younger nonsmokers, however, carriers of the MTHFR codon 222 and MTR codon 919 variant alleles showed a decrease in the level of CTGs and total CAs, respectively. In conclusion, polymorphisms of GSTT1, EPHX1, MTHFR, MTR and NAT2 differentially affect the frequency of CTAs, CSAs and CTGs, showing interaction with smoking and age. It appears that CA subtypes rather than total CAs should be considered in this type of studies.

  4. Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse.

    Science.gov (United States)

    Mata, Mariana M; Napier, T Celeste; Graves, Steven M; Mahmood, Fareeha; Raeisi, Shohreh; Baum, Linda L

    2015-04-01

    The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last operant session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4(+), CD8(+), CD200(+) and CD11b/c(+) lymphocytes in the spleen. Rats that self-administered methamphetamine had a lower frequency of CD4(+) T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4(+) T cells. Methamphetamine using rats had a higher frequency of CD8(+) T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Our data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection.

  5. The effects of sex, age and cigarette smoking on micronucleus and degenerative nuclear alteration frequencies in human buccal cells of healthy Bosnian subjects

    OpenAIRE

    Hilada Nefić; Jasmin Mušanović; Kemajl Kurteshi; Enida Prutina; Elvira Turcalo

    2013-01-01

    Introduction: This study was performed to establish a baseline value of micronucleus frequency in buccal cells and to estimate the impact of the most common factors (sex and age, and smoking) on micronucleus and degenerative nuclear alteration frequencies in the sample of healthy Bosnian subjects.Methods: The Buccal Micronucleus Cytome (BMCyt) assay, based on scoring not only micronucleus frequency but also other genome damage markers, dead or degenerated cells, provides a measure of cytotoxi...

  6. Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self.

    Science.gov (United States)

    Lehmann, D; Faber, P L; Achermann, P; Jeanmonod, D; Gianotti, L R; Pizzagalli, D

    2001-11-30

    Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions. PMID:11738545

  7. Altered low frequency oscillations of cortical vessels in patients with cerebrovascular occlusive disease – a NIRS study

    DEFF Research Database (Denmark)

    Phillip, Dorte; Iversen, Helle K; Schytz, Henrik W;

    2013-01-01

    patients with both symptomatic carotid occlusive disease and cerebral hypoperfusion in comparison to healthy controls. Each hemisphere was examined with two NIRS channels using a 3 cm source detector distance. Arterial blood pressure (ABP) was measured via a finger plethysmograph. Using transfer function......Analysis of cerebral autoregulation by measuring spontaneous oscillations in the low frequency spectrum of cerebral cortical vessels might be a useful tool for assessing risk and investigating different treatment strategies in carotid artery disease and stroke. Near infrared spectroscopy (NIRS...... analysis ABP-oxyHb phase shift and gain as well as inter-hemispheric phase shift and amplitude ratio were assessed. We found that inter-hemispheric amplitude ratio was significantly altered in hypoperfusion patients compared to healthy controls (P = 0.010), because of relatively lower amplitude...

  8. An association, in adult Japanese, between the occurrence of rogue cells among cultured lymphocytes (JC virus activity) and the frequency of simple chromosomal damage among the lymphocytes of persons exhibiting these rogue cells

    Energy Technology Data Exchange (ETDEWEB)

    Neel, J.V. [Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Human Genetics

    1998-08-01

    Data from a previous study of the cytogenetic effects, in cultured lymphocytes, of exposure to the atomic bomb in Hiroshima have been reanalyzed to determine the relationship between the occurrence of rogue cells in an individual and the frequency of simple chromosomal damage in the nonrogue cells of the same individual. Rogue cells are cells with complex chromosomal damage, currently believed to be a manifestation of the activity of a human polyoma virus termed JC. Among a total of 1,835 persons examined, there were 45 exhibiting rogue cells. A total of 179,599 cells were scored for simple chromosomal damage. In both the exposed and the control populations, there was an absolute increase of {approximately}1.5% in the frequency of simple chromosomal damage in the nonrogue cells of those exhibiting rogue cells, when compared with the frequencies observed in those not exhibiting rogue cells, which is a statistically significant difference. It is argued that this phenomenon, occurring not only in lymphocytes but possibly also in other cells/tissues, may play a contributory role in the origin of malignancies characterized by clonal chromosome abnormalities. Unexpectedly, among those exhibiting rogue cells, there was a disproportionately greater representation of persons who had received relatively high radiation exposures from the bomb. The reason for this is unclear, but it is tempting to relate the finding to some lingering effect of the exposure (or the circumstances surrounding the exposure) on immunocompetence.

  9. Molecular genetics of X chromosome-linked color vision among populations of African and Japanese ancestry: High frequency of a shortened red pigment gene among Afro-Americans

    Energy Technology Data Exchange (ETDEWEB)

    Joergensen, A.L.; Deeb, S.S.; Motulsky, A.G. (Univ. of Washington, Seattle (USA))

    1990-09-01

    Red-green color vision in humans is mediated by the X chromosome-linked highly homologous red and green pigment genes. Color vision defects are caused by deletions and fusions involving these genes. However, the authors found the frequency of molecular abnormalities among Caucasians to be twice as high as that of phenotypic color vision defects. Among Japanese the frequency of phenotypic and molecular color vision defects was similar. Among Afro-Americans, molecular defects were at least five times more frequent than phenotypic color vision defects. In addition, 35% of Afro-Americans, 2% of Japanese, and <1% of Caucasians had a shortened red pigment gene not associated with phenotpyic color vision defects. This gene lacked 1.9 kilobases in its first intron and had the identical size as the green pigment gene from which it presumably originated by gene conversion in an ancestral African population. This gene and the closely linked glucose-6-phosphate dehydrogenase A{sup +} variant were in linkage equilibrium. A model for the evolutionary origin of the color vision pigment genes in higher primates is portrayed.

  10. Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos.

    Science.gov (United States)

    Vázquez-Diez, Cayetana; Yamagata, Kazuo; Trivedi, Shardul; Haverfield, Jenna; FitzHarris, Greg

    2016-01-19

    Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis.

  11. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

    Science.gov (United States)

    Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

    2013-01-01

    The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat. PMID:23884766

  12. Integrated copy number and expression analysis identifies profiles of whole-arm chromosomal alterations and subgroups with favorable outcome in ovarian clear cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Yuriko Uehara

    Full Text Available Ovarian clear cell carcinoma (CCC is generally associated with chemoresistance and poor clinical outcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs and endometrioid carcinomas (ECs are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism analysis with 57 epithelial ovarian cancers (31 CCCs, 14 SCs, and 12 ECs and microarray expression analysis with 55 cancers (25 CCCs, 16 SCs, and 14 ECs. We then evaluated PIK3CA mutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs, significantly lower than for SCs (93%, P < 0.01 and ECs (50%, P = 0.017. The ratio of whole-arm to all CNAs was higher in CCCs (46.9% than SCs (21.7%; P < 0.0001. SCs with loss of heterozygosity (LOH of BRCA1 (85% also had LOH of NF1 and TP53, and LOH of BRCA2 (62% coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10 showed more favorable prognosis than the CCC-1 and CCC-3 clusters (P = 0.041. Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64% than in CCC-2 (0/10, 0%; P < 0.01. Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis.

  13. The effects of sex, age and cigarette smoking on micronucleus and degenerative nuclear alteration frequencies in human buccal cells of healthy Bosnian subjects

    Directory of Open Access Journals (Sweden)

    Hilada Nefić

    2013-12-01

    Full Text Available Introduction: This study was performed to establish a baseline value of micronucleus frequency in buccal cells and to estimate the impact of the most common factors (sex and age, and smoking on micronucleus and degenerative nuclear alteration frequencies in the sample of healthy Bosnian subjects.Methods: The Buccal Micronucleus Cytome (BMCyt assay, based on scoring not only micronucleus frequency but also other genome damage markers, dead or degenerated cells, provides a measure of cytotoxic and genotoxic effects.Results: Our results showed the baseline buccal micronucleus frequency was 0.135% or 1.35‰, as well as positive correlations between micronucleus frequencies and formations of degenerative nuclear alterations (nuclear buds, karyolytic and karyorrhectic cells. The number of micronuclei in buccal cells was significantly higher in females than in males. There was positive association between the age and frequency of analysed cytogenetic biomarkers. Buccal cell micronuclei and degenerative nuclear alternations were more frequent among cigarette smokers than non-smokers and significantly higher in female smokers than in male smokers. Cytogenetic damages showed significantly positive correlation between intensity of smoking and the number of nuclear alterations. The years of smoking had a significant influence not only on the number of nuclear alterations but also in micronuclei and nuclear buds in buccal cells.Conclusions: The sex influences the number of micronuclei in human buccal cells. The ageing increased the number of micronuclei and other biomarkers of DNA damage. The cigarette smoking significantly increases the frequencies of micronuclei and nuclear buds, pyknotic, karyolytic and karyorrhectic cells.

  14. Artifically inserting a reticuloendotheliosis virus long terminal repeat into a bacterial artificial chromosome clone of Marek's disease virus (MDV) alters expression of nearby MDV genes

    Science.gov (United States)

    The long terminal repeat (LTR) sequence of reticuloendotheliosis virus (REV) was inserted into the very virulent Marek’s disease virus (MDV) Md5 bacterial artificial chromosome clone. The insertion site was nearly identical to the REV LTR that was naturally inserted into the JM/102W strain of MDV fo...

  15. Early Exposure to Intermediate-Frequency Magnetic Fields Alters Brain Biomarkers without Histopathological Changes in Adult Mice

    Directory of Open Access Journals (Sweden)

    Tin-Tin Win-Shwe

    2015-04-01

    Full Text Available Recently we have reported that intermediate-frequency magnetic field (IF-MF exposure transiently altered the mRNA expression levels of memory function-related genes in the hippocampi of adult male mice. However, the effects of IF-MF exposure during brain development on neurological biomarkers have not yet been clarified. In the present study, we investigated the effect of IF-MF exposure during development on neurological and immunological markers in the mouse hippocampus in 3- and 7-week-old male mice. Pregnant C57BL/6J mice were exposed to IF-MF (21 kHz, 3.8 mT for one hour per day from organogenesis period day 7 to 17. At adolescence, some IF-MF-exposed mice were further divided into exposure, recovery, and sham-exposure groups. The adolescent-exposure groups were exposed again to IF-MF from postnatal day 27 to 48. The expression of mRNA in the hippocampi was examined using a real-time RT-PCR method, and microglia activation was examined by immunohistochemical analysis. The expression levels of NR1 and NR2B as well as transcription factors (CaMKIV, CREB1, inflammatory mediators (COX2, IL-1 b,TNF-α, and the oxidative stress marker heme-oxygenase (HO-1 were significantly increased in the IF-MF-exposed mice, compared with the control group, in the 7-week-old mice, but not in the 3-week-old mice. Microglia activation was not different between the control and other groups. This study provides the first evidence that early exposure to IF-MF reversibly affects the NMDA receptor, its related signaling pathways, and inflammatory mediators in the hippocampus of young adult mice; these changes are transient and recover after termination of exposure without histopathological changes.

  16. 泰国少精无精不育男性中Y染色体微缺失和染色体异常的发病率%Frequency of Y chromosome microdeletions and chromosomal abnormalities in infertile Thai men with oligozoospermia and azoospermia

    Institute of Scientific and Technical Information of China (English)

    T.Vutyavanich; W.Piromlertamorn; W.Sirirungsi; S.Sirisukkasem

    2007-01-01

    Aim:To investigate the possible causes of oligozoospermia and azoospermia in infertile Thai men, and to find the frequencies of Y chromosome microdeletions and cytogenetic abnormalities in this group. Methods: From June 2003 to November 2005, 50 azoospermic and 80 oligozoospermic men were enrolled in the study. A detailed history was taken for each man, followed by general and genital examinations. Y chromosome microdeletions were detected by multiplex polymerase chain reaction (PCR) using 11 gene-specific primers that covered all three regions of the azoospermic factor (AZFa, AZFb and AZFc). Fifty men with normal semen analysis were also studied. Karyotyping was done with the standard G- and Q-banding. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone were measured by electrochemiluminescence immunoassays (ECLIA). Results: Azoospermia and oligozoospermia could be explained by previous orchitis in 22.3%, former bilateral cryptorchidism in 19.2%, abnormal karyotypes in 4.6% and Y chromosome microdeletions in 3.8% of the subjects. The most frequent deletions were in the AZFc region (50%), followed by AZFb (33%) and AZFbc (17%).No significant difference was detected in hormonal profiles of infertile men, with or without microdeletions.Conclusion: The frequencies of Y chromosome microdeletions and cytogenetic abnormalities in oligozoospermic and azoospermic Thai men are comparable with similarly infertile men from other Asian and Western countries.

  17. The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

    OpenAIRE

    Jabbi, Mbemba; Kippenhan, J. Shane; Kohn, Philip; Marenco, Stefano; Mervis, Carolyn B.; Morris, Colleen A.; Meyer-Lindenberg, Andreas; Berman, Karen Faith

    2012-01-01

    Although it is widely accepted that genes can influence complex behavioral traits such as human temperament, the underlying neurogenetic mechanisms remain unclear. Williams syndrome (WS), a rare disorder caused by a hemizygous deletion on chromosome 7q11.23, including genes important for neuronal migration and maturation (LIMK1 and CLIP2), is typified by a remarkable hypersocial but anxious personality and offers a unique opportunity to investigate this open issue. Based on the documented rol...

  18. Frequency-dependent brain regional homogeneity alterations in patients with mild cognitive impairment during working memory state relative to resting state

    Directory of Open Access Journals (Sweden)

    Pengyun eWang

    2016-03-01

    Full Text Available Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI. However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control subjects. Therefore, using the index of regional homogeneity (ReHo, we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex in the slow-3 band (0.073–0.198 Hz, and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex, the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01–0.027 Hz. Furthermore, in normal controls, the value of ReHo in clusters belonging to the default mode network decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients.This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states.

  19. Sex chromosome aneuploidy in cytogenetic findings of referral patients from south of Iran

    Directory of Open Access Journals (Sweden)

    Najmeh Jouyan

    2012-01-01

    Full Text Available Background: Chromosome abnormality (CA including Sex chromosomes abnormality (SCAs is one of the most important causes of disordered sexual development and infertility. SCAs formed by numerical or structural alteration in X and Y chromosomes, are the most frequently CA encountered at both prenatal diagnosis and at birth. Objective: This study describes cytogenetic findings of cases suspected with CA referred for cytogenetic study. Materials and Methods: Blood samples of 4151 patients referred for cytogenetic analysis were cultured for chromosome preparation. Karyotypes were prepared for all samples and G-Banded chromosomes were analyzed using x100 objective lens. Sex chromosome aneuploidy cases were analyzed and categorized in two groups of Turners and Klinefelter’s syndrome (KFS. Results: Out of 230 (5.54% cases with chromosomally abnormal karyotype, 122 (30% cases suspected of sexual disorder showed SCA including 46% Turner’s syndrome, 46% KFS and the remaining other sex chromosome abnormalities. The frequency of classic and mosaic form of Turner’s syndrome was 33% and 67%, this was 55% and 45% for KFS, respectively. Conclusion: This study shows a relatively high sex chromosome abnormality in this region and provides cytogenetic data to assist clinicians and genetic counselors to determine the priority of requesting cytogenetic study. Differences between results from various reports can be due to different genetic background or ethnicity.

  20. Comparative evaluation of changes in the absorbed doses of neutron radiation and chromosome aberration frequency in human blood lymphocytes by a water phantom depth during irradiation with a medico-biological beam at the BR-10 reactor

    International Nuclear Information System (INIS)

    Distribution of the chromosome aberration frequency in human blood lymphocyte samples and absorbed doses have been compared by the water phantom depth during irradiation with 1.5 Gy neutrons (mean energy of 0.85 MeV). There is a good concordance of their depth distribution. The half-fall layer of the absorbed dose within the tissue-equivalent medium is similar (∼ 5 cm) with both measurements done. The aberration frequency in the biological samples placed outside the radiation field in the phantom increases which indicates that the neutron beem bounds are indistinct upon passing the tissue-equivalent medium

  1. A novel balanced chromosomal translocation found in subjects with schizophrenia and schizotypal personality disorder: Altered L-serine level associated with disruption of PSAT1 gene expression

    OpenAIRE

    Ozeki, Yuji; Pickard, Benjamin S; Kano, Shin-ichi; Malloy, Mary P.; Zeledon, Mariela; SUN, DANIEL Q.; Fujii, Kumiko; Wakui, Keiko; Shirayama, Yukihiko; Fukushima, Yoshimitsu; Kunugi, Hiroshi; Hashimoto, Kenji; Muir, Walter J; Blackwood, Douglas H; Sawa, Akira

    2011-01-01

    L-Serine is required for the synthesis of glycine and D-serine, both of which are NMDA receptor coagonists. Although roles for D-serine and glycine have been suggested in schizophrenia, little is known about the role of the L-serine synthesizing cascade in schizophrenia or related psychiatric conditions. Here we report a patient with schizophrenia carrying a balanced chromosomal translocation with the breakpoints localized to 3q13.12 and 9q21.2. We examined this proband and her son with schiz...

  2. Altered Cortical Responsiveness to Pain Stimuli after High Frequency Electrical Stimulation of the Skin in Patients with Persistent Pain after Inguinal Hernia Repair

    OpenAIRE

    Broeke, E.N. van den; Koeslag, L.; Arendsen, L.J.; Nienhuijs, S.W.; Rosman, C.; van Rijn, C.M.

    2013-01-01

    Background High Frequency electrical Stimulation (HFS) of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP) N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate whether this enhanced ERP N1 amplitude could be a potential marker for altered cortical sensory processing in patients with persistent pain after surgery. Materials and Methods Nineteen male patients...

  3. Altered Cortical Responsiveness to Pain Stimuli after High Frequency Electrical Stimulation of the Skin in Patients with Persistent Pain after Inguinal Hernia Repair

    OpenAIRE

    van den Broeke, Emanuel N; Lonneke Koeslag; Arendsen, Laura J.; Nienhuijs, Simon W; Camiel Rosman; van Rijn, Clementina M.; Oliver H G Wilder-Smith; Harry van Goor

    2013-01-01

    BACKGROUND: High Frequency electrical Stimulation (HFS) of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP) N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate whether this enhanced ERP N1 amplitude could be a potential marker for altered cortical sensory processing in patients with persistent pain after surgery. MATERIALS AND METHODS: Nineteen male patien...

  4. Association of a Chromosomal Rearrangement Event with Mouse Posterior Polymorphous Corneal Dystrophy and Alterations in Csrp2bp, Dzank1, and Ovol2 Gene Expression.

    Directory of Open Access Journals (Sweden)

    Anna L Shen

    Full Text Available We have previously described a mouse model of human posterior polymorphous corneal dystrophy (PPCD and localized the causative mutation to a 6.2 Mbp region of chromosome 2, termed Ppcd1. We now show that the gene rearrangement linked to mouse Ppcd1 is a 3.9 Mbp chromosomal inversion flanked by 81 Kbp and 542 bp deletions. This recombination event leads to deletion of Csrp2bp Exons 8 through 11, Dzank1 Exons 20 and 21, and the pseudogene Znf133. In addition, we identified translocation of novel downstream sequences to positions adjacent to Csrp2bp Exon 7 and Dzank1 Exon 20. Twelve novel fusion transcripts involving Csrp2bp or Dzank1 linked to downstream sequences have been identified. Eight are expressed at detectable levels in PPCD1 but not wildtype eyes. Upregulation of two Csrp2bp fusion transcripts, as well as upregulation of the adjacent gene, Ovol2, was observed. Absence of the PPCD1 phenotype in animals haploinsufficient for Csrp2bp or both Csrp2bp and Dzank1 rules out haploinsufficiency of these genes as a cause of mouse PPCD1. Complementation experiments confirm that PPCD1 embryonic lethality is due to disruption of Csrp2bp expression. The ocular expression pattern of Csrp2bp is consistent with a role for this protein in corneal development and pathogenesis of PPCD1.

  5. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus.

    Science.gov (United States)

    Brooks, Wesley H; Renaudineau, Yves

    2015-01-01

    Autoimmune diseases occur more often in females, suggesting a key role for the X chromosome. X chromosome inactivation, a major epigenetic feature in female cells that provides dosage compensation of X-linked genes to avoid overexpression, presents special vulnerabilities that can contribute to the disease process. Disruption of X inactivation can result in loss of dosage compensation with expression from previously sequestered genes, imbalance of gene products, and altered endogenous material out of normal epigenetic context. In addition, the human X has significant differences compared to other species and these differences can contribute to the frequency and intensity of the autoimmune disease in humans as well as the types of autoantigens encountered. Here a link is demonstrated between autoimmune diseases, such as systemic lupus erythematosus, and the X chromosome by discussing cases in which typically non-autoimmune disorders complicated with X chromosome abnormalities also present lupus-like symptoms. The discussion is then extended to the reported spatial and temporal associations of the inactive X chromosome with the nucleolus. When frequent episodes of cellular stress occur, the inactive X chromosome may be disrupted and inadvertently become involved in the nucleolar stress response. Development of autoantigens, many of which are at least transiently components of the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex assembly in the nucleolus, increase further during cell stress, and appear to have an important role in the autoimmune disease process. Autoantigenic endogenous material can potentially be stabilized by polyamines. This presents a new paradigm for autoimmune diseases: that many are antigen-driven and the autoantigens originate from altered endogenous material due to episodes of cellular stress that disrupt epigenetic control. This suggests that epigenetics and the X chromosome are important aspects of autoimmune

  6. Level alterations of the 2f (1)-f (2) distortion product due to hypoxia in the guinea pig depend on the stimulus frequency.

    Science.gov (United States)

    Olzowy, Bernhard; von Gleichenstein, Gregor; Canis, Martin; Plesnila, Nikolaus; Strieth, Sebastian; Deppe, Christoph; Mees, Klaus

    2010-03-01

    Increased intracranial pressure (ICP) is known to affect the levels of distortion product otoacoustic emissions (DPOAEs) in a frequency-specific manner. DPOAEs might, therefore, be used for monitoring the ICP non-invasively. Hypoxia can also cause alterations of DPOAE levels, which can be distinguished from ICP-related changes only, when their characteristics, in particular frequency specificity, are known in detail. DPOAEs at f (2) = 2, 4, 8, 12 and 16 kHz and oxygen saturation (SaO(2)) were continuously monitored in nine spontaneously breathing guinea pigs, anaesthetized by i.m. administration of midazolam, medetomidin and fentanyl, during the respiration of a gas mixture of N(2)O and O(2) containing either 30% O(2) or 13% O(2). Fourteen hypoxic intervals in eight animals were included into final data analysis. Characteristic hypoxic level alterations with a level decrease and a remarkable level destabilization during hypoxia, and a pronounced reversible level decrease after reoxygenation were observed at the frequencies of 4, 8 and 16 kHz. At 2 and 12 kHz, the only reproducible effect of hypoxia was an increased fluctuation of the DPOAE level, which was significantly less pronounced compared with the other frequencies (P < 0.05 for 12 vs. 16 and 8 kHz and for 2 vs. 16 kHz). DPOAE level alterations due to hypoxia depend on the frequency in guinea pigs. Studies in human are warranted to improve non-invasive ICP monitoring with DPOAE by the detection of hypoxia-related changes. PMID:19629511

  7. Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain.

    Science.gov (United States)

    Duarte, Rodrigo R R; Troakes, Claire; Nolan, Matthew; Srivastava, Deepak P; Murray, Robin M; Bray, Nicholas J

    2016-09-01

    Chromosome 10q24.32-q24.33 is one of the most robustly supported risk loci to emerge from genome-wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele-specific expression to assess cis-regulatory effects associated with the two best-supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis-effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27004590

  8. Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain.

    Science.gov (United States)

    Duarte, Rodrigo R R; Troakes, Claire; Nolan, Matthew; Srivastava, Deepak P; Murray, Robin M; Bray, Nicholas J

    2016-09-01

    Chromosome 10q24.32-q24.33 is one of the most robustly supported risk loci to emerge from genome-wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele-specific expression to assess cis-regulatory effects associated with the two best-supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis-effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

  9. Genome‐wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis‐regulation of BORCS7, AS3MT, and NT5C2 in the human brain

    Science.gov (United States)

    Duarte, Rodrigo R. R.; Troakes, Claire; Nolan, Matthew; Srivastava, Deepak P.; Murray, Robin M.

    2016-01-01

    Chromosome 10q24.32‐q24.33 is one of the most robustly supported risk loci to emerge from genome‐wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele‐specific expression to assess cis‐regulatory effects associated with the two best‐supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis‐effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27004590

  10. 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.

  11. Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles-a TMS Study.

    Science.gov (United States)

    Sale, Martin V; Rogasch, Nigel C; Nordstrom, Michael A

    2016-01-01

    The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

  12. PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor: implications for active surveillance.

    Science.gov (United States)

    Trock, Bruce J; Fedor, Helen; Gurel, Bora; Jenkins, Robert B; Knudsen, B S; Fine, Samson W; Said, Jonathan W; Carter, H Ballentine; Lotan, Tamara L; De Marzo, Angelo M

    2016-07-01

    Men who enter active surveillance because their biopsy exhibits only Gleason grade 3 (G3) frequently have higher grade tumor missed by biopsy. Thus, biomarkers are needed that, when measured on G3 tissue, can predict the presence of higher grade tumor in the whole prostate. We evaluated whether PTEN loss, chromosome 8q gain (MYC) and/or 8p loss (LPL) measured only on G3 cores is associated with un-sampled G4 tumor. A tissue microarray was constructed of prostatectomy tissue from patients whose prostates exhibited only Gleason score 3+3, only 3+4 or only 4+3 tumor (n=50 per group). Cores sampled only from areas of G3 were evaluated for PTEN loss by immunohistochemistry, and PTEN deletion, LPL/8p loss and MYC/8q gain by fluorescence in situ hybridization. Biomarker results were compared between Gleason score 6 vs 7 tumors using conditional logistic regression. PTEN protein loss, odds ratio=4.99, P=0.033; MYC/8q gain, odds ratio=5.36, P=0.010; and LPL/8p loss, odds ratio=3.96, P=0.003 were significantly more common in G3 cores derived from Gleason 7 vs Gleason 6 tumors. PTEN gene deletion was not statistically significant. Associations were stronger comparing Gleason 4+3 vs 6 than for Gleason 3+4 vs 6. MYC/8q gain, LPL/8p loss and PTEN protein loss measured in G3 tissue microarray cores strongly differentiate whether the core comes from a Gleason 6 or Gleason 7 tumor. If validated to predict upgrading from G3 biopsy to prostatectomy these biomarkers could reduce the likelihood of enrolling high-risk men and facilitate safe patient selection for active surveillance.

  13. Insertion of reticuloendotheliosis virus long terminal repeat into a bacterial artificial chromosome clone of a very virulent Marek's disease virus alters its pathogenicity.

    Science.gov (United States)

    Mays, Jody K; Silva, Robert F; Kim, Taejoong; Fadly, Aly

    2012-01-01

    Co-cultivation of the JM/102W strain of Marek's disease virus (MDV) with reticuloendotheliosis virus (REV) resulted in the generation of a recombinant MDV containing the REV long terminal repeat (LTR) named the RM1 strain of MDV, a strain that was highly attenuated for oncogenicity but induced severe bursal and thymic atrophy. We hypothesize that the phenotypic changes were solely due to the LTR insertion. Furthermore, we hypothesize that insertion of REV LTR into an analogous location in a different MDV would result in a similar phenotypic change. To test these hypotheses, we inserted the REV LTR into a bacterial artificial chromosome (BAC) clone of a very virulent strain of MDV, Md5, and designated the virus rMd5-RM1-LTR. The rMd5-RM1-LTR virus and the rMd5 virus were passaged in duck embryo fibroblast cells for up to 40 passages before pathogenicity studies. Susceptible chickens were inoculated intra-abdominally at hatch with the viruses rMd5-RM1-LTR, rMd5 BAC parental virus, wild-type strain Md5, or strain RM1 of MDV. The rMd5-RM1-LTR virus was attenuated at cell culture passage 40, whereas the rMd5 BAC without RM1 LTR retained its pathogenicity at cell culture passage 40. Using polymerase chain analysis, the RM1 LTR insert was detected in MDV isolated from buffy coat cells collected from chickens inoculated with rMd5-RM1-LTR, but only at 1 week post inoculation. The data suggest that the presence of the RM1 LTR insert within MDV genome for 1 week post inoculation with virus at hatch is sufficient to cause a reduction in pathogenicity of strain Md5 of MDV.

  14. [The effect of mixed cultivation of lymphocytes irradiated at a dose of 1 Gy and non-irradiated lymphocytes on the frequency of chromosomal aberration].

    Science.gov (United States)

    Kolesnikova, I S

    2012-01-01

    The mutual influence of irradiated (1 Gy) and non-irradiated cells was demonstrated on the model of the mixed culture oflymphocytes from opposite gender donors using chromosome aberrations (ChA) as an endpoint. The number of ChA in non-irradiated lymphocytes in mixed cultures with irradiated ones increased as compared to the corresponding monocultures. At the same time, the number of induced ChA decreased in the irradiated lymphocytes cultivated with non-irradiated ones.

  15. Meiotic abnormalities in metaphase I human spermatocytes from infertile males: frequencies, chromosomes involved, and the relationships with polymorphic karyotype and seminal parameters

    OpenAIRE

    Zaida Sarrate; Francesca Vidal; Joan Blanco

    2014-01-01

    The aim of this study was to look in depth at the relationship between meiotic anomalies and male infertility, such as the determination of the chromosomes involved or the correlation with patient features. For this purpose, a total of 31 testicular tissue samples from individuals consulting for fertility problems were analyzed. Metaphase I cells were evaluated using a sequential methodology combining Leishman stained procedures and multiplex fluorescence in situ hybridization protocols. The ...

  16. Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML

    DEFF Research Database (Denmark)

    Preiss, Birgitte S; Bergman, Olav J; Friis, Lone S;

    2010-01-01

    During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients...... (P = 0.01). We conclude that population-based cytogenetic studies of adult s-AML and age- and sex-matched de novo AML show comparable distributions of chromosome abnormalities....

  17. Flow cytometric detection of aberrant chromosomes

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-05-11

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

  18. Molecular genetic approach to human meningioma: loss of genes on chromosome 22

    Energy Technology Data Exchange (ETDEWEB)

    Seizinger, B.R.; De La Monte, S.; Atkins, L.; Gusella, J.F.; Martuza, R.L.

    1987-08-01

    A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, the authors propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.

  19. Effect of higher frequency components and duration of vibration on bone tissue alterations in the rat-tail model.

    Science.gov (United States)

    Peelukhana, Srikara V; Goenka, Shilpi; Kim, Brian; Kim, Jay; Bhattacharya, Amit; Stringer, Keith F; Banerjee, Rupak K

    2015-01-01

    To formulate more accurate guidelines for musculoskeletal disorders (MSD) linked to Hand-Arm Vibration Syndrome (HAVS), delineation of the response of bone tissue under different frequencies and duration of vibration needs elucidation. Rat-tails were vibrated at 125 Hz (9 rats) and 250 Hz (9 rats), at 49 m/s(2), for 1D (6 rats), 5D (6 rats) and 20D (6 rats); D=days (4 h/d). Rats in the control group (6 rats for the vibration groups; 2 each for 1D, 5D, and 20D) were left in their cages, without being subjected to any vibration. Structural and biochemical damages were quantified using empty lacunae count and nitrotyrosine signal-intensity, respectively. One-way repeated-measure mixed-model ANOVA at pbone, structural damage quantified through empty lacunae count was significant (pbone while the trabecular bone showed significant (pbone tissue are dependent upon higher vibration frequencies of 125 Hz, 250 Hz and the duration of vibration (5D, 20D).

  20. Odd-paired controls frequency doubling in Drosophila segmentation by altering the pair-rule gene regulatory network

    Science.gov (United States)

    Clark, Erik; Akam, Michael

    2016-01-01

    The Drosophila embryo transiently exhibits a double-segment periodicity, defined by the expression of seven 'pair-rule' genes, each in a pattern of seven stripes. At gastrulation, interactions between the pair-rule genes lead to frequency doubling and the patterning of 14 parasegment boundaries. In contrast to earlier stages of Drosophila anteroposterior patterning, this transition is not well understood. By carefully analysing the spatiotemporal dynamics of pair-rule gene expression, we demonstrate that frequency-doubling is precipitated by multiple coordinated changes to the network of regulatory interactions between the pair-rule genes. We identify the broadly expressed but temporally patterned transcription factor, Odd-paired (Opa/Zic), as the cause of these changes, and show that the patterning of the even-numbered parasegment boundaries relies on Opa-dependent regulatory interactions. Our findings indicate that the pair-rule gene regulatory network has a temporally modulated topology, permitting the pair-rule genes to play stage-specific patterning roles. DOI: http://dx.doi.org/10.7554/eLife.18215.001 PMID:27525481

  1. Polymer models of chromosome (re)organization

    Science.gov (United States)

    Mirny, Leonid

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

  2. Artificially inserting a reticuloendotheliosis virus long terminal repeat into a bacterial artificial chromosome clone of Marek's disease virus (MDV) alters expression of nearby MDV genes.

    Science.gov (United States)

    Kim, Taejoong; Mays, Jody; Fadly, Aly; Silva, Robert F

    2011-06-01

    Researchers reported that co-cultivating the JM/102W strain of Marek's disease virus (MDV) with reticuloendotheliosis virus (REV) resulted in an REV long terminal repeat (LTR) being inserted into the internal repeat short (IRS) region of JM/102W. When the resulting recombinant virus was serially passed in cell culture, the initial LTR was duplicated and a second LTR spontaneously appeared in the terminal repeat short (TRS) region of the MDV genome. The virus, designated RM1, was significantly attenuated but still induced severe bursal and thymic atrophy (Isfort et al. PNAS 89:991-995). To determine whether the altered phenotype was due solely to the LTR, we cloned the LTR from the RM1 IRS region and inserted it into the IRS region of a very virulent bacterial artificial clone (BAC) of the Md5 strain of MDV, which we designated rMd5-RM1-LTR. During blind passage in duck embryo fibroblast cultures, the initial LTR in the rMd5-RM1-LTR was also duplicated, with LTRs appearing in both IRS and TRS regions of the MDV genome. The inserted LTR sequences and transcripts associated with the MDV open reading frames MDV085, MDV086, SORF2, US1, and US10 were molecularly characterized. The parental Md5 BAC contains a family of transcripts of 3, 2, and 1 kb that all terminate at the end of the US10 gene. The rMd5-RM1-LTR and RM1 viruses both express an additional 4 kb transcript that originates in the LTR and also terminates after US10. Collectively, the data suggest that our engineered rMd5-RM1-LTR virus very closely resembles the RM1 virus in its structure and transcription patterns.

  3. Treatment with anti-OX40L or anti-TSLP does not alter the frequency of T regulatory cells in allergic asthmatics.

    Science.gov (United States)

    Baatjes, A J; Smith, S G; Dua, B; Watson, R; Gauvreau, G M; O'Byrne, P M

    2015-11-01

    OX40-OX40L interactions and thymic stromal lymphopoietin (TSLP) are important in the induction and maintenance of Th2 responses in allergic disease, whereas T regulatory cells (Treg) have been shown to suppress pro-inflammatory Th2 responses. Both OX40L and TSLP have been implicated in the negative regulation of Treg. The effect of anti-asthma therapies on Treg is not well known. Our aim was to assess the effects of two monoclonal antibody therapies (anti-OX40L and anti-TSLP) on Treg frequency using a human model of allergic asthma. We hypothesized that the anti-inflammatory effects of these therapies would result in an increase in circulating Treg (CD4(+) CD25(+) CD127(low) Foxp3(+) cells) frequency. We measured Treg using flow cytometry, and our results showed that neither allergen challenge nor monoclonal antibody therapy altered circulating Treg frequency. These data highlight the need for assessment of airway Treg and for a more complete understanding of Treg biology so as to develop pharmacologics/biologics that modulate Treg for asthma therapy. PMID:26213896

  4. 健康成人自发染色体畸变率与微核率的本底状况再分析%Re-investigation on spontaneous frequencies of chromosome aberration and micronucleus in healthy adults

    Institute of Scientific and Technical Information of China (English)

    张学清; 陈英; 王治东; 王远; 周平坤

    2014-01-01

    目的:了解环境因素对人类遗传物质的影响,以便正确评估放射从业人员以及低剂量辐射的健康效应。方法:选自北京市87名接受健康体检的成年人,每人用肝素钠抗凝管抽取外周静脉血2 mL。采用提前加秋水仙素和松胞素B法分别制备染色体与微核标本,Metafer自动分析系统结合人工分析染色体畸变与双核淋巴细胞微核,按不同年龄段与不同性别分组进行统计比较。结果:87名受检者的染色单体型畸变率平均为0.70%,染色体型畸变率为0.20%,其中双着丝粒体+环为0.13%,单纯无着丝粒体为0.06%。微核与微核细胞率分别为25.30‰和21.56‰。除单体型畸变外,染色体型畸变率与微核率均随年龄的增加而增加(P0.05)。结论:健康成人染色体型畸变(双着丝粒体+环)率与双核淋巴细胞微核率未超过国内外报道的本底范围,但较国内以往报道的本底值有增高趋势。P%OBJECTIVE: In order to understand genetic effect from environment factors and to assess correctly the health effect of low dose radiation on occupational personnel. METHODS:The investigated objects came from 87 healthy adults who took routine physical examination and living in Beijing city. 2 mL peripheral venous blood from each person was drawn into heparinized tubes. Conventional chromosome culture with adding colchicines at the beginning and Cyt-B micronuclei (MN) methods were applied. Chromosomal aberrations (CA) and binucleated lymphocyte MN were analyzed using Metafer scanning system combined with manual work. Comparisons according to different age groups and both genders were carried out. RESULTS:The average spontaneous frequencies of chromatid-type and chromosomal-type aberrations in 87 tested persons were 0.70%and 0.20%,respectively. In chromosomal-type aberrations,the dicentrics plus rings (dic+r) were 0.13%,acentrics alone were 0.06%. Spontaneous MN and MNC frequencies were 23.43

  5. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

    Energy Technology Data Exchange (ETDEWEB)

    Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S. [Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, Newark, New Jersey 07103 (United States); Santhakumar, Vijayalakshmi, E-mail: santhavi@njms.rutgers.edu [Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, Newark, New Jersey 07103 (United States); Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, Newark, New Jersey 07103 (United States)

    2013-12-15

    Gamma frequency oscillations have been proposed to contribute to memory formation and retrieval. Fast-spiking basket cells (FS-BCs) are known to underlie development of gamma oscillations. Fast, high amplitude GABA synapses and gap junctions have been suggested to contribute to gamma oscillations in FS-BC networks. Recently, we identified that, apart from GABAergic synapses, FS-BCs in the hippocampal dentate gyrus have GABAergic currents mediated by extrasynaptic receptors. Our experimental studies demonstrated two specific changes in FS-BC GABA currents following experimental seizures [Yu et al., J. Neurophysiol. 109, 1746 (2013)]: increase in the magnitude of extrasynaptic (tonic) GABA currents and a depolarizing shift in GABA reversal potential (E{sub GABA}). Here, we use homogeneous networks of a biophysically based model of FS-BCs to examine how the presence of extrasynaptic GABA conductance (g{sub GABA-extra}) and experimentally identified, seizure-induced changes in g{sub GABA-extra} and E{sub GABA} influence network activity. Networks of FS-BCs interconnected by fast GABAergic synapses developed synchronous firing in the dentate gamma frequency range (40–100 Hz). Systematic investigation revealed that the biologically realistic range of 30 to 40 connections between FS-BCs resulted in greater coherence in the gamma frequency range when networks were activated by Poisson-distributed dendritic synaptic inputs rather than by homogeneous somatic current injections, which were balanced for FS-BC firing frequency in unconnected networks. Distance-dependent conduction delay enhanced coherence in networks with 30–40 FS-BC interconnections while inclusion of gap junctional conductance had a modest effect on coherence. In networks activated by somatic current injections resulting in heterogeneous FS-BC firing, increasing g{sub GABA-extra} reduced the frequency and coherence of FS-BC firing when E{sub GABA} was shunting (−74 mV), but failed to alter average

  6. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

    Science.gov (United States)

    Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S.; Santhakumar, Vijayalakshmi

    2013-12-01

    Gamma frequency oscillations have been proposed to contribute to memory formation and retrieval. Fast-spiking basket cells (FS-BCs) are known to underlie development of gamma oscillations. Fast, high amplitude GABA synapses and gap junctions have been suggested to contribute to gamma oscillations in FS-BC networks. Recently, we identified that, apart from GABAergic synapses, FS-BCs in the hippocampal dentate gyrus have GABAergic currents mediated by extrasynaptic receptors. Our experimental studies demonstrated two specific changes in FS-BC GABA currents following experimental seizures [Yu et al., J. Neurophysiol. 109, 1746 (2013)]: increase in the magnitude of extrasynaptic (tonic) GABA currents and a depolarizing shift in GABA reversal potential (EGABA). Here, we use homogeneous networks of a biophysically based model of FS-BCs to examine how the presence of extrasynaptic GABA conductance (gGABA-extra) and experimentally identified, seizure-induced changes in gGABA-extra and EGABA influence network activity. Networks of FS-BCs interconnected by fast GABAergic synapses developed synchronous firing in the dentate gamma frequency range (40-100 Hz). Systematic investigation revealed that the biologically realistic range of 30 to 40 connections between FS-BCs resulted in greater coherence in the gamma frequency range when networks were activated by Poisson-distributed dendritic synaptic inputs rather than by homogeneous somatic current injections, which were balanced for FS-BC firing frequency in unconnected networks. Distance-dependent conduction delay enhanced coherence in networks with 30-40 FS-BC interconnections while inclusion of gap junctional conductance had a modest effect on coherence. In networks activated by somatic current injections resulting in heterogeneous FS-BC firing, increasing gGABA-extra reduced the frequency and coherence of FS-BC firing when EGABA was shunting (-74 mV), but failed to alter average FS-BC frequency when EGABA was depolarizing

  7. Chromosome Microarray.

    Science.gov (United States)

    Anderson, Sharon

    2016-01-01

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

  8. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    Directory of Open Access Journals (Sweden)

    Daniela Mierla

    2012-06-01

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

  9. Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform-consistent alterations encoding for cell transformation and predicting ovarian cancer survival.

    Science.gov (United States)

    Sankaranarayanan, Preethi; Schomay, Theodore E; Aiello, Katherine A; Alter, Orly

    2015-01-01

    The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD), which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV) tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs). We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient's prognosis, is independent of the tumor's stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell's immortality, and a patient's shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival. In Xq, PABPC5

  10. Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform-consistent alterations encoding for cell transformation and predicting ovarian cancer survival.

    Directory of Open Access Journals (Sweden)

    Preethi Sankaranarayanan

    Full Text Available The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD, which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs. We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient's prognosis, is independent of the tumor's stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell's immortality, and a patient's shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival

  11. Tensor GSVD of Patient- and Platform-Matched Tumor and Normal DNA Copy-Number Profiles Uncovers Chromosome Arm-Wide Patterns of Tumor-Exclusive Platform-Consistent Alterations Encoding for Cell Transformation and Predicting Ovarian Cancer Survival

    Science.gov (United States)

    Sankaranarayanan, Preethi; Schomay, Theodore E.; Aiello, Katherine A.; Alter, Orly

    2015-01-01

    The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD), which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV) tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs). We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient’s prognosis, is independent of the tumor’s stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell’s immortality, and a patient’s shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival. In Xq

  12. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    OpenAIRE

    Daniela Mierla; Viorica Radoi; Veronica Stoian

    2012-01-01

    Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, ka...

  13. Meningitis Caused by Toscana Virus Is Associated with Strong Antiviral Response in the CNS and Altered Frequency of Blood Antigen-Presenting Cells

    Directory of Open Access Journals (Sweden)

    Stefania Varani

    2015-11-01

    Full Text Available Toscana virus (TOSV is a Phlebotomus-transmitted RNA virus and a frequent cause of human meningitis and meningoencephalitis in Southern Europe during the summer season. While evidence for TOSV-related central nervous system (CNS cases is increasing, little is known about the host defenses against TOSV. We evaluated innate immune response to TOSV by analyzing frequency and activation of blood antigen-presenting cells (APCs and cytokine levels in plasma and cerebrospinal fluid (CSF from patients with TOSV neuroinvasive infection and controls. An altered frequency of different blood APC subsets was observed in TOSV-infected patients, with signs of monocytic deactivation. Nevertheless, a proper or even increased responsiveness of toll-like receptor 3 and 7/8 was observed in blood APCs of these patients as compared to healthy controls. Systemic levels of cytokines remained low in TOSV-infected patients, while levels of anti-inflammatory and antiviral mediators were significantly higher in CSF from TOSV-infected patients as compared to patients with other infectious and noninfectious neurological diseases. Thus, the early host response to TOSV appears effective for viral clearance, by proper response to TLR3 and TLR7/8 agonists in peripheral blood and by a strong and selective antiviral and anti-inflammatory response in the CNS.

  14. Chromosomal abnormalities in spontaneous abortion after assisted reproductive treatment

    Directory of Open Access Journals (Sweden)

    Kim You

    2010-11-01

    Full Text Available Abstract Background We evaluated cytogenetic results occurring with first trimester pregnancy loss, and assessed the type and frequency of chromosomal abnormalities after assisted reproductive treatment (ART and compared them with a control group. We also compared the rate of chromosomal abnormalities according to infertility causes in ICSI group. Methods A retrospective cohort analysis was made of all patients who were referred to the Genetics Laboratory of Fertility Center of CHA Gangnam Medical Center from 2005 to 2009 because of clinical abortion with a subsequent dilation and evacuation (D&E performed, and patients were grouped by type of conception as follows: conventional IVF (in vitro fertilization (n = 114, ICSI (intracytoplasmic sperm injection (n = 140, and control (natural conception or intrauterine insemination [IUI] (n = 128. Statistical analysis was performed using SPSS software. Results A total 406 specimens were referred to laboratory, ten abortuses were excluded, and in 14 cases, we did not get any spontaneous metaphase, chromosomal constitutions of 382 specimens were successfully obtained with conventional cytogenetic methods. Overall, 52.62% of the miscarriages were found to be cytogenetically abnormal among all patients, the frequency was 48.4% in the control group, 54.3% of miscarriages after ICSI and 55.3% after conventional IVF (p = 0.503. The most prevalent abnormalities were autosomal trisomy, however, nine (11.69% sex chromosome aneuploidy were noted in the ICSI group vs. four (6.45% and two (3.23% cases in the conventional IVF group and control group. We compared chromosomal abnormalities of miscarriages after ICSI according to infertility factor. 55.71% underwent ICSI due to male factors, 44.29% due to non-male factors. ICSI group having male factors showed significantly higher risk of chromosomal abnormalities than ICSI group having non-male factors (65.8% vs. 34.2%, p = 0.009, odds ratio = 1.529, 95% CI = 1

  15. Molecular Characterisation of Structural Chromosomal Abnormalities Associated with Congenital Disorders

    OpenAIRE

    Mansouri, Mahmoud R.

    2006-01-01

    Chromosomal abnormalities are defined as changes in the chromosome structure and fall in one of two categories. The first category is numerical alterations while the second category consists of structural abnormalities. Structural chromosomal abnormalities do not always interrupt genes in order to cause disease. They can also affect gene expression by separating a gene and its promoter element from distant regulatory elements. We have used characterisation of structural chromosomal abnormalit...

  16. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    Directory of Open Access Journals (Sweden)

    Wang Jun

    2009-03-01

    Full Text Available Abstract Background A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers. Methods We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk. Results We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the Fst value closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping. Conclusion The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yunes, Samira Nogarol

    2010-07-01

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

  18. Chromosome heteromorphisms in the Japanese, 3

    International Nuclear Information System (INIS)

    The type and frequency of chromosome variants detected by the C-staining method were ascertained in 1,857 individuals residing in Hiroshima. The most frequent heteromorphic variant was the total inversion of the C-band in chromosome 9 found in 27 individuals (1.45%). The total inversion of the C-band in chromosome 1 was not seen in this sample, but the partial inversion of the C-band in chromosome 1 was found in 18 persons (0.97%). Partial inversion was also detected in the C-band in chromosome 9 in 22 individuals (1.18%). In chromosome 16, neither total nor partial inversion of the C-band was observed in the present study. The frequencies of chromosomes 1, 9, and 16 with a very large C-band were 0.70%, 0.22%, and 0.54%, respectively. Aside from these (1, 9, and 16) a very large C-band was found occasionally in chromosomes 4, 5, 6, 11, 12, 14, and 15, and an unusual insertion of the Y chromosome was observed. A total of 128 C-band variants (6.89%) was found in the 1,857 Hiroshima residents. (author)

  19. Nanometer-scale elongation rate fluctuations in the Myriophyllum aquaticum (Parrot feather) stem were altered by radio-frequency electromagnetic radiation.

    Science.gov (United States)

    Senavirathna, Mudalige Don Hiranya Jayasanka; Asaeda, Takashi; Thilakarathne, Bodhipaksha Lalith Sanjaya; Kadono, Hirofumi

    2014-01-01

    The emission of radio-frequency electromagnetic radiation (EMR) by various wireless communication base stations has increased in recent years. While there is wide concern about the effects of EMR on humans and animals, the influence of EMR on plants is not well understood. In this study, we investigated the effect of EMR on the growth dynamics of Myriophyllum aquaticum (Parrot feather) by measuring the nanometric elongation rate fluctuation (NERF) using a statistical interferometry technique. Plants were exposed to 2 GHz EMR at a maximum of 1.42 Wm(-2) for 1 h. After continuous exposure to EMR, M. aquaticum plants exhibited a statistically significant 51 ± 16% reduction in NERF standard deviation. Temperature observations revealed that EMR exposure did not cause dielectric heating of the plants. Therefore, the reduced NERF was due to a non-thermal effect caused by EMR exposure. The alteration in NERF continued for at least 2.5 h after EMR exposure and no significant recovery was found in post-EMR NERF during the experimental period.

  20. Detection of chromosomal abnormality and Y chromosome microdeletion in patients with azoospermia and oligozoospermia

    Institute of Scientific and Technical Information of China (English)

    Shi Yun-fang; Shao Min-jie; Zhang Ying; Zhang Xiu-ling; Li Yan

    2008-01-01

    Objective:To investigate the chromosomal abnormality and Y chromosome microdeletion in patients with azoospermia and oligozoospermia.Methods:Cytogenetic karyotype analysis and multiplex PCR were used to detect chromosomal abnormality and Y chromosome microdeletion in 99 azoospermic and 57 oligospermic patients(total 156).45 fertile men were includ-ed as controls.Results:31 patients were found with chromosomal abnormalities in 156 cases(31/156,19.9 %),20 cases showed 47,XXY,2 cases showed 46,XY/47,XXY,7 cases had Y chromosome structural abnormalities and 2 had autosomal chromosome abnormalities.There were significant differences between the frequency of AZF microde-letion in 125 cases with normal karyotype and 45 controls(P0.05).AZFa,AZFb,AZFa+b,AZFb+c,AZFa+b+d and AZFb+c+d mierodeletions were found in azoospermic patients.AZFb,AZFc,AZFd,AZFb+c+d and AZFc+d microdeletions were found in oligo-spermic patients.Conxlusion:The frequency of chromosomal abnormality was 19.9% and the frequency of Y chromosome mi-crodeletion was 15.2% in patient with azoospermia and oligozoospermia.We should pay close attention to this prob-lem.

  1. Chromatin structure and ionizing-radiation-induced chromosome aberrations

    International Nuclear Information System (INIS)

    The possible influence of chromatic structure or activity on chromosomal radiosensitivity was studied. A cell line was isolated which contained some 105 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 G0, 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

  2. PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms.

    Science.gov (United States)

    Gisselsson, D; Hibbard, M K; Dal Cin, P; Sciot, R; Hsi, B L; Kozakewich, H P; Fletcher, J A

    2001-09-01

    Lipoblastomas are rare soft tissue tumors that occur primarily in young children. They typically contain variably differentiated adipocytes, primitive mesenchymal cells, myxoid matrix, and fibrous trabeculae. Abnormalities in chromosome 8, leading to rearrangements of the PLAG1 gene, were demonstrated recently in four lipoblastomas. In the present report, we determine the frequency of PLAG1 alterations in 16 lipoblastomas from children aged 13 years or younger, and we also evaluate the stages of lipoblastoma differentiation at which PLAG1 genomic alterations are found. Eleven lipoblastomas (69%), including those with either classic or lipoma-like histology, had rearrangements of the 8q12 PLAG1 region. Another three lipoblastomas had polysomy for chromosome 8 in the absence of PLAG1 rearrangement. Only two cases (13%) lacked a chromosome 8 abnormality. Notably, the lipoblastomas with chromosome 8 polysomy had up to five copies of chromosome 8 as an isolated cytogenetic finding in an otherwise diploid cell. We also demonstrate that PLAG1 alterations are found in a spectrum of mesenchymal cell types in lipoblastomas, including lipoblasts, mature adipocytes, primitive mesenchymal cells, and fibroblast-like cells. This finding is consistent with neoplastic origin in a primitive mesenchymal precursor and with variable differentiation to a mature adipocyte end-point. Hence, our studies provide biological validation for the clinical observation that lipoblastomas can evolve into mature, lipoma-like, lesions. They also suggest that PLAG1 dosage alterations caused by polysomy 8 might represent an alternative oncogenic mechanism in lipoblastoma.

  3. Radiation-induced chromosomal instability

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-03-01

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

  4. Chromosomal abnormalities in patients with sperm disorders

    Directory of Open Access Journals (Sweden)

    L. Y. Pylyp

    2013-02-01

    Full Text Available Chromosomal abnormalities are among the most common genetic causes of spermatogenic disruptions. Carriers of chromosomal abnormalities are at increased risk of infertility, miscarriage or birth of a child with unbalanced karyotype due to the production of unbalanced gametes. The natural selection against chromosomally abnormal sperm usually prevents fertilization with sperm barring in cases of serious chromosomal abnormalities. However, assisted reproductive technologies in general and intracytoplasmic sperm injection in particular, enable the transmission of chromosomal abnormalities to the progeny. Therefore, cytogenetic studies are important in patients with male factor infertility before assisted reproduction treatment. The purpose of the current study was to investigate the types and frequencies of chromosomal abnormalities in 724 patients with infertility and to estimate the risk of chromosomal abnormalities detection in subgroups of patients depending on the severity of spermatogenic disruption, aiming at identifying groups of patients in need of cytogenetic studies. Karyotype analysis was performed in 724 blood samples of men attending infertility clinic. Chromosomal preparation was performed by standard techniques. At least 20 GTG-banded metaphase plates with the resolution from 450 to 750 bands per haploid set were analysed in each case. When chromosomal mosaicism was suspected, this number was increased to 50. Abnormal karyotypes were observed in 48 (6.6% patients, including 67% of autosomal abnormalities and 33% of gonosomal abnormalities. Autosomal abnormalities were represented by structural rearrangements. Reciprocal translocations were the most common type of structural chromosomal abnormalities in the studied group, detected with the frequency of 2.6% (n = 19, followed by Robertsonian translocation, observed with the frequency of 1.2% (n = 9. The frequency of inversions was 0.6% (n = 4. Gonosomal abnormalities included 14 cases

  5. Temporary alterations to postpartum milking frequency affect whole-lactation milk production and the energy status of pasture-grazed dairy cows.

    Science.gov (United States)

    Phyn, C V C; Kay, J K; Rius, A G; Morgan, S R; Roach, C G; Grala, T M; Roche, J R

    2014-11-01

    This study investigated the immediate and long-term effects of temporary alterations to postpartum milking frequency (MF) on milk production, body condition score (BCS), and indicators of energy status in pasture-grazed cows supplemented with concentrates. Multiparous Holstein-Friesian cows (n = 150) were randomly assigned to 1 of 5 groups at calving: milked twice daily (2 ×) throughout lactation (control), or milked either once daily (1 ×) or 3 times daily (3 ×) for 3 or 6 wk immediately postpartum, and then 2 × for the remainder of lactation. During wk 1 to 3 postpartum, cows milked 1 × produced 15% less milk and 17% less energy-corrected milk (ECM) than cows milked 2 ×. This immediate production loss increased to 20% less milk and 22% less ECM during wk 4 to 6 postpartum for cows that remained on 1 × milking; these animals also produced less than 1 × cows switched to 2 × milking after 3 wk. During wk 8 to 32, when all cows were milked 2 ×, those previously milked 1 × had sustained reductions in milk (-6%) and ECM (-8%) yields, which were not affected by the duration of reduced postpartum MF. In contrast, cows milked 3 × postpartum had 7% greater milk yields during wk 1 to 6 compared with 2 × controls, irrespective of the duration of increased MF. Milk yields also remained numerically greater (+5%) during wk 8 to 32 in cows previously milked 3 ×. Nevertheless, yields of ECM were not increased by 3 × milking, because of lower milk fat and protein contents that persisted for the rest of lactation. In addition, indicators of cow energy status reflected an increasing state of negative energy balance with increasing MF. Cows milked 1 × postpartum had greater plasma glucose and lower plasma nonesterified fatty acid concentrations during the reduced MF, and plasma glucose remained lower for 2 wk after cows had switched to 2 × milking. Moreover, BCS was improved relative to 2 × controls from wk 5 to 6. In contrast, cows milked 3 × had lower plasma

  6. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

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

    2012-11-01

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

  7. Y chromosome microdeletions in Turkish infertile men

    OpenAIRE

    Zamani Ayse; Kutlu Ruhusen; Durakbasi-Dursun H; Gorkemli Huseyin; Acar Aynur

    2006-01-01

    AIMS: To detect the frequency and types of both chromosomal abnormalities and Y chromosome microdeletions in infertile men attending to our university intracytoplasmic sperm injection ICSI/IVF centre and fertile control subjects in our patient population. SETTINGS AND DESIGN: A total of 50 infertile men who were referred to IVF center of Meram medical faculty were selected for the molecular azospermia factor (AZF) screening program. MATERIALS AND METHODS: Karyotype analysis and polymeras...

  8. Adaptation through chromosomal inversions in Anopheles

    Directory of Open Access Journals (Sweden)

    Diego eAyala

    2014-05-01

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

  9. Nonrandom involvement of chromosomal segments in human hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J. D.

    1977-01-01

    The consistent occurrence of nonrandom chromosome changes in human malignancies suggests that they are not trivial epiphenomena. Whereas we do not understand their significance at present, one possible role which they may fulfill is to provide the chromosomally aberrant cells with a proliferative advantage as the result of alteration of the number and/or location of genes related to nucleic acid biosynthesis. It would be expected that the proliferative advantage provided by various chromosome aberrations differs in patients with different genetic constitutions.

  10. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    Directory of Open Access Journals (Sweden)

    Maria Maurer

    2015-07-01

    Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

  11. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology.

    Science.gov (United States)

    Qaddoumi, Ibrahim; Orisme, Wilda; Wen, Ji; Santiago, Teresa; Gupta, Kirti; Dalton, James D; Tang, Bo; Haupfear, Kelly; Punchihewa, Chandanamali; Easton, John; Mulder, Heather; Boggs, Kristy; Shao, Ying; Rusch, Michael; Becksfort, Jared; Gupta, Pankaj; Wang, Shuoguo; Lee, Ryan P; Brat, Daniel; Peter Collins, V; Dahiya, Sonika; George, David; Konomos, William; Kurian, Kathreena M; McFadden, Kathryn; Serafini, Luciano Neder; Nickols, Hilary; Perry, Arie; Shurtleff, Sheila; Gajjar, Amar; Boop, Fredrick A; Klimo, Paul D; Mardis, Elaine R; Wilson, Richard K; Baker, Suzanne J; Zhang, Jinghui; Wu, Gang; Downing, James R; Tatevossian, Ruth G; Ellison, David W

    2016-06-01

    Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and 'adult-type' diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials. PMID:26810070

  12. 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...

  13. Chromosome Disorder Outreach

    Science.gov (United States)

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

  14. Cytological alteration of cultured rat liver cells by 3'-methyl-4-dimethylaminoazobenzene with special reference to chromosome changes, changes of growth patterns at a colony level and alpha-fetoprotein production.

    Directory of Open Access Journals (Sweden)

    Tokiwa,Takayoshi

    1980-06-01

    Full Text Available A near diploid clone derived from a rat liver cell line was continuously treated with various concentrations of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB in culture. By treatment with 2.8 micrograms/ml, cells with 41 chromosomes formed a mode and which then shifted to 39. The chromosome numbers of cells treated with 5.4 micrograms/ml were widely distributed at early stages, but later the mode shifted to hypotetraploid region. Untreated control cells were confirmed as near diploid. Increased plating efficiency by 3'-Me-DAB as well as the appearance of large sized colonies was obtained. The production of alpha-fetoprotein (AFP by the cells was slightly enhanced by treatment with 3'-Me-DAB. The cells treated with and without 3'-Me-DAB did not produce any tumor in rats 6 months after their intraperitoneal injection.

  15. High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation.

    NARCIS (Netherlands)

    Jehee, F.S.; Krepischi-Santos, A.C.; Rocha, K.M.; Cavalcanti, D.P.; Kim, C.A.; Bertola, D.R.; Alonso, L.G.; D'Angelo, C.S.; Mazzeu, J.F.; Froyen, G.; Lugtenberg, D.; Vianna-Morgante, A.M.; Rosenberg, C.; Passos-Bueno, M.R.

    2008-01-01

    We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric

  16. ZEBRAFISH CHROMOSOME-BANDING

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1995-01-01

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

  17. Chromosome painting in plants.

    NARCIS (Netherlands)

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

    2001-01-01

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

  18. Meiotic chromosomal variation resulting from irradiation of pollen in maize

    International Nuclear Information System (INIS)

    The objective of this study was to standardize an induction strategy of chromosome aberrations in maize inbred line L-869. Pollen grains irradiated with 0, 36 and 72 Gy were used for fertilization. Resulting seeds were planted in a greenhouse to assess the number of abnormal meiotic cells. Germination, height, sterility and mortality were verified. Cells with delayed separation of chromosomes, translocation, deficiency, abnormal pairing, later condensation and anaphase bridges were observed. The number of abnormalities increased as the dosage increased but chromosome aberration types were the same regardless of the dosages used. Various chromosome-altered plants were obtained without viability loss. (author)

  19. Antiviral Treatment Alters the Frequency of Activating and Inhibitory Receptor-Expressing Natural Killer Cells in Chronic Hepatitis B Virus Infected Patients

    Directory of Open Access Journals (Sweden)

    Juan Lv

    2012-01-01

    Full Text Available Natural killer (NK cells play a critical role in innate antiviral immunity, but little is known about the impact of antiviral therapy on the frequency of NK cell subsets. To this aim, we performed this longitudinal study to examine the dynamic changes of the frequency of different subsets of NK cells in CHB patients after initiation of tenofovir or adefovir therapy. We found that NK cell numbers and subset distribution differ between CHB patients and normal subjects; furthermore, the association was found between ALT level and CD158b+ NK cell in HBV patients. In tenofovir group, the frequency of NK cells increased during the treatment accompanied by downregulated expression of NKG2A and KIR2DL3. In adefovir group, NK cell numbers did not differ during the treatment, but also accompanied by downregulated expression of NKG2A and KIR2DL3. Our results demonstrate that treatment with tenofovir leads to viral load reduction, and correlated with NK cell frequencies in peripheral blood of chronic hepatitis B virus infection. In addition, treatments with both tenofovir and adefovir in chronic HBV infected patients induce a decrease of the frequency of inhibitory receptor+ NK cells, which may account for the partial restoration of the function of NK cells in peripheral blood following treatment.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-01-01

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

  1. Low-frequency electromagnetic fields do not alter responses of inflammatory genes and proteins in human monocytes and immune cell lines

    NARCIS (Netherlands)

    Bouwens, M.; Kleijn, de S.; Cuppen, J.J.M.; Savelkoul, H.F.J.; Verburg-van Kemenade, B.M.L.

    2012-01-01

    The effects of low frequency electromagnetic fields (LF EMF) on human health are the subject of on-going research and serious public concern. These fields potentially elicit small effects that have been proposed to have consequences, either positive or negative, for biological systems. To reveal pot

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

    Directory of Open Access Journals (Sweden)

    Ogilvie Caroline

    2008-06-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  4. Non-disjunction of chromosome 18

    DEFF Research Database (Denmark)

    Bugge, M; Collins, A; Petersen, M B;

    1998-01-01

    A sample of 100 trisomy 18 conceptuses analysed separately and together with a published sample of 61 conceptuses confirms that an error in maternal meiosis II (MII) is the most frequent cause of non-disjunction for chromosome 18. This is unlike all other human trisomies that have been studied......, which show a higher frequency in maternal meiosis I (MI). Maternal MI trisomy 18 shows a low frequency of recombination in proximal p and medial q, but not the reduction in proximal q observed in chromosome 21 MI non-disjunction. Maternal MII non-disjunction does not fit the entanglement model...... that predicts increased recombination, especially near the centromere. Whereas recent data on MII trisomy 21 show the predicted increase in recombination proximally, maternal MII trisomy 18 has non-significantly reduced recombination. Therefore, chromosome-specific factors must complicate the simple model...

  5. The Precarious Prokaryotic Chromosome

    OpenAIRE

    Kuzminov, Andrei

    2014-01-01

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

  6. ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot

    OpenAIRE

    Jiying Sun; Yukako Oma; Masahiko Harata; Kazuteru Kono; Hiroki Shima; Aiko Kinomura; Tsuyoshi Ikura; Hidekazu Suzuki; Shuki Mizutani; Roland Kanaar; Satoshi Tashiro

    2010-01-01

    textabstractChromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the m...

  7. Ring chromosome 13

    DEFF Research Database (Denmark)

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

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...... with the probe L1.26 confirmed the derivation from chromosome 13 and DNA polymorphism analysis showed maternal origin of the ring chromosome. Our results, together with a review of previous reports of cases with ring chromosome 13 with identified breakpoints, could neither support the theory of distinct clinical...

  8. Small Supernumerary Marker Chromosomes in Human Infertility.

    Science.gov (United States)

    Armanet, Narjes; Tosca, Lucie; Brisset, Sophie; Liehr, Thomas; Tachdjian, Gérard

    2015-01-01

    Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be unambiguously identified by banding cytogenetics. The objective of this study was to provide an overview of sSMC frequency and characterization in a context of infertility and to review the literature describing sSMC in relation with male and female infertility. Therefore, a systematic literature review on sSMC associated with infertility was conducted by means of a PubMed literature and a sSMC database (http://ssmc-tl.com/sSMC.html) search. A total of 234 patients with infertility were identified as carriers of sSMC. All chromosomes, except chromosomes 10, 19 and the X, were involved in sSMC, and in 72% the sSMC originated from acrocentric chromosomes. Euchromatic imbalances were caused by the presence of sSMC in 30% of the cases. Putative genes have been identified in only 1.2% of sSMC associated with infertility. The implication of sSMC in infertility could be due to a partial trisomy of some genes but also to mechanical effects perturbing meiosis. Further precise molecular and interphase-architecture studies on sSMC are needed in the future to characterize the relationship between this chromosomal anomaly and human infertility.

  9. The Meiotic Behavior of an Alien Chromosome in Triticum aestivum-Haynaldia villosa Monosomic Addition Lines

    Institute of Scientific and Technical Information of China (English)

    LI Rui-fen; LIANG Hong-xia; ZHAO Mao-lin

    2002-01-01

    By the combination of cytological analysis and using genomic in situ hybridization technique to identify an alien chromosome in wheat-Haynaldia villosa monosomic addition lines, we studied the meiotic behavior of the alien chromosome. The results indicated that the frequency of bivalent pairing was lower than the value expected in PMCs of two monosomic addition lines, the frequency of wheat chromosomes unpairing increased, and the wheat homologous chromosome pairing was interfered with by the added chromosome 6V at metaphase I. The chromosome 6V lagged in 20.3% -29.3% of PMCs, sister chromatids 6V early divided in 29.0% - 34.1% of PMCs, the single chromosome 6V in 18.2% - 26.1% of PMCs went to a pole randomly,the breakage frequency of chromosome 6V was 1.2% - 2.9%. Meanwhile, it was also found that several wheat chromosomes showed earlier division, lagging and breakage in a few PMCs. It revealed that the added chromosome 6V influenced the behavior of wheat chromosomes at anaphase. It was also found that the translocation was produced between 6V and wheat chromosomes in 1.2% of PMCs. It offered evidence for translocation between wheat and Haynaldia villosa 6V chromosomes.

  10. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli;

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two chromoso...

  11. Meiotic behaviour of individual chromosomes in allotriploid Alstroemeria hybrids.

    Science.gov (United States)

    Kamstra, S A; de Jong, J H; Jacobsen, E; Ramanna, M S; Kuipers, A G J

    2004-07-01

    Chromosome association and chiasma formation were studied in pollen mother cells at metaphase I of four allotriplod BC1 plants (2n=3x=24) obtained from the backcross of the hybrid Alstroemeria aurea x A. inodora with its parent A. inodora. We distinguished the chromosomes of both parental species by genomic in situ hybridization (GISH), whereas the individual chromosomes were identified on the basis of their multicolour FISH banding patterns obtained after a second hybridization with two species-specific satellite repeats as probes. All the four BC1 plants possessed two genomes of A. inodora and one of A. aurea. Variable numbers of recombinant chromosomes, resulting from meiotic recombination in the interspecific hybrid, were present in these plants. The homologous A. inodora chromosomes generally formed bivalents, leaving the homoeologous A. aurea chromosomes unassociated. High frequencies of trivalents were observed for the chromosome sets that contained recombinant chromosomes, even when the recombinant segments were small. Chromosome associations in the trivalents were restricted to homologous segments. The implications of the absence of homoeologous chromosome pairing on gamete constitution and prospects for introgression in Alstroemeria are discussed. PMID:15100711

  12. lck-Driven Cre Expression Alters T Cell Development in the Thymus and the Frequencies and Functions of Peripheral T Cell Subsets.

    Science.gov (United States)

    Carow, Berit; Gao, Yu; Coquet, Jonathan; Reilly, Marie; Rottenberg, Martin E

    2016-09-15

    Conditional gene targeting using the bacteriophage-derived Cre recombinase is widely applied for functional gene studies in mice. Mice transgenic for Cre under the control of the lck gene promoter are used to study the role of loxP-targeted genes in T cell development and function. In this article, we show a striking 65% reduction in cellularity, preferential development of γδ versus αβ T cells, and increased expression of IL-7R in the thymus of mice expressing Cre under the proximal lck promoter (lck-cre(+) mice). The transition from CD4/CD8 double-negative to double-positive cells was blocked, and lck-cre(+) double-positive cells were more prone to apoptosis and showed higher levels of Cre expression. Importantly, numbers of naive T cells were reduced in spleens and lymph nodes of lck-cre(+) mice. In contrast, frequencies of γδ T cells, CD44(+)CD62L(-) effector T cells, and Foxp3(+) regulatory T cells were elevated, as was the frequency of IFN-γ-secreting CD4(+) and CD8(+) T cells. A literature survey of 332 articles that used lck-cre(+) mice for deletion of floxed genes indicated that results are statistically influenced by the control used (lck-cre(+) or lck-cre(-)), more frequently resembling the lck-cre(+) phenotype described in this article if lck-cre(-) controls were used. Altogether, care should be taken when interpreting published results and to properly control targeted gene deletions using the lck-cre(+) strain. PMID:27503210

  13. The fragile Y hypothesis: Y chromosome aneuploidy as a selective pressure in sex chromosome and meiotic mechanism evolution.

    Science.gov (United States)

    Blackmon, Heath; Demuth, Jeffery P

    2015-09-01

    Loss of the Y-chromosome is a common feature of species with chromosomal sex determination. However, our understanding of why some lineages frequently lose Y-chromosomes while others do not is limited. The fragile Y hypothesis proposes that in species with chiasmatic meiosis the rate of Y-chromosome aneuploidy and the size of the recombining region have a negative correlation. The fragile Y hypothesis provides a number of novel insights not possible under traditional models. Specifically, increased rates of Y aneuploidy may impose positive selection for (i) gene movement off the Y; (ii) translocations and fusions which expand the recombining region; and (iii) alternative meiotic segregation mechanisms (achiasmatic or asynaptic). These insights as well as existing evidence for the frequency of Y-chromosome aneuploidy raise doubt about the prospects for long-term retention of the human Y-chromosome despite recent evidence for stable gene content in older non-recombining regions.

  14. Wpkci, Encoding an Altered Form of PKCI, Is Conserved Widely on the Avian W Chromosome and Expressed in Early Female Embryos: Implication of Its Role in Female Sex Determination

    OpenAIRE

    Hori, Tetsuya; Asakawa, Shuichi; Itoh, Yuichiro; Shimizu, Nobuyoshi; Mizuno, Shigeki

    2000-01-01

    Two W chromosome–linked cDNA clones, p5fm2 and p5fm3, were obtained from a subtracted (female minus male) cDNA library prepared from a mixture of undifferentiated gonads and mesonephroi of male or female 5-d (stages 26–28) chicken embryos. These two clones were demonstrated to be derived from the mRNA encoding an altered form of PKC inhibitor/interacting protein (PKCI), and its gene was named Wpkci. The Wpkci gene reiterated ∼40 times tandemly and located at the no...

  15. Diffusing Polymers in Confined Microdomains and Estimation of Chromosomal Territory Sizes from Chromosome Capture Data

    Science.gov (United States)

    Amitai, A.; Holcman, D.

    2013-06-01

    Is it possible to extract the size and structure of chromosomal territories (confined domain) from the encounter frequencies of chromosomal loci? To answer this question, we estimate the mean time for two monomers located on the same polymer to encounter, which we call the mean first encounter time in a confined microdomain (MFETC). We approximate the confined domain geometry by a harmonic potential well and obtain an asymptotic expression that agrees with Brownian simulations for the MFETC as a function of the polymer length, the radius of the confined domain, and the activation distance radius ɛ at which the two searching monomers meet. We illustrate the present approach using chromosome capture data for the encounter rate distribution of two loci depending on their distances along the DNA. We estimate the domain size that restricts the motion of one of these loci for chromosome II in yeast.

  16. Plasmid-Chromosome Recombination of Irradiated Shuttle Vector DNA in African Green Monkey Kidney Cells.

    Science.gov (United States)

    Mudgett, John Stuart

    1987-09-01

    An autonomously replicating shuttle vector was used to investigate the enhancement of plasmid-chromosome recombination in mammalian host cells by ultraviolet light and gamma radiation. Sequences homologous to the shuttle vector were stably inserted into the genome of African Green Monkey kidney cells to act as the target substrate for these recombination events. The SV40- and pBR322-derived plasmid DNA was irradiated with various doses of radiation before transfection into the transformed mammalian host cells. The successful homologous transfer of the bacterial ampicillin resistance (amp^{rm r}) gene from the inserted sequences to replace a mutant amp^->=ne on the shuttle vector was identified by plasmid extraction and transformation into E. coli host cells. Ultraviolet light (UV) was found not to induce homologous plasmid-chromosome recombination, while gamma radiation increased the frequency of recombinant plasmids detected. The introduction of specific double -strand breaks in the plasmid or prolonging the time of plasmid residence in the mammalian host cells also enhanced plasmid-chromosome recombination. In contrast, plasmid mutagenesis was found to be increased by plasmid UV irradiation, but not to change with time. Plasmid survival, recombination, and mutagenesis were not affected by treating the mammalian host cells with UV light prior to plasmid transfection. The amp^{rm r} recombinant plasmid molecules analyzed were found to be mostly the result of nonconservative exchanges which appeared to involve both homologous and possibly nonhomologous interactions with the host chromosome. The observation that these recombinant structures were obtained from all of the plasmid alterations investigated suggests a common mechanistic origin for plasmid -chromosome recombination in these mammalian cells.

  17. Peripheral drive in Aα/β-fiber neurons is altered in a rat model of osteoarthritis: changes in following frequency and recovery from inactivation

    Directory of Open Access Journals (Sweden)

    Wu Q

    2013-03-01

    Full Text Available Qi Wu, James L HenryDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, CanadaPurpose: To determine conduction fidelity of Aα/β-fiber low threshold mechanoreceptors in a model of osteoarthritis (OA.Methods: Four weeks after cutting the anterior cruciate ligament and removing the medial meniscus to induce the model, in vivo intracellular recordings were made in ipsilateral L4 dorsal root ganglion neurons. L4 dorsal roots were stimulated to determine the refractory interval and the maximum following frequency of the evoked action potential (AP. Neurons exhibited two types of response to paired pulse stimulation. Results: One type of response was characterized by fractionation of the evoked AP into an initial nonmyelinated-spike and a later larger-amplitude somatic-spike at shorter interstimulus intervals. The other type of response was characterized by an all-or-none AP, where the second evoked AP failed altogether at shorter interstimulus intervals. In OA versus control animals, the refractory interval measured in paired pulse testing was less in all low threshold mechanoreceptors. With train stimulation, the maximum rising rate of the nonmyelinated-spike was greater in OA nonmuscle spindle low threshold mechanoreceptors, possibly due to changes in fast kinetics of currents. Maximum following frequency in Pacinian and muscle spindle neurons was greater in model animals compared to controls. Train stimulation also induced an inactivation and fractionation of the AP in neurons that showed fractionation of the AP in paired pulse testing. However, with train stimulation this fractionation followed a different time course, suggesting more than one type of inactivation.Conclusion: The data suggest that joint damage can lead to changes in the fidelity of AP conduction of large diameter sensory neurons, muscle spindle neurons in particular, arising from articular and nonarticular tissues in OA animals compared to

  18. Sequential cloning of chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, S.A.

    1991-12-31

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

  19. CHROMOSOMES OF AMERICAN MARSUPIALS.

    Science.gov (United States)

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

    1965-06-18

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

  20. Chromosome aberrations in pesticide-exposed greenhouse workers

    DEFF Research Database (Denmark)

    Lander, B F; Knudsen, Lisbeth E.; Gamborg, M O;

    2000-01-01

    OBJECTIVES: The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. METHODS: In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116...... greenhouse workers exposed to a complex mixture of almost 50 insecticides, fungicides, and growth regulators and also for 29 nonsmoking, nonpesticide-exposed referents. RESULTS: The preseason frequencies of chromosome aberrations were slightly but not statistically significantly elevated for the greenhouse...... workers when they were compared with the referents. After a summer season of pesticide spraying in the greenhouses, the total frequencies of cells with chromosome aberrations were significantly higher than in the preseason samples (P=0.02) and also higher than for the referents (P=0.05). This finding...

  1. The buccal cytome and micronucleus frequency is substantially altered in Down's syndrome and normal ageing compared to young healthy controls

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Philip [CSIRO Human Nutrition, PO Box 10041, Adelaide BC, Adelaide, SA 5000 (Australia); Discipline of Physiology, School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, SA 5005 (Australia)], E-mail: philip.thomas@csiro.au; Harvey, Sarah; Gruner, Tini [Southern Cross University, PO Box 157, Lismore, NSW 2480 (Australia); Fenech, Michael [CSIRO Human Nutrition, PO Box 10041, Adelaide BC, Adelaide, SA 5000 (Australia)], E-mail: michael.fenech@csiro.au

    2008-02-01

    The buccal micronucleus cytome assay was used to investigate biomarkers for DNA damage, cell death and basal cell frequency in buccal cells of healthy young, healthy old and young Down's syndrome cohorts. With normal ageing a significant increase in cells with micronuclei (P < 0.05, average increase +366%), karyorrhectic cells (P < 0.001, average increase +439%), condensed chromatin cells (P < 0.01, average increase +45.8%) and basal cells (P < 0.001, average increase +233%) is reported relative to young controls. In Down's syndrome we report a significant increase in cells with micronuclei (P < 0.001, average increase +733%) and binucleated cells (P < 0.001, average increase +84.5%) and a significant decrease in condensed chromatin cells (P < 0.01, average decrease -52%), karyolytic cells (P < 0.001, average decrease -51.8%) and pyknotic cells (P < 0.001, average decrease -75.0%) relative to young controls. These changes show distinct differences between the cytome profile of normal ageing relative to that for a premature ageing syndrome, and highlight the diagnostic value of the cytome approach for measuring the profile of cells with DNA damage, cell death and proportion of cells with proliferative potential (i.e., basal cells). Significant correlations amongst cell death biomarkers observed in this study were used to propose a new model of the inter-relationship of cell types scored within the buccal micronucleus cytome assay. This study validates the use of a cytome approach to investigate DNA damage, cell death and cell proliferation in buccal cells with ageing.

  2. Mathematical Modeling of Carcinogenesis Based on Chromosome Aberration Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-bo Li

    2009-01-01

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

  3. Chromosomal replicons of higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Van' t Hof, J.

    1987-03-16

    This brief discussion of replicons of higher plants offers a glimpse into the properties of chromosomal DNA replication. It gives evidence that the S phase of unrelated plant species is comprised of temporally ordered replicon families that increase in number with genome size. This orderly process, which assures a normal inheritance of genetic material to recipient daughter cells, is maintained at the level of replicon clusters by two mutually exclusive mechanisms, one involving the rate at which single replicons replicate their allotment of DNA, and another by means of the tempo-pause. The same two mechanisms are used by cells to alter the pattern of chromosomal DNA replication just prior to and during normal development. Both mechanisms are genetically determined and produce genetic effects when disturbed of disrupted by additional non-conforming DNAs. Further insight into how these two mechanisms operate requires more molecular information about the nature of replicons and the factors that govern when a replicon family replicates. Plant material is a rich and ideal source for this information just awaiting exploitation. 63 refs.

  4. Why it is crucial to analyze non clonal chromosome aberrations or NCCAs?

    Science.gov (United States)

    Heng, Henry H Q; Regan, Sarah M; Liu, Guo; Ye, Christine J

    2016-01-01

    Current cytogenetics has largely focused its efforts on the identification of recurrent karyotypic alterations, also known as clonal chromosomal aberrations (CCAs). The rationale of doing so seems simple: recurrent genetic changes are relevant for diseases or specific physiological conditions, while non clonal chromosome aberrations (NCCAs) are insignificant genetic background or noise. However, in reality, the vast majority of chromosomal alterations are NCCAs, and it is challenging to identify commonly shared CCAs in most solid tumors. Furthermore, the karyotype, rather than genes, represents the system inheritance, or blueprint, and each NCCA represents an altered genome system. These realizations underscore the importance of the re-evaluation of NCCAs in cytogenetic analyses. In this concept article, we briefly review the definition of NCCAs, some historical misconceptions about them, and why NCCAs are not insignificant "noise," but rather a highly significant feature of the cellular population for providing genome heterogeneity and complexity, representing one important form of fuzzy inheritance. The frequencies of NCCAs also represent an index to measure both internally- and environmentally-induced genome instability. Additionally, the NCCA/CCA cycle is associated with macro- and micro-cellular evolution. Lastly, elevated NCCAs are observed in many disease/illness conditions. Considering all of these factors, we call for the immediate action of studying and reporting NCCAs. Specifically, effort is needed to characterize and compare different types of NCCAs, to define their baseline in various tissues, to develop methods to access mitotic cells, to re-examine/interpret the NCCAs data, and to develop an NCCA database. PMID:26877768

  5. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

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

  6. Chromosome condensation and segmentation

    International Nuclear Information System (INIS)

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

  7. Chromosomal Abnormalties with Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available The correlation between specific chromosome abnormalties and various epilepsies was investigated by a study of 76 patients’ records obtained by questionnaires distributed to members of Kyoto Multi-institutional Study Group of Pediatric Neurology.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-01-01

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

  9. Chromosome doubling method

    Science.gov (United States)

    Kato, Akio

    2006-11-14

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

  10. Microchimeric Cells, Sex Chromosome Aneuploidies and Cancer.

    Science.gov (United States)

    Korkmaz, Deniz Taştemir; Demirhan, Osman; Abat, Deniz; Demirberk, Bülent; Tunç, Erdal; Kuleci, Sedat

    2015-09-01

    The phenomenon of feta-maternal microchimerisms inspires numerous questions. Many questions remain to be answered regarding this new avenue of genetics. The X and Y chromosomes have been associated with malignancy in different types of human tumors. We aimed to investigate the numerical aberrations of chromosomes X and Y in lung cancer (LC) and bladder cancer (BC) and review recent evidence for possible roles of microchimeric cells (McCs) in these cancers. We carried out cytogenetic analysis of the tumor and blood sampling in 52 cases of people with BC and LC, and also with 30 healthy people. A total of 48 (92.3 %) of the patients revealed sex chromosome aneuploidies (SCAs). A total SCAs was found in 9.8 % of 2282 cells that were analyzed as one or more cells in each case. The 68 and 95 SCAs were found in the 1952 (8.4 %) cells in peripheral blood, and 41 and 19 SCAs in the 330 (18.2 %) cells in the tumoral tissues respectively. There was a significant difference in the frequencies of SCAs between the patients and the control groups determined by the Fischer's Exact Test (p chromosome monosomies. Largely a Y chromosome loss was present in 77.8 % of the men, and the 47, XXY karyotype was found in 33.3 % of them. The second most common SCA was monosomy X, and was found in 71.4 % of the women. McCs were observed in 26.9 % of the 52 patients, and the frequencies of McCs were higher in the blood than in the tissues (p aneuploidies of X and Y chromosomes play a role in the pathogenesis of cancers.

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

    International Nuclear Information System (INIS)

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

  12. Micromechanics of human mitotic chromosomes

    International Nuclear Information System (INIS)

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

  13. Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Silva Veiga, L.C. [Departamento de Genética, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP (Brazil); Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Bérgamo, N.A. [Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, GO (Brazil); Reis, P.P. [Departamento de Cirurgia e Ortopedia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP (Brazil); Kowalski, L.P. [Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, Hospital A.C. Camargo, São Paulo, SP (Brazil); Rogatto, S.R. [Laboratório NeoGene, Departamento de Urologia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP (Brazil); Departamento de Pesquisa, Hospital A.C. Camargo,Fundação Antônio Prudente, São Paulo, SP (Brazil)

    2012-01-20

    Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas.

  14. Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

    International Nuclear Information System (INIS)

    Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas

  15. Y chromosome microdeletions in Turkish infertile men

    Directory of Open Access Journals (Sweden)

    Zamani Ayse

    2006-01-01

    Full Text Available AIMS: To detect the frequency and types of both chromosomal abnormalities and Y chromosome microdeletions in infertile men attending to our university intracytoplasmic sperm injection ICSI/IVF centre and fertile control subjects in our patient population. SETTINGS AND DESIGN: A total of 50 infertile men who were referred to IVF center of Meram medical faculty were selected for the molecular azospermia factor (AZF screening program. MATERIALS AND METHODS: Karyotype analysis and polymerase chain reaction amplification using 15 Y-specific sequence-tagged sites of AZF region were done. RESULTS: The total prevalence of chromosomal abnormalities was found to be 10% (5/50, including 4 patients with numerical and 1 patient with structural abnormalities. Overall, 4 of the 50 patients tested (8% exhibited deletions of the Y chromosome, 3 of them being azospermic and 1 of them oligospermic men. The frequency of the microdeletions in subgroups with azospermia and oligozoospermia was found to be 10.7% (3/29 and 4.7% (1/21 respectively. Microdeletions of AZFb and AZFc regions were detected in all of the 4 patients. Neither AZFa nor AZFd microdeletions were indicated. CONCLUSIONS: Our findings suggest that one must know whether there is a genetic cause for male infertility before patients can be subjected to ISCI or testicular sperm extraction (TESE/ISCI treatment.

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To analyse the microsatellite instability (MI) and loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). Methods: MI and LOH at chromosome 17 were checked in 35 cases of NSCLC tumor-normal paired tissues using four microsatellite markers TP53 (17p13.1), THRA1 (17q11.2-12), D17S579 (17q12-21) and D17S855 (17q21) by PCR based analysis. Mutations of P53 exons 5-8 were also tested using PCR-single strand conformation polymorphism (PCR-SSCP) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis. Results: 22 of 35 tumors (62.8%) displayed MI or LOH. 14 tumors (40.0%) exhibited MI, 11 tumors (31.4%) exhibited LOH, while 3 tumors (8.6%) exhibited MI and LOH concurrently. 23 tumors (65.7%) exhibited P53 gene mutations. The frequency of MI or LOH was obviously higher in the early-stage (stages I and II, 78.9%) than in the advanced-stage (stage III, 43.8%). However, the frequency of MI or LOH had no difference either between high-grade (75.0%) and low-grade (52.6%) differentiated NSCLC or between the tumors with P53 mutations (59.1%) and those without P53 mutations (69.2%). No relationship was observed between the presence of MI or LOH and the histologic subtype of NSCLC. Conclusion: The results suggest that MI and LOH at chromosome 17 may play a alterations on chromosome 17 in tumors of non-small cell lung cancer (NSCLC). In addition, studies reported contradictory results concerning the incidence of these alterations and the relationship between these genetic alterations and the clinical behavior of NSCLC. The aim of this study was to investigate the incidence of MI and LOH at chromosome 17 in tumors of patients with NSCLC and its association with clinical and histologic features of NSCLC.

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

    Directory of Open Access Journals (Sweden)

    Mohr Brigitte

    2003-01-01

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

  18. Alteration in frequency and function of CD4⁺CD25⁺FOXP3⁺ regulatory T cells in patients with immune thrombocytopenic purpura.

    Directory of Open Access Journals (Sweden)

    Nargess Arandi

    2014-04-01

    Full Text Available Immune thrombocytopenic purpura (ITP is an autoimmune bleeding disorder characterized by production of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs have a major role in controlling immune homeostasis and preventing autoimmunity.To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age- and sex-matched healthy controls were recruited. The peripheral blood mononuclear cells were isolated and the proportion of Tregs was defined by flow cytometry method. The expression of immune-regulatory markers, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4 and glucocorticoid induced tumor necrosis factor receptor (GITR were also assessed by quantitative Real-time PCR TaqMan method. For evaluation of Treg function, Tregs were enriched and their ability to inhibit proliferation of T cells was measured and levels of immune-regulatory cytokines IL-10 and TGF-β were also measured.Results showed that the frequency of Tregs and the mean fluorescence intensity of FOXP3 protein significantly decreased in ITP patients compared to those in healthy controls. In addition, there was a significant reduction in relative expression of both CTLA-4 and GITR mRNA in ITP patients (P=0.02 and P=0.006, respectively. The suppressive function of Tregs also diminished in ITP patients compared to that in controls. Both IL-10 and TGF-β cytokines were produced in lower amounts in ITP patients than controls.It could be concluded that alteration in Treg frequency and functional characteristics might be responsible for loss of self-tolerance and subsequently destructive immune responses observed in ITP patients.

  19. The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results

    Directory of Open Access Journals (Sweden)

    L. Migliore

    2011-09-01

    Full Text Available Objective: aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc or diffuse (dSSc Systemic Slerosis, using the micronucleus (MN assay. Methods: we evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile. Results: compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8±4.5 vs. 27.8±13.7, p<0.001. No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1±17.0 and 19.8±2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9±15.0, as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7±8.2. Conclusions: our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies.

  20. Loss of heterozygosity on chromosome 22 in sporadic schwannoma and its relation to the proliferation of tumor cells

    Institute of Scientific and Technical Information of China (English)

    BIAN Liu-guan; SUN Qing-fang; Tirakotai Wuttipong; ZHAO Wei-guo; SHEN Jian-kang; LUO Qi-zhong; Bertalanffy Helmut

    2005-01-01

    Background Schwannoma is the tumor arising mainly from the cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type 2 (NF2). The NF2 gene has been cloned with comprehensive analysis of its mutations in schwannoma. However, most studies focused on vestibular schwannoma. There are differences in proliferation of tumor cell and ultrastructure between vestibular and spinal schwannomas. It is unknown whether genetic alterations in vestibular schwannoma are different from those in non-vestibular schwannoma. We analyzed the loss of heterozygosity (LOH) on chromosome 22 in patients with sporadic schwannoma including vestibular and spinal schwannomas and correlated this genetic alteration with tumor proliferation. Methods In 54 unrelated patients without clinical NF1 or NF2, 36 patients had sporadic vestibular schwannoma, and 18 dorsal spinal root schwannoma. Four highly polymorphic linkage to NF2 gene microsatellite DNA markers (D22S264, D22S268, D22S280, CRYB2) were used to analyze LOH. The proliferative index was evaluated by Ki-67 and proliferative cell nuclear antigen (PCNA) immunostaining. Student's t test was used to analyze the difference of the proliferative index between schwannoma with LOH and that without LOH. The difference of the frequency of LOH in vestibular and spinal schwannomas was investigated by the chi-square test. Results Twenty-three schwannomas (42.6%, 23/54) showed allele loss. The frequency of LOH in vestibular schwannoma was significantly higher than that in spinal schwannoma (χ2=5.14, P<0.05). The proliferative index of schwannoma with LOH was significantly higher than that without LOH (tki-67=2.97, P=0.0045; tPCNA=2.93, P=0.0051). Conclusions LOH on chromosome 22 is a frequent event in the tumorigenesis of sporadic schwannoma. And, there is a correlation between LOH on chromosome 22 and proliferative activity in schwannoma. The frequency of LOH in vestibular schwannoma is significantly different from

  1. Studies on chromosome aberrations in workers occupationally exposed to radiation

    International Nuclear Information System (INIS)

    Cytogenetic assays for unstable chromosomes were performed on 54 medical radiation workers who are occupationally exposed to radiation and 42 controls. A total of 15,577 metaphase cells were scored. The frequencies of dicentrics and acentric chromosomes on controls were 0.52*10-3 and 0.82*10-2, respectively. On radiation workers those were 2.28*10-3 and 1.34*10-2, respectively. Though the frequencies of all types of chromosome aberrations in the workers were higher than those in the controls, the only significant difference was found in the case of dicentrics (P 0.05) except exposure dose of recent one year (P < 0.05). These results could indicate that low level exposure to ionizing radiation can induce unstable chromosome aberrations in blood lymphocytes

  2. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

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

  3. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

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

  4. Chromosome aberrations and sister chromatid exchanges in Swedish paint industry workers

    Energy Technology Data Exchange (ETDEWEB)

    Haglund, U.; Lundberg, I.; Zech, L.

    1980-12-01

    Workers in the Swedish paint industry exposed to a mixture of organic solvents, mainly containing xylene or toluene, were investigated for genotoxic effects. No difference in the frequency of sister chromatid exchanges (SCE), 0.192 and 0.193 per chromosome, respectively, was noted in the peripheral lymphocytes of the exposed group of 17 workers and their matched reference group. No correlation was found between xylene or toluene exposure and SCE frequency nor between total solvent exposure and SCE frequency. The frequency of chromosome aberrations was also investigated for the five most exposed workers and their matched referents, and no difference was found. There was no correlation between SCE and chromosome breaks.

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

    OpenAIRE

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

    2001-01-01

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

  6. APL1, an altered peptide ligand derived from human heat-shock protein 60, increases the frequency of Tregs and its suppressive capacity against antigen responding effector CD4 + T cells from rheumatoid arthritis patients.

    Science.gov (United States)

    Barberá, Ariana; Lorenzo, Noraylis; van Kooten, Peter; van Roon, Joel; de Jager, Wilco; Prada, Dinorah; Gómez, Jorge; Padrón, Gabriel; van Eden, Willem; Broere, Femke; Del Carmen Domínguez, María

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by a chronic relapsing-remitting joint inflammation. Perturbations in the balance between CD4 + T cells producing IL-17 and CD4 + CD25(high)FoxP3 + Tregs correlate with irreversible bone and cartilage destruction in RA. APL1 is an altered peptide ligand derived from a CD4+ T-cell epitope of human HSP60, an autoantigen expressed in the inflamed synovium, which increases the frequency of CD4 + CD25(high)FoxP3+ Tregs in peripheral blood mononuclear cells from RA patients. The aim of this study was to evaluate the suppressive capacity of Tregs induced by APL1 on proliferation of effector CD4+ T cells using co-culture experiments. Enhanced Treg-mediated suppression was observed in APL1-treated cultures compared with cells cultured only with media. Subsequent analyses using autologous cross-over experiments showed that the enhanced Treg suppression in APL1-treated cultures could reflect increased suppressive function of Tregs against APL1-responsive T cells. On the other hand, APL1-treatment had a significant effect reducing IL-17 levels produced by effector CD4+ T cells. Hence, this peptide has the ability to increase the frequency of Tregs and their suppressive properties whereas effector T cells produce less IL-17. Thus, we propose that APL1 therapy could help to ameliorate the pathogenic Th17/Treg balance in RA patients. PMID:27241313

  7. A cohesin-based structural platform supporting homologous chromosome pairing in meiosis.

    Science.gov (United States)

    Ding, Da-Qiao; Haraguchi, Tokuko; Hiraoka, Yasushi

    2016-08-01

    The pairing and recombination of homologous chromosomes during the meiotic prophase is necessary for the accurate segregation of chromosomes in meiosis. However, the mechanism by which homologous chromosomes achieve this pairing has remained an open question. Meiotic cohesins have been shown to affect chromatin compaction; however, the impact of meiotic cohesins on homologous pairing and the fine structures of cohesion-based chromatin remain to be determined. A recent report using live-cell imaging and super-resolution microscopy demonstrated that the lack of meiotic cohesins alters the chromosome axis structures and impairs the pairing of homologous chromosomes. These results suggest that meiotic cohesin-based chromosome axis structures are crucial for the pairing of homologous chromosomes. PMID:26856595

  8. Identification of the origin of chromosomal aberrations by laser microdissection: Double minutes observed in two cases derive from different chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Rajcan-Separovic, E. [Univ. of Ottawa (Canada); Wang, H.S.; Janes, L. [Children`s Hospital of Eastern Ontario, Ottawa (Canada)

    1994-09-01

    Single copies of tiny chromosome fragments appearing as double minutes were observed in high frequency in amniotic fluid cultures of two mothers who underwent prenatal testing because of advanced age. In case 1, the minutes were C band and NOR negative, while in case 2 they were C band positive, NOR negative. In both cases centromeric DNA sequences were detected on double minutes by fluorescence in situ hybridization (FISH) using all human centromeric probe (ONCOR). We applied the laser microdissection method to diagnose the origin of double minutes. The diagnostic procedures consisted of microdissection of double minutes from single cells, polymerase chain reaction (PCR) amplification of the dissected DNA and subsequent FISH using PCR products as a probe pool on metaphase chromosomes from the patient`s amniocytes and fibroblasts from a karyotypically normal newborn. Using this strategy we observed strong FISH signals on double minutes and centromeres of a D and G group chromosome in case 1 amniocyytes, while in case 2 the signal was present on double minutes and a C group chromosome centromere. Hybridization of amniocyte chromosome spreads with centromeric {alpha}-satellite probes for the candidate chromosomes 13/21 and 14/22 (ONCOR) in case 1 revealed FISH signals on double minutes only with the 13/21 probe. In case 2, {alpha}-satellite probes for candidate chromosomes 10 and 12 (ONCOR) were used, and only the probe for chromosome 12 hybridized to double minutes. With the laser microdissection method we were thus able to diagnose and confirm that the double minutes observed in human amniocytes derived from centromeres of chromosomes 13/21 in case 1, and from centomeres of chromosome 12 in case 2. This demonstrates the utility of laser microdissection for identification of chromosomal abnormalities of unknown origin.

  9. Chromosome painting and prematurely condensed chromosomes (PCC) - new methods of biological dosimetry

    International Nuclear Information System (INIS)

    Classic methods of biological dosimetry - micronucleus and dicentric assay pose several problems. In the case of micronucleus there is a wide range of spontaneous frequencies and smoking and age are powerfull contributing factors. In the case of dicentrics - low mitotic index in some individuals especially in the elderly or accidentally exposed to high radiation doses. So, there are 2 quite new molecular techniques which at least in part solve these problems: chromosome painting and PCC. Chromosome painting by employing chromosome-specific DNA probes allow easy identification and quantification of translocations. recently, it was shown that calyculin A or okadaic acid, inhibitors of 1 and 2A protein phosphatases, induce PCC in peripheral blood cells. This is an easy biodosimetric method with a high PCC index and independent of the ability of cells to divide e.g. after high (20 Gy) doses when the mitotic index is extremely low. (author)

  10. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

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

  11. Chromosomes, cancer and radiosensitivity

    International Nuclear Information System (INIS)

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

  12. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

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

  13. 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

  14. Study on micronucleus frequency and chromosomal aberration ratios of mouse testicle cells induced by methylene-dioxymethamphetamine%3,4亚甲基二氧基甲基苯丙胺对小鼠微核率及染色体畸变率的影响

    Institute of Scientific and Technical Information of China (English)

    赵忠桂; 刘霜; 刘艳华; 李雅欣; 伍爱荣; 周业成

    2015-01-01

    Objective To study the effects of 3,4-methylenedioxymethamphetamine (MDMA) on micronucleus frequency and chromosomal aberration ratios of male mouse testicle cells. Methods Healthy adult male rats were randomly divided into four groups. Different doses of MDMA (0, 5, 10 and 20 mg/kg) were administrated to the rats every days for 20 days. The rats were killed after the last test substance given for 24 h. Each rat′s micronucleus frequency and chromosomal aberration ratio of testicle cell were detected by using micronucleus test and chromosomal aberration test. Results The micronucleus frequencies of rats testicle cell in high dose group was significantly different from the control group and low dose group(P<0.01). With the control group, the chromosomal aberration ratios in testis of rats in high and middle dose group increased, the difference was significant (P<0.05), that in high dose group was also significantly different from the low and middle dose group (P<0.05). Conclusion It was suggested that MDMA might damage genetic material of rat testicle cells.%目的:通过连续20 d对雄性小鼠灌胃染毒3,4亚甲基二氧基甲基苯丙胺(MDMA)后,探究MDMA对雄性小鼠睾丸组织细胞微核率及染色体畸变率的影响。方法将雄性小鼠随机数字表法分为 MDMA 低(5.0 mg/kg)、中(10.0 mg/kg)、高(20.0 mg/kg)3个染毒剂量组,采用0.9%氯化钠注射液做阴性对照,每日染毒1次。于末次给药后第2天,取小鼠睾丸组织细胞,采用常规微核(MN)试验,检测小鼠睾丸细胞微核率的改变;同时采用染色体畸变试验探究MDMA对小鼠睾丸细胞染色体畸变率的影响。结果微核试验结果表明MDMA高剂量与低剂量组小鼠睾丸细胞微核率及阴性对照组比较,差异有统计学意义(P<0.01)。染色体畸变试验结果中,MDM高、中剂量组染色体畸变率分别与阴性对照组比较,差异有统计学意义(P<0.05),高

  15. Nondisjunction of chromosome 15: Origin and recombination

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A.; Mutirangura, A.; Ledbetter, D.H. (Baylor College of Medicine, Houston, TX (United States)); Langlois, S. (Univ. of Britisch Columbia, Vancouver (Canada)); Morris, M.A.; Malcolm, S.

    1993-09-01

    Thirty-two cases of uniparental disomy (UPD), ascertained from Prader-Willi syndrome patients (N=27) and Angelman syndrome patients (N-5), are used to investigate the pattern of recombination associated with nondisjunction of chromosome 15. In addition, the meiotic stage of nondisjunction is inferred by using markers mapping near the centromere. Two basic approaches to the analysis of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recombinant class (i.e., zero, one, two, three, or more observable crossovers) is compared with expected values. This is useful for testing whether the reduction in recombination can be attributed solely to a proportion of cases with no recombination at all (because of asynapsis), with the remaining groups showing normal recombination (or even excess recombination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-recombinant classes, with a corresponding increase in both the zero- and one-recombinant classes over expected values. The majority, more than 82%, of the extra chromosomes in maternal UPD(15) cases are due to meiotic I nondisjunction events. In contrast, more paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra paternal chromosome. 33 refs., 1 fig., 7 tabs.

  16. IMACULAT - an open access package for the quantitative analysis of chromosome localization in the nucleus.

    Directory of Open Access Journals (Sweden)

    Ishita Mehta

    Full Text Available The alteration in the location of the chromosomes within the nucleus upon action of internal or external stimuli has been implicated in altering genome function. The effect of stimuli at a whole genome level is studied by using two-dimensional fluorescence in situ hybridization (FISH to delineate whole chromosome territories within a cell nucleus, followed by a quantitative analysis of the spatial distribution of the chromosome. However, to the best of our knowledge, open access software capable of quantifying spatial distribution of whole chromosomes within cell nucleus is not available. In the current work, we present a software package that computes localization of whole chromosomes - Image Analysis of Chromosomes for computing localization (IMACULAT. We partition the nucleus into concentric elliptical compartments of equal area and the variance in the quantity of any chromosome in these shells is used to determine its localization in the nucleus. The images are pre-processed to remove the smudges outside the cell boundary. Automation allows high throughput analysis for deriving statistics. Proliferating normal human dermal fibroblasts were subjected to standard a two-dimensional FISH to delineate territories for all human chromosomes. Approximately 100 images from each chromosome were analyzed using IMACULAT. The analysis corroborated that these chromosome territories have non-random gene density based organization within the interphase nuclei of human fibroblasts. The ImageMagick Perl API has been used for pre-processing the images. The source code is made available at www.sanchak.com/imaculat.html.

  17. ATM modulates the loading of recombination proteins onto a chromosomal translocation breakpoint hotspot

    NARCIS (Netherlands)

    J. Sun (Jiying); Y. Oma (Yukako); M. Harata (Masahiko); K. Kono (Kazuteru); H. Shima (Hiroki); A. Kinomura (Aiko); T. Ikura (Tsuyoshi); H. Suzuki (Hidekazu); S. Mizutani (Shuki); R. Kanaar (Roland); S. Tashiro (Satoshi)

    2010-01-01

    textabstractChromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, incre

  18. Clinical Expression of an Inherited Unbalanced Translocation in Chromosome 6

    Directory of Open Access Journals (Sweden)

    Bani Bandana Ganguly

    2011-01-01

    Full Text Available Unbalanced chromosomal rearrangements are not common; however, they have a significant clinical expression. The parental balanced translocation produces unbalanced chromosome, which is transmitted to next generation through fertilization of gametes carrying the derivative chromosome. The carriers of balanced rearrangements mostly do not have recognizable phenotypic expression. We report a family comprising of healthy and non-consanguineous young parents and their preemie newborn severely affected with congenital anomalies and systemic disorders. Conventional Gbanding analysis of somatic chromosomes identified a balanced translocation, t(6;10(p23;q24, in mother and an unbalanced rearrangement, der(6t(6:10(p23;q24mat, in the child. The child has inherited a derivative chromosome 6 with partial deletion of 6(p23-pter and partial trisomy 10(q24-qter, which has resulted in fusion of genes of two different chromosomes. The prominent phenotypic features of del(6p, including high forehead, flat nasal bridge, agenesis of left ear, atrial septal defect (ASD, craniosynostosis, and growth retardation, are overlapping with specific Axenfeld-Reiger-, Larsen-, and Ritscher-Sinzel/3-C syndromes, however, lacking in ocular anomalies, skeletal laxity, or cerebellar malformation. Therefore, this paper rules out the isolated effect of del(6p23 or trisomy 10(q24 on distinct previously reported syndromes and proposes the combined effect of unbalanced chromosomal alteration.

  19. Activation of proto-oncogenes by disruption of chromosome neighborhoods.

    Science.gov (United States)

    Hnisz, Denes; Weintraub, Abraham S; Day, Daniel S; Valton, Anne-Laure; Bak, Rasmus O; Li, Charles H; Goldmann, Johanna; Lajoie, Bryan R; Fan, Zi Peng; Sigova, Alla A; Reddy, Jessica; Borges-Rivera, Diego; Lee, Tong Ihn; Jaenisch, Rudolf; Porteus, Matthew H; Dekker, Job; Young, Richard A

    2016-03-25

    Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecting chromosome neighborhood boundaries were found in many types of cancer. Thus, oncogene activation can occur via genetic alterations that disrupt insulated neighborhoods in malignant cells.

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

    Science.gov (United States)

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

    2010-02-01

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

  1. Transfer of small chromosome fragments of Agropyron elongatum to wheat chromosome via asymmetric somatic hybridization

    Institute of Scientific and Technical Information of China (English)

    WANG Jing; XIANG Fengning; XIA Guangmin; CHEN Huimin

    2004-01-01

    The chromosome constitution of hybrids and chromatin patterns of Agropyron elongatum(Host)Neviski in F5 somatic hybrid lines Ⅱ -1-3 and I-1-9 between Triticum aestivum L.and A.Elongatum were analyzed.Based on the statistic data of pollen mother cells,F5 I-1-9 and Ⅱ-1-3 had 20-21 bivalents with a frequency of 84.66% and 85.28%,of which,89.83% and 89.57% were ring bivalents.The result indicated that both hybrid lines were basically stable in the chromosome constitution and behavior.RAPD analysis showed that the two hybrids contained biparental and integrated DNA.GISH(Genome in situ hybridization)revealed that in the form of small chromosome segments,A.Elongatum chromatin was scattered on 4-6 wheat chromosomes near by the region of centromere and telomere in the two hybrid lines.SSR analysis indicated that A.Elongatum DNA segments were distributed on the 2A,5B,6B and 2D wheat chromosomes in the hybrids,which was in accordance with the GISH results that small-segments intercalated poly-site.

  2. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

    Science.gov (United States)

    Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Abnet, Christian C.; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Arslan, Alan A.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Brinton, Louise A.; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Canzian, Federico; Carreón, Tania; Chaffee, Kari G.; Chang, I-Shou; Chatterjee, Nilanjan; Chen, Chu; Chen, Constance; Chen, Kexin; Chung, Charles C.; Cook, Linda S.; Crous Bou, Marta; Cullen, Michael; Davis, Faith G.; De Vivo, Immaculata; Ding, Ti; Doherty, Jennifer; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Friedenreich, Christine M.; Fuchs, Charles S.; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hsiung, Chao A.; Hu, Nan; Hu, Wei; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Alison P.; Klein, Robert; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Lan, Qing; Landi, Maria Teresa; Marchand, Loic Le; Li, Donghui; Liang, Xiaolin; Liao, Linda M.; Lin, Dongxin; Liu, Jianjun; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Malats, Nuria; Matsuo, Keitaro; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Moore, Lee; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Patiño-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Pooler, Loreall; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Risch, Harvey A.; Rodriguez-Santiago, Benjamin; Ruder, Avima M.; Savage, Sharon A.; Schumacher, Fredrick; Schwartz, Ann G.; Schwartz, Kendra L.; Seow, Adeline; Wendy Setiawan, Veronica; Severi, Gianluca; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Van Den Berg, David; Visvanathan, Kala; Wacholder, Sholom; Wang, Jiu-Cun; Wang, Zhaoming; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Ziegler, Regina G.; Perez-Jurado, Luis A.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.

    2016-01-01

    To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. PMID:27291797

  3. SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas

    Directory of Open Access Journals (Sweden)

    Behboudi Afrouz

    2011-06-01

    Full Text Available Abstract Background Genomic alterations are common features of cancer cells, and some of these changes are proven to be neoplastic-specific. Such alterations may serve as valuable tools for diagnosis and classification of tumors, prediction of clinical outcome, disease monitoring, and choice of therapy as well as for providing clues to the location of crucial cancer-related genes. Endometrial carcinoma (EC is the most frequently diagnosed malignancy of the female genital tract, ranking fourth among all invasive tumors affecting women. Cytogenetic studies of human ECs have not produced very conclusive data, since many of these studies are based on karyotyping of limited number of cases and no really specific karyotypic changes have yet been identified. As the majority of the genes are conserved among mammals, the use of inbred animal model systems may serve as a tool for identification of underlying genes and pathways involved in tumorigenesis in humans. In the present work we used spectral karyotyping (SKY to identify cancer-related aberrations in a well-characterized experimental model for spontaneous endometrial carcinoma in the BDII rat tumor model. Results Analysis of 21 experimental ECs revealed specific nonrandom numerical and structural chromosomal changes. The most recurrent numerical alterations were gains in rat chromosome 4 (RNO4 and losses in RNO15. The most commonly structural changes were mainly in form of chromosomal translocations and were detected in RNO3, RNO6, RNO10, RNO11, RNO12, and RNO20. Unbalanced chromosomal translocations involving RNO3p was the most commonly observed structural changes in this material followed by RNO11p and RNO10 translocations. Conclusion The non-random nature of these events, as documented by their high frequencies of incidence, is suggesting for dynamic selection of these changes during experimental EC tumorigenesis and therefore for their potential contribution into development of this malignancy

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

    Science.gov (United States)

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

    2002-05-15

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

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

    Science.gov (United States)

    Muravenko, O V; Zelenin, A V

    2009-11-01

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

  6. Guidelines of Special Care Dentistry in Patients with Chromosomal and Genetic syndromes

    OpenAIRE

    Cremonesi, Ilaria

    2015-01-01

    Chromosomal and genetic syndromes are frequently associated with dental and cranio-facial alterations. The aim of our study is to identify and describe the dental and craniofacial alterations typical of six genetic and chromosomal syndromes examined. Materials and Methods- A dental visit was performed to 195 patients referred from Sant’Orsola Hospital of Bologna, University of Bologna, to Service of Special Need Dentistry, Dental Clinic, Department of Biomedical and Neuromotor Science, U...

  7. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

    Directory of Open Access Journals (Sweden)

    Shinya Akatsuka

    Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

  8. Significance of molecular genetic alterations of chromosome 1p/19q in differential diagnosis of oligodendroglioma and astrocytoma%1p/19q分子遗传学改变在少突胶质细胞瘤和星形细胞瘤鉴别诊断中意义

    Institute of Scientific and Technical Information of China (English)

    李俊芝; 侯国胜; 蒋茂芬; 张巍

    2011-01-01

    Objective To study the significance of molecular genetic alterations of chromosome 1p/ 19q in differential diagnosis of oligodendroglioma and astrocytoma. Methods Molecular genetic alterations of chromosome lp/19q were detected with fluorescence in situ hybridization in 63 patients with oligodendroglioma or astrocytoma. Results Polyploid of lp/19q was in 5 cases (3 cases of astrocytoma and 2 cases of oligodendroglioma). Loss lp/19q heterozygosity was in 58 cases (41 cases oligodendroglioma and 17 cases of astrocytoma). The loss rates of chromosome lp, 19q and lp/19q were 65.9%, 68. 5% and 58. 5% respectively in 41 cases of oligodendroglioma, and were 17. 6%, 29.4% and 17. 6% respectively in 17 cases of astrocytoma, which showed significant differences between two groups(P = 0. 001, P = 0. 006, P = 0. 004). Twenty-one cases (87. 5%) and 9 cases (52.9%) had typical oligodendrocyte morphological characteristics in 24 oligodendroglioma cases of lp/19q heterozygosity loss and 17 oligodendroglioma cases of no lp/19q heterozygosity loss resprctively, which showed significant differences between two groups (P = 0. 014). Conclusion Loss rate of lp/19q heterozygosity is higher in oligodendroglioma than that in astrocytoma, and more likely to occur in oligodendroglioma with typical histological features. Polyploidy of chromosome lp/19q is more common in astrocytoma subtypes.%目的:探讨1p/19q分子遗传学改变在少突胶质细胞瘤和星形细胞瘤鉴别诊断中的意义。方法:少突胶质细胞瘤和星形细胞瘤共63例,采用荧光原位杂交技术检测染色体1p/19q分子遗传学改变。结果:1p/19q呈多倍体改变5例,其中星形细胞瘤3例,少突胶质细胞瘤2例;1p和19q杂合性缺失58例,其中少突胶质细胞肿瘤41例,星形细胞肿瘤17例。少突胶质细胞瘤染色体1p,19q及1p/19q缺失率分别为65.9%,68.3%和58.5%,星形细胞瘤分别为17.6%,29.4%和1 7.6%,

  9. [Early loss of heterozygosity on chromosome arm 16q in flat epithelial atypia of the breast. Detection by microsatellite analyses].

    Science.gov (United States)

    Schmidt, H; Dahrenmöller, C; Agelepoulos, K; Hungermann, D; Böcker, W

    2008-11-01

    With the improvement of breast carcinoma screening, pre-malignant cell lesions such as flat epithelial atypia (FEA) are detected more frequently. Several studies have demonstrated that FEA show features of a ductal neoplasia, but is it really a precursor lesion? We have started a comparative genetic analysis of a panel of nine microsatellite markers on six different chromosomal regions to investigate whether FEAs show the same characteristic genetic alterations as ductal carcinomas in situ (DCISs) and invasive carcinoma of the breast. FEAs, DCISs and invasive carcinomas of the same patients were microdissected using PALM micro laser technology. DNA was isolated using the QIAamp DNA Micro Kit (QIAGEN). We have investigated a set of the polymorphic microsatellite markers D7S522, D8S522, NEFL, D10S541 (PTEN), D13S153 (RB1), D16S400, D16S402, D16S422 and D17S855 (BRCA1) using multiplex PCR for the detection of allelic imbalances. Most of the investigated FEAs showed a lower frequency of loss of heterozygosity than associated DCISs or invasive carcinomas. However, we were able to detect the same alterations in FEAs as in DCISs or invasive carcinomas in a number of cases. Notably, the microsatellite marker on 16q showed more prevalent allelic imbalances in FEAs than the other investigated markers. One of the hallmarks in the pathogenesis of a large subgroup of invasive breast carcinomas is the early loss of chromosome arm 16q. In this study, we were able to detect frequent genetic alterations on chromosome 16q in FEAs, associated DCISs and invasive carcinomas. This suggests that FEA is a precursor lesion in the low-grade pathway.

  10. Construction of human chromosome 21-specific yeast artificial chromosomes.

    Science.gov (United States)

    McCormick, M K; Shero, J H; Cheung, M C; Kan, Y W; Hieter, P A; Antonarakis, S E

    1989-12-01

    Chromosome 21-specific yeast artificial chromosomes (YACs) have been constructed by a method that performs all steps in agarose, allowing size selection by pulsed-field gel electrophoresis and the use of nanogram to microgram quantities of DNA. The DNA sources used were hybrid cell line WAV-17, containing chromosome 21 as the only human chromosome and flow-sorted chromosome 21. The transformation efficiency of ligation products was similar to that obtained in aqueous transformations and yielded YACs with sizes ranging from 100 kilobases (kb) to greater than 1 megabase when polyamines were included in the transformation procedure. Twenty-five YACs containing human DNA have been obtained from a mouse-human hybrid, ranging in size from 200 to greater than 1000 kb, with an average size of 410 kb. Ten of these YACs were localized to subregions of chromosome 21 by hybridization of RNA probes (corresponding to the YAC ends recovered in Escherichia coli) to a panel of somatic cell hybrid DNA. Twenty-one human YACs, ranging in size from 100 to 500 kb, with an average size of 150 kb, were obtained from approximately equal to 50 ng of flow-sorted chromosome 21 DNA. Three were localized to subregions of chromosome 21. YACs will aid the construction of a physical map of human chromosome 21 and the study of disorders associated with chromosome 21 such as Alzheimer disease and Down syndrome.

  11. Structural organization of the inactive X chromosome in the mouse.

    Science.gov (United States)

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job

    2016-07-28

    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  12. Structural organization of the inactive X chromosome in the mouse.

    Science.gov (United States)

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job

    2016-07-28

    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  13. MDMA(3,4亚甲基二氧甲基苯丙胺)对小鼠睾丸细胞微核率及染色体畸变率的影响%Effect of MDMA on Micronucleus Frequency and Chromosomal Aberration Ratio of Rats’ Testicle Cells

    Institute of Scientific and Technical Information of China (English)

    赵忠桂; 刘霜; 刘艳华; 李雅欣; 伍爱荣; 周业成

    2015-01-01

    通过连续20 d对雄性小鼠灌胃染毒3,4-亚甲基二氧基甲基苯丙胺(3,4-methylenedioxymethamphetamine, MDMA)后,探究MDMA对雄性小鼠睾丸组织细胞微核率及染色体畸变率的影响.将雄性小鼠随机分为MDMA低(5.0mg/kg)、中(10.0mg/kg)、高(20.0 mg/kg)三个染毒剂量组,采用生理盐水做阴性对照,每日染毒1次.于末次给药后第二天,取小鼠睾丸组织细胞,采用常规微核( micronucleus,MN)试验,检测小鼠睾丸细胞微核率的改变;同时采用染色体畸变试验( chromosomal aberration test)探究MDMA对小鼠睾丸细胞染色体畸变率的影响.微核试验结果表明MDMA中、低剂量组小鼠睾丸细胞微核率与阴性对照组比较差异无显著性(P>0.05),而高剂量与低剂量组小鼠睾丸细胞微核率及阴性对照组比较,差异均有显著性(P0. 05), while that in high dose group was significantly different from the control group and low dose group ( P<0 . 01 ) . Compared with the control group, the chromosomal aberration ratios in testis of rats in high and middle dose group increased, the difference was not significant (P<0. 05), but that in low dose group was also significantly different from the control group(P<0. 05). It suggested that high dose of MDMA lead to the increase of micronucleus frequency. Besides,high dose group and middle dose group could make the chro-mosomal aberration ratio increase. So MDMA might damage genetic material of rat testicle cells. 4figs. , 2tabs. ,10refs.

  14. Chromosomal aberrations related to metastasis of human solid tumors

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin

    2002-01-01

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

  15. Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kakinuma, Shizuko, E-mail: skakinum@nirs.go.jp [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Amasaki, Yoshiko; Takada, Mayumi; Yamauchi, Kazumi; Sudo, Satomi; Shang, Yi [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Doi, Kazutaka; Yoshinaga, Shinji [Regulatory Sciences Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Yoshiya [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2012-09-01

    Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplan's method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-indcued point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens.

  16. Nonhomologous Chromosome Pairing in Aegilops-Secale Hybrids.

    Science.gov (United States)

    Su, Yarui; Zhang, Dale; Li, Yuge; Li, Suoping

    2015-01-01

    Intergeneric hybrids and amphidiploid hybrids from crosses of Aegilopstauschii and Secale cereale were produced using young embryo rescue. The hybrids showed complete sets of both parental chromosomes. The dihaploid plants showed an average meiotic pairing configuration of 10.84 I + 1.57 II + 0.01 III. Genomic in situ staining revealed 3 types of bivalent associations, i.e. D-D, R-R and D-R at frequencies of 8.6, 8.2 and 83.3%, respectively. Trivalents consisted of D-R-D or R-D-R associations. These results suggested that both intra- and intergenomic chromosome homology were contributed to chromosome pairing. Derived amphidiploids with 2n = 28 paired at metaphase I of meiosis as 4.51 I + 11.70 II + 0.03 III. Chromosome pairing of amphidiploids appeared more or less regular, i.e. bivalent-like with some trivalent configurations. PMID:26950342

  17. Evidence from mutagenesis on the possible involvement of Cu++ and Mg++ ions in the eukaryotic chromosome structure

    International Nuclear Information System (INIS)

    The low thermostability of the DNA induced in vitro by Cu++ ions is coupled with a higher frequency of radiation-induced chromosomal aberrations while the high thermostability of the DNA induced in vitro by Mg++ ions is coupled with a lower frequency of radiation-induced chromosomal aberrations. The possible effects of bivalent ions on the structure and the mutagenicity of mammalian chromosomes are discussed. (author)

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

    Science.gov (United States)

    Guilherme, Roberta Santos; Moysés-Oliveira, Mariana; Dantas, Anelisa Gollo; Meloni, Vera Ayres; Colovati, Mileny Esbravatti; Kulikowski, Leslie Domenici; Melaragno, Maria Isabel

    2016-05-01

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

  19. Genetic Diversity and Differentiation in Urban and Indigenous Populations of Mexico: Patterns of Mitochondrial DNA and Y-Chromosome Lineages.

    Science.gov (United States)

    González-Sobrino, Blanca Z; Pintado-Cortina, Ana P; Sebastián-Medina, Leticia; Morales-Mandujano, Fabiola; Contreras, Alejandra V; Aguilar, Yasnaya E; Chávez-Benavides, Juan; Carrillo-Rodríguez, Aurelio; Silva-Zolezzi, Irma; Medrano-González, Luis

    2016-01-01

    Aside from the admixture between indigenous people and people from overseas, populations in Mexico changed drastically after the Spanish conquest of the sixteenth century, forming an intricate history that has been underutilized in understanding the genetic population structure of Mexicans. To infer historical processes of isolation, dispersal, and assimilation, we examined the phylogeography of mitochondrial (mt) DNA and Y-chromosome lineages in 3,026 individuals from 10 urban and nine indigenous populations by identifying single nucleotide polymorphisms. A geographic array with a predominance of Amerindian lineages was observed for mtDNA, with northern indigenous populations being divergent from the central and southern indigenous populations; urban populations showed low differentiation with isolation by distance. Y-chromosome variation distinguished urban and indigenous populations through the Amerindian haplogroup Q frequency. The MtDNA and the Y-chromosome together primarily distinguished urban and indigenous populations, with different geographic arrays for both. Gene flow across geographical distance and between the urban and indigenous realms appears to have altered the pre-Hispanic phylogeography in central and southern Mexico, mainly by displacement of women, while maintaining the indigenous isolation in the north, southeast, and Zapotec regions. Most Amerindian mtDNA diversity currently occurs in urban populations and appears to be reduced among indigenous people. PMID:27050033

  20. Chromosomal aberrations induced by the restriction endonucleases Alu I and Bam HI: comparison with X-rays

    International Nuclear Information System (INIS)

    Dose-effect relationships for the frequencies of polycentric chromosomes induced by the restriction endonucleases Alu I and Bam HI and by X-rays in Chinese hamster ovary (CHO) cells were analyzed and compared. 1 Gy of X-rays produce the same frequency of polycentric chromosomes as 2 units Alu I and 7.9 units Bam HI. (author)

  1. 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.

  2. Breakage-fusion-bridge cycles and de novo telomere formation on broken chromosomes in maize callus cultures.

    Science.gov (United States)

    Santos-Serejo, Janay A; Aguiar-Perecin, Margarida L R

    2016-06-01

    Breakpoints involved in chromosome alterations associated with heterochromatin have been detected in maize plants regenerated from callus culture. A cytogenetic analysis of plants regenerated from a maize callus was performed aiming to analyze the stability of a chromosome 7 bearing a deficiency-duplication (Df-Dp), which was interpreted as derived from a chromatid type breakage-fusion-bridge (BFB) cycle. The Df-Dp chromosome 7 was stable in mitotic and meiotic cells of the regenerated plants. Fluorescence in situ hybridization showed signals of telomeric sequences on the broken chromosome arm and provided evidence of de novo telomere formation. The stability of two types of altered chromosome 7 was investigated in C-banded metaphases from samples of the original callus that were collected during a period of 30-42 months after culture initiation. New alterations involving heterochromatic knobs of chromosomes 7 and 9 were observed. The aberrant chromosomes were stable in the subcultures, thus providing evidence of broken chromosome healing. The examination of anaphases showed the presence of bridges, which was consistent with the occurrence of BFB cycles. De novo telomere formation occurred in euchromatic and heterochromatic chromosome termini. The results point to events of chromosomal evolution that might occur in plants. PMID:27203556

  3. The role of myosin phosphorylation in anaphase chromosome movement.

    Science.gov (United States)

    Sheykhani, Rozhan; Shirodkar, Purnata V; Forer, Arthur

    2013-01-01

    This work deals with the role of myosin phosphorylation in anaphase chromosome movement. Y27632 and ML7 block two different pathways for phosphorylation of the myosin regulatory light chain (MRLC). Both stopped or slowed chromosome movement when added to anaphase crane-fly spermatocytes. To confirm that the effects of the pharmacological agents were on the presumed targets, we studied cells stained with antibodies against mono- or bi-phosphorylated myosin. For all chromosomes whose movements were affected by a drug, the corresponding spindle fibres of the affected chromosomes had reduced levels of 1P- and 2P-myosin. Thus the drugs acted on the presumed target and myosin phosphorylation is involved in anaphase force production. Calyculin A, an inhibitor of MRLC dephosphorylation, reversed and accelerated the altered movements caused by Y27632 and ML-7, suggesting that another phosphorylation pathway is involved in phosphorylation of spindle myosin. Staurosporine, a more general phosphorylation inhibitor, also reduced the levels of MRLC phosphorylation and caused anaphase chromosomes to stop or slow. The effects of staurosporine on chromosome movements were not reversed by Calyculin A, confirming that another phosphorylation pathway is involved in phosphorylation of spindle myosin. PMID:23566798

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

    Science.gov (United States)

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

    2016-05-01

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

  5. Effect of chromosome tethering on nuclear organization in yeast.

    Directory of Open Access Journals (Sweden)

    Barış Avşaroğlu

    Full Text Available Interphase chromosomes in Saccharomyces cerevisiae are tethered to the nuclear envelope at their telomeres and to the spindle pole body (SPB at their centromeres. Using a polymer model of yeast chromosomes that includes these interactions, we show theoretically that telomere attachment to the nuclear envelope is a major determinant of gene positioning within the nucleus only for genes within 10 kb of the telomeres. We test this prediction by measuring the distance between the SPB and the silent mating locus (HML on chromosome III in wild-type and mutant yeast strains that contain altered chromosome-tethering interactions. In wild-type yeast cells we find that disruption of the telomere tether does not dramatically change the position of HML with respect to the SPB, in agreement with theoretical predictions. Alternatively, using a mutant strain with a synthetic tether that localizes an HML-proximal site to the nuclear envelope, we find a significant change in the SPB-HML distance, again as predicted by theory. Our study quantifies the importance of tethering at telomeres on the organization of interphase chromosomes in yeast, which has been shown to play a significant role in determining chromosome function such as gene expression and recombination.

  6. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  7. Chromosome assortment in Saccharum.

    Science.gov (United States)

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

    1994-12-01

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

  8. Structural variation of chromosomes in autism spectrum disorder.

    Science.gov (United States)

    Marshall, Christian R; Noor, Abdul; Vincent, John B; Lionel, Anath C; Feuk, Lars; Skaug, Jennifer; Shago, Mary; Moessner, Rainald; Pinto, Dalila; Ren, Yan; Thiruvahindrapduram, Bhooma; Fiebig, Andreas; Schreiber, Stefan; Friedman, Jan; Ketelaars, Cees E J; Vos, Yvonne J; Ficicioglu, Can; Kirkpatrick, Susan; Nicolson, Rob; Sloman, Leon; Summers, Anne; Gibbons, Clare A; Teebi, Ahmad; Chitayat, David; Weksberg, Rosanna; Thompson, Ann; Vardy, Cathy; Crosbie, Vicki; Luscombe, Sandra; Baatjes, Rebecca; Zwaigenbaum, Lonnie; Roberts, Wendy; Fernandez, Bridget; Szatmari, Peter; Scherer, Stephen W

    2008-02-01

    Structural variation (copy number variation [CNV] including deletion and duplication, translocation, inversion) of chromosomes has been identified in some individuals with autism spectrum disorder (ASD), but the full etiologic role is unknown. We performed genome-wide assessment for structural abnormalities in 427 unrelated ASD cases via single-nucleotide polymorphism microarrays and karyotyping. With microarrays, we discovered 277 unbalanced CNVs in 44% of ASD families not present in 500 controls (and re-examined in another 1152 controls). Karyotyping detected additional balanced changes. Although most variants were inherited, we found a total of 27 cases with de novo alterations, and in three (11%) of these individuals, two or more new variants were observed. De novo CNVs were found in approximately 7% and approximately 2% of idiopathic families having one child, or two or more ASD siblings, respectively. We also detected 13 loci with recurrent/overlapping CNV in unrelated cases, and at these sites, deletions and duplications affecting the same gene(s) in different individuals and sometimes in asymptomatic carriers were also found. Notwithstanding complexities, our results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility. Our most compelling result discovered CNV at 16p11.2 (p = 0.002) (with characteristics of a genomic disorder) at approximately 1% frequency. Some of the ASD regions were also common to mental retardation loci. Structural variants were found in sufficiently high frequency influencing ASD to suggest that cytogenetic and microarray analyses be considered in routine clinical workup.

  9. Increased likelihood of post-polycythemia vera myelofibrosis in Ph-negative MPN patients with chromosome 12 abnormalities.

    Science.gov (United States)

    Benton, Christopher B; Tanaka, Maria; Wilson, Catherine; Pierce, Sherry; Zhou, Lingsha; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2015-04-01

    Chromosome 12 (Chr12) abnormalities have been described for individual patients with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPN), however the frequency, characteristics, and outcomes of such patients as a whole have not been investigated. We reviewed a database of 1787 consecutive Ph-neg MPN patients seen at our institution and determined that 2% of Ph-neg MPN patients harbored an alteration involving Chr12 by cytogenetic evaluation. Retrospective chart review revealed that patients with Chr12 abnormalities had a higher likelihood of having myelofibrosis (MF) compared to patients without a Chr12 abnormality, and were more likely to have post-polycythemia vera MF. The most common alterations in Chr12 in MF patients involved 12q13, 12q15, 12q24, and trisomy 12, and >40% of Chr12 Ph-neg MPN patients had cytogenetic evolution. Chr12 abnormalities did not significantly correlate with JAK2 status, progression to acute myeloid leukemia, or survival, however patients with 12q24 abnormalities trended toward poorer outcomes.

  10. Chromosome breakages associated with 45S ribosomal DNA sequences in spotted snakehead fish Channa punctatus.

    Science.gov (United States)

    Singh, Mamta; Barman, Anindya Sundar

    2013-01-01

    It is well known that transcriptionally inactive rRNA genes are correlated with DNA hyper-methylation and histone hypo-methylation and there is clear evidence in humans that DNA and histone modification which alter chromatin structure are related to chromosome fragility. Very little is known about the biological cause of 45S rDNA fragility. In this report we characterized the chromosome breakage or gap associated with 45S rDNA in a fish species Channa punctatus. The rDNA mapping in C. punctatus, showed many chromosome breakages or gap formations, and all occurred exclusively in the 45S rDNA sites in anterior kidney cells. We observed that the number of chromosomes plus chromosome fragments was often more than the expected 32 in most cells. Total 67 % metaphase spread showed the expected or normal 32 chromosomes, while 33 % metaphase spread showed 33 and/or 34 chromosomes and/or chromosome fragments. The chromosome lesions observed in this study are very similar cytologically to that of fragile sites observed in human chromosomes. Possible causes for the spontaneous expression of fragile sites and their potential biological significance are also discussed in present report.

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  12. ETOPOSIDE INDUCES CHROMOSOMAL ABNORMALITIES IN SPERMATOCYTES AND SPERMATOGONIAL STEM CELLS

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Pearson, F S; Bishop, J B; Wyrobek, A J

    2005-07-15

    Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukemia, lymphomas and many solid tumors, such as testicular and ovarian cancers, that affect patients in their reproductive years. The purpose of the study was to use sperm FISH analyses to characterize the long-term effects of ET on male germ cells. We used a mouse model to characterize the induction of chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. ET treatment resulted in major increases in the frequencies of sperm carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. These results demonstrate that male meiotic germ cells are considerably more sensitive to ET than spermatogonial stem-cell and that increased frequencies of sperm with structural aberrations persist after spermatogonial stem-cell treatment. These findings predict that patients who undergo chemotherapy with ET may have transient elevations in the frequencies of aneuploid sperm, but more importantly, may have persistent elevations in the frequencies of sperm with chromosomal aberrations, placing them at higher risk for abnormal reproductive outcomes long after the end of their chemotherapy.

  13. X chromosome inactivation: Activation of Silencing

    NARCIS (Netherlands)

    I.H. Jonkers (Iris)

    2009-01-01

    textabstractX chromosome inactivation is a process that ensures equal expression of the X chromosomes between males, which have one X and one Y chromosome, and females, which have two X chromosomes, in mammals. Females initiate inactivation of one of their two X chromosomes early during embryogenesi

  14. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  15. X-chromosome workshop.

    Science.gov (United States)

    Paterson, A D

    1998-01-01

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

  16. Y chromosomal STR analysis using Pyrosequencing technology.

    Science.gov (United States)

    Edlund, Hanna; Allen, Marie

    2009-03-01

    Analysis of Y chromosome STR markers has proven to be useful in forensic cases where the samples contain a mixture of DNA from several individuals. STR markers are commonly genotyped based on length separation of PCR products. In this study we evaluated if Pyrosequencing can be used as an alternative method for determining Y-STR variants. In total 70 unrelated Swedish males were typed for the Y chromosomal markers (DYS19, DYS389 I-II, DYS390, DYS391, DYS392, DYS393 and DYS438) using Pyrosequencing. Using the 8 markers, 57 unique haplotypes were observed with a discrimination capacity of 0.81. At four loci, the Pyrosequencing analysis revealed sequence variants. The sequence variants were found in the DYS389 II, DYS390, DYS391, and DYS393 loci in frequencies between 1.43% and 14.3%. Pyrosequencing has here been shown to be a useful tool for typing Y chromosomal STRs and the method can provide a complement to conventional forensic Y STR analyses. Moreover, the Pyrosequencing method can be used to rapidly evaluate novel markers. PMID:19215881

  17. Smectite alteration

    International Nuclear Information System (INIS)

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  18. The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis

    OpenAIRE

    Ben-David, Uri; Ha, Gavin; Khadka, Prasidda; Jin, Xin; Wong, Bang; Franke, Lude; Golub, Todd R.

    2016-01-01

    Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalogue of chromosomal aberrations in cancer GEMMs. Mining this resource, we find that most chromosomal aberrations accumulate late during breast tu...

  19. Biodosimetry of heavy ions by interphase chromosome painting

    Science.gov (United States)

    Durante, M.; Kawata, T.; Nakano, T.; Yamada, S.; Tsujii, H.

    1998-11-01

    We report measurements of chromosomal aberrations in peripheral blood lymphocytes from cancer patients undergoing radiotherapy treatment. Patients with cervix or esophageal cancer were treated with 10 MV X-rays produced at a LINAC accelerator, or high-energy carbon ions produced at the HIMAC accelerator at the National Institute for Radiological Sciences (NIRS) in Chiba. Blood samples were obtained before, during, and after the radiation treatment. Chromosomes were prematurely condensed by incubation in calyculin A. Aberrations in chromosomes 2 and 4 were scored after fluorescence in situ hybridization with whole-chromosome probes. Pre-treatment samples were exposed in vitro to X-rays, individual dose-response curves for the induction of chromosomal aberrations were determined, and used as calibration curves to calculate the effective whole-body dose absorbed during the treatment. This calculated dose, based on the calibration curve relative to the induction of reciprocal exchanges, has a sharp increase after the first few fractions of the treatment, then saturates at high doses. Although carbon ions are 2-3 times more effective than X-rays in tumor sterilization, the effective dose was similar to that of X-ray treatment. However, the frequency of complex-type chromosomal exchanges was much higher for patients treated with carbon ions than X-ray.

  20. Chromosomal abnormalities and environmental exposures in acute nonlymphocytic leukemia

    International Nuclear Information System (INIS)

    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

  1. The prevalence of Y chromosome microdeletions in Pakistani infertile men

    Directory of Open Access Journals (Sweden)

    Rubina Tabassum Siddiqui

    2013-01-01

    Full Text Available Background: Microdeletions of the azoospermia factor locus of the long arm of Y chromosome are an etiological factor of severe oligozoospermia or azoospermia. Objective: The aim of this study was to investigate the prevalence of Y-chromosome microdeletions in AZF region and their role in infertility in Pakistani population. Materials and Methods: The type of deletions in AZF locus were detected in infertile men (n=113 and the association of Y chromosome microdeletions with male infertility was assessed by including men (50 with normal karyotype and having children. Y chromosome microdeletions were detected by multiplex PCR using 10 sequence tagged sites namely sY81, sY130, sY141, sY142, sY155, sY157, sY160, sY182, sY231, and sY202 that covered all three regions of AZF. Results: Individuals with severe oligozoospermia showed 2.86% deletion frequency in AZFc region as compared to azoospermic males (5.5%. Conclusion: The results of our study showed that deletions in Y chromosome are not playing major part in male infertility. Moreover, multiplex-PCR strategy might preferably be employed for the detection of Y chromosome microdeletions allied to male infertility.

  2. Chromosome 7 Aneusomy. A Marker for Metastatic Melanoma?

    Directory of Open Access Journals (Sweden)

    Martin Udart

    2001-01-01

    Full Text Available Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR play an important role in a variety of malignant neoplasias, making the search for aberrations in the relevant chromosomes an important issue. Differential expression of the EGFR gene was investigated by reverse transcriptase (RT-PCR on tissue samples of normal skin, nevi, primary melanomas, and melanoma metastases. The EGFR gene is located on chromosome 7p12.3-p12.1. To determine the number of chromosomes 7 in cell nuclei of the mentioned tissue samples we performed fluorescence in situ hybridization (FISH on touch preparations, using a DNA probe that hybridizes specifically to the centromeric region of chromosome 7. Additionally, chromosome 7 number in interphase nuclei was determined in short-term primary cell cultures of nevi, primary melanomas, and metastases. The highest EGFR gene expression frequency was found in melanoma metastases. By FISH we detected the highest fraction of cell nuclei with more than two chromosomes 7 in the group of metastases. Our results suggest that overexpression of the EGFR gene might play an important role in metastasis of malignant melanoma. This is well reflected by polysomy 7, possibly accounting for an increased EGFRgene copy number.

  3. Chromosome 14 translocations in non-Burkitt lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Fukuhara, S.; Rowley, J.D.

    1978-01-01

    Chromosome studies were performed on malignant cells obtained from 27 patients with non-Burkitt lymphomas. A marker chromosome affecting the long arm of No. 14 (14q+) was the single most frequent abnormality and was noted in 17 of these patients. The frequency of the 14q+ marker varied with the type of lymphoma. For patients with malignant lymphoma, histiocytic, the frequency was 5 or 8; for mixed-cell type, 1 of 3; for poorly differentiated lymphocytic, 8 of 8; for well-differentiated lymphocytic, 0.3; for lymphoblastic, 0 of 1; for Hodgkin's disease, 2 of 3; and for mycosis fungoides, 1 of 1. The donor chromosome involved in the 14q translocation was identified in 12 cases; certain chromosomes appeared to be affected more frequently than others. Although the break point was band 14q32 in most cases, the exact location of the receptor site on 14q was not always consistent. The distal part of 14q24 was also involved as a receptor site in at least one translocation. These findings suggest that, in some types of lymphoid malignancy, cells with a 14q translocation have a proliferative advantage over cells with other chromosome rearrangements. The presence of the 14q translocation may be important in the future for the distinction among morphologically different, but functionally comparable, subgroups of lymphoid malignancies.

  4. Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations.

    Directory of Open Access Journals (Sweden)

    Miguel R Branco

    2006-05-01

    Full Text Available After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability.

  5. Causes of oncogenic chromosomal translocation

    OpenAIRE

    Aplan, Peter D.

    2005-01-01

    Non-random chromosomal translocations are frequently associated with a variety of cancers, especially hematologic malignancies and childhood sarcomas In addition to their diagnostic utility, chromosomal translocations are increasingly being used in the clinic to guide therapeutic decisions. However, the mechanisms which cause these translocations remain poorly understood. Illegit...

  6. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  7. History of chromosome rearrangements reflects the spatial organization of yeast chromosomes.

    Science.gov (United States)

    Khrameeva, Ekaterina E; Fudenberg, Geoffrey; Gelfand, Mikhail S; Mirny, Leonid A

    2016-04-01

    Three-dimensional (3D) organization of genomes affects critical cellular processes such as transcription, replication, and deoxyribo nucleic acid (DNA) repair. While previous studies have investigated the natural role, the 3D organization plays in limiting a possible set of genomic rearrangements following DNA repair, the influence of specific organizational principles on this process, particularly over longer evolutionary time scales, remains relatively unexplored. In budding yeast S.cerevisiae, chromosomes are organized into a Rabl-like configuration, with clustered centromeres and telomeres tethered to the nuclear periphery. Hi-C data for S.cerevisiae show that a consequence of this Rabl-like organization is that regions equally distant from centromeres are more frequently in contact with each other, between arms of both the same and different chromosomes. Here, we detect rearrangement events in Saccharomyces species using an automatic approach, and observe increased rearrangement frequency between regions with higher contact frequencies. Together, our results underscore how specific principles of 3D chromosomal organization can influence evolutionary events.

  8. Genetics Home Reference: ring chromosome 20 syndrome

    Science.gov (United States)

    ... 3 links) Encyclopedia: Chromosome Encyclopedia: Epilepsy Health Topic: Epilepsy Genetic and Rare Diseases Information Center (1 link) Ring chromosome 20 Additional NIH Resources (2 links) National Human Genome Research Institute: Chromosome Abnormalities National Institute of ...

  9. Genetics Home Reference: ring chromosome 14 syndrome

    Science.gov (United States)

    ... Encyclopedia: Chromosome Health Topic: Developmental Disabilities Health Topic: Epilepsy Genetic and Rare Diseases Information Center (1 link) Ring chromosome 14 Additional NIH Resources (2 links) National Human Genome Research Institute: Chromosome Abnormalities National Institute of ...

  10. Bacterial chromosome organization and segregation.

    Science.gov (United States)

    Badrinarayanan, Anjana; Le, Tung B K; Laub, Michael T

    2015-01-01

    If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation. PMID:26566111

  11. Higher order structure of chromosomes.

    Science.gov (United States)

    Okada, T A; Comings, D E

    1979-04-01

    Isolated Chinese hamster metaphase chromosomes were resuspended in 4 M ammonium acetate and spread on a surface of distilled water or 0.15 to 0.5 M ammonium acetate. The DNA was released in the form of a regular series of rosettes connected by interrossette DNA. The mean length of the rosette DNA was 14 micron, similar to the mean length of 10 micron for chromomere DNA of Drosophila polytene chromosomes. The mean interrosette DNA was 4.2 micron. SDS gel electrophoresis of the chromosomal nonhistone proteins showed them to be very similar to nuclear nonhistone proteins except for the presence of more actin and tubulin. Nuclear matrix proteins were present in the chromosomes and may play a role in forming the rosettes. Evidence that the rosette pattern is artifactual versus the possibility that it represents a real organizational substructure of the chromosomes is reviewed.

  12. Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma.

    Science.gov (United States)

    Plentz, Ruben R; Schlegelberger, Brigitte; Flemming, Peer; Gebel, Michael; Kreipe, Hans; Manns, Michael P; Rudolph, K Lenhard; Wilkens, Ludwig

    2005-09-01

    Chromosomal instability (CIN) leads to an increase in aneuploidy and chromosomal aberrations in human hepatocellular carcinoma (HCC). Telomere shortening appears as one mechanism fostering the development of CIN. Whether telomere shortening correlates to specific genetic changes that characterize a certain type of cancer has yet to be established. In our recent study, we combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosome 8-one of the hallmark chromosomal alterations in hepatocellular carcinoma (HCC). We investigated 15 cytological fine-needle biopsies of aneuploid HCC and 5 touch prints of cadaver livers without cancer. Hepatocyte-specific TFI and the measurement of centromere-specific probe for chromosome 8 were both performed by quantitative fluorescence in situ hybridization (qFISH) or FISH. Combined analysis of both methods (coFISH) allowed measurement of telomere length and chromosome 8 copy number on a single cell level. We observed that telomere shortening correlates significantly with increasing copy number of chromosome 8 in HCC on the cellular level. Above the level of 5 copies of chromosome 8 per nucleus, no further shortening of telomeres was found, indicating that telomeres had reached a critically short length at this stage of aneuploidy. In conclusion, our study gives direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC. PMID:16116624

  13. ADN et chromosomes

    OpenAIRE

    Hayes, Hélène

    2000-01-01

    Chaque chromosome contient une seule molécule d’ADN. L’ADN déroulé d’un noyau de cellule humaine mesurerait environ 1,8 m : chaque molécule d’ADN est enroulée et compactée en plusieurs étapes, grâce à l’association de différentes protéines, et loge dans le noyau de 6 µm de diamètre. Le degré de condensation de l’ADN est variable selon les régions chromosomiques et les régions les moins condensées sont les plus riches en gènes. L’ADN est composé d’une variété de séquences codantes ou non et ré...

  14. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-06-01

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

  15. X-Chromosome dosage compensation.

    Science.gov (United States)

    Meyer, Barbara J

    2005-01-01

    In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the

  16. Identification of chromosome abnormalities in the horse using a panel of chromosome-specific painting probes generated by microdissection.

    Science.gov (United States)

    Bugno, Monika; Słota, Ewa; Pieńkowska-Schelling, Aldona; Schelling, Claude

    2009-09-01

    Fluorescent in situ hybridisation (FISH) using a panel of molecular probes for all chromosome pairs obtained by chromosome microdissection of the domestic horse ( Equus caballus ) was used to diagnose karyotype abnormalities in 35 horses (32 mares, 2 stallions and 1 intersex), which were selected for the study due to infertility (23 horses), reduced fertility (10 horses) and developmental anomalies (2 horses). The use of the FISH technique with probes for each horse chromosome pair enabled the diagnosis of many different chromosome aberrations in this population. Among the horses analysed, 21 animals had normal karyotype - 64,XX (19 mares) and 64,XY (2 stallions). Fourteen animals, constituting 40% of the population studied, showed the following chromosome abnormalities: 63,X (1 mare); 63,X/64,XX (6 mares); 63,X/64,XX/65,XXX (3 mares); 63,X/65,XXX (1 mare); 64,XX/65,XX+Xp (1 mare); 63,X/64,XX/65,XX+Xq (1 mare), and 63,X/64,XX/65,XX+delY (1 intersex). When only the mares studied because of complete infertility were taken into consideration, this proportion exceeded 56%. Due to the increased frequency of the above-mentioned aberrations in the mosaic form of two or more lines, it was necessary to analyse a large number (100-300) of metaphase spreads. The use of specific molecular probes obtained by chromosome microdissection made these diagnoses much easier.

  17. Chromosome synapsis and recombination in simple and complex chromosomal heterozygotes of tuco-tuco (Ctenomys talarum: Rodentia: Ctenomyidae).

    Science.gov (United States)

    Basheva, Ekaterina A; Torgasheva, Anna A; Gomez Fernandez, Maria Jimena; Boston, Emma; Mirol, Patricia; Borodin, Pavel M

    2014-09-01

    The chromosomal speciation hypothesis suggests that irregularities in synapsis, recombination, and segregation in heterozygotes for chromosome rearrangements may restrict gene flow between karyotypically distinct populations and promote speciation. Ctenomys talarum is a South American subterranean rodent inhabiting the coastal regions of Argentina, whose populations polymorphic for Robertsonian and tandem translocations seem to have a very restricted gene flow. To test if chromosomal differences are involved in isolation among its populations, we examined chromosome pairing, recombination, and meiotic silencing of unsynapsed chromatin in male meiosis of simple and complex translocation heterozygotes using immunolocalization of the MLH1 marking mature recombination nodules and phosphorylated histone γH2A.X marking unrepaired double-strand breaks. We observed small asynaptic areas labeled by γH2A.X in pericentromeric regions of the chromosomes involved in the trivalents and quadrivalents. We also observed a decrease of recombination frequency and a distalization of the crossover distribution in the heterozygotes and metacentric homozygotes compared to acrocentric homozygotes. We suggest that the asynapsis of the pericentromeric regions are unlikely to induce germ cell death and decrease fertility of the heterozygotes; however, suppressed recombination in pericentromeric areas of the multivalents may reduce gene flow between chromosomally different populations of the Talas tuco-tuco. PMID:24924853

  18. Allele frequencies of 5 short tandem repeat loci of Kashin-Beck disease patients on chromosome 12%大骨节病患者12号染色体5个短串联重复序列位点基因频率分析

    Institute of Scientific and Technical Information of China (English)

    平智广; 刘莉; 郭雄

    2008-01-01

    Objective To analyze the allele frequencies of 5 short tandem repeat(STR)loci(D12S313,D12S304,D12S1640,D12S1708 and D12S1583)on chromosome 12 among Kashin-Beck disease(KBD)patients and the control population living in the area suffered from KBD.Methods Fifty KBD patient8 and 50 non-KBD patients were chosen in endemic afea of Shaanxi Province,5 STR loci on chromosome 12 were genotyped by the technology of polymerase chain reacfion(PCR)and capillary electmphoresis.The pelymorphisms of STR in these popIllations were analyzed.The allele and genotype frequencies of each STR in the corresponding groups were caleulated and compared. Results In KBD group,the 5 STR loci had 8,6,7,5 and 11 types ofalleles and 17,11,15,8 and 28 genotypes, respectively;while in the control group,the number of aUele types of 5 STR loci were 6,8,6,4 and 10,the number of genotype of those loci were 13,21,14,8 and 23,respectively The allele frequence of D12S304 locus was statiBtically significant between KBD patients and controls(P<0.05),especially for the 319 bp allele(P<0.006 25). Conclusion There is an association between D12S304 locus and KBD.The 319 bp allele might play the key role.%目的 分析大骨节病(Kashin-Beck disease,KBD)病区患者与非患者在12号染色体上5个短串联重复序列(short tandem repeat,STR)位点的多态性并比较其差异.方法 在陕西省KBD病区选择KBD患者(病例组)和非KBD患者(对照组)各50人,采集静脉血,利用PCR扩增和毛细管电泳技术,对12号染色体上5个STR位点(D12S313、D12S304、D12S1640、D12S1708和D12S1583)进行分型,分析各位点在上述人群中的多态性,计算5个位点在相应人群中等位基因与基因型频率,对各位点的等位基冈及基因型频率进行比较.结果 上述5种位点,病例组分别检出8,6、7、5和11种等位基因以及17、11、15、8和28种基因型;在对照组中检出6、8、6、4和10种等位基因以及13、21、14、8和23种基因型;在D12S304位点,病

  19. 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.

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

    Science.gov (United States)

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

    2015-07-30

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

  1. Mitotic chromosome loss in a radiation-sensitive strain of the yeast Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Mortimer, R.K.; Contopoulou, R.; Schild, D.

    1981-09-01

    Cells of Saccharomyces cerevisiae with mutations in the RAD52 gene have previously been shown to be defective in meiotic and mitotic recombination, in sporulation, and in repair of radiation-induced damage to DNA. In this study we show that diploid cells homozygous for rad52 lose chromosomes at high frequencies and that these frequencies of loss can be increased dramatically by exposure of these cells to x-rays. Genetic analyses of survivors of x-ray treatment demonstrate that chromosome loss events result in the conversion of diploid cells to cells with near haploid chromosome numbers.

  2. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

  3. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  4. A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

    Directory of Open Access Journals (Sweden)

    Gyorgy Petrovics

    2015-12-01

    Full Text Available Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA and Caucasian American (CA CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients. Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies.

  5. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  6. Manipulation of Homologous and Homoeologous Chromosome Recombination in Wheat.

    Science.gov (United States)

    Lukaszewski, Adam J

    2016-01-01

    Given the sizes of the three genomes in wheat (A, B, and D) and a limited number of chiasmata formed in meiosis, recombination by crossing-over is a very rare event. It is also restricted to very similar homologues; the pairing homoeologous (Ph) system of wheat prevents differentiated chromosomes from pairing and crossing-over. This chapter presents an overview and describes several systems by which the frequency or density of crossing-over can be increased, both in homologues and homoeologues. It also presents the standard system of E.R. Sears for engineering alien chromosome transfers into wheat. PMID:27511168

  7. Shannon Information and Power Law Analysis of the Chromosome Code

    Directory of Open Access Journals (Sweden)

    J. A. Tenreiro Machado

    2012-01-01

    Full Text Available This paper studies the information content of the chromosomes of twenty-three species. Several statistics considering different number of bases for alphabet character encoding are derived. Based on the resulting histograms, word delimiters and character relative frequencies are identified. The knowledge of this data allows moving along each chromosome while evaluating the flow of characters and words. The resulting flux of information is captured by means of Shannon entropy. The results are explored in the perspective of power law relationships allowing a quantitative evaluation of the DNA of the species.

  8. Chromosome aberrations in ataxia telangiectasia cells exposed to heavy ions

    Science.gov (United States)

    Kawata, T.; Cucinotta, F.; George, K.; Wu, H.; Shigematsu, N.; Furusawa, Y.; Uno, T.; Isobe, K.; Ito, H.

    Understanding of biological effects of heavy ions is important to assess healt h risk in space. One of the most important issues may be to take into account individual susceptibility. Ataxia telangiectasia (A-T) cells are known to exhibit abnormal responses to radiations but the mechanism of hyper radiosensitivity of A-T still remains unknown. We report chromosome aberrations in normal human fibroblasts and AT fibroblasts exposed to low- and high-LET radiations. A chemical-induced premature chromosome condensation (PCC) technique combined with chromosome- painting technique was applied to score chromosome aberrations in G2/M-phase cells. Following gamma irradiation, GM02052 cells were approximately 5 times more sensitive to g-rays than AG1522 cells. GM02052 cells had a much higher frequency of deletions and misrejoining than AG1522 cells. When the frequency of complex type aberrations was compared, GM02052 cells showed more than 10 times higher frequency than AG1522 cells. The results will be compared with those obtained from high-LET irradiations.

  9. An evolutionary conserved early replicating segment on the sex chromosomes of man and the great apes.

    Science.gov (United States)

    Weber, B; Schempp, W; Wiesner, H

    1986-01-01

    Replication studies on prometaphase chromosomes of man, the chimpanzee, the pygmy chimpanzee, the gorilla, and the orangutan reveal great interspecific homologies between the autosomes. The early replicating X chromosomes clearly show a high degree of conservation of both the pattern and the time course of replication. An early replicating segment on the short arm of the X chromosomes of man (Xp22.3) which escapes inactivation can be found on the X chromosomes of the great apes as well. Furthermore, the most early replicating segment on the Y chromosomes of all species tested appears to be homologous to this segment on the X chromosomes. Therefore, these early replicating segments in the great apes may correspond to the pseudoautosomal segment proposed to exist in man. From further cytogenetic characterization of the Y chromosomes it is evident that structural alterations have resulted in an extreme divergence in both the euchromatic and heterochromatic parts. It is assumed, therefore, that, in contrast to the X chromosomes, the Y chromosomes have undergone a rapid evolution within the higher primates. PMID:3096642

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

    Directory of Open Access Journals (Sweden)

    Bijan Fouladi

    2000-01-01

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

  11. Partial trisomy 11q involving chromosome 1 detected by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, M.; Bereziouk, O.; McCorquodale, D.J. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    Partial trisomy 11q was detected in an infant delivered 3-4 weeks prematurely. The phenotype included slanted palpebral fissures, high arched palate, developmental delay, microcephaly, and cardiac defects, all of which occur in the majority of cases with this syndrome. Other features included a column-shaped skull, preauricular pit, single palmar crease, short, broad great toes, flat occiput, unilateral kidney agenesis, and strabismus. Chromosomes obtained from peripheral blood cells revealed the presence of extra material on the long arm of chromosome 1. The G-banding pattern of this extra material indicated that it might be derived from chromosome 1 or 11. Chromosomal {open_quotes}paints{close_quotes} showed that it was not chromosome 1 material, but was chromosome 11 material extending from band q21 to qter. Partial trisomy 11q arising from translocation of the 11q material to chromosome 2, 3, 4, 5, 6, 9, 10, 13, 17, 21, 22, and X has been reported previously, whereas translocation to chromosome 1 has not. The chromosome to which the 11q material is translocated does not alter the most frequent features of the partial trisomy 11q syndrome, but may influence other less common features.

  12. Chromosomal abnormalities in couples with repeated fetal loss: An Indian retrospective study

    Directory of Open Access Journals (Sweden)

    Frenny J Sheth

    2013-01-01

    Full Text Available Background: Recurrent pregnancy loss is a common occurrence and a matter of concern for couples planning the pregnancy. Chromosomal abnormalities, mainly balanced rearrangements, are common in couples with repeated miscarriages. Purpose: The purpose of this study is to evaluate the contribution of chromosomal anomalies causing repeated spontaneous miscarriages and provide detailed characterization of a few structurally altered chromosomes. Materials and Methods: A retrospective cytogenetic study was carried out on 4859 individuals having a history of recurrent miscarriages. The cases were analyzed using G-banding and fluorescence in situ hybridization wherever necessary. Results: Chromosomal rearrangements were found in 170 individuals (3.5%. Translocations were seen in 72 (42.35% cases. Of these, reciprocal translocations constituted 42 (24.70% cases while Robertsonian translocations were detected in 30 (17.64% cases. 7 (4.11% cases were mosaic, 8 (4.70% had small supernumerary marker chromosomes and 1 (0.6% had an interstitial microdeletion. Nearly, 78 (1.61% cases with heteromorphic variants were seen of which inversion of Y chromosome (57.70% and chromosome 9 pericentromeric variants (32.05% were predominantly involved. Conclusions: Chromosomal analysis is an important etiological investigation in couples with repeated miscarriages. Characterization of variants/marker chromosome enable calculation of a more precise recurrent risk in a subsequent pregnancy thereby facilitating genetic counseling and deciding further reproductive options.

  13. Stable Chromosome Condensation Revealed by Chromosome Conformation Capture.

    Science.gov (United States)

    Eagen, Kyle P; Hartl, Tom A; Kornberg, Roger D

    2015-11-01

    Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to 10-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes. PMID:26544940

  14. Numerous transitions of sex chromosomes in Diptera.

    Directory of Open Access Journals (Sweden)

    Beatriz Vicoso

    2015-04-01

    Full Text Available Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot, but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes. Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa.

  15. Familial transmission of a deletion of chromosome 21 derived from a translocation between chromosome 21 and an inverted chromosome 22.

    Science.gov (United States)

    Aviv, H; Lieber, C; Yenamandra, A; Desposito, F

    1997-06-27

    Chromosome analysis of a newborn boy with Down syndrome resulted in the identification of a family with an unusual derivative chromosome 22. The child has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization (FISH) studies show that the derivative chromosome is chromosome 22 with evidence of both paracentric and pericentric inversions, joined to the long arm of chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy 21 extending from 21q21.2 to 21q terminus in the patient. The child's mother, brother, maternal aunt, and maternal grandmother are all carriers of the derivative chromosome. All have 45 chromosomes, with one normal chromosome 21, one normal chromosome 22, and the derivative chromosome 22. The rearrangement results in the absence of the short arm, the centromere, and the proximal long arm of chromosome 21 (del 21pter-21q21.2) in carriers. Carriers of the derivative chromosome in this family have normal physical appearance, mild learning disabilities and poor social adjustment. PMID:9182781

  16. Meiosis and chromosome painting of sex chromosome systems in Ceboidea.

    Science.gov (United States)

    Mudry, M D; Rahn, I M; Solari, A J

    2001-06-01

    The identity of the chromosomes involved in the multiple sex system of Alouatta caraya (Aca) and the possible distribution of this system among other Ceboidea were investigated by chromosome painting of mitotic cells from five species and by analysis of meiosis at pachytene in two species. The identity of the autosome #7 (X2) involved in the multiple system of Aca and its breakage points were demonstrated by both meiosis and chromosome painting. These features are identical to those described by Consigliere et al. [1996] in Alouatta seniculus sara (Assa) and Alouatta seniculus arctoidea (Asar). This multiple system was absent in the other four Ceboidea species studied here. However, data from the literature strongly suggest the presence of this multiple in other members of this genus. The presence of this multiple system among several species and subspecies that show high levels of chromosome rearrangements may suggest a special selective value of this multiple. The meiotic features of the sex systems of Aca and Cebus apella paraguayanus (Cap) are strikingly different at pachytene, as the latter system is similar to the sex pair of man and other primates. The relatively large genetic distances between species presently showing this multiple system suggest that its origin is not recent. Other members of the same genus should be investigated at meiosis and by chromosome painting in order to know the extent and distribution of this complex sex-chromosome system. PMID:11376445

  17. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

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

    Science.gov (United States)

    Lee, Hyunsook

    2014-10-31

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

  19. 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......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  20. Induction of micronuclei and erythrocyte alterations in the catfish Clarias batrachus by 2,4-dichlorophenoxyacetic acid and butachlor.

    Science.gov (United States)

    Ateeq, Bushra; Abul farah, M; Niamat Ali, M; Ahmad, Waseem

    2002-07-25

    The micronucleus test (MNT) in fish erythrocytes has increasingly been used to detect the genotoxic effects of environmental mutagens and its frequency is considered to reflect the genotoxic damage to cells, mainly the chromosomes. Besides, morphologically altered erythrocyte is taken as an index of cytotoxicity. Both parameters were used in the present study by two herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D, in 25, 50 and 75ppm concentrations) and 2-chloro-2,6-diethyl-N-(butoxymethyl) acetanilide (butachlor, in 1, 2 and 2.5ppm concentrations) for genotoxic and cytotoxic endpoints. The study was carried out by an in vivo method on peripheral erythrocytes of catfish Clarias batrachus using multiple sampling times (48, 72 and 96h). Cytogenetic preparations were made by haematoxylin-eosin staining technique. Pycnotic and granular micronuclei (MN) were consistently observed irrespective of chemical tested. A wide range of altered cells was also observed. Echinocytes accompanied by altered nuclei and vacuoles were prominent feature of 2,4-D, whereas, anisochromasia and anisocytosis of erythrocytes were characteristic of butachlor. Increase in MN as well as altered cells frequencies were significant. A positive dose-response relationship in all exposures and sampling times was observed. Herbicides used were found to be genotoxic as well as cytotoxic in this fish. The suitability of the adopted parameters for the screening of the aquatic genotoxicants is discussed.

  1. Chromosome aberration analysis based on a beta-binomial distribution

    International Nuclear Information System (INIS)

    Analyses carried out here generalized on earlier studies of chromosomal aberrations in the populations of Hiroshima and Nagasaki, by allowing extra-binomial variation in aberrant cell counts corresponding to within-subject correlations in cell aberrations. Strong within-subject correlations were detected with corresponding standard errors for the average number of aberrant cells that were often substantially larger than was previously assumed. The extra-binomial variation is accomodated in the analysis in the present report, as described in the section on dose-response models, by using a beta-binomial (B-B) variance structure. It is emphasized that we have generally satisfactory agreement between the observed and the B-B fitted frequencies by city-dose category. The chromosomal aberration data considered here are not extensive enough to allow a precise discrimination between competing dose-response models. A quadratic gamma ray and linear neutron model, however, most closely fits the chromosome data. (author)

  2. Chromosomal Aberrations in Humans Induced by Urban Air Pollution

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, Hannu; Gamborg, Michael O.;

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes...... that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  3. Epilepsy and ring chromosome 20: case report

    Directory of Open Access Journals (Sweden)

    Gomes Marleide da Mota

    2002-01-01

    Full Text Available We present the clinical, electroencephalographic, neuroimaging (brain magnetic resonance image - MRI and spectroscopy by MRI and cytogenetic findings of a young male patient with a rare cytogenetic anomaly characterised by a de novo 46,XY,r(20(p13q13.3 karyotype. He presents with mental retardation, emotional liability, and strabismus, without any other significant dysmorphies. There are brain anomalies characterised by corpus callosum, uvula, nodule and cerebellum pyramid hypoplasias, besides arachnoid cysts in the occipital region. He had seizures refractory to pharmacotherapy and long period of confusional status with or without a motor component. The authors recognised that the EEG pattern was not fixed but changed over time, specially for bursts of slow waves with great amplitude accompanied or not by sharp components, and bursts of theta waves sharply contoured. Previously, epilepsy solely has been assigned to region 20q13. However, the important structural cerebral alterations present in our case has not been reported associated to such chromosomal abnormality and may indicate possible new chromosomal sites where such atypical neurological characteristics could be mapped.

  4. Chromosome Architecture and Genome Organization

    OpenAIRE

    Giorgio Bernardi

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few...

  5. Chromosome evolution in Neotropical butterflies

    OpenAIRE

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

    2013-01-01

    We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results i...

  6. Methods for chromosome-specific staining

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel

    1995-01-01

    Methods and compositions for chromosome-specific staining are provided. Compositions comprise heterogenous mixtures of labeled nucleic acid fragments having substantially complementary base sequences to unique sequence regions of the chromosomal DNA for which their associated staining reagent is specific. Methods include methods for making the chromosome-specific staining compositions of the invention, and methods for applying the staining compositions to chromosomes.

  7. Origin and domestication of papaya Yh chromosome

    Science.gov (United States)

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

  8. The Incidence and Type of Chromosomal Translocations from Prenatal Diagnosis of 3800 Patients in the Republic of Macedonia

    OpenAIRE

    Vasilevska, M; Ivanovska, E; Kubelka Sabit, K; E. Sukarova-Angelovska; Dimeska, G

    2013-01-01

    Robertsonian and reciprocal chromosomal translocations are the most frequent type of structural chromosomal aberrations in the human population. We report the frequency and type of detected translocations in 10 years of prenatal diagnosis of 3800 prenatal samples. The materials came from amniocentesis and chorionic villus samples (CVS). We detected seven Robertsonian translocations (0.18%), eight autosomal reciprocal translocations (0.21%) and one sex chromosome translocation (0.03%). The ove...

  9. Chromosome evolution in Neotropical butterflies.

    Science.gov (United States)

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

    2013-06-01

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

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

    Science.gov (United States)

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

    2012-08-15

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

  11. 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.

  12. Chromosomal instability in the lymphocytes of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Harsimran Kaur

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Influence of DMSO on Carbon K ultrasoft X-rays induced chromosome aberrations in V79 Chinese hamster cells

    International Nuclear Information System (INIS)

    Ultrasoft X-rays have been shown to be very efficient in inducing chromosomal aberrations in mammalian cells. The present study was aimed to evaluate the modifying effects of DMSO (a potent scavenger of free radicals) on the frequencies of chromosome aberrations induced by soft X-rays. Confluent held G1 Chinese hamster cells (V79) were irradiated with Carbon K ultrasoft X-rays in the presence and absence of 1 M DMSO and frequencies of chromosome aberrations in the first division cells were determined. DMSO reduced the frequencies of exchange types of aberrations (dicentrics and centric rings) by a factor of 2.1-3.5. The results indicate that free radicals induced by ultrasoft X-rays contribute to a great extent to the induction of chromosome aberrations. The possible implications of these results in interpreting the mechanisms involved in the high efficiency of ultrasoft X-rays in the induction of chromosome aberrations are discussed.

  15. The Chromosome Microdissection and Microcloning Technique.

    Science.gov (United States)

    Zhang, Ying-Xin; Deng, Chuan-Liang; Hu, Zan-Min

    2016-01-01

    Chromosome microdissection followed by microcloning is an efficient tool combining cytogenetics and molecular genetics that can be used for the construction of the high density molecular marker linkage map and fine physical map, the generation of probes for chromosome painting, and the localization and cloning of important genes. Here, we describe a modified technique to microdissect a single chromosome, paint individual chromosomes, and construct single-chromosome DNA libraries. PMID:27511173

  16. Evolution of Sex Chromosomes in Insects

    OpenAIRE

    Kaiser, Vera B; Bachtrog, Doris

    2010-01-01

    Sex chromosomes have many unusual features relative to autosomes. Y (or W) chromosomes lack genetic recombination, are male- (female-) limited, and show an abundance of genetically inert heterochromatic DNA but contain few functional genes. X (or Z) chromosomes also show sex-biased transmission (i.e., X chromosomes show female-biased and Z-chromosomes show male-biased inheritance) and are hemizygous in the heterogametic sex. Their unusual ploidy level and pattern of inheritance imply that sex...

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

    Science.gov (United States)

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

    2014-01-01

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

  18. M-BAND Study of Radiation-Induced Chromosome Aberrations in Human Epithelial Cells: Radiation Quality and Dose Rate Effects

    Science.gov (United States)

    Hada, Megumi; Cucinotta, Francis; Wu, Honglu

    2009-01-01

    The advantage of the multicolor banding in situ hybridization (mBAND) technique is its ability to identify both inter- (translocation to unpainted chromosomes) and intra- (inversions and deletions within a single painted chromosome) chromosome aberrations simultaneously. To study the detailed rearrangement of low- and high-LET radiation induced chromosome aberrations in human epithelial cells (CH184B5F5/M10) in vitro, we performed a series of experiments with Cs-137 gamma rays of both low and high dose rates, neutrons of low dose rate and 600 MeV/u Fe ions of high dose rate, with chromosome 3 painted with multi-binding colors. We also compared the chromosome aberrations in both 2- and 3-dimensional cell cultures. Results of these experiments revealed the highest chromosome aberration frequencies after low dose rate neutron exposures. However, detailed analysis of the radiation induced inversions revealed that all three radiation types induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intra-chromosomal aberrations but few inversions were accompanied by inter-chromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosomal exchanges. The location of the breaks involved in chromosome exchanges was analyzed along the painted chromosome. The breakpoint distribution was found to be randomly localized on chromosome 3 after neutron or Fe ion exposure, whereas non-random distribution with clustering breakpoints was observed after -ray exposure. Our comparison of chromosome aberration yields between 2- and 3-dimensional cell cultures indicated a significant difference for gamma exposures, but not for Fe ion exposures. These experimental results indicated that the track structure of the radiation and the cellular/chromosome structure can both affect radiation-induced chromosome

  19. Engineering targeted chromosomal amplifications in human breast epithelial cells.

    Science.gov (United States)

    Springer, Simeon; Yi, Kyung H; Park, Jeenah; Rajpurohit, Anandita; Price, Amanda J; Lauring, Josh

    2015-07-01

    Chromosomal amplifications are among the most common genetic alterations found in human cancers. However, experimental systems to study the processes that lead to specific, recurrent amplification events in human cancers are lacking. Moreover, some common amplifications, such as that at 8p11-12 in breast cancer, harbor multiple driver oncogenes, which are poorly modeled by conventional overexpression approaches. We sought to develop an experimental system to model recurrent chromosomal amplification events in human cell lines. Our strategy is to use homologous-recombination-mediated gene targeting to deliver a dominantly selectable, amplifiable marker to a specified chromosomal location. We used adeno-associated virus vectors to target human MCF-7 breast cancer cells at the ZNF703 locus, in the recurrent 8p11-12 amplicon, using the E. coli inosine monophosphate dehydrogenase (IMPDH) enzyme as a marker. We applied selective pressure using IMPDH inhibitors. Surviving clones were found to have increased copy number of ZNF703 (average 2.5-fold increase) by droplet digital PCR and FISH. Genome-wide array comparative genomic hybridization confirmed that amplifications had occurred on the short arm of chromosome 8, without changes on 8q or other chromosomes. Patterns of amplification were variable and similar to those seen in primary human breast cancers, including "sawtooth" patterns, distal copy number loss, and large continuous regions of copy number gain. This system will allow study of the cis- and trans-acting factors that are permissive for chromosomal amplification and provide a model to analyze oncogene cooperativity in amplifications harboring multiple candidate driver genes.

  20. Somatic pairing, endomitosis and chromosome aberrations in snakes (Viperidae and Colubridae

    Directory of Open Access Journals (Sweden)

    Beçak Maria Luiza

    2003-01-01

    Full Text Available The positioning of macrochromosomes of Bothrops jararaca and Bothrops insularis (Viperidae was studied in undistorted radial metaphases of uncultured cells (spermatogonia and oogonia not subjected to spindle inhibitors. Colchicinized metaphases from uncultured (spleen and intestine and cultured tissues (blood were also analyzed. We report two antagonic non-random chromosome arrangements in untreated premeiotic cells: the parallel configuration with homologue chromosomes associated side by side in the metaphase plate and the antiparallel configuration having homologue chromosomes with antipolar distribution in the metaphase ring. The antiparallel aspect also appeared in colchicinized cells. The spatial chromosome arrangement in both configurations is groupal size-dependent and maintained through meiosis. We also describe, in untreated gonia cells, endomitosis followed by reductional mitosis which restores the diploid number. In B. jararaca males we observed that some gonad regions present changes in the meiotic mechanism. In this case, endoreduplicated cells segregate the diplochromosomes to opposite poles forming directly endoreduplicated second metaphases of meiosis with the suppression of first meiosis. By a successive division, these cells form nuclei with one set of chromosomes. Chromosome doubling in oogonia is known in hybrid species and in parthenogenetic salamanders and lizards. This species also presented chromosome rearrangements leading to aneuploidies in mitosis and meiosis. It is suggested that somatic pairing, endomitosis, meiotic alterations, and chromosomal aberrations can be correlated processes. Similar aspects of nuclei configurations, endomitosis and reductional mitosis were found in other Viperidae and Colubridae species.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  2. Chromosome numbers and meiotic analysis in the pre-breeding of Brachiaria decumbens (Poaceae)

    Indian Academy of Sciences (India)

    Gléia Cristina Laverde Ricci; Alice Maria De Souza-Kaneshima; Mariana Ferrari Felismino; Andrea Beatriz Mendes-Bonato; Maria Suely Pagliarini; Cacilda Borges Do Valle

    2011-08-01

    A total of 44 accessions of Brachiaria decumbens were analysed for chromosome count and meiotic behaviour in order to identify potential progenitors for crosses. Among them, 15 accessions presented $2n = 18$; 27 accessions, $2n = 36$; and 2 accessions, $2n = 45$ chromosomes. Among the diploid accessions, the rate of meiotic abnormalities was low, ranging from 0.82% to 7.93%. In the 27 tetraploid accessions, the rate of meiotic abnormalities ranged from 18.41% to 65.83%. The most common meiotic abnormalities were related to irregular chromosome segregation, but chromosome stickiness and abnormal cytokinesis were observed in low frequency. All abnormalities can compromise pollen viability by generating unbalanced gametes. Based on the chromosome number and meiotic stability, the present study indicates the apomictic tetraploid accessions that can act as male genitor to produce interspecific hybrids with B. ruziziensis or intraspecific hybrids with recently artificially tetraploidized accessions.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Spatial positioning of all 24 chromosomes in the lymphocytes of six subjects: evidence of reproducible positioning and spatial repositioning following DNA damage with hydrogen peroxide and ultraviolet B.

    Directory of Open Access Journals (Sweden)

    Dimitrios Ioannou

    Full Text Available The higher-order organization of chromatin is well-established, with chromosomes occupying distinct positions within the interphase nucleus. Chromatin is susceptible to, and constantly assaulted by both endogenous and exogenous threats. However, the effects of DNA damage on the spatial topology of chromosomes are hitherto, poorly understood. This study investigates the organization of all 24 human chromosomes in lymphocytes from six individuals prior to- and following in-vitro exposure to genotoxic agents: hydrogen peroxide and ultraviolet B. This study is the first to report reproducible distinct hierarchical radial organization of chromosomes with little inter-individual differences between subjects. Perturbed nuclear organization was observed following genotoxic exposure for both agents; however a greater effect was observed for hydrogen peroxide including: 1 More peripheral radial organization; 2 Alterations in the global distribution of chromosomes; and 3 More events of chromosome repositioning (18 events involving 10 chromosomes vs. 11 events involving 9 chromosomes for hydrogen peroxide and ultraviolet B respectively. Evidence is provided of chromosome repositioning and altered nuclear organization following in-vitro exposure to genotoxic agents, with notable differences observed between the two investigated agents. Repositioning of chromosomes following genotoxicity involved recurrent chromosomes and is most likely part of the genomes inherent response to DNA damage. The variances in nuclear organization observed between the two agents likely reflects differences in mobility and/or decondensation of chromatin as a result of differences in the type of DNA damage induced, chromatin regions targeted, and DNA repair mechanisms.

  5. New Advances in Chromosome Architecture.

    Science.gov (United States)

    Leake, Mark C

    2016-01-01

    Our knowledge of the "architecture" of chromosomes has grown enormously in the past decade. This new insight has been enabled largely through advances in interdisciplinary research methods at the cutting-edge interface of the life and physical sciences. Importantly this has involved several state-of-the-art biophysical tools used in conjunction with molecular biology approaches which enable investigation of chromosome structure and function in living cells. Also, there are new and emerging interfacial science tools which enable significant improvements to the spatial and temporal resolution of quantitative measurements, such as in vivo super-resolution and powerful new single-molecule biophysics methods, which facilitate probing of dynamic chromosome processes hitherto impossible. And there are also important advances in the methods of theoretical biophysics which have enabled advances in predictive modeling of this high quality experimental data from molecular and physical biology to generate new understanding of the modes of operation of chromosomes, both in eukaryotic and prokaryotic cells. Here, I discuss these advances, and take stock on the current state of our knowledge of chromosome architecture and speculate where future advances may lead. PMID:27283297

  6. Dean flow fractionation of chromosomes

    Science.gov (United States)

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

    2016-03-01

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

  7. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

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

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

    OpenAIRE

    Paliulis, Leocadia V.; Nicklas, R. Bruce

    2000-01-01

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

  9. Chromosome doubling in vine cacti hybrids.

    Science.gov (United States)

    Tel-Zur, N; Abbo, S; Bar-Zvi, D; Mizrahi, Y

    2003-01-01

    We performed reciprocal crosses between the tetraploid Selenicereus megalanthus and the diploid Hylocereus species, H. undatus and H. polyrhizus. S. megalanthus x H. undatus gave rise to viable hexaploids and 6x-aneuploid hybrids rather than to the expected triploids. No genuine hybrids were obtained in the reciprocal cross. The pollen diameter of the tetraploid S. megalanthus varied widely, indicating the occurrence of unreduced gametes, while that of H. undatus pollen was very uniform, indicating an extremely low frequency of unreduced gametes. This finding suggests that the hexaploids were formed by chromosome doubling after the formation of the hybrid triploid zygote rather than by fusion of unreduced gametes of the two species. PMID:12920104

  10. Establishment of a markerless mutation delivery system in Bacillus subtilis stimulated by a double-strand break in the chromosome.

    Directory of Open Access Journals (Sweden)

    Ting Shi

    Full Text Available Bacillus subtilis has been a model for gram-positive bacteria and it has long been exploited for industrial and biotechnological applications. However, the availability of facile genetic tools for physiological analysis has generally lagged substantially behind traditional genetic models such as Escherichia coli and Saccharomyces cerevisiae. In this work, we have developed an efficient, precise and scarless method for rapid multiple genetic modifications without altering the chromosome of B. subtilis. This method employs upp gene as a counter-selectable marker, double-strand break (DSB repair caused by exogenous endonuclease I-SceI and comK overexpression for fast preparation of competent cell. Foreign dsDNA can be simply and efficiently integrated into the chromosome by double-crossover homologous recombination. The DSB repair is a potent inducement for stimulating the second intramolecular homologous recombination, which not only enhances the frequency of resolution by one to two orders of magnitude, but also selects for the resolved product. This method has been successfully and reiteratively used in B. subtilis to deliver point mutations, to generate in-frame deletions, and to construct large-scale deletions. Experimental results proved that it allowed repeated use of the selectable marker gene for multiple modifications and could be a useful technique for B. subtilis.

  11. Protective Effect of Curcumin on γ - radiation Induced Chromosome Aberrations in Human Blood Lymphocytes

    International Nuclear Information System (INIS)

    The present work is aimed at evaluating the radioprotective effect of curcumin on γ radiation induced genetic toxicity. The DNA damage was analyzed by the frequencies of chromosome aberrations assay. Human lymphocytes were treated in vitro with 5.0 γg/ml of curcumin for 30 min at 37 degree C then exposed to 1, 2 and 4 Gy gamma-radiation. The lymphocytes which were pre-treated with curcumin exhibited a significant decrease in the frequency of chromosome aberration at 1 and 2 Gy radiation-induced chromosome damage as compared with the irradiated cells which did not receive the curcumin pretreatment. Thus, pretreatment with curcumin gives protection to lymphocytes against γ-radiation induced chromosome aberration at certain doses. (author)

  12. Phenotypic correlations in a patient with ring chromosome 22

    Directory of Open Access Journals (Sweden)

    Demirhan Osman

    2010-01-01

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

  13. Effect of therapeutic hypothermia on chromosomal aberration in perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Bahubali D Gane

    2016-01-01

    Full Text Available Introduction: Perinatal asphyxia is a major cause for neonatal mortality and morbidity around the world. The reduction of O2results in the generation of reactive oxygen species which interact with nucleic acid and make alteration in the structure and functioning of the genome. We studied the effect of therapeutic hypothermia on chromosomes with karyotyping. Subjects and Methods: Babies in the hypothermia group were cooled for the first 72 h, using gel packs. Rectal temperature of 33–34°C was maintained. Blood sample was collected after completion of therapeutic hypothermia for Chromosomal analysis. It was done with IKAROS Karyotyping system, Metasystems, based on recommendations of International system of human cytogenetic nomenclature. Results: The median chromosomal aberration was lower in hypothermia [2(0-5] than control group [4(1-7] and chromatid breakage was commonest aberration seen. Chromosomal aberration was significantly higher in severe encephalopathy group than moderate encephalopathy group. Conclusion: We conclude that the TH significantly reduces DNA damage in perinatal asphyxia.

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

    Directory of Open Access Journals (Sweden)

    Saleh A. Bakheet

    2011-01-01

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

  15. Genomic sequence of a mutant strain of Caenorhabditis elegans with an altered recombination pattern

    Directory of Open Access Journals (Sweden)

    Marra Marco

    2010-02-01

    Full Text Available Abstract Background The original sequencing and annotation of the Caenorhabditis elegans genome along with recent advances in sequencing technology provide an exceptional opportunity for the genomic analysis of wild-type and mutant strains. Using the Illumina Genome Analyzer, we sequenced the entire genome of Rec-1, a strain that alters the distribution of meiotic crossovers without changing the overall frequency. Rec-1 was derived from ethylmethane sulfonate (EMS-treated strains, one of which had a high level of transposable element mobility. Sequencing of this strain provides an opportunity to examine the consequences on the genome of altering the distribution of meiotic recombination events. Results Using Illumina sequencing and MAQ software, 83% of the base pair sequence reads were aligned to the reference genome available at Wormbase, providing a 21-fold coverage of the genome. Using the software programs MAQ and Slider, we observed 1124 base pair differences between Rec-1 and the reference genome in Wormbase (WS190, and 441 between the mutagenized Rec-1 (BC313 and the wild-type N2 strain (VC2010. The most frequent base-substitution was G:C to A:T, 141 for the entire genome most of which were on chromosomes I or X, 55 and 31 respectively. With this data removed, no obvious pattern in the distribution of the base differences along the chromosomes was apparent. No major chromosomal rearrangements were observed, but additional insertions of transposable elements were detected. There are 11 extra copies of Tc1, and 8 of Tc2 in the Rec-1 genome, most likely the remains of past high-hopper activity in a progenitor strain. Conclusion Our analysis of high-throughput sequencing was able to detect regions of direct repeat sequences, deletions, insertions of transposable elements, and base pair differences. A subset of sequence alterations affecting coding regions were confirmed by an independent approach using oligo array comparative genome

  16. Working Memory Impairment in Calcineurin Knock-out Mice Is Associated with Alterations in Synaptic Vesicle Cycling and Disruption of High-Frequency Synaptic and Network Activity in Prefrontal Cortex

    OpenAIRE

    Cottrell, Jeffrey R.; Levenson, Jonathan M.; Kim, Sung Hyun; Gibson, Helen E.; Richardson, Kristen A.; Sivula, Michael; Li, Bing; Ashford, Crystle J.; Heindl, Karen A.; Babcock, Ryan J.; Rose, David M.; Hempel, Chris M; Wiig, Kjesten A.; Laeng, Pascal; Levin, Margaret E.

    2013-01-01

    Working memory is an essential component of higher cognitive function, and its impairment is a core symptom of multiple CNS disorders, including schizophrenia. Neuronal mechanisms supporting working memory under normal conditions have been described and include persistent, high-frequency activity of prefrontal cortical neurons. However, little is known about the molecular and cellular basis of working memory dysfunction in the context of neuropsychiatric disorders. To elucidate synaptic and n...

  17. Micronuclei versus Chromosomal Aberrations Induced by X-Ray in Radiosensitive Mammalian Cells.

    Directory of Open Access Journals (Sweden)

    Cristina Plamadeala

    2015-03-01

    Full Text Available An experimental study was accomplished to compare estimation methods of ionizing radiations genotoxicity in mammalian cell cultures by means of two cytogenetic parameters with focus on aberrant cells characterized by multiple chromosomal damages.In vitro study was carried out on the genotoxicity of low-medium doses of 190 kV X-rays absorbed in Chinese hamster ovary cell cultures. Micronuclei and ten types of chromosomal aberrations were identified with Giemsa dying and optical microscope screening.The first parameter consisting in micronuclei relative frequency has led to higher linear correlation coefficient than the second one consistent with chromosomal aberrations relative frequency. However, the latter parameter estimated as the sum of all chromosomal aberrations appeared to be more sensitive to radiation dose increasing in the studied dose range, from 0 to 3 Gy. The number of micronuclei occurring simultaneously in a single cell was not higher than 3, while the number of chromosomal aberrations observed in the same cell reached the value of 5 for doses over 1 Gy.Polynomial dose-response curves were evidenced for cells with Ni micronuclei (i=1,3 while non-monotonic curves were evidenced through detailed analysis of aberrant cells with Ni chromosomal changes [Formula: see text] - in concordance with in vitro studies from literature. The investigation could be important for public health issues where micronucleus screening is routinely applied but also for research purposes where various chromosomal aberrations could be of particular interest.

  18. Chromosomal manipulation by site-specific recombinases and fluorescent protein-based vectors.

    Directory of Open Access Journals (Sweden)

    Munehiro Uemura

    Full Text Available Feasibility of chromosomal manipulation in mammalian cells was first reported 15 years ago. Although this technique is useful for precise understanding of gene regulation in the chromosomal context, a limited number of laboratories have used it in actual practice because of associated technical difficulties. To overcome the practical hurdles, we developed a Cre-mediated chromosomal recombination system using fluorescent proteins and various site-specific recombinases. These techniques enabled quick construction of targeting vectors, easy identification of chromosome-rearranged cells, and rearrangement leaving minimum artificial elements at junctions. Applying this system to a human cell line, we successfully recapitulated two types of pathogenic chromosomal translocations in human diseases: MYC/IgH and BCR/ABL1. By inducing recombination between two loxP sites targeted into the same chromosome, we could mark cells harboring deletion or duplication of the inter-loxP segments with different colors of fluorescence. In addition, we demonstrated that the intrachromosomal recombination frequency is inversely proportional to the distance between two recombination sites, implicating a future application of this frequency as a proximity sensor. Our method of chromosomal manipulation can be employed for particular cell types in which gene targeting is possible (e.g. embryonic stem cells. Experimental use of this system would open up new horizons in genome biology, including the establishment of cellular and animal models of diseases caused by translocations and copy-number variations.

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

    International Nuclear Information System (INIS)

    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

  20. Effects of polymorphisms in XRCC1 and APE1 on vinyl chloride-induced chromosome damage

    Institute of Scientific and Technical Information of China (English)

    王金伟

    2014-01-01

    Objective To evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride(VC)-induced chromosomal damage in peripheral lymphocytes.Methods In this study,317 workers occupationally exposed to VC were recruited from a factory in Shandong Province,China.The micronucleus(MN)frequency in peripheral lymphocytes was used as an indicator of chromosomal damage.Polymerase chain reaction-restriction fragment length polymorphism and created restriction site

  1. Biodosimetry: chromosome aberration in lymphocytes and electron paramagnetic resonance in tooth enamel from atomic bomb survivors

    International Nuclear Information System (INIS)

    One hundred enamel samples isolated from extracted teeth donated by atomic bomb survivors were subjected to free radical measurement by means of electron paramagnetic resonance (ESR). Results comparing ESR with the chromosome aberration frequency in lymphocytes of the tooth donors, and with the physically estimated DS86 dose suggested that ESR data correlated more closely with chromosome data than with the estimated DS86 doses, probably because DS86 may depend on erroneous memory in some cases. 9 refs, 4 figs

  2. Y-chromosome variability in four Native American populations from Panama.

    Science.gov (United States)

    The allele and haplotype frequencies for 13 Y-chromosome short tandem repeats (STRs) [nine STRs loci of the minimal Y chromosome haplotype (DYS19/DYS385a/DYS385b/DYS389-I/DYS389-II/DYS390/ DYS391/DYS392/ DYS393) plus four additional loci (DYS388/DYS426/DYS439/ DXYS156)] were determined in 99 males f...

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

    OpenAIRE

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

    1994-01-01

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

  4. Research on spontaneously emerged chromosomal aberrations in the periphery blood lymphocytes in cattle ('Busa' breed).

    Science.gov (United States)

    Hasanbasić, Danica; Rukavina, Dunja; Hodzić, Aida; Brka, Muhamed; Vegara, Mensur; Hamamdzić, Muhidin

    2007-11-01

    Knowledge of spontaneous aberrations, namely, of their frequency in non-irradiated cells is of paramount importance not only in cytogenetic research, but also in contemporary animal production. The paper deals with research on spontaneously emerged chromosomal aberrations in the peripheral blood lymphocytes in the cattle of 'Busa' breed. To obtain metaphase chromosomes the conventional method of lymphocyte cultivation was used, albeit slightly modified and adapted to the examined animals and the laboratory conditions. The research findings indicate that a certain percent of spontaneously emerged chromosomal aberrations of chromatid type (gap and break) have been found in the peripheral blood lymphocytes in the cattle of 'Busa' breed.

  5. The peopling of Europe and the cautionary tale of Y chromosome lineage R-M269

    OpenAIRE

    Busby, George B J; Brisighelli, Francesca; Sánchez-Diz, Paula; Ramos-Luis, Eva; Martinez-Cadenas, Conrado; Thomas, Mark G.; Bradley, Daniel G; Gusmão, Leonor; Winney, Bruce; Bodmer, Walter; Vennemann, Marielle; Coia, Valentina; Scarnicci, Francesca; Tofanelli, Sergio; Vona, Giuseppe

    2011-01-01

    Recently, the debate on the origins of the major European Y chromosome haplogroup R1b1b2-M269 has reignited, and opinion has moved away from Palaeolithic origins to the notion of a younger Neolithic spread of these chromosomes from the Near East. Here, we address this debate by investigating frequency patterns and diversity in the largest collection of R1b1b2-M269 chromosomes yet assembled. Our analysis reveals no geographical trends in diversity, in contradiction to expectation under the Neo...

  6. Tumor microenvironmental genomic alterations in juvenile nasopharyngeal angiofibroma

    DEFF Research Database (Denmark)

    Silveira, Sara Martoreli; Custódio Domingues, Maria Aparecida; Butugan, Ossamu;

    2012-01-01

    % of chromosomal alterations were common by both components. Gene expression analyses revealed a positive correlation between endothelial and stromal components for ASPM, CDH1, CTNNB1, FGF18, and SUPT16H. A significant difference was found for FGF18 and AURKB overexpression in stromal cells and AR down...

  7. Chromosomal Abnormalities in Iranian Infertile Males who are Candidates for Assisted Reproductive Techniques

    Directory of Open Access Journals (Sweden)

    Iman Salahshourifar

    2007-01-01

    Full Text Available Background: The present study offers our contribution on the topic by a retrospective analysis of the prevalence of chromosomal abnormalities in a population of Iranian infertile men attending assisted reproduction programs.Materials and Methods: Cytogenetic analysis was performed according to standard methods on cultured cells obtained from the patient peripheral blood. In all, 874 files belonging to male partner of each couple were classified as follows: azoospermic, oligozoospermic and patients with low sperm quality in respect of morphology and motility.Results: Chromosomal abnormalities were observed in 136(15.5% individuals of the whole population studied including 12.0 %, 1.2 % and 2.0% of azoospermic, oligozoospermic and patients with low sperm quality, respectively. Of those, 116 (13.2% had sex chromosome abnormalities and 20(2.3% had autosomal chromosome abnormalities.Conclusion: We observed high frequency of aneuploidy and sex chromosomal mosaicism in azoospermic men and high structural aberrations in males with low sperm quality. We suggested that type of chromosomal abnormalities had an inverse relation to sperm count. So that, high chromosomal aneuploidy was detected in males with lower sperm count and high structural aberration was detected in males with low sperm quality. Chromosomal abnormalities are a major cause of male infertility. Consequently, Genetic testing and counselling is indicated for infertile men with abnormal semen parameters with either abnormal karyotype or normal karyotype before applying assisted reproductive techniques.

  8. Characterization of chromosome structures of Falconinae (Falconidae, Falconiformes, Aves) by chromosome painting and delineation of chromosome rearrangements during their differentiation

    OpenAIRE

    Nishida, Chizuko; Ishijima, Junko; KOSAKA, Ayumi; Tanabe, Hideyuki; Habermann, Felix A.; Griffin, Darren K.; MATSHUDA, Yoichi; 秀之, 田辺

    2008-01-01

    Karyotypes of most bird species are characterized by around 2n = 80 chromosomes, comprising 7–10 pairs of large- and medium-sized macrochromosomes including sex chromosomes and numerous morphologically indistinguishable microchromosomes. The Falconinae of the Falconiformes has a different karyotype from the typical avian karyotype in low chromosome numbers, little size difference between macrochromosomes and a smaller number of microchromosomes. To characterize chromosome structures of Falcon...

  9. Characterization of chromosome structures of Falconinae (Falconidae, Falconiformes, Aves) by chromosome painting and delineation of chromosome rearrangements during their differentiation

    OpenAIRE

    Nishida, Chizuko; Ishijima, Junko; KOSAKA, Ayumi; Tanabe, Hideyuki; Habermann, Felix A.; Griffin, Darren K.; Matsuda, Yoichi

    2008-01-01

    Karyotypes of most bird species are characterized by around 2n = 80 chromosomes, comprising 7Y10 pairs of large- and medium-sized macrochromosomes including sex chromosomes and numerous morphologically indistinguishable microchromosomes. The Falconinae of the Falconiformes has a different karyotype from the typical avian karyotype in low chromosome numbers, little size difference between macrochromosomes and a smaller number of microchromosomes. To characterize chromosome structures of Falcon...

  10. A comparison of chromosomal aberrations induced by in vivo radiotherapy in human sperm and lymphocytes

    International Nuclear Information System (INIS)

    Chromosomal aberrations in human sperm and lymphocytes were compared before and after in vivo radiation treatment of 13 cancer patients. The times of analyses after radiotherapy (RT) were 1, 3, 12, 24, 36, 48 and 60 months. The median total radiation dose was 30 Gy and the testicular dose varied from 0.4 to 5.0 Gy. Human sperm chromosome complements were analysed after fusion with golden hamster eggs. There were no abnormalities in sperm or lymphocytes before RT. Following RT there was an increase in the frequency of numerical and structural chromosomal abnormalities in both lymphocytes and sperm. For structural abnormalities there were more rejoined lesions (dicentrics, rings) in lymphocytes and more unrejoined lesions (chromosome breaks, fragments) in sperm. It appears that the frequency of lymphocyte chromosomal abnormalities had an initial marked increase after RT followed by a gradual decrease with time whereas the frequency of sperm chromosomal abnormalities was elevated when sperm production recovered and remained elevated from 24 to 60 mo. post-RT. This difference in the effect of time makes it very difficult to compare abnormality rates in lymphocytes and sperm and to use analysis of induced damage in somatic cells as surrogates for germ cells since the ratio between sperm and lymphocytes varied from 1:1 (at 24 mo. post-RT) to 5:1 (at 60 mo. post-RT). (author). 14 refs.; 2 figs.; 5 tabs

  11. Possible role of chromatin alteration in the radiosensitivity of ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Hittelman, W.N. [Anderson (M.D.) Cancer Center, Houston, TX (United States); Pandita, T.K. [Columbia Univ., New York, NY (United States). Dept. of Radiation Oncology

    1994-12-01

    Cells derived from individuals with ataxia-telangiectasia (A-T) are known to exhibit increased sensitivity to ionizing radiation and certain radiomimetic chemical agents. Here we summarize our findings regarding the role of chromosome damage and repair in this radiosensitivity. Lymphoblastoid cells derived from A-T homozygotes were characterized for initial chromosome (premature chromosome condensation) and DNA (neutral filter elution) damage and repair kinetics in cells from G1 and G2 cell cycle phases. Despite initial levels of DNA damage being similar to normal controls, A-T cells exhibited nearly a two-fold higher initial amount of chromosome damage. Different A-T cell lines exhibited differing chromosome repair capacities compared with control lymphoblastoid cell lines. These results suggest that A-T cells have an altered chromatin structure whereby DNA double-strand breaks are apparently more efficiently converted into chromosome breaks. (author).

  12. Possible role of chromatin alteration in the radiosensitivity of ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Cells derived from individuals with ataxia-telangiectasia (A-T) are known to exhibit increased sensitivity to ionizing radiation and certain radiomimetic chemical agents. Here we summarize our findings regarding the role of chromosome damage and repair in this radiosensitivity. Lymphoblastoid cells derived from A-T homozygotes were characterized for initial chromosome (premature chromosome condensation) and DNA (neutral filter elution) damage and repair kinetics in cells from G1 and G2 cell cycle phases. Despite initial levels of DNA damage being similar to normal controls, A-T cells exhibited nearly a two-fold higher initial amount of chromosome damage. Different A-T cell lines exhibited differing chromosome repair capacities compared with control lymphoblastoid cell lines. These results suggest that A-T cells have an altered chromatin structure whereby DNA double-strand breaks are apparently more efficiently converted into chromosome breaks. (author)

  13. Molecular analysis of the distribution of chromosomal breakpoints: characterization of a 'hot' region for breaks in human chromosome 11

    International Nuclear Information System (INIS)

    Full text: Ionizing radiation randomly damages DNA and chromosomes whereas subsequent chromosome breaks are non-random. Assuming, as an ideal and naive but useful proposition, that breaks are equally likely anywhere in the chromosome and that a deletion always occurs between two breaks, the frequency of fragments would decrease linearly with increasing fragment size. This simple distribution is not, however, observed. To shed light on the 'real' situation of break formation we mapped breakpoints in the human chromosome no. 11 of 353 independent CD59- mutants isolated from human/hamster hybrid AL cells exposed to radiations (high and low dose-rate gamma rays, high LET carbon or nitrogen ions, protons) or chemicals (arsenic or irradiated, mutagenic histidine) or unexposed. The number of breaks per unit length of DNA differed significantly in different regions of chromosome 11.The highest level of breaks (140/mbp) were in the 0.8 mbp segment between CD59 and Catalase (CAT). Finer mapping of break points was carried out using 26 PCR primer pairs spread across this interval in 15 independent mutants. In two mutants, the break point was in a 107 bp fragment; in the other 13 the breaks were in a single 35 mbp fragment, but not all were at exactly the same site; 4 of 13 occurred in 3 different 3 mbp sub-segments. We are sequencing these fragments to look for such features as repeats: 'colder' regions like that between CD59 and WT will also be analyzed. But, since at least some breaks occurred at different sites and the frequency and distribution of breaks was about the same for all treatments, our we postulate that hot (and cold spots) may be due more to structural features or specific repair than to sequence or type of damage

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  15. Frequency standards

    CERN Document Server

    Riehle, Fritz

    2006-01-01

    Of all measurement units, frequency is the one that may be determined with the highest degree of accuracy. It equally allows precise measurements of other physical and technical quantities, whenever they can be measured in terms of frequency.This volume covers the central methods and techniques relevant for frequency standards developed in physics, electronics, quantum electronics, and statistics. After a review of the basic principles, the book looks at the realisation of commonly used components. It then continues with the description and characterisation of important frequency standards

  16. Studies of Tumor Suppressor Genes via Chromosome Engineering

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kugoh

    2015-12-01

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

  17. Chromosome Territory Modeller and Viewer

    Science.gov (United States)

    Idziak-Helmcke, Dominika; Robaszkiewicz, Ewa; Hasterok, Robert

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi–a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license. PMID:27505434

  18. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...

  19. CHROMOSOMAL MULTIPLICITY IN BURKHOLDERIA CEPACIA

    Science.gov (United States)

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

  20. Chromosomal disorders and male infertility

    Institute of Scientific and Technical Information of China (English)

    Gary L Harton; Helen G Tempest

    2012-01-01

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

  1. Chromosome Territory Modeller and Viewer.

    Science.gov (United States)

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

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi-a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license. PMID:27505434

  2. Drosophila SAF-B links the nuclear matrix, chromosomes, and transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Catalina Alfonso-Parra

    Full Text Available Induction of gene expression is correlated with alterations in nuclear organization, including proximity to other active genes, to the nuclear cortex, and to cytologically distinct domains of the nucleus. Chromosomes are tethered to the insoluble nuclear scaffold/matrix through interaction with Scaffold/Matrix Attachment Region (SAR/MAR binding proteins. Identification and characterization of proteins involved in establishing or maintaining chromosome-scaffold interactions is necessary to understand how the nucleus is organized and how dynamic changes in attachment are correlated with alterations in gene expression. We identified and characterized one such scaffold attachment factor, a Drosophila homolog of mammalian SAF-B. The large nuclei and chromosomes of Drosophila have allowed us to show that SAF-B inhabits distinct subnuclear compartments, forms weblike continua in nuclei of salivary glands, and interacts with discrete chromosomal loci in interphase nuclei. These interactions appear mediated either by DNA-protein interactions, or through RNA-protein interactions that can be altered during changes in gene expression programs. Extraction of soluble nuclear proteins and DNA leaves SAF-B intact, showing that this scaffold/matrix-attachment protein is a durable component of the nuclear matrix. Together, we have shown that SAF-B links the nuclear scaffold, chromosomes, and transcriptional activity.

  3. Chromosomal and Genetic Analysis of a Human Lung Adenocarcinoma Cell Line OM

    Institute of Scientific and Technical Information of China (English)

    Yong-Wu Li; Lin Bai; Lyu-Xia Dai; Xu He; Xian-Ping Zhou

    2016-01-01

    Background: Lung cancer has become the leading cause of death in many regions.Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes.The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM.Methods: We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations.In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer-related genes were also detected by polymerase chain reaction (PCR).Results: We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19.Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations.CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33 and 17p 13.1-13.3.And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG).Conclusions: The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis.We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33, and 17p 13.1-13.3.Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM.

  4. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH SPERM DISORDERS

    OpenAIRE

    L. Y. Pylyp; L. A. Spinenko; V. D. Zukin; N. M. Bilko

    2013-01-01

    Chromosomal abnormalities are among the most common genetic causes of spermatogenic disruptions. Carriers of chromosomal abnormalities are at increased risk of infertility, miscarriage or birth of a child with unbalanced karyotype due to the production of unbalanced gametes. The natural selection against chromosomally abnormal sperm usually prevents fertilization with sperm barring in cases of serious chromosomal abnormalities. However, assisted reproductive technologies in general and intrac...

  5. Multicolor spectral karyotyping of human chromosomes.

    Science.gov (United States)

    Schröck, E; du Manoir, S; Veldman, T; Schoell, B; Wienberg, J; Ferguson-Smith, M A; Ning, Y; Ledbetter, D H; Bar-Am, I; Soenksen, D; Garini, Y; Ried, T

    1996-07-26

    The simultaneous and unequivocal discernment of all human chromosomes in different colors would be of significant clinical and biologic importance. Whole-genome scanning by spectral karyotyping allowed instantaneous visualization of defined emission spectra for each human chromosome after fluorescence in situ hybridization. By means of computer separation (classification) of spectra, spectrally overlapping chromosome-specific DNA probes could be resolved, and all human chromosomes were simultaneously identified. PMID:8662537

  6. Frequencies of mutagen-induced coincident mitotic recombination at unlinked loci in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Kathryn M. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States); Hoffmann, George R. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)]. E-mail: ghoffmann@holycross.edu

    2007-03-01

    Frequencies of coincident genetic events were measured in strain D7 of Saccharomyces cerevisiae. This diploid strain permits the detection of mitotic gene conversion involving the trp5-12 and trp5-27 alleles, mitotic crossing-over and gene conversion leading to the expression of the ade2-40 and ade2-119 alleles as red and pink colonies, and reversion of the ilv1-92 allele. The three genes are on different chromosomes, and one might expect that coincident (simultaneous) genetic alterations at two loci would occur at frequencies predicted by those of the single alterations acting as independent events. Contrary to this expectation, we observed that ade2 recombinants induced by bleomycin, {beta}-propiolactone, and ultraviolet radiation occur more frequently among trp5 convertants than among total colonies. This excess among trp5 recombinants indicates that double recombinants are more common than expected for independent events. No similar enrichment was found among Ilv{sup +} revertants. The possibility of an artifact in which haploid yeasts that mimic mitotic recombinants are generated by a low frequency of cryptic meiosis has been excluded. Several hypotheses that can explain the elevated incidence of coincident mitotic recombination have been evaluated, but the cause remains uncertain. Most evidence suggests that the excess is ascribable to a subset of the population being in a recombination-prone state.

  7. Transcriptional burst frequency and burst size are equally modulated across the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Dar, Roy D. [University of Tennessee, Knoxville (UTK); Simpson, Michael L [ORNL; Weinberger, Leor S. [University of California, San Diego; Razooky, B [University of California, San Diego; Cox, Chris D. [University of Tennessee, Knoxville (UTK); McCollum, James M. [Miami University; Trimeloni, Tom [Virginia Commonwealth University, Richland; Singh, A [University of California, San Diego

    2012-01-01

    Gene expression occurs either as an episodic process, characterized by pulsatile bursts or as a constitutive, Poisson-like accumulation of gene products. It is not clear which mode of gene expression (constitutive versus bursty) predominates across a genome or how transcriptional dynamics are influenced by genomic position and promoter sequence. Here, we use time-lapse fluorescence microscopy, building off of theoretical studies that exploit the time-resolved structure of stochastic fluctuations in gene expression, to develop a three-dimensional method for mapping underlying gene-regulatory mechanisms. Over 8,000 individual human genomic loci were analyzed, and at virtually all loci, episodic bursting as opposed to constitutive expression was found to be the predominant mode of expression. Quantitative analysis of the expression dynamics at these 8,000 loci indicates that both frequency and size of transcriptional bursts vary equally across the human genome independent of promoter sequence. Strikingly, weaker expression loci modulate burst frequency to increase activity, while stronger expression loci modulate burst size to increase activity. Transcriptional activators, such as TNF, generate similar patterns of change in burst frequency and burst size. In summary, transcriptional bursting dominates across the human genome, both burst frequency and burst size vary by chromosomal location, and transcriptional activators alter burst frequency and burst size, depending on the expression level of the locus.

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

    Science.gov (United States)

    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. PMID:23536543

  9. The Relationship between Chromosome Number and its Variation in the Plants and Habitats%植物染色体数目及其变异与生境关系初探

    Institute of Scientific and Technical Information of China (English)

    王琼; 苏智先; 宋会兴; 汤泽生

    2001-01-01

    Based on the data collected on chromosome number of 1027 species and ecological environment of plants,the relationships between environmental factors and the changing rules of chromosome number,polyploidy,B chromosome were discussed.The results showed that under different light,moisture content and soil conditions,the chromosome number of plant is different in multiformity,variation extent and the highest frequency.The frequency of polyploid is relative to habitats and growing habits.The plant with B chromosome is often distributed over the subtropics and humid environment.

  10. Chromosomal mosaicism of extraembryonic cells detected by prenatal diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Zolotukhina, T.V.; Shilova, N.V. [Institute of Clinical Genetics, Moscow (Russian Federation)

    1995-09-01

    Data on detection of chromosomal mosaicism in amniotic cells and chorionic villi obtained by prenatal cytogenetic diagnosis are presented. The frequency of chromosomal mosaicism in preparations of amniotic fluid cell culture was 2.6% (6 out of 226), and that in {open_quotes}direct{close_quotes} villus preparations was 1.6% (13 out of 774). The necessity to perform an additional analysis of other fetal cells or neonatal lymphocytes to specify the diagnosis was shown. The analysis of the outcome of pregnancies during which chromosomal mosaicism in the extraembryonic cells was detected indicates that these women form a high-risk group, both genetically and obstetrically; in only 8 out of 19 cases did pregnancies end in normal deliveries at term; in three cases, spontaneous abortions occurred at 16-31 weeks of gestation; in three cases, the pregnancies were terminated due to fetal chromosomal aberrations in nonmosaic form; the outcome of pregnancy in five cases was preterm delivery of an underweight newborn. 26 refs., 1 tab.

  11. Propranolol induced chromosomal aberrations in Chinese hamster ovary cell line

    Directory of Open Access Journals (Sweden)

    Mozhgan Sedigh-Ardekani

    2013-03-01

    Full Text Available Propranolol (PL, a non-selective beta-blocker, is a cardiovascular drug widely used to treat hypertension. The present study was concerned with assessing the cytogenetic effects of this drug on Chinese hamster ovary (CHO cell line. MTT assay was then carried out to determine the cytotoxicity index (IC50 of the drug. The IC50 value of PL was 0.43±0.02 mM. To investigate the clastogenic effects of the drug, chromatid and chromosome breaks and polyploidy in metaphases were analyzed. CHO cells were exposed to different concentrations of the drug (0.1, 0.2, 0.3, 0.4 mM for 24 hours. Considering that PL has liver metabolism, experiments were carried out in the presence and absence of the metabolic activation system (S9 mix. Mitomycin-C and sodium arsenite were used as positive controls. It was observed that in cells treated with different PL concentrations as 0.1, 0.2 and 0.3 mM, the frequency of chromatid and chromosome breaks as well as polyploidy increased when compared with untreated CHO cells. The addition of S9 mix significantly decreased the chromatid breaks, chromosome breaks and polyploidy compared to the treatment of PL alone. It is concluded that, PL causes chromatid and chromosome aberrations in CHO cell line and the metabolic activation system (S9 mix, playing an important role in drug cytotoxicity reduction.

  12. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    1987-01-01

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

  13. Genetic dosage and position effect of small supernumerary marker chromosome (sSMC) in human sperm nuclei in infertile male patient.

    Science.gov (United States)

    Olszewska, Marta; Wanowska, Elzbieta; Kishore, Archana; Huleyuk, Nataliya; Georgiadis, Andrew P; Yatsenko, Alexander N; Mikula, Mariya; Zastavna, Danuta; Wiland, Ewa; Kurpisz, Maciej

    2015-11-30

    Chromosomes occupy specific distinct areas in the nucleus of the sperm cell that may be altered in males with disrupted spermatogenesis. Here, we present alterations in the positioning of the human chromosomes 15, 18, X and Y between spermatozoa with the small supernumerary marker chromosome (sSMC; sSMC(+)) and spermatozoa with normal chromosome complement (sSMC(-)), for the first time described in the same ejaculate of an infertile, phenotypically normal male patient. Using classical and confocal fluorescent microscopy, the nuclear colocalization of chromosomes 15 and sSMC was analyzed. The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat. Analysis of meiotic segregation showed a 1:1 ratio of sSMC(+) to sSMC(-) spermatozoa, while evaluation of sperm aneuploidy status indicated an increased level of chromosome 13, 18, 21 and 22 disomy, up to 7 × (2.7 - 15.1). Sperm chromatin integrity assessment did not reveal any increase in deprotamination in the patient's sperm chromatin. Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC. This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.

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

    Directory of Open Access Journals (Sweden)

    Hong Wei Yang

    2012-01-01

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

  15. Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis.

    Science.gov (United States)

    Wandke, Cornelia; Barisic, Marin; Sigl, Reinhard; Rauch, Veronika; Wolf, Frank; Amaro, Ana C; Tan, Chia H; Pereira, Antonio J; Kutay, Ulrike; Maiato, Helder; Meraldi, Patrick; Geley, Stephan

    2012-09-01

    Chromokinesins are microtubule plus end-directed motor proteins that bind to chromosome arms. In Xenopus egg cell-free extracts, Xkid and Xklp1 are essential for bipolar spindle formation but the functions of the human homologues, hKID (KIF22) and KIF4A, are poorly understood. By using RNAi-mediated protein knockdown in human cells, we find that only co-depletion delayed progression through mitosis in a Mad2-dependent manner. Depletion of hKID caused abnormal chromosome arm orientation, delayed chromosome congression, and sensitized cells to nocodazole. Knockdown of KIF4A increased the number and length of microtubules, altered kinetochore oscillations, and decreased kinetochore microtubule flux. These changes were associated with failures in establishing a tight metaphase plate and an increase in anaphase lagging chromosomes. Co-depletion of both chromokinesins aggravated chromosome attachment failures, which led to mitotic arrest. Thus, hKID and KIF4A contribute independently to the rapid and correct attachment of chromosomes by controlling the positioning of chromosome arms and the dynamics of microtubules, respectively. PMID:22945934

  16. Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe

    Indian Academy of Sciences (India)

    Aditya S Pratihar; Vishnu P Tripathi; Mukesh P Yadav; Dharani D Dubey

    2015-12-01

    Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2OO4, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2OO4 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727-associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2OO4 or ars727 remains unaltered by the extended chromosomal context.

  17. Aneuploidy: the impact of chromosome imbalance on nuclear organization and overall genome expression.

    Science.gov (United States)

    Hervé, B; Coussement, A; Gilbert, T; Dumont, F; Jacques, S; Cuisset, L; Chicard, M; Hizem, S; Bourdoncle, P; Letourneur, F; Dupont, C; Vialard, F; Choiset, A; Dupont, J-M

    2016-07-01

    The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression. PMID:27283765

  18. Chromosomal bands affected by acute oil exposure and DNA repair errors.

    Directory of Open Access Journals (Sweden)

    Gemma Monyarch

    Full Text Available BACKGROUND: In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. OBJECTIVES: We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. METHODS: Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. RESULTS: Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016. CONCLUSION: The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.

  19. Somatic pairing of chromosome 19 in renal oncocytoma is associated with deregulated EGLN2-mediated [corrected] oxygen-sensing response.

    Directory of Open Access Journals (Sweden)

    Julie M Koeman

    Full Text Available Chromosomal abnormalities, such as structural and numerical abnormalities, are a common occurrence in cancer. The close association of homologous chromosomes during interphase, a phenomenon termed somatic chromosome pairing, has been observed in cancerous cells, but the functional consequences of somatic pairing have not been established. Gene expression profiling studies revealed that somatic pairing of chromosome 19 is a recurrent chromosomal abnormality in renal oncocytoma, a neoplasia of the adult kidney. Somatic pairing was associated with significant disruption of gene expression within the paired regions and resulted in the deregulation of the prolyl-hydroxylase EGLN2 [corrected] a key protein that regulates the oxygen-dependent degradation of hypoxia-inducible factor (HIF. Overexpression of EGLN2 [corrected] in renal oncocytoma increased ubiquitin-mediated destruction of HIF and concomitantly suppressed the expression of several HIF-target genes, including the pro-death BNIP3L gene. The transcriptional changes that are associated with somatic pairing of chromosome 19 mimic the transcriptional changes that occur following DNA amplification. Therefore, in addition to numerical and structural chromosomal abnormalities, alterations in chromosomal spatial dynamics should be considered as genomic events that are associated with tumorigenesis. The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma.

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

    OpenAIRE

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

    2015-01-01

    Abstract B chromosomes are dispensable genomic elements found in different groups of animals and plants. In the present study, a whole chromosome probe was generated from a specific heterochromatic B chromosome occurring in cells of the characidae fish Moenkhausia sanctaefilomenae (Steindachner, 1907). The chromosome painting probes were used in fluorescence in situ hybridization (FISH) experiments for the assessment of metaphase chromosomes obtained from individuals from three populations of...

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

    Directory of Open Access Journals (Sweden)

    Wen Ying

    2010-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  3. Novel insights into mitotic chromosome condensation

    Science.gov (United States)

    Piskadlo, Ewa; Oliveira, Raquel A.

    2016-01-01

    The fidelity of mitosis is essential for life, and successful completion of this process relies on drastic changes in chromosome organization at the onset of nuclear division. The mechanisms that govern chromosome compaction at every cell division cycle are still far from full comprehension, yet recent studies provide novel insights into this problem, challenging classical views on mitotic chromosome assembly. Here, we briefly introduce various models for chromosome assembly and known factors involved in the condensation process (e.g. condensin complexes and topoisomerase II). We will then focus on a few selected studies that have recently brought novel insights into the mysterious way chromosomes are condensed during nuclear division.

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

    Science.gov (United States)

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

    2016-05-01

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

  5. Further delineation of complex chromosomal rearrangements in fertile male using multicolor banding

    Directory of Open Access Journals (Sweden)

    Weise Anja

    2008-08-01

    Full Text Available Abstract Background Complex chromosomal rearrangements (CCRs are defined as structural chromosomal rearrangements with at least three breakpoints and exchange of genetic material between two or more chromosomes. Complex chromosomal translocations are rarely seen in the general population but the frequency of occurrence is anticipated to be much higher due balanced states with no phenotypic presentation. Here, we report a severely mentally retarded fertile male patient in whom further delineation of CCR involving chromosomes 1, 4 and 2 was carried out by using high resolution multicolor banding (MCB technique. As a FISH based novel chromosome banding approach, high resolution MCB allows for the differentiation of chromosome region specific areas at band and subband levels. Results Cytogenetic studies using high resolution banding of the proband necessitated further delineation of the breakpoints because of their uncertainty: 46,XY,t(1;4;2(p21~31;q31.3;q31. After using high resolution MCB based on microdissection derived region-specific libraries, the exact nature of chromosomal rearrangements for chromosomes 1, 2 and 4 were revealed and these breakpoints were located on 1p31.1, 1q24.3 and 4q31.3 giving rise to a balanced situation. Conclusion Further delineations are certainly required to provide detailed information about the relationship between balanced CCRs and their phenotypes in order to offer proper counseling to the families concerned. Carriers must be investigated with high resolution banding and molecular cytogenetic techniques to determine the exact locations of the breakpoints. High resolution MCB is an alternative and an efficient method to other FISH based chromosome banding techniques and can serve in clarifying the nature of CCR.

  6. On the demultiplexing of chromosome capture conformation data.

    Science.gov (United States)

    Junier, Ivan; Spill, Yannick G; Marti-Renom, Marc A; Beato, Miguel; le Dily, François

    2015-10-01

    How to describe the multiple chromosome structures that underlie interactions among genome loci and how to quantify the occurrence of these structures in a cell population remain important challenges to solve, which can be addressed via a proper demultiplexing of chromosome capture conformation related data. Here, we first aim to review two main methodologies that have been proposed to tackle this problem: restrained-based methods, in which the resulting chromosome structures stem from the multiple solutions of a distance satisfaction problem; and thermodynamic-based methods, in which the structures stem from the simulation of polymer models. Next, we propose a novel demultiplexing method based on a matrix decomposition of contact maps. To this end, we extend the notion of topologically associated domains (TADs) by introducing that of statistical interaction domains (SIDs). SIDs can overlap and occur in a cell population at certain frequencies, and we propose a simple method to estimate these frequency values. As an application, we show that SIDs that measure 100kb to tens of Mb long occur both frequently and specifically in the human genome. PMID:26054977

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

    Science.gov (United States)

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

    2013-03-01

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

  8. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, January 1, 1981-December 31, 1981

    International Nuclear Information System (INIS)

    The overall aim is to determine whether there is a relationship between exposure to radiation, environmental pollutants, and/or genetic background and the development of ANLL or other hematologic malignancies. I will try to define the factors that influence the development of ANLL as a second malignancy in patients who have been exposed to large doses of radiotherapy and/or chemotherapeutic agents. Two long-term goals are (1) to identify the genes that are located at the sites of consistent translocations, and then to determine the alterations in gene function that are associated with these translocations and (2) to establish the baseline frequency of various chromosome changes (mutations) in myeloid cells and then to analyze the influence of various types of environmental exposure or medical treatment on this baseline mutation rate. Ultimately, it may be possible to determine the extent of mutagenic exposure in various populations through an analysis of the leukemic cells of that populations

  9. Thinner abuse alters peak of frequency of EEG spectra analyses El abuso de tíner altera el pico de frecuencia del análisis espectral del EEG

    Directory of Open Access Journals (Sweden)

    Adrián Poblano

    2006-12-01

    Full Text Available STUDY OBJECTIVE: The aim of the investigation was to use electroencephalography (EEG to study whether long-term thinner abuse may result in the slowing, disorganization and asymmetry of the EEG cortical rhythms. METHOD: Twenty-two patients attending with antecedent of thinner abuse only, and twenty two controls without alcohol, smoking, and drug abuse in the same age range and gender were studied. EEG recording were compared by means of the analyses of peak of frequency (POF, frequency of disorganization, and asymmetry of the background activity in patients and controls at rest eyes-closed condition in electrodes P3, P4, O1, and O2. RESULTS: Significant differences in POF among groups was observed in P3 and P4 location showing lower values in thinner abusers, but not in O1 and O2 locations. Frequencies of disorganization and asymmetry showed significantly higher proportions in thinner abusers. Bivariate correlations among POF at the four electrode location and time of thinner abuse showed significant values. However after partial correlation calculation correcting for age, significant values disappeared. CONCLUSION: Thus thinner abuse relates with slowing of POF in the EEG of patients with thinner abuse associated with disorganization, and asymmetry depending on time of abuse.OBJETIVO: Utilizar el electroencefalograma (EEG para estudiar si el abuso o intoxicación crónica por tíner produce lentificación, desorganización y asimetría de la actividad eléctrica cortical. MÉTODO: Se estudiaron 22 pacientes con antecedentes de intoxicación crónica por tíner y 22 sujetos sin antecedentes de abuso de tíner, alcohol, cigarro o drogas en el mismo rango de edad y en igual número de acuerdo al género. Se registro el EEG cuantitativo y se compararon: el promedio del pico de frecuencia (PoF, la frecuencia de desorganización de la actividad de fondo y la presencia de asimetría inter-hemisférica en la condición de reposo físico y mental entre

  10. Dynamics of chromosome segregation in Escherichia coli

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck

    2007-01-01

    Since the 1960’es the conformation and segregation of the chromosome in Escherichia coli has been a subject of interest for many scientists. However, after 40 years of research, we still know incredibly little about how the chromosome is organized inside the cell, how it manages to duplicate...... method enabled us to start the analysis on the distribution of various chromosomal loci inside slowly growing cells. With the actual counting and measuring no longer being any problem we could easily analyze 14 loci distributed on the E.coli chromosome. More than 15.000 cells were analyzed in total...... the new system, which is based on the pMT1 par system from Yersenia pestis, we labeled loci on opposite sides of the E.coli chromosome simultaneously and were able to show that the E.coli chromosome is organized with one chromosomal arm in each cell half. This astounding result is described in Paper III...

  11. Mitosis. Microtubule detyrosination guides chromosomes during mitosis.

    Science.gov (United States)

    Barisic, Marin; Silva e Sousa, Ricardo; Tripathy, Suvranta K; Magiera, Maria M; Zaytsev, Anatoly V; Pereira, Ana L; Janke, Carsten; Grishchuk, Ekaterina L; Maiato, Helder

    2015-05-15

    Before chromosomes segregate into daughter cells, they align at the mitotic spindle equator, a process known as chromosome congression. Centromere-associated protein E (CENP-E)/Kinesin-7 is a microtubule plus-end-directed kinetochore motor required for congression of pole-proximal chromosomes. Because the plus-ends of many astral microtubules in the spindle point to the cell cortex, it remains unknown how CENP-E guides pole-proximal chromosomes specifically toward the equator. We found that congression of pole-proximal chromosomes depended on specific posttranslational detyrosination of spindle microtubules that point to the equator. In vitro reconstitution experiments demonstrated that CENP-E-dependent transport was strongly enhanced on detyrosinated microtubules. Blocking tubulin tyrosination in cells caused ubiquitous detyrosination of spindle microtubules, and CENP-E transported chromosomes away from spindle poles in random directions. Thus, CENP-E-driven chromosome congression is guided by microtubule detyrosination. PMID:25908662

  12. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

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

    2009-01-01

    -positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane...... chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival'' genes is associated with poor outcome in estrogen receptor...... resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents....

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

    Science.gov (United States)

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

  14. Chromosomal instability determines taxane response

    OpenAIRE

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

    2009-01-01

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

  15. Environmental pollution, chromosomes, and health

    Science.gov (United States)

    Bell, Peter M.

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

  16. GSK-3 inhibitors induce chromosome instability

    Directory of Open Access Journals (Sweden)

    Staples Oliver D

    2007-08-01

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

  17. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.

    1982-01-01

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

  18. Chromosome rearrangements and transposable elements.

    Science.gov (United States)

    Lonnig, Wolf-Ekkehard; Saedler, Heinz

    2002-01-01

    There has been limited corroboration to date for McClintock's vision of gene regulation by transposable elements (TEs), although her proposition on the origin of species by TE-induced complex chromosome reorganizations in combination with gene mutations, i.e., the involvement of both factors in relatively sudden formations of species in many plant and animal genera, has been more promising. Moreover, resolution is in sight for several seemingly contradictory phenomena such as the endless reshuffling of chromosome structures and gene sequences versus synteny and the constancy of living fossils (or stasis in general). Recent wide-ranging investigations have confirmed and enlarged the number of earlier cases of TE target site selection (hot spots for TE integration), implying preestablished rather than accidental chromosome rearrangements for nonhomologous recombination of host DNA. The possibility of a partly predetermined generation of biodiversity and new species is discussed. The views of several leading transposon experts on the rather abrupt origin of new species have not been synthesized into the macroevolutionary theory of the punctuated equilibrium school of paleontology inferred from thoroughly consistent features of the fossil record. PMID:12429698

  19. [239Pu and chromosomal aberrations in human peripheral blood lymphocytes].

    Science.gov (United States)

    Okladnikova, N D; Osovets, S V; Kudriavtseva, T I

    2009-01-01

    The genome status in somatic cells was assessed using the chromosomal aberration (CA) test in peripheral blood lymphocytes from 194 plutonium workers exposed to occupational radiation mainly from low-transportable compounds of airborne 230Pu. Pu body burden at the time of cytogenetic study varied from values close to the method sensitivity to values multiply exceeding the permissible level. Standard (routine) methods of peripheral blood lymphocytes cultivation were applied. Chromatid- and chromosomal-type structural changes were estimated. Aberrations were estimated per 100 examined metaphase cells. The quantitative relationship between the CA frequency and Pu body burden and the absorbed dose to the lung was found. Mathematical processing of results was carried out based on the phenomenological model. The results were shown as theoretical and experimental curves. The threshold of the CA yield was 0.43 +/- 0.03 kBq (Pu body burden) and 6.12 +/- 1.20 cGy (absorbed dose to the lung).

  20. Is Native American R Y-Chromosome of African Origin?

    Directory of Open Access Journals (Sweden)

    Clyde Winters

    2011-11-01

    Full Text Available Controversey surrounds the phylogeography and origin of the R haplotype among Native Americans. Some researchers have suggested that Europeans spread this haplotype among Native Americans. The purpose of this study was to determine the origin of the R-M173 y-chromosome among Native Americans . It is the third most frequent y-chromosome possessed by Native Americans. Native Americans with the highest frequency of R-M173 haplotypes like the Ojibwa and Seminoles mated frequently with African males. Our findings indicate that the African male, Native American female pattern of mating in the United States probably led to the introduction and spread of R-M173 among Native Americans during slavery.

  1. Chromosomal anomalies in radiation-induced fibrosis in the pig

    International Nuclear Information System (INIS)

    R-banded karyotypes were established on fibroblasts from fibrotic tissues derived from experimental fibrosis induced in pigs, either surgically or by 64 Gy of γ-rays from iridium-192. No chromosome aberrations were observed in the surgical fibrosis. In radiation-induced fibrosis, the high frequency of abnormal karyotypes and frequent complexity of the chromosomal rearrangements suggest that the fibroblasts originated either from the 64-Gy area, or from the penumbra, but certainly not from non-irradiated areas. At early passages in vitro, almost all karyotypes were different, demonstrating a multiclonal origin of fibrotic tissue. At late passages (above 24), the situation was quite different, with the persistence of one or two clones only, demonstrating a strong selective pressure occurring in vitro. (author). 23 refs., 2 figs., 2 tabs

  2. Association testing to detect gene-gene interactions on sex chromosomes in trio data

    Directory of Open Access Journals (Sweden)

    Yeonok eLee

    2013-11-01

    Full Text Available Autism Spectrum Disorder (ASD occurs more often among males than females in a 4:1 ratio. Among theories used to explain the causes of ASD, the X chromosome and the Y chromosome theories attribute ASD to X-linked mutation and the male-limited gene expressions on the Y chromosome, respectively. Despite the rationale of the theory, studies have failed to attribute the sex-biased ratio to the significant linkage or association on the regions of interest on X chromosome. We further study the gender biased ratio by examining the possible interaction effects between two genes in the sex chromosomes. We propose a logistic regression model with mixed effects to detect gene-gene interactions on sex chromosomes. We investigated the power and type I error rates of the approach for a range of minor allele frequencies and varying linkage disequilibrium between markers and QTLs. We also evaluated the robustness of the model to population stratification. We applied the model to a trio-family data set with an ASD affected male child to study gene-gene interactions on sex chromosomes.

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

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    Pedro Simões

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

  4. CHROMOSOME 17P MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

    Institute of Scientific and Technical Information of China (English)

    胡杰; 江澄川; 吴浩强; 彭颂先; 唐婉君

    2002-01-01

    Objective: To investigate whether deletion of chromosome 17 is involved in the carcinogenesis of primary glioblastoma multiforme and to localize the possible common deletion region in the aforementioned chromosome. Methods: Polymerase chain reaction-based microsatellite analysis was used to assess loss of heterozygosity (LOH) on chromosome 17 in 20 primary glioblastoma multiforme (GBM). Fifteen fluorescent dye-labeled polymorphic markers were used. Results: Thirteen of twenty (65%) GBM displayed LOH on at least one marker of chromosome 17p. Two tumors showed either LOH or non-informativeness on all markers tested. The most frequent LOH was observed at loci including D17s799 (53.3%), Dl7s1852 (53.8%), Dl7s938 (63.20/o), Dl7s831 (55.6%). The loci D17s831 (on 17pl3) and D17s799(Dl7sl852 (17p11.2(pl2) are distal and proximal to p53 respectively. The frequencies of LOH at all loci examined on chromosome 17q were relatively low (<30%). None of informative loci exhibited microsatellite instability in this study. Conclusion: Loss of genetic material on chromosome 17p may play an important role in the pathogenesis of GBM. Besides the well-known TSG p53 on 17p, other unknown TSCs associated with GBM may be present on the chromosomal regions 17pl3 and 17p11.2(pl2, which are distal and proximal to p53 respectively.

  5. The epitheliogenesis imperfecta locus maps to equine chromosome 8 in American Saddlebred horses.

    Science.gov (United States)

    Lieto, L D; Cothran, E G

    2003-01-01

    Epitheliogenesis imperfecta (EI) is a hereditary junctional mechanobullous disease that occurs in newborn American Saddlebred foals. The pathological signs of epitheliogenesis imperfecta closely match a similar disease in humans known as Herlitz junctional epidermolysis bullosa, which is caused by a mutation in one of the genes (LAMA3, LAMB3 and LAMC2) coding for the subunits of the laminin 5 protein (laminin alpha3, laminin beta3 and laminin gamma2). The LAMA3 gene has been assigned to equine chromosome 8 and LAMB3 and LAMC2 have been mapped to equine chromosome 5. Linkage disequilibrium between microsatellite markers that mapped to equine chromosome 5 and equine chromosome 8 and the EI disease locus was tested in American Saddlebred horses. The allele frequencies of microsatellite alleles at 11 loci were determined for both epitheliogenesis imperfecta affected and unaffected populations of American Saddlebred horses by genotyping and direct counting of alleles. These were used to determine fit to Hardy-Weinberg equilibrium for control and EI populations using Chi square analysis. Two microsatellite loci located on equine chromosome 8q, ASB14 and AHT3, were not in Hardy-Weinberg equilibrium in affected American Saddlebred horses. In comparison, all of the microsatellite markers located on equine chromosome 5 were in Hardy-Weinberg equilibrium in affected American Saddlebred horses. This suggested that the EI disease locus was located on equine chromosome 8q, where LAMA3 is also located. PMID:14970704

  6. Risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jun-Zhen Qin

    Full Text Available BACKGROUND: Studies on the risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology (ART are relatively controversial and insufficient. Thus, to obtain a more precise evaluation of the risk of embryonic chromosomal abnormalities in first-trimester miscarriage after ART, we performed a meta-analysis of all available case-control studies relating to the cytogenetic analysis of chromosomal abnormalities in first-trimester miscarriage after ART. METHODS: Literature search in the electronic databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL based on the established strategy. Meta-regression, subgroup analysis, and Galbraith plots were conducted to explore the sources of heterogeneity. RESULTS: A total of 15 studies with 1,896 cases and 1,186 controls relevant to the risk of chromosomal abnormalities in first- trimester miscarriage after ART, and 8 studies with 601 cases and 602 controls evaluating frequency of chromosome anomaly for maternal age≥35 versus <35 were eligible for the meta-analysis. No statistical difference was found in risk of chromosomally abnormal miscarriage compared to natural conception and the different types of ART utilized, whereas the risk of fetal aneuploidy significantly increased with maternal age≥35 (OR 2.88, 95% CI: 1.74-4.77. CONCLUSIONS: ART treatment does not present an increased risk for chromosomal abnormalities occurring in a first trimester miscarriage, but incidence of fetal aneuploidy could increase significantly with advancing maternal age.

  7. A three-nucleotide mutation altering the Maize streak virus Rep pRBR-interaction motif reduces symptom severity in maize and partially reverts at high frequency without restoring pRBR-Rep binding.

    Science.gov (United States)

    Shepherd, Dionne N; Martin, Darren P; McGivern, David R; Boulton, Margaret I; Thomson, Jennifer A; Rybicki, Edward P

    2005-03-01

    Geminivirus infectivity is thought to depend on interactions between the virus replication-associated proteins Rep or RepA and host retinoblastoma-related proteins (pRBR), which control cell-cycle progression. It was determined that the substitution of two amino acids in the Maize streak virus (MSV) RepA pRBR-interaction motif (LLCNE to LLCLK) abolished detectable RepA-pRBR interaction in yeast without abolishing infectivity in maize. Although the mutant virus was infectious in maize, it induced less severe symptoms than the wild-type virus. Sequence analysis of progeny viral DNA isolated from infected maize enabled detection of a high-frequency single-nucleotide reversion of C(601)A in the 3 nt mutated sequence of the Rep gene. Although it did not restore RepA-pRBR interaction in yeast, sequence-specific PCR showed that, in five out of eight plants, the C(601)A reversion appeared by day 10 post-inoculation. In all plants, the C(601)A revertant eventually completely replaced the original mutant population, indicating a high selection pressure for the single-nucleotide reversion. Apart from potentially revealing an alternative or possibly additional function for the stretch of DNA that encodes the apparently non-essential pRBR-interaction motif of MSV Rep, the consistent emergence and eventual dominance of the C(601)A revertant population might provide a useful tool for investigating aspects of MSV biology, such as replication, mutation and evolution rates, and complex population phenomena, such as competition between quasispecies and population turnover. PMID:15722543

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

    Science.gov (United States)

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

    2015-01-01

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

  9. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  11. The Influence of Perfusion Values of Renal Cortex on Altering Image Frequency and Slice Thickness at CT Scan%扫描频率和层厚选择对肾皮质CT灌注参数值的影响

    Institute of Scientific and Technical Information of China (English)

    王琦; 时高峰; 王士杰; 田志辉

    2011-01-01

    目的 研究选择不同扫描频率和层厚对肾皮质CT灌注参数值的影响.方法 15例志愿者行肾脏CT灌注扫描,扫描时间为32 s.扫描层厚为5 mm,重建层厚2.5 mm.采用cine扫描模式完成扫描.然后依据间隔1 s、2 s、3 s分别选取一系列图像进行灌注分析,观察不同时间间隔灌注参数血流量(BF)、血容量(BV)、平均通过时间(MTT)、毛细血管表面通透性(PS)4项灌注参数值的差异.2种层厚的对照研究采用单变量计量资料中的配对t检验;不同频率选择采用配伍设计的方差分析.结果 通过cine模式、层厚5 mm连续扫描获得肾皮质的BF、BV、MTT、PS参数值分别为(407.10±86.69) ml·min-1·100 ml-1、(21.59±3.93) ml/100 g、(3.37±0.65) s、(56.42±16.30) ml·min-1·100 ml-1.与层厚为2.5 mm肾皮质的灌注参数值比较,不同层厚BF、BV、MTT和PS组间均无统计学意义(P>0.05).另与间隔1 s、间隔2 s、间隔3 s的肾皮质灌注参数值比较,前3种扫描时间间隔对BF、BV及PS灌注参数影响不大(P>0.05).间隔3 s的图像较少,得到的各项灌注参数值均明显不同于其他的序列,且相关性较差.结论 对肾皮质CT灌注成像,间隔1 s或2 s是值得提倡的扫描模式.5 mm和2.5 mm层厚的选择对CT灌注参数值没有影响.%Objective To study the influcnce of perfusion values of renal cortex on image frequency and slice thickness at CT scan . Methods 15 volunteers underwent renal CT cine perfusion during 32 second with 5 mm slice thickness and reconstructed 2. 5 mm slice thickness. The series of images in the interval at 1,2 and 3 second were chosen to analyse the blood flow(BF) , blood volume( BV) , mean transit time ( MTT) , permeability surface ( PS) of the renal cortex. The comparison between 2. 5 mm and 5 mm slice thickness was analayzed with paired t-test for depcndent samples. The comparison of the different image frequency was analayzed with two-way analysis of variance( ANOVA) and linear

  12. Chromosomal aberration analysis of persons occupationally exposed to radiation in Iran (2)

    International Nuclear Information System (INIS)

    The results of chromosome aberration analysis on lymphocytes from 333 persons suspected of being overexposed to X and gamma rays in recent years at Iran is presented. 91 persons were associated with industrial radiography, 124 with radiology and 118 with medical research and therapy centers. The total yields of chromosome aberration per 100 cells were respectively 3.76, 2.92 and 2.96. The frequencies of dicentrics which are important in biological dosimetry were respectively 0.18, 0.17 and 0.21. In this investigation, 50 subjects were also examined as control with a mean aberration of 1.14 per 100 cells. With regard to incidence of chromosome aberrations as mentioned, the rate of chromosome aberrations in industrial radiographers was the most significant

  13. The nonlinear relationship of radiation dose to chromosome aberrations among atomic bomb survivors, Hiroshima and Nagasaki

    International Nuclear Information System (INIS)

    The quantitative relationship of the frequency of cells with radiation-induced chromosome aberrations in peripheral leukocytes in atomic bomb survivors has been evaluated as a function of gamma and neutron doses. Three different models have been examined; each assumes a nonlinear-response to gamma rays and a linear-response to neutrons. From the standpoint of the goodness of fit of these models, the model which ''best'' fits the data of radiation-induced chromosome aberrations is the exponit model, where the frequency of aberrant cells increases exponentially with dose. It is of radiobiological interest that the goodness of fit for this model shows the frequencies of cells with any chromosome aberration or an exchange aberration to be dependent cubically on the gamma ray dose and linearly on the neutron dose. The relative biological effectiveness (RBE) of neutrons is calculated to be 129Dn sup(-2/3) (95% confidence intervals: (121 -- 137)Dn sup(-2/3)) for frequency of cells with any chromosome aberration, and 125Dn sup(-2/3) (95% confidence intervals: (117 -- 132)Dn sup(-2/3)) for the frequency of cells with an exchange aberration where Dn is the neutron dose. (author)

  14. Chromosome analysis of arsenic affected cattle

    Directory of Open Access Journals (Sweden)

    S. Shekhar

    2014-10-01

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

  15. Frequency spirals

    Science.gov (United States)

    Ottino-Löffler, Bertrand; Strogatz, Steven H.

    2016-09-01

    We study the dynamics of coupled phase oscillators on a two-dimensional Kuramoto lattice with periodic boundary conditions. For coupling strengths just below the transition to global phase-locking, we find localized spatiotemporal patterns that we call "frequency spirals." These patterns cannot be seen under time averaging; they become visible only when we examine the spatial variation of the oscillators' instantaneous frequencies, where they manifest themselves as two-armed rotating spirals. In the more familiar phase representation, they appear as wobbly periodic patterns surrounding a phase vortex. Unlike the stationary phase vortices seen in magnetic spin systems, or the rotating spiral waves seen in reaction-diffusion systems, frequency spirals librate: the phases of the oscillators surrounding the central vortex move forward and then backward, executing a periodic motion with zero winding number. We construct the simplest frequency spiral and characterize its properties using analytical and numerical methods. Simulations show that frequency spirals in large lattices behave much like this simple prototype.

  16. The peripheral chromosome scaffold, a novel structural component of mitotic chromosomes.

    Science.gov (United States)

    Sheval, Eugene V; Polyakov, Vladimir Y

    2008-06-01

    Using an original high-salt extraction protocol, we observed a novel chromosome substructure, referred to as the peripheral chromosome scaffold. This chromosome domain contained the perichromosomal layer proteins pKi-67, B23/nucleophosmin and fibrillarin, but no DNA fragments (i.e., the loop domain bases were not associated with the peripheral scaffold). Modern models of chromosome organization do not predict the existence of a peripheral chromosome scaffold domain, and thus our observations have conceptual implications for understanding chromosome architecture. PMID:18337132

  17. Large-scale polymorphism near the ends of several human chromosomes analyzed by using fluorescence in situ hybridization (FISH)

    Energy Technology Data Exchange (ETDEWEB)

    Trask, B.J.; Friedman, C. [Univ. of Washington, Seattle, WA (United States); Giorgi, D. [CNRS, Montpelier (France)] [and others

    1994-09-01

    We have discovered a large DNA segment that is polymorphically present at the ends of several human chromosomes. The segment, f7501, was originally derived form a human chromosome 19-specific cosmid library. FISH was used to determine the cosmid`s chromosomal distribution on 44 unrelated humans and several closely related primates. The human subjects represent a diversity of reproductively isolated ethnic populations. FISH analysis revealed that sequences highly homologous to the cosmid`s insert are present on both homologs at 3q, 15q,. and 19p in almost all individuals (88, 85, and 87 of 88 homologs, respectively). Other chromosomes sites were labeled much more rarely in the sampled individuals. For example, 56 of the 88 analyzed chromosomes 11 were labeled (18+/+, 6-/-, and 20+/- individuals). In contrast, 2q was labeled on only 1/88 sampled chromosomes. The termini of 2q, 5q, 6p, 6q, 7p, 8p, 9p, 9q, 11p, 12q, 16p, 19q, and 20q and an interstitial site at 2q13-14 were labeled in at least one individual of the set. EcoR1-fragments derived from the cosmid showed the same hybridization pattern as the entire cosmid, indicating that at least 40 kbp is shared by these chromosome ends. Ethnic differences in the allele frequency of these polymorphic variants was observed. For example, signals were observed on 8/10 and 7/10 of the chromosomes 7p and 16q, respectively, derived form Biakan Pygmies, but these sites were infrequently labeled in non-Pygmy human populations (2/68, respectively). This region has undergone significant changes in chromosome location during human evolution. Strong signal was seen on chimpanzee and gorilla chromosome 3, which is homologous to human chromosome 4, a chromosome unlabeled in any of the humans we have analyzed.

  18. Possible roles of actin and myosin during anaphase chromosome movements in locust spermatocytes.

    Science.gov (United States)

    Fabian, Lacramioara; Forer, Arthur

    2007-01-01

    We tested whether the mechanisms of chromosome movement during anaphase in locust (Locusta migratoria L.) spermatocytes might be similar to those described for crane-fly spermatocytes. Actin and myosin have been implicated in anaphase chromosome movements in crane-fly spermatocytes, as indicated by the effects of inhibitors and by the localisations of actin and myosin in spindles. In this study, we tested whether locust spermatocyte spindles also utilise actin and myosin, and whether actin is involved in microtubule flux. Living locust spermatocytes were treated with inhibitors of actin (latrunculin B and cytochalasin D), myosin (BDM), or myosin phosphorylation (Y-27632 and ML-7). We added drugs (individually) during anaphase. Actin inhibitors alter anaphase: chromosomes either completely stop moving, slow, or sometimes accelerate. The myosin inhibitor, BDM, also alters anaphase: in most cases, the chromosomes drastically slow or stop. ML-7, an inhibitor of MLCK, causes chromosomes to stop, slow, or sometimes accelerate, similar to actin inhibitors. Y-27632, an inhibitor of Rho-kinase, drastically slows or stops anaphase chromosome movements. The effects of the drugs on anaphase movement are reversible: most of the half-bivalents resumed movement at normal speed after these drugs were washed out. Actin and myosin were present in the spindles in locations consistent with their possible involvement in force production. Microtubule flux along kinetochore fibres is an actin-dependent process, since LatB completely removes or drastically reduces the gap in microtubule acetylation at the kinetochore. These results suggest that actin and myosin are involved in anaphase chromosome movements in locust spermatocytes. PMID:17922265

  19. Differential radio-sensitivities of human chromosomes 1 and 2 in one donor in interphase- and metaphase-spreads after 60Co γ-irradiation

    International Nuclear Information System (INIS)

    Radiation-induced chromosome aberrations lead to a plethora of detrimental effects at cellular level. Chromosome aberrations provide broad spectrum of information ranging from probability of malignant transformation to assessment of absorbed dose. Studies mapping differences in radiation sensitivities between human chromosomes are seldom undertaken. Consequently, health risk assessment based on radio-sensitivities of individual chromosomes may be erroneous. Our efforts in this article, attempt to demonstrate differences in radio-sensitivities of human chromosome-1 and/or -2, both in interphase and metaphase spreads. Upon blood collection, dosimetry and irradiation were performed. Lymphocytes were isolated after whole-blood irradiation with 60Co γ-rays in the dose range of 0–5 Gy for both interphase, and metaphase aberration studies. Induction of premature chromosome condensation in interphase cells was accomplished using a phosphatase inhibitor, calyculin-A. Metaphase spreads were harvested from short-term peripheral blood lymphocyte cultures following colcemid arrest and using an automated metaphase harvester and spreader. Aberration analysis in both interphase and metaphase spreads were done using FISH. In interphase, aberrant cell and aberration frequency involving chromosome 1 and/or 2 increased linearly with radiation dose. In metaphase, aberrations increased in a linear-quadratic manner with dose. Our studies ascertain that chromosome-2 is more radio-sensitive than chromosome-1 in both interphase and metaphase stages, albeit the DNA content of chromosome-2 is lesser than chromosome-1 by almost 10 million base pairs. Differences in radio-sensitivities of chromosomes have implications in genetic damage, chromosome organization, and chromosome function. Designing research experiments based on our vital findings may bring benefit to radiation-induced risk assessment, therapeutics and development of chromosome specific biomarkers

  20. Radiation induced chromosome instability in human fibroblasts

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

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

    International Nuclear Information System (INIS)

    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

  3. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Castanos-Velez Esmeralda

    2006-09-01

    Full Text Available Abstract Background Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression. Results We investigated genome-wide gene expression in colorectal carcinoma (CRC and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC. Conclusion An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.

  4. Interphase Chromosome Conformation and Chromatin-Chromatin Interactions in Human Epithelial Cells Cultured Under Different Gravity Conditions

    Science.gov (United States)

    Zhang, Ye; Wong, Michael; Hada, Megumi; Wu, Honglu

    2015-01-01

    Microgravity has been shown to alter global gene expression patterns and protein levels both in cultured cells and animal models. It has been suggested that the packaging of chromatin fibers in the interphase nucleus is closely related to genome function, and the changes in transcriptional activity are tightly correlated with changes in chromatin folding. This study explores the changes of chromatin conformation and chromatin-chromatin interactions in the simulated microgravity environment, and investigates their correlation to the expression of genes located at different regions of the chromosome. To investigate the folding of chromatin in interphase under various culture conditions, human epithelial cells, fibroblasts, and lymphocytes were fixed in the G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome as separate colors. After images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multi-mega base pair scale. In order to determine the effects of microgravity on chromosome conformation and orientation, measures such as distance between homologous pairs, relative orientation of chromosome arms about a shared midpoint, and orientation of arms within individual chromosomes were all considered as potentially impacted by simulated microgravity conditions. The studies revealed non-random folding of chromatin in interphase, and suggested an association of interphase chromatin folding with radiation-induced chromosome aberration hotspots. Interestingly, the distributions of genes with expression changes over chromosome 3 in cells cultured under microgravity environment are apparently clustered on specific loci and chromosomes. This data provides important insights into how mammalian cells respond to microgravity at molecular level.

  5. How does DNA break during chromosomal translocations?

    OpenAIRE

    Nambiar, Mridula; Raghavan, Sathees C.

    2011-01-01

    Chromosomal translocations are one of the most common types of genetic rearrangements and are molecular signatures for many types of cancers. They are considered as primary causes for cancers, especially lymphoma and leukemia. Although many translocations have been reported in the last four decades, the mechanism by which chromosomes break during a translocation remains largely unknown. In this review, we summarize recent advances made in understanding the molecular mechanism of chromosomal t...

  6. Novel Gene Acquisition on Carnivore Y Chromosomes

    OpenAIRE

    Murphy, William J.; A J Pearks Wilkerson; Terje Raudsepp; Richa Agarwala; Schäffer, Alejandro A.; Roscoe Stanyon; Chowdhary, Bhanu P

    2006-01-01

    Despite its importance in harboring genes critical for spermatogenesis and male-specific functions, the Y chromosome has been largely excluded as a priority in recent mammalian genome sequencing projects. Only the human and chimpanzee Y chromosomes have been well characterized at the sequence level. This is primarily due to the presumed low overall gene content and highly repetitive nature of the Y chromosome and the ensuing difficulties using a shotgun sequence approach for assembly. Here we...

  7. Meiosis I: When Chromosomes Undergo Extreme Makeover

    OpenAIRE

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

    2013-01-01

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

  8. Multiple chromosomes of Azotobacter vinelandii.

    OpenAIRE

    1989-01-01

    The number of copies of the genes leuB, nifH, nifD, and nifK per cell of Azotobacter vinelandii has been determined to be about 80. A beta-lactamase gene was integrated into the A. vinelandii chromosome by single-point crossover. Subsequently, we have been able to detect nearly 80 copies of this beta-lactamase gene per cell of A. vinelandii when cultured for a large number of generations in the presence of ampicillin. The multiple copies of the beta-lactamase gene do not seem to be present on...

  9. Genetic and epigenetic changes of genes on chromosome 3 in human urogenital tumors

    Directory of Open Access Journals (Sweden)

    Gordiyuk V. V.

    2011-02-01

    Full Text Available Numerous disorders of genes and alterations of their expression are observed on a short arm of human chromosome 3, particularly in 3p14, 3p21, 3p24 compact regions in epithelial tumors. These aberrations affect the key biological processes specific for cancerogenesis. Such genes or their products could be used for diagnostics and prognosis of cancer. Genetical and epigenetical changes of a number of genes on chromosome 3 in human urogenital cancer, their role in cellular processes and signal pathways and perspectives as molecular markers of cancer diseases are analyzed in the review

  10. Microtubule detyrosination guides chromosomes during mitosis

    OpenAIRE

    Barisic, Marin; Silva e Sousa, Ricardo; Tripathy, Suvranta K.; Magiera, Maria M.; Zaytsev, Anatoly V.; Pereira, Ana L.; Janke, Carsten; Grishchuk, Ekaterina L.; Maiato, Helder

    2015-01-01

    Before chromosomes segregate into daughter cells they align at the mitotic spindle equator, a process known as chromosome congression. CENP-E/Kinesin-7 is a microtubule plus-end-directed kinetochore motor required for congression of pole-proximal chromosomes. Because the plus-ends of many astral microtubules in the spindle point to the cell cortex, it remains unknown how CENP-E guides pole-proximal chromosomes specifically towards the equator. Here we found that congression of pole-proximal c...

  11. Movement of chromosomes with severed kinetochore microtubules.

    Science.gov (United States)

    Forer, Arthur; Johansen, Kristen M; Johansen, Jørgen

    2015-05-01

    Experiments dating from 1966 and thereafter showed that anaphase chromosomes continued to move poleward after their kinetochore microtubules were severed by ultraviolet microbeam irradiation. These observations were initially met with scepticism as they contradicted the prevailing view that kinetochore fibre microtubules pulled chromosomes to the pole. However, recent experiments using visible light laser microbeam irradiations have corroborated these earlier experiments as anaphase chromosomes again were shown to move poleward after their kinetochore microtubules were severed. Thus, multiple independent studies using different techniques have shown that chromosomes can indeed move poleward without direct microtubule connections to the pole, with only a kinetochore 'stub' of microtubules. An issue not yet settled is: what propels the disconnected chromosome? There are two not necessarily mutually exclusive proposals in the literature: (1) chromosome movement is propelled by the kinetochore stub interacting with non-kinetochore microtubules and (2) chromosome movement is propelled by a spindle matrix acting on the stub. In this review, we summarise the data indicating that chromosomes can move with severed kinetochore microtubules and we discuss proposed mechanisms for chromosome movement with severed kinetochore microtubules. PMID:25576435

  12. Cognitive and medical features of chromosomal aneuploidy.

    Science.gov (United States)

    Hutaff-Lee, Christa; Cordeiro, Lisa; Tartaglia, Nicole

    2013-01-01

    This chapter describes the physical characteristics, medical complications, and cognitive and psychological profiles that are associated with chromosomal aneuploidy conditions, a group of conditions in which individuals are born with one or more additional chromosome. Overall, chromosomal aneuploidy conditions occur in approximately 1 in 250 children. Information regarding autosomal disorders including trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) are presented. Sex chromosome aneuploidy conditions such as Klinefelter syndrome (47,XXY), XYY, trisomy X, and Turner syndrome (45,X), in addition to less frequently occurring tetrasomy and pentasomy conditions are also covered. Treatment recommendations and suggestions for future research directions are discussed.

  13. 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.

  14. Cognitive and medical features of chromosomal aneuploidy.

    Science.gov (United States)

    Hutaff-Lee, Christa; Cordeiro, Lisa; Tartaglia, Nicole

    2013-01-01

    This chapter describes the physical characteristics, medical complications, and cognitive and psychological profiles that are associated with chromosomal aneuploidy conditions, a group of conditions in which individuals are born with one or more additional chromosome. Overall, chromosomal aneuploidy conditions occur in approximately 1 in 250 children. Information regarding autosomal disorders including trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) are presented. Sex chromosome aneuploidy conditions such as Klinefelter syndrome (47,XXY), XYY, trisomy X, and Turner syndrome (45,X), in addition to less frequently occurring tetrasomy and pentasomy conditions are also covered. Treatment recommendations and suggestions for future research directions are discussed. PMID:23622175

  15. Study on Pollen Chromosome Doubling in Zenjimaru Persimmon

    Institute of Scientific and Technical Information of China (English)

    GU Xiao-feng; LUO Zheng-rong

    2003-01-01

    The factors influencing pollen chromosome doubling in Zenjimaru persimmon were studied,based on the knowledge of meiosis process of pollen mother cells. The results showed: (1) the suitable concen-tration of colchicine was 0.3 - 0.5%; (2) the best doubling effect could be obtained during the period fromthe dipiotene stage to the diakinasis stage, and the highest proportion was up to 40.6 %; (3) considering giantpollen ratio and proportion of staminate-flower collection, the better treating frequency was 3 times; (4) giantpollen, which formed mainly from dyad and had bigger cell nucleus volume, was unreduced and hexaploid.

  16. Fragile site X chromosomes in mentally retarded boys.

    OpenAIRE

    Moon, H. R.; Moon, S. Y.

    1993-01-01

    The fragile X syndrome is a common X-linked mental retardation and autism, affecting females as well as males. The fragile site X chromosomes were studied in a series of 153 mentally retarded boys of unknown etiology to determine the frequency of fragile X syndrome, and to assess the feasibility of making a clinical diagnosis of the fragile X syndrome in young boys before cytogenetic results were known. The 10 boys (6.4%) were positive for fra (X) (q27). The phenotype of fra (X) (q27) positiv...

  17. Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

    Directory of Open Access Journals (Sweden)

    Goldstein Alisa M

    2006-11-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Results Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP array, including loss of heterozygosity (LOH and copy number alterations (CNA, for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q, including 20 novel LOH regions (10 kb to 4.26 Mb. Fifteen CNA-loss regions (200 kb to 4.3 Mb and 36 CNA-gain regions (200 kb to 9.3 Mb were also identified. Conclusion These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

  18. Epigenetic Remodeling of Meiotic Crossover Frequency in Arabidopsis thaliana DNA Methyltransferase Mutants

    NARCIS (Netherlands)

    Yelina, N.E.; Choi, K.; Chelysheva, L.; Macaulay, M.; Snoo, de B.; Wijnker, T.G.; Miller, N.; Drouaud, J.; Grelon, M.; Copenhaver, G.P.; Mezard, C.; Kelly, K.A.; Henderson, I.R.

    2012-01-01

    Meiosis is a specialized eukaryotic cell division that generates haploid gametes required for sexual reproduction. During meiosis, homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover (CO). Meiotic CO frequency varies along the physical length of chromosomes and is d

  19. 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

  20. Sexual dimorphism in white campion: complex control of carpel number is revealed by Y chromosome deletions

    International Nuclear Information System (INIS)

    Sexual dimorphism in the dioecious plant white campion (Silene latifolia = Melandrium album) is under the control of two main regions on the Y chromosome. One such region, encoding the gynoecium-suppressing function (GSF), is responsible for the arrest of carpel initiation in male flowers. To generate chromosomal deletions, we used pollen irradiation in male plants to produce hermaphroditic mutants (bsx mutants) in which carpel development was restored. The mutants resulted from alterations in at least two GSF chromosomal regions, one autosomal and one located on the distal half of the (p)-arm of the Y chromosome. The two mutations affected carpel development independently, each mutation showing incomplete penetrance and variegation, albeit at significantly different levels. During successive meiotic generations, a progressive increase in penetrance and a reduction in variegation levels were observed and quantified at the level of the Y-linked GSF (GSF-Y). Possible mechanisms are proposed to explain the behavior of the bsx mutations: epigenetic regulation or/and second-site mutation of modifier genes. In addition, studies on the inheritance of the hermaphroditic trait showed that, unlike wild-type Y chromosomes, deleted Y chromosomes can be transmitted through both the male and the female lines. Altogether, these findings bring experimental support, on the one hand, to the existence on the Y chromosome of genic meiotic drive function(s) and, on the other hand, to models that consider that dioecy evolved through multiple mutation events. As such, the GSF is actually a system containing more than one locus and whose primary component is located on the Y chromosome

  1. Uniparental disomy of chromosome 16 in offsprings of Familial Mediterranean Fever (FMF) patients treated with colchicine

    Energy Technology Data Exchange (ETDEWEB)

    Korenstein, A.; Avivi, L. [Tel-Avivi University (Israel); Ravia, Y. [Sheba Medical Center, Tel-Hashomer (Israel)

    1994-09-01

    Uniparental disomy (UPD), an altered mode of Mendelian inheritance, may reveal expression of recessive alleles due to the loss of heterozygosity, as well as imprinted genes. The mechanism causing UPD can be best elucidated in offsprings of individuals at high risk for chromosomal non-disjunction. Such individuals are Familial Mediterranean Fever (FMF) patients, who are routinely treated with the antimitotic agent colchicine, and, therefore, are expected to be at an increased risk for aneuploidy. A dominant mode of inheritance was observed in four FMF offsprings having one parent exhibiting the FMF phenotype (homozygote recessive) while the other was free of the mutant allele (as assumed from his ethnic background). Out of these, two exhibited UPD of chromosome 16, which carries the FMF gene, as judged from four different RFLP markers along this chromosome. Since in both case the UPD was of maternal origin, it is suggested that the colchicine-treated FMF mothers contributed two doses of chromosome 16, presumably due to meiotic non-disjunction, followed by a somatic loss of the paternal chromosome 16 in the embryo. The somatic chromosome loss is also assumed to be caused by the antimitotic drug since the mother continued to receive it during pregnancy. Whether the UPD arises from the colchicine treatment, from the high tendency of chromosome 16 to maternal non-disjunction or from both remains to be elucidated. Our results highlighted the importance of taking UPD into account when counseling individuals who are either treated with antimitotic agents or are carriers of recessive mutant alleles which are mapped to chromosomes prone to aneuploidy.

  2. Low Dose-Rate Effects on Chromosomal Aberrations in Workers Occupationally Exposed to Ionising Radiation

    International Nuclear Information System (INIS)

    Full text: Occupational exposure to ionising radiation can be assessed by chromosomal aberrations detected in peripheral blood lymphocytes. Blood samples were collected from 47 occupationally exposed individuals (X-ray diagnostic machines and industrial gamma defectoscopy). The chromosomal aberrations were analysed from at least 500 metaphases per person and their frequencies were compared with those obtained from 110 control individuals. It has been noticed the higher frequency of chromosomal aberrations in the exposed group related to the control. The increase was analysed according to the age groups (31-40, 41-50, and 51-60), sex and duration of employment. The higher frequency of dicentrics was not directly correlated with the age or duration of employment in the exposed group. The acentric fragments were encountered with much higher frequency in the exposed group. The chromosomal aberrations induced by low dose-rate in occupationally exposed people revealed the degree of individual sensitivity and the severity of the initial damage depending on the biological-pathological conditions. (author)

  3. Reactivation of inactive X chromosome in buccal smear of carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Natekar Prashant

    2008-01-01

    Full Text Available Buccal mucosal smears of 100 female patients of carcinoma of breast were compared with 100 controls matched accordingly. The frequency of Barr bodies was significantly lower in carcinoma of breast patients (menstruating and menopausal women P < 0.001 when compared with controls indicating reactivation of the inactive X chromosome.

  4. Cosegregation of hypertrophic cardiomyopathy and a fragile site on chromosome 16 in a large Italian family.

    OpenAIRE

    M. Ferraro; Scarton, G; Ambrosini, M

    1990-01-01

    We studied the karyotypes of 10 members of a family in whom hypertrophic cardiomyopathy is segregating as an autosomal dominant trait. In all those affected by the disease, a fragile site on the long arm of chromosome 16 was found, expressed with different frequencies, but the unaffected family members did not show this trait.

  5. CHANGES IN RELATIVE FITNESS WITH TEMPERATURE AMONG 2ND CHROMOSOME ARRANGEMENTS IN DROSOPHILA-MELANOGASTER

    NARCIS (Netherlands)

    VANDELDEN, W; KAMPING, A

    1991-01-01

    Development time and body weight of In(2L)t, R (a putative short inversion on the left arm of the second chromosome) and ST (standard) karyotypes of Drosophila melanogaster were measured at different temperatures. Frequency changes were followed in populations polymorphic for In(2L)t and ST and kept

  6. Genetic and physical mapping of two centromere-proximal regions of chromosome IV in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Aleksenko, Alexei Y.; Nielsen, Michael Lynge; Clutterbuck, A.J.

    2001-01-01

    revision of the genetic map of the chromosome, including the position of the centromere, Comparison of physical and genetic maps indicates that meiotic recombination is low in subcentromeric DNA, its frequency being reduced from 1 crossover per 0.8 Mb to approximately 1 crossover per 5 Mb per meiosis...

  7. The Philadelphia chromosome in leukemogenesis

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  8. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  9. Chromosomal instability determines taxane response.

    Science.gov (United States)

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

    2009-05-26

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

  10. Xeroderma pigmentosum and medulloblastoma: chromosomal damage to lymphocytes during radiotherapy

    International Nuclear Information System (INIS)

    The effects of radiotherapy on a patient with xeroderma pigmentosum (XP) of complementation group C and medulloblastoma are reported. His lymphocytes showed no x-ray-induced chromatid damage, but unstable chromosomal aberrations increased throughout the course of radiotherapy as observed also in two other children (patients 2 and 3) with a similar tumor. Such damage was more dependent on spinal than cranial irradiation, lowest in the XP patient and highest in patient 3. Interindividual differences seemed largely due to the relative volume of body irradiated, but the damage in patient 3 remained relatively high even after accounting for such a factor. A maximum of 36, 68, and 77% of lymphocytes had aberrations in the XP and patients 2 and 3, respectively, but chromosomal damage did not show a Poisson distribution and indicated admixture of irradiated and nonirradiated cells. The relative frequency of the irradiated cells was estimated and seemed proportional to the ratios of the average irradiated field to the total body area. The XP patient showed no preferential loss of highly damaged cells and seemed not to suffer excessive chromosomal damage; he had a normal clinical response to and a favorable outcome of radiotherapy. These findings reduce anxiety on the use of radiotherapy in XP patients or at least in those of group C

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

    International Nuclear Information System (INIS)

    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

  12. Genetic variation of goat Y chromosome in the Sardinian population

    Directory of Open Access Journals (Sweden)

    Antonello Carta

    2010-01-01

    Full Text Available Sardinian goat population is commonly considered a crossbred of autochthonous animals with improved Mediterranean breeds, mainly the Maltese. It has been demonstrated by using autosomal microsatellites that the Sardinian goats can be divided into three subpopulations: Sardinian, crossbred with Maltese, and Maltese. The aim of this study was to evaluate sequence variation at Y chromosome in Sardinian bucks and to integrate autosomal microsatellites data. Blood from 190 bucks from 68 farms spread in the main Sardinian goat farming areas was sampled. Three ECONOGENE project primer pairs plus an additional one corresponding to a total of 7 SNPs were used. For all common SNPs, the most frequent allele corresponded to the ECONOGENE one. The additional analysed SNP showed allelic frequencies similar to the other markers. The comparison with haplotypes based on the 6 common SNPs showed that the Sardinian most frequent haplotype corresponded to the predominant one in Central Europe. Results of this study showed that the Sardinian goat population has 8 haplotypes resulting in a large diversity of paternal lineages. The next step will be linking autosomal information to Y chromosome data. In fact, up to date, it seems unfeasible to detect recent upgrading breeds by using Y chromosome variation only.

  13. A collaborative study of the EDNAP group regarding Y-chromosome binary polymorphism analysis

    DEFF Research Database (Denmark)

    Brion, María; Dupuy, Berit M; Heinrich, Marielle;

    2005-01-01

    typing. A total of 535 samples from six different European populations were also analysed. In Galicia (NW Spain) and Belgium, the most frequent haplogroup was R1b*(xR1b1,R1b3df). Haplogroup F*(xK) is one of the most frequent in Austria and Denmark, while the lowest frequency appear in Belgium. Haplogroup...... frequencies found in this collaborative study were compared with previously published European Y-chromosome haplogroup data....

  14. Stable chromosome aberrations in the reconstruction of radiation doses

    International Nuclear Information System (INIS)

    Chromosome-type aberrations, such as dicentric and translocation chromosomes, are biomarkers of exposure to ionizing radiation. So far, analysis of dicentric chromosomes in peripheral blood lymphocytes has been the only method routinely used in biological dose assessment. During division of T cell precursors, proliferative death of cells containing dicentric chromosomes reduces the number of such lymphocytes in peripheral blood. Dicentrics are thus suitable for dose calculations during a reasonably short period after exposure to radiation. Unlike dicentrics, translocations persist in cell division and enable dose estimation over long time periods following exposure. A recent development in molecular biology, the FISH (fluorescence in situ hybridization) chromosome-painting technique, has opened the possibility for accurate recognition of translocations and thus retrospective determination of dose. The purpose of the present study was to evaluate the applicability of translocation analysis by means of FISH chromosome painting for retrospective dosimetry. In the construction of acute dose-effect curves for 60Co g-ray-induced chromosomal aberrations using FISH chromosome painting, translocations showed a linear-quadratic relationship to dose, similar to that seen in dicentrics. Donor-dependent translocation frequencies at control level and at low doses were observed. The linear part of the calibration curve for two way translocations, i.e. both translocation chromosomes present, proved to be more reliable than the comparable low-dose response for total translocations, which include both two- and one-way translocations. The results indicate that the linear part of the curve requires precise determination, particularly since application of the technique will probably cover mainly chronically exposed subjects. An opportunity to gain direct information on translocation persistence over time was opened by obtaining repeated samples from subjects accidentally exposed to

  15. Molecular cytogenetic characterization of a recombinant chromosome rec(22)dup(22q)inv(22)(p13q12.2).

    Science.gov (United States)

    Tonk, Vijay S; Jesurun, C A; Morgan, David L; Lockhart, Lillian H; Velagaleti, Gopalrao V N

    2004-01-01

    Pericentric inversions occur at a frequency of 0.12-0.7% in humans. However, pericentric inversions of chromosome 22 appear to be common, especially in patients originating from the Guadalajara region of Mexico. Here, we report a seventh case of a pericentric inversion of chromosome 22, the resulting recombinant chromosome, and describe the phenotypic features associated with such a recombinant chromosome. It is interesting that five of the seven patients with inv(22) come from Mexico, and four of the five patients from the Guadalajara region.

  16. [Monitoring chromosome mutations in large-scale breeding operations].

    Science.gov (United States)

    Rubes, J; Raszyk, J; Horínová, Z; Gajdůsková, V; Masek, J; Docekalová, H; Bartos, J; Neumannová, M

    1988-03-01

    The frequency of chromosomal aberrations and exchanges of sister chromatids (SCEs) in peripheral lymphocytes was studied in 65 pigs from five large breeding herds. Four groups comprised fattened pigs and the fifth group consisted of sows from a large multiplier breeding herd. During the investigation, the dust from the sites was analyzed for the presence of zinc, lead, cadmium, mercury, aflatoxin B1, PCB, DDT, and lindane. The average frequency of aberrant cells (AB.B) in the pigs of group I was 3.85 +/- 1.60%, in group II 2.10 +/- 1.52%, in group III 5.01 +/- 2.1%, in group IV 3.50 +/- 1.58%, and in group V 6.20 +/- 3.21%. The cytogenetic finding corresponded to the differences in the amount of foreign substances found in the dust on the premises where the animals of all groups were kept. The average frequency of the SCEs was 7.00 +/- 1.10 (I), 6.51 +/- 0.89 (II), 6.92 +/- 0.72 (III), 7.10 +/- 0.85 (IV) and 7.06 +/- 1.47 (V) per one cell. Statistically significant differences in the numbers of AB.B. were recorded between groups II and I, II and IV, I and III, IV and V (p less than 0.05) and between groups II and III, II and V (p less than 0.01). There was no statistically significant difference in the frequency of SCEs. The determination of the frequency of chromosomal aberrations can be used for the hygienic control of the degree of exposure of pigs to mutagens. PMID:3129856

  17. Measurement of background translocation frequencies in individuals with clones

    Energy Technology Data Exchange (ETDEWEB)

    Wade, M.J.

    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.

  18. Developmental characterization and chromosomal mapping of the 5-azacytidine-sensitive fluF locus of Aspergillus nidulans.

    Science.gov (United States)

    Tamame, M; Antequera, F; Santos, E

    1988-01-01

    In Aspergillus nidulans, a fungus that possesses negligible, if any, levels of methylation in its genome, low concentrations of 5-azacytidine (5-AC) convert a high percentage of the cell population to fluffy phenotypic variants through a heritable modification of a single nuclear gene (M. Tamame, F. Antequera, J. R. Villanueva, and T. Santos, Mol. Cell. Biol. 3:2287-2297, 1983). This new 5-AC-altered locus, designated here fluF1, was mapped as the closest marker to the centromere that has been identified so far on the right arm of chromosome VIII. Of all mutagens tested, only 5-AC induced the fluffy phenotype with a significant frequency. Furthermore, we determined that the wild-type, dominant allele of the fluF gene was primarily accessible to modification by 5-AC at the initial stages of fungal vegetative growth. These results indicated that 5-AC does not act through random mutagenic action but, rather, that fluF constitutes a specific target for this drug during a well-defined period of fungal development. Alteration of fluF by 5-AC resulted in a dramatic modification of the developmental program of A. nidulans. The resulting fluffy clones were characterized by massive, uncontrolled proliferation of undifferentiated hyphae, a drastic delay in the onset of asexual differentiation (conidiation), and colonies with an invasive nature. These features are reminiscent of the malignant properties of tumor cells. We propose that the locus fluF plays a primary role in the control of cell proliferation in A. nidulans and that its alteration by 5-AC produces pleiotropic modifications of the developmental program of this fungus. Images PMID:2463470